Ehac 515

European Heart Journal (2023) 44, 262–279 SPECIAL ARTICLE
https://doi.org/10.1093/eurheartj/ehac515
Acute, periprocedural and longterm

antithrombotic therapy in older adults
2022 Update by the ESC Working Group on Thrombosis
Felicita Andreotti 1,2*, Tobias Geisler 3*†, Jean-Philippe Collet 4, Bruna Gigante5,
Downloaded from https://academic.oup.com/eurheartj/article/44/4/262/6881548 by guest on 18 June 2023

Diana A. Gorog6,7, Sigrun Halvorsen8, Gregory Y. H. Lip9, Joao Morais10,
Eliano Pio Navarese11,12, Carlo Patrono 13,14, Bianca Rocca13,14, Andrea Rubboli15,
Dirk Sibbing 16, Robert F. Storey17, Freek W.A. Verheugt18, and Gemma Vilahur19,20
1
Department of Cardiovascular Sciences, Fondazione Policlinico Universitario Gemelli IRCCS, Largo F Vito 1, 00168 Rome, Italy; 2Department of Cardiovascular and Pneumological
Sciences, Catholic University, Rome, Italy; 3Department of Cardiology and Angiology, University Hospital, Eberhard-Karls-University Tuebingen, Otfried-Müller-Straße 10, 72076
Tuebingen, Germany; 4Paris Sorbonne Université (UPMC), ACTION Study Group, INSERM UMR_S 1166, Institut de Cardiologie, Pitié-Salpêtrière Hospital (AP-HP), Paris, France; 5Division
of Cardiovascular Medicine, Department of Medicine, Karolinska Institutet and Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden; 6National
Heart and Lung Institute, Imperial College, London, UK; 7Postgraduate Medical School, University of Hertfordshire, Hertfordshire, UK; 8Department of Cardiology, Oslo University Hospital
Ulleval, University of Oslo, Oslo, Norway; 9Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK; 10Serviço de
Cardiologia, Centro Hospitalar de Leiria and Center for Innovative Care and Health Technology (ciTechCare), Leiria Polytechnic Institute, Leiria, Portugal; 11Department of Cardiology,
Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland; 12SIRIO MEDICINE Network and Faculty of Medicine University of Alberta, Edmonton, Canada; 13Department of
Safety and Bioethics, Section on Pharmacology, Catholic University School of Medicine, Rome, Italy; 14Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy; 15Division of
Cardiology, Department of Cardiovascular Diseases—AUSL Romagna, S. Maria delle Croci Hospital, Ravenna, Italy; 16Privatklinik Lauterbacher Mühle am Ostersee, Seeshaupt, Germany &
Ludwig-Maximilians-Universität (LMU) München, Munich, Germany; 17Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK; 18Department
of Cardiology, Heartcenter, Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam, The Netherlands; 19Cardiovascular Program-ICCC, Research Institute-Hospital de la Santa Creu i Sant Pau,
IIB-Sant Pau, Barcelona, Spain; and 20CIBERCV, Instituto Salud Carlos III, Madrid, Spain
Received 25 November 2021; revised 22 July 2022; accepted 7 September 2022; online publish-ahead-of-print 7 December 2022
Graphical Abstract
Bleeding/thrombotic risk stratification by factors below or other tools (e.g. ARC HBR trade-off)
syndrome patients fibrillation patients

No routine P2Y12 inhibitor pre-angiography for NSTE-ACS
and CCS.
Improving medical
* Corresponding authors. Emails: felicita.andreotti@unicatt.it; tobias.geisler@med.uni-tuebingen.de

†
Share first and corresponding authorship.
© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Antithrombotic therapy in the elderly 263
Antithrombotic therapy in older adults: challenges and selected consensus points. AC, anticoagulant; ACS, acute coronary syn
drome; AF, atrial fibrillation; AP, antiplatelet; APT, antiplatelet therapy; ARC HBR, Academic Research Consortium High Bleeding Risk; ATT, antith
rombotic therapy; BP, blood pressure; CCS, chronic coronary syndrome; DAPT, dual antiplatelet therapy; EMA, European Medicines Agency; Hb,
haemoglobin; LAAC, left atrial appendage closure; MI, myocardial infarction; NOAC, non-vitamin K antagonist oral anticoagulant; NSTE, non-ST-
elevation; NSAID, non-steroidal anti-inflammatory drugs; PAD, peripheral artery disease; PPI, proton pump inhibitor; TAT, triple antithrombotic
therapy; TAVI, transcatheter aortic valve implantation; TNK, tenecteplase.
Abstract
The first international guidance on antithrombotic therapy in the elderly came from the European Society of Cardiology Working Group on
Thrombosis in 2015. This same group has updated its previous report on antiplatelet and anticoagulant drugs for older patients with acute or chronic
coronary syndromes, atrial fibrillation, or undergoing surgery or procedures typical of the elderly (transcatheter aortic valve implantation and left atrial

appendage closure). The aim is to provide a succinct but comprehensive tool for readers to understand the bases of antithrombotic therapy in older
patients, despite the complexities of comorbidities, comedications and uncertain ischaemic- vs. bleeding-risk balance. Fourteen updated consensus
statements integrate recent trial data and other evidence, with a focus on high bleeding risk. Guideline recommendations, when present, are highlighted,
as well as gaps in evidence. Key consensus points include efforts to improve medical adherence through deprescribing and polypill use; adoption of
universal risk definitions for bleeding, myocardial infarction, stroke and cause-specific death; multiple bleeding-avoidance strategies, ranging from gas
troprotection with aspirin use to selection of antithrombotic-drug composition, dosing and duration tailored to multiple variables (setting, history, over
all risk, age, weight, renal function, comedications, procedures) that need special consideration when managing older adults.
.............................................................................................................................................................................................
Keywords Elderly • Antiplatelet • Anticoagulant • Coronary syndromes • Atrial fibrillation • Surgery • TAVI • LAAC
Introduction to preventable cardiovascular outcomes.13–16 In older adults with CVD,

poor cognition/health literacy, low socioeconomic status, race/ethnicity,
Declining birth rates and prevention or postponement of major causes of as well as side-effects, costs, complexity, and duration of treatment are
death are causing older segments of the population to grow faster than any associated with reduced adherence.13,15,17 On the other hand, among eld
other.1–3 In 2020, ∼100 million Europeans were ≥65 years and 25 million erly patients with AF-related stroke, caregiver administration, functional
>80, with the latter estimated to reach 75 million in 2100.1 dependency, and previous antithrombotic therapy are associated with in
Atherothrombotic cardiovascular diseases (CVDs) remain the leading creased adherence to oral anticoagulation (OAC).16 Deprescribing, de
cause of death among adults worldwide,4 and multimorbidity (defined as fined as the supervised reduction of inappropriate polypharmacy, and
≥2 chronic diseases) affects 55%–98% of people >65 years.3 Regardless use of polypills may increase adherence by ∼30%18–22 and lead to im
of sex, the incidence of CVD and bleeding increase continuously beyond proved efficacy, as suggested by an individual-patient-data meta-analysis
50–55 years.5–8 Degenerative valvular heart disease9 and conditions re of randomized controlled trials (RCTs).23 The latter (mean ± standard de
quiring percutaneous interventions or surgery also prevail in older adults.10 viation age 63 ± 7 years) showed that a fixed-dose combination polypill
Given the temporal trends in age-related morbidities and new evidence containing at least two blood pressure lowering agents plus a statin
from antithrombotic trials, the European Society of Cardiology (ESC) (with or without aspirin) reduced adverse cardiovascular events over a
Working Group on Thrombosis has updated its 2015 scientific document median follow-up of 5 years compared to usual care [hazard ratio (HR)
on antithrombotic therapy in the elderly.11 Paired authors searched major 0.62, 95% confidence interval (CI) 0.53–0.73, P < 0.0001] without signifi
literature databases on CVD, atrial fibrillation (AF), and interventions up to cantly increasing major bleeding.23 The benefits were consistent across
April 2022; venous thromboembolism, non-cardioembolic stroke, and age (<60, 60–66, and >66 years).23
peripheral artery disease (PAD) were deliberately omitted. While age
≥75 years is widely accepted to define ‘elderly’, a rigid inferior cut-off
was intentionally avoided given: (i) different thresholds across studies; Bleeding in older adults: risk assessment,
(ii) generally healthier contemporary older adults compared to past prevention, and general management
age-matched individuals; (iii) linear rather than stepwise increases in
Tools to estimate the benefits and risks of antithrombotic therapies and
bleeding and thrombotic risks.5,6,12 The key consensus points of this
to avoid undertreatment driven by perceived bleeding risk alone11 include
age-focused document are provided in Table 1.
the CHA2DS2-VASc, HAS-BLED, BleeMACS, ABC, DAPT, and
PRECISE-DAPT thrombotic and/or bleeding risk scores.7,24–27 All incorp
Improving antithrombotic-drug orate age and require some calculation or specific biomarker measure.
adherence in older adults For patients undergoing percutaneous coronary intervention (PCI), the
Adherence is considered the extent to which patients take medications Academic Research Consortium (ARC) has quantified high bleeding risk
as prescribed,13 including duration (persistence).14 Measures include pill (HBR) as a 1-year major bleeding rate ≥4%; it has also defined HBR quali
count, pharmacy records, electronic monitoring, and proportion of tatively by the presence of one major or two minor simple routine fea
days covered.13 Antithrombotic-drug adherence is crucial for optimal tures (Table 2).28,29 While age ≥75 represents a minor bleeding risk
efficacy and safety13 and a cut-off >80% of days covered (generally feature, studies have reported major bleeding events ≥4% at 1 year in
used to define good adherence) may be too low a threshold in relation this age group,29 likely owing to concomitant renal impairment, anaemia
264 F. Andreotti et al.
or non-steroidal anti-inflammatory drug (NSAID) use that enhance bleed dose aspirin monotherapy are generally similar to those with ticagrelor (in
ing risk further (Table 2).28 The guideline-recommended PRECISE-DAPT cluding in the elderly),51–53 and higher compared to unguided clopidogrel
score, estimating major and minor bleeding events in patients undergoing monotherapy (see section ‘Safer antiplatelet regimens’).54
PCI and integrating age as a continuous variable, prompts short rather For primary CVD prevention, among adults ≥70 years without evidence
than prolonged dual antiplatelet therapy (DAPT) for scores ≥25.30–32 of atherosclerotic CVD and with an estimated risk of major adverse cardio
Unlike PRECISE-DAPT, the ARC-HBR score includes surgery, cancer, vascular events <1% per year, current data indicate an unfavourable bene
and liver and brain diseases.28 Lack of head-to-head validation of fit–risk balance of longterm low-dose aspirin that does not justify its
PRECISE-DAPT and ARC-HBR scores in older adults prevents the rec initiation on a routine basis.55–58 Elderly subjects at higher CVD risk and
ommendation of one over the other.33 Since age is one of many criteria without HBR may benefit from aspirin in primary prevention, as suggested
(several of which affected by age), both scores likely trend towards a ceil by a recent individual-patient-data meta-analysis.23
ing effect ≥75 years.34 Of note, few bleeding scores to date have been de
veloped specifically in the elderly.35 For AF patients, HAS-BLED remains Dual antiplatelet therapy in older adults with acute
the guideline-recommended bleeding risk score.24 coronary syndrome and/or undergoing percutaneous
Although antithrombotic therapy in elderly CVD patients (including coronary intervention

those at HBR) yields net clinical benefit given the increased thrombotic Regardless of age, current guidelines recommend a P2Y12 inhibitor in
risk with age,11,24,36–39 systematic HBR assessment is recommended by combination with aspirin (i.e. DAPT) after ACS and/or coronary stenting,
multiple ESC guidelines to drive safer strategies.24,30–32,40,41 Indeed, recent for variable durations according to patient bleeding and ischaemic
studies indicate that older age may predict bleeding more than thrombotic risks.30–32,40,41 The choice of P2Y12 inhibitor is driven by efficacy, safety,
events and that the trade-off of bleeding vs. thrombotic events can be es and tolerability data, by clinical presentation (discussed below), and by
timated through a balanced integration of different risk predictors management strategy, particularly in comorbid, comedicated elderly pa
(Graphical Abstract).26,42,43 Common preventive measures against intra- tients. Dyspnoea is a common side-effect of ticagrelor that may lead to
and extracranial bleeding include optimal blood pressure control, gastro treatment discontinuation,59 whereas wide interindividual variability in
protection with proton pump inhibitors (PPIs), appropriate criteria for platelet inhibition has been shown for clopidogrel.60 Pharmacokinetic
revascularisation,31,44 avoidance of routine P2Y12 inhibitor before coron and pharmacodynamic data indicate that older age affects the metabol
ary angiography for chronic or non-ST-elevation acute coronary syn ism and maximum antiplatelet effect of prasugrel and ticagrelor to a less
drome (NSTE-ACS) patients,31,44 use of radial arterial access,32,45 stent er extent than of clopidogrel, although with undetermined clinical
selection,31,44 modulation of DAPT composition/duration,31,44 and tailor implications.61–64 For chronic coronary syndromes (CCSs), in older as
ing drug regimens to age, body weight,36 renal function, prior stroke, and in younger patients undergoing PCI, clopidogrel remains the current
bleeding risk category, according to European Medicines Agency (EMA) ESC guideline-recommended P2Y12 inhibitor of choice.30,32
recommendations (Table 3). A PPI along with antithrombotic therapy is On the background of aspirin, compared to clopidogrel 75 mg daily,
indicated for concomitant steroid or NSAID administration, for combined superior efficacy was shown in RCTs for prasugrel 10 mg daily in
antiplatelet and OAC therapy, for DAPT,30 and for gastrointestinal bleed PCI-treated ACS patients over a median of 14.5 months and for ticagre
ing risk factors (e.g. prior peptic ulcer, prior gastrointestinal bleed, ad lor 90 mg twice daily in ACS patients with or without PCI over a median
vanced age) (see below).30,31,46,47 With clopidogrel, guidelines favour of 9 months, although the bleeding risk was enhanced.65,66 A subgroup
pantoprazole or rabeprazole PPIs over omeprazole or esomeprazole, as analysis of 2878 ACS patients ≥75 years indicated that ticagrelor
the latter may have clinically relevant interactions.30 When bleeding oc 90 mg twice daily can favourably be used vs. clopidogrel in this group
curs, reducing drug number or adjusting the dose (when appropriate), as in younger patients.67 On the other hand, among 1002 randomized pa
along with other secondary prevention measures (i.e. gastroprotection, tients all ≥70 years with NSTE-ACS, clopidogrel compared to ticagrelor
Helicobacter pylori eradication) usually enables continuation or resumption led to less bleeding without increasing the composite of all-cause death,
of antithrombotic therapy after bleeding.45 MI, stroke, or bleeding over 12 months.68 SWEDEHEART registry data
of 14 005 ACS patients ≥80 years suggest that ticagrelor use may be as
sociated with 17% and 48% higher relative risks of death and bleeding,
Oral antithrombotic-drug and with 20% and 22% relative risk reductions of MI and stroke, respect
ively, compared to clopidogrel-treated patients.69 The EMA and ESC
strategies in older adults guidelines31 recommend prasugrel dose reduction from 10 to 5 mg daily
for patients ≥75 years, based on pharmacokinetic and clinical data.70–72
Primary and secondary cardiovascular
At these doses, prasugrel showed comparable efficacy and safety to clo
disease prevention pidogrel in randomized ACS patients ≥75 years managed either invasively
Antiplatelet monotherapy (n = 1443)70 or medically (n = 2083),71 and superior efficacy compared
For secondary CVD prevention, the benefit vs. risk profile of longterm low- to ticagrelor in a recent ACS trial of 4018 patients. In the latter, however,
dose aspirin vs. no antiplatelet agent is favourable in older as in younger only 982 patients were ≥75 years.73 A recent meta-analysis of 12 rando
age.48,49 Gastrointestinal mucosal injury affects >90% of patients on aspirin mized trials excluding open-label ones [mean 66 (range 62–80) years]
or clopidogrel monotherapy.50 In patients ≥75 years, the longterm risk of found that ticagrelor and prasugrel, compared to clopidogrel, were asso
disabling or fatal bleeding with antiplatelet agents is higher than in younger ciated with increased major bleeding risk, and that ticagrelor but not pra
age,8 half of the major bleeds are upper gastrointestinal, and the estimated sugrel was associated with decreased mortality.74 Figure 1 summarizes
numbers needed to treat for routine PPI use to prevent a major upper antithrombotic treatment decisions in patients ≥75 undergoing PCI, ac
gastrointestinal bleed are particularly low (from 338 < 65 years to cording to HBR, indication for OAC, and clinical setting.
25 > 85 years).8 We therefore support PPI comedication with antiplatelet Current ESC guidelines recommend up to 12-month aspirin plus a
therapy in elderly patients. Contemporary secondary prevention trials— P2Y12 inhibitor-based DAPT after ACS, with or without PCI, extend
accepting their limitations—indicate that major bleeding rates with low- able beyond 12 months for selected post-MI patients at high ischaemic
Table 1 Key consensus points on antithrombotic therapy in older adults
Clinical scenario and strategy Key point

......................................................................................................................................................................................
Medical adherence in older adults We encourage pharmacological and nonpharmacological strategies to improve medical adherence in older adults, such as
with CVD or AF deprescribing, polypill use, reminder tools, and educational interventions.
Bleeding and thrombotic risk We propose a systematic estimate of bleeding vs. thrombotic risk trade-off in older adults through the integration of
assessment in older adults with different risk predictors. Among CVD patients, current evidence suggests that older age predicts bleeding more than
CVD or AF thrombotic events.
Aspirin in older adults for primary Longterm low-dose aspirin, especially with PPI comedication, has favourable benefit/risk effects in older adults with overt
and secondary CVD prevention CVD and SR.
Among adults ≥70 years without overt CVD and with an estimated risk of major CVD events <1% per year, current data
do not support the initiation of low-dose aspirin.

P2Y12 inhibitors in older ACS and/ Efficacy-to-safety balance should drive P2Y12-inhibitor choice. For PCI-treated ACS patients ≥75 years, the
or PCI patients EMA-approved prasugrel dose is 5 mg daily. Clopidogrel-based DAPT is recommended by guidelines for PCI-treated
CCS patients, regardless of age and bleeding risk, and for HBR patients after ACS. Clopidogrel or ticagrelor or aspirin
monotherapy after at least 1-month DAPT are emerging strategies after ACS or PCI. We generally discourage DAPT
beyond 12 months for age ≥75.
Oral anticoagulation for older Advanced age should not be a reason for underuse of VKA or NOACs. In the absence of severe CKD, mechanical valves
adults with AF or mitral stenosis, VKA is generally second choice to NOACs.
Dabigatran is preferable to VKA (unless contraindicated). For age ≥80, the EMA-approved dose is 110 mg twice daily.
FXa inhibitors have favourable efficacy/safety effects in elderly AF patients and are preferable to VKA (unless
contraindicated).
Antiplatelet strategies to reduce Reasonable options to reduce bleeding risk in older ACS and/or PCI patients include refraining from routine P2Y12-
bleeding risk in older ACS and/ inhibitor administration before angiography in NSTE-ACS and CCS patients, de-escalating from ticagrelor or prasugrel
or PCI patients to clopidogrel or lower dose prasugrel, or monotherapy with aspirin, clopidogrel or ticagrelor after 1–3 months of
DAPT.
Dual pathway inhibition for For older patients with CCS and/or PAD who are at high risk of ischaemic events but not at HBR, DPI with rivaroxaban
secondary CVD prevention in 2.5 mg twice daily plus aspirin is reasonable. Current data support DPI in elderly patients with PAD undergoing
older patients peripheral artery revascularization.
Antithrombotic therapy for older For older AF patients with ACS and/or undergoing PCI, DAT (NOAC + clopidogrel) is advisable after a short period of
AF patients with ACS or TAT (1–2 weeks). TAT can be prolonged to 1 month if high-ischaemic risk and/or anatomical/procedural
undergoing PCI characteristics outweigh the bleeding risk. For older AF patients with CCS, (N)OAC monotherapy is advisable.
Periprocedural cangrelor and GPIs For older P2Y12 inhibitor-naïve patients undergoing PCI, intravenous cangrelor is a reasonable option. Intravenous GPI is
for older, high-ischaemic risk generally limited to emergency bailout or preoperative bridging in high-ischaemic risk patients.
patients
Heparins, fondaparinux and For elderly STEMI or NSTE-ACS patients, UFH or enoxaparin is generally administered when immediate PCI is planned.
bivalirudin for older ACS For conservatively-managed older NSTE-ACS patients, fondaparinux is preferable in the absence of severe kidney
patients disease. Routine preference of bivalirudin over UFH in the elderly is not advised.
Fibrinolysis for older STEMI For older STEMI patients unable to undergo primary PCI within 120 min from diagnosis, fibrinolysis is advised after careful
patients consideration of contraindications and adjusting the doses of tenecteplase and adjunctive therapy for age ≥75.
Antithrombotic therapy for TAVI Single antiplatelet therapy is preferable to DAPT, and OAC monotherapy preferable to combined OAC and clopidogrel
patients (for those requiring longterm OAC). Based on guidelines and trials, NOACs may be preferred over VKA, although
individual factors (e.g. GI bleeding risk) should guide OAC choice. OACs are contraindicated in patients undergoing
TAVI who do not have a clear indication for OAC.
Antithrombotic therapy for AF For AF patients at very HBR undergoing percutaneous LAAC, short-term (e.g. 45 days) OAC or 1–6-month DAPT
patients at very HBR (aspirin plus clopidogrel) followed by single antiplatelet or no antithrombotic therapy are reasonable options.
undergoing percutaneous
LAAC
Perioperative antithrombotic Perioperative antithrombotic therapy is generally similar in younger and older patients undergoing cardiac and noncardiac
therapy surgery.
ACS, acute coronary syndrome; AF, atrial fibrillation; CCS, chronic coronary syndrome; CKD, chronic kidney disease; CVD, atherothrombotic cardiovascular disease; DAPT, dual
antiplatelet therapy; DAT, dual antithrombotic therapy; DPI, dual pathway inhibition; EMA, European Medicines Agency; F, factor; GI, gastrointestinal; GPI, glycoprotein IIb/IIIa
inhibitor; HBR, high bleeding risk; LAAC, left atrial appendage closure; NOAC, non-vitamin K antagonist oral anticoagulant; NSTE, non-ST-elevation; OAC, oral anticoagulant; PAD,
peripheral artery disease; PCI, percutaneous coronary intervention; PPI, proton pump inhibitor; SR, sinus rhythm; STEMI, ST-elevation myocardial infarction; TAT, triple
antithrombotic therapy; TAVI, transcatheter aortic valve implantation; UFH, unfractionated heparin; VKA, vitamin K antagonist.
Table 2 Academic Research Consortium high bleeding risk defined by at least 1 major or 2 minor features
1 MAJOR 2 MINOR FEATURES

OR
......................................................................................................................................................................................
Anticipated longterm oral anticoagulationa Age ≥75 years
Estimated GFR <30 mL/min Estimated GFR 30–59 mL/min
Haemoglobin <11 g/dL Haemoglobin 11–12.9 g/dL for men and 11–11.9 g/dL for women
Spontaneous bleed requiring hospitalization or transfusion within Spontaneous bleed requiring hospitalization or transfusion within 12
6 months or recurrent bleed months not meeting major feature
Platelet count <100 × 109 per litre Chronic use of NSAIDs or steroids

Bleeding diathesis or cirrhosis with portal hypertension Any ischaemic stroke not meeting major feature
b
Active malignancy (excluding non-melanoma skin cancer) within
12 months
Previous spontaneous ICH (at any time)
Previous traumatic ICH within the past 12 months
Presence of a bAVM
Moderate or severe ischaemic strokec within 6 months
Non-deferrable major surgery on DAPT
Recent major surgery or trauma within 30 days
ARC, Academic Research Consortium; bAVM, brain arterio-venous malformation; DAPT, dual antiplatelet therapy; GFR, glomerular filtration rate; ICH, intracranial haemorrhage; NSAID,
non-steroidal anti-inflammatory drug.
a
This excludes dual pathway inhibition doses.
b
Active malignancy defined as diagnosis within 12 months and/or ongoing requirement for treatment (including surgery, chemotherapy, or radiotherapy).
c
National Institutes of Health Stroke Scale score ≥5. Modified from [28].
and low bleeding risk.30,77–80 In the elderly, however, subgroup analyses In meta-analyses of randomized or adjusted observational studies of
of RCTs show attenuated net benefit of DAPT beyond 12 months AF patients ≥75 years, warfarin appeared less effective than NOACs
(combining low-dose aspirin with either ticagrelor 60 mg twice daily, in preventing thromboembolism, with higher rates of ICH, higher or
clopidogrel 75 mg daily, or prasugrel 5 mg daily).11,77–80 Our consensus comparable major bleeding, and lower or comparable gastrointestinal
is that extended DAPT in older patients should be carefully evaluated, bleeding.85–87 Multiple drug–drug and drug–food interactions need to
after taking into account bleeding and ischaemic risk factors, or be be considered when using warfarin or other VKAs in comorbid, come
avoided, particularly in patients with prior non-cardioembolic transient dicated elderly patients.88
ischaemic attack or stroke;81 rather, reducing DAPT duration should be
considered in line with recent trial data (see below).31,75
The direct thrombin inhibitor dabigatran
The RE-LY trial randomized 18 113 AF patients to warfarin or dabiga
Antithrombotic therapies for stroke
tran (110 or 150 mg twice daily); 40% (n = 7245) were >74 years.89,90
prevention in atrial fibrillation Regardless of age, the incidence of stroke/systemic embolism was simi
Stroke prevention by vitamin K antagonists lar with dabigatran 110 mg and significantly lower with dabigatran
The BAFTA trial randomized 973 patients ≥75 years (mean 82 ± 4) 150 mg compared to warfarin; ICH rates were lower with both dabiga
with AF and no mechanical heart valve or severe mitral stenosis to vita tran doses, whereas gastrointestinal bleeds were more common with
min K antagonist (VKA) or low-dose aspirin for an average of 2.7 dabigatran 150 mg.89,90 Dabigatran 110 or 150 mg twice daily com
years.82 The relative risk of stroke/systemic embolism strongly favoured pared to warfarin resulted in significantly lower overall incidences of
OAC over aspirin (0.48, 95% CI 0.28–0.80, P = 0.003), without signifi major extracranial bleeds <75 years, but in a similar risk with 110 mg
cantly different rates of intracranial haemorrhage (ICH, 8 vs. 6).82 Given and a trend toward higher risk with 150 mg ≥75 years.90 Age is an in
limited randomized data on VKAs in older adults, what follows includes dependent predictor of increased dabigatran plasma concentra
observational studies. In an AF cohort ≥90 years, warfarin was asso tions.91 The EMA states that 110 mg twice daily should be
ciated with apparent net clinical benefit compared to antiplatelet or considered for AF patients of 75–79 years and is required for those
no antithrombotic therapy, but higher risk of ICH compared to ≥80.92 Dabigatran is contraindicated with creatinine clearance
non-VKA oral anticoagulants (NOACs).83 In a meta-analysis of 26 ran (CrCl) <30 mL/min and with concomitant dronedarone, cyclospor
domized and observational studies of AF patients ≥65 years, warfarin ine, and certain antimycotic or antiretroviral drugs.92,93 The
appeared superior to aspirin or no antithrombotic therapy for stroke dabigatran-specific intravenous antidote, idarucizumab, is effective
prevention, with a nonsignificant increase in risk of major bleeding.84 and well tolerated regardless of age.94,95
Table 3 European Medicines Agency-approved antithrombotic regimens for older adults
Drug and dose Indication Age, weight or renal EMA-approved considerations

adjusted dosing
......................................................................................................................................................................................
Oral antiplatelet drugs
Aspirin 75–100 mg od (150–300 mg load) Acute and chronic coronary None
syndromes
Clopidogrel 75 mg od (600 mg load) Acute and chronic coronary No loading dose with fibrinolysis
syndromes for age ≥75
Ticagrelor 90 mg bid (180 mg load) ACS None Avoid with prior ICH
Ticagrelor 60 mg bid Post-MI None Avoid with prior ICH

Prasugrel 10 mg od (60 mg load) PCI in ACS 5 mg od for age ≥75 Avoid with prior stroke (including
or weight <60 kg ICH) or TIA
IV antiplatelet drugs
Cangrelor 30 μg/kg bolus + immediate 4 μg/kg/min P2Y12-inhibitor-naïve patients None No overall differences in safety or
infusion for ≥2 h. Oral P2Y12 inhibitor load with ACS undergoing PCI efficacy <75 vs. ≥75 years
during (for ticagrelor or prasugrel) or at end
(for clopidogrel) of infusion
Eptifibatide 180 μg/kg bolus + 2 μg/kg/min infusion No-reflow or thrombotic Avoid if CrCl <30 mL/min. Avoid with prior ICH, ischaemic
complication during PCI. 50% infusion dose if CrCl 30– stroke within 30 days, fibrinolysis,
Preoperative bridge in 49 mL/min or <100 000 platelets/mma
high-ischaemic risk patients
Tirofiban 25 μg/kg bolus + 0.15 μg/kg/min infusion No-reflow or thrombotic 50% dose if CrCl <30 mL/min Avoid with prior ICH, ischaemic
complication during PCI. stroke within 30 days, fibrinolysis,
Preoperative bridge in or <100.000 platelets/mma
high-ischaemic risk patients
Oral anticoagulants
Apixaban 5 mg bid AF Avoid if CrCl <15 mL/min. Monitor renal function
2.5 mg bid if ≥2 of:
• age ≥80
• weight ≤60 kg
• serum Cr ≥1.5 mg/dL
or CrCl 15–29 mL/min as single
criterion
Dabigatran 150 or 110 mg bid AF Avoid if CrCl <30 mL/min. Monitor renal function
110 mg bid for age ≥80.
Consider 110 mg bid for age 75–79
Edoxaban 60 mg od AF Avoid if CrCl <15 mL/min. Monitor renal function
30 mg od if CrCl 15–50 mL/min,
weight <60 kg or concomitant
cyclosporine, dronedarone,
erythromycin or ketoconazole
Rivaroxaban 20 mg od AF Avoid if CrCl <15 mL/min. Monitor renal function
15 mg od if CrCl 15–49 mL/min
Rivaroxaban 2.5 mg bid with aspirin CAD and/or PAD patientsb Avoid if CrCl <15 mL/min Evaluate ischaemic vs. bleeding risks
100 mg od carefully
Vitamin K antagonists AF, mechanical heart valve With age, lower doses required More frequent INR monitoring with
to reach target INR age
Parenteral anticoagulants
UFH IV dose adjusted to aPTT ACS, PCI None Can be used with CrCl <15 mL/min
Continued
Table 3 Continued
Drug and dose Indication Age, weight or renal EMA-approved considerations

adjusted dosing
......................................................................................................................................................................................
LMWH dose and route vary by compound and ACS, PCI Avoid enoxaparin if CrCl
indication <15 mL/min.
Half-dose enoxaparin for CrCl
15–30 mL/min.
For age ≥75, no initial IV 30 mg
enoxaparin bolus.
For age ≥75, consider enoxaparin
0.75 instead of 1 mg/kg bid
therapeutic SC dose

Fondaparinux 2.5 mg ACS Avoid if CrCl <20 mL/min Generally limited to conservatively
SC od managed NSTE-ACS patients
without severe kidney disease
Bivalirudin 0.75 mg/kg IV bolus (further 0.3 mg/kg PCI in ACS Avoid if CrCl <30 mL/min. Avoid with active bleeding, malignant
bolus if ACT after 5 min <225 s) + 1.75-mg/kg/h Reduce infusion to 1.4 mg/kg/h hypertension, subacute bacterial
infusion for up to 4 h if CrCl 30–59 mL/min endocarditis
Fibrinolytic agents
Tenecteplase single IV bolus of 30, 35, 40, 45, or STEMI if primary PCI Half-dose tenecteplase if age ≥75 Avoid with prior ICH or ischaemic
50 mg (for weight <60, 60–70, 70–80, 80–90, unavailable <120 min of stroke/TIA within 6 monthsa
or >90 kg, respectively) diagnosis
ACS, acute coronary syndrome; ACT, activated clotting time; AF, atrial fibrillation; bid, twice daily; aPTT, activated partial thromboplastin time; CrCl, creatinine clearance; EMA, European
Medicines Agency; ICH, intracranial haemorrhage; INR, international normalized ratio; IV, intravenous; LMWH, low-molecular-weight heparin; MI, myocardial infarction; NSTE,
non-ST-elevation; od, once daily; PAD, peripheral artery disease; PCI, percutaneous coronary intervention; SC, subcutaneous; STEMI, ST-elevation myocardial infarction; TIA,
transient ischaemic attack; UFH, unfractionated heparin.
a
Further contraindications: recent trauma or surgery, active bleed, bleeding diathesis, acute pericarditis, suspected aortic dissection, intracranial/intraspinal neoplasm, arterio-venous
malformation or aneurysm, severe uncontrolled hypertension, INR ≥2, severe liver disease, hypersensitivity.
b
Reimbursement criteria vary by national health system.
Direct factor (F) Xa inhibitors: rivaroxaban, apixaban, CrCl is 15–29 mL/min (irrespective of age) and (for those with CrCl
and edoxaban ≥30 mL/min) in the presence of ≥2 factors among age ≥80 years,
In the ROCKET AF,96 ARISTOTLE97, and ENGAGE AF-TIMI 48 trials,98 body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL;93 edoxaban
20 136 AF patients ≥75 years were randomized to rivaroxaban 20 mg and rivaroxaban doses need no adjustment for age, but do for CrCl
daily, apixaban 5 mg twice daily, or edoxaban 60 or 30 mg daily vs. war ≤50 or ≤49 mL/min, respectively.93 The intravenous antidote against
farin (44%, 31%, and 40% of the overall populations).96–99 Subgroup FXa inhibitors, andexanet alfa, was well tolerated and effective regard
analyses indicated superiority or noninferiority of each FXa inhibitor less of age.105 Intravenous ciraparantag also provides rapid, safe, and
vs. warfarin for stroke prevention regardless of age.99–102 Rates of sustained reversal of FXa inhibition in 50- to 75-year-old adults.106
ICH were significantly lower with all FXa inhibitors vs. warfarin.96–98
An increased rate of gastrointestinal bleeding vs. warfarin was seen
with rivaroxaban and higher-dose edoxaban, but not with apixaban Emerging antithrombotic strategies
or the lower (unlicensed) edoxaban dose.96–98 Safer antiplatelet regimens
Among 984 Japanese AF patients ≥80 years (mean 87 ± 4) who were Most elderly patients are at HBR (see above). To limit DAPT-related
not candidates for standard-dose anticoagulation (on the basis of bleed bleeding, ESC guidelines recommend refraining from routine P2Y12-in
ing history, comedications, kidney disease, or very low body weight), hibitor administration before coronary angiography for NSTE-ACS pa
edoxaban 15 mg once daily (currently not licensed) was superior to pla tients (in case diagnoses requiring coronary or aortic surgery are
cebo over a median of 1.3 years in preventing stroke/systemic embolism made),31 shortening DAPT duration to 6, 3, or even 1 month followed
(absolute annual reduction 4.4%, P < 0.001) without significantly increas by antiplatelet monotherapy, and de-escalating P2Y12 inhibitors among
ing major bleeding (absolute annual increase 1.5%, P = 0.09).103 Whether ACS patients.30,40,51,68,75,76,107–115 For HBR patients, ESC guidelines spe
these findings are generalizable to other ethnicities is unknown. cifically indicate that DAPT can be shortened to 1 month after elective
Compared to warfarin, less bleeding in older vs. younger patients has PCI and to 3 months (or even 1 month in very HBR) after ACS, followed
been reported with apixaban and edoxaban.99,100,104 In the absence of by aspirin or clopidogrel monotherapy.30,31,40,41 Ticagrelor monotherapy
randomized head-to-head comparisons, however, whether one is allowed after 3–6 months DAPT depending on bleeding and ischaemic
NOAC is safer than another is uncertain. The EMA contraindicates risk balance.31,76,116 The above ESC recommendations are driven by re
FXa inhibitors with CrCl <15 mL/min and with some antimycotic cent RCTs generally reporting noninferior or superior safety and similar
and antiretroviral drugs.93 The apixaban dose should be halved when efficacy after 1–3 months of DAPT, followed by ticagrelor, clopidogrel,
Patient ≥75 yrs treated with PCI
High bleeding risk evaluation

e.g. ≥1 major or 1 additional minor feature*
HBR yes HBR no
Indication for OAC ? Up to 1 yr ASA + prasugrel or ASA + ticagrelor

after ACS# and 6 mo ASA + clopidogrel
Yes No in CCS,** followed by SAPT
Ticagrelor alone (after 3 mo ASA + ticagrelor)
For both ACS DAPT for up to 6 mo
may be an option for both ACS or CCS with
and CCS, up to after ACS (preferably
≥1 high risk angiographic factor ¥

1 yr (N)OAC + clopidogrel-based) or
clopidogrel (+ up to 1-3 mo in CCS**
initial days- De-escalated DAPT at
weeks ASA) 14 days in ACS, or 1- In patients with CCS
followed by 3 mo DAPT followed and/or LEAD, careful
(N)OAC alone by clopidogrel or balance of benefits
ticagrelor≠ or ASA versus risks prior to
alone, for both ACS prolonged combined
and CCS, are antithrombotic treatment,
emerging strategies including DPI
Figure 1 Antithrombotic therapy in older adults undergoing percutaneous coronary intervention, according to bleeding risk,
indication for oral anticoagulation, and clinical setting. *High bleeding risk according to Table 2. #For contraindications and dosing see
Table 3. ≠MASTER DAPT trial results.75 ¥At least one high-risk angiographic factor: multivessel coronary disease, total stent >30 mm, thrombotic lesion,
bifurcation requiring at least two stents, left main stem (≥50%) or proximal left anterior descending artery (≥70%) lesion, calcified target lesion(s) requiring
atherectomy.76 **In older as in younger chronic coronary syndrome patients undergoing percutaneous coronary intervention, clopidogrel + aspirin is the
treatment of choice. ACS, acute coronary syndrome; ASA, aspirin; CCS, chronic coronary syndrome; DAPT, dual antiplatelet therapy; DPI, dual pathway
inhibition; HBR, high bleeding risk; LEAD, lower extremity artery disease; mo, month; (N)OAC, (non-vitamin K antagonist) oral anticoagulant; PCI, per
cutaneous coronary intervention; SAPT, single antiplatelet therapy.
or aspirin monotherapy, compared to longer DAPT regimens among for 2 years.54 Clopidogrel showed superior combined efficacy and
ACS or CCS patients (Table 4).51,76,107,111–113,117 The very recent safety unrelated to age (≥ or <65 years), with no significant difference
STOPDAPT-2 ACS trial of 4136 East Asian ACS patients, mostly not in all-cause mortality [51 deaths (1.9%) with clopidogrel vs. 36 (1.3%)
at HBR (mean 67 ± 12 years) and receiving drug-eluting stents, has chal with aspirin (HR 1.43, 95% CI 0.93–2.19, P = 0.101)] and similar trends
lenged previous results, since noninferiority for the 1 year combined for both cardiac and noncardiac deaths.54 Whether these findings are
safety and ischaemic outcome of 1-month DAPT followed by clopidogrel generalizable to other geographical settings is pending.
monotherapy vs. 12-month DAPT was not met (Table 4).114 In contrast, For elderly patients, we support avoiding routine P2Y12-inhibitor ad
the very recent MASTER DAPT trial of 4579 patients with ACS or CCS ministration before coronary angiography in the setting of NSTE-ACS
(mean 76 ± 9 years) all at HBR (with age ≥75 as a HBR criterion), receiv and CCS. For HBR patients post-ACS or PCI, we generally support
ing a thin-strut drug-eluting stent and 1-month DAPT, showed that clopidogrel-based DAPT or, alternatively, antiplatelet monotherapy
aspirin or P2Y12-inhibitor monotherapy compared to DAPT prolonga with either clopidogrel, ticagrelor or aspirin, after at least 1 month of
tion for 3 months or longer was noninferior for combined adverse events DAPT (Table 1, Figure 1).
and major cardiocerebral events at 11 months, with less major or clinic
ally relevant nonmajor bleeding.75 The results of both very recent trials
were consistent across age strata (Table 4). Of note, most of the above Dual pathway inhibition
RCTs included mixed populations (ACS and CCS), were underpowered Dual pathway inhibition (DPI) refers to concomitant inhibition of plate
for efficacy, and had open-label assessor-masked designs. lets and coagulation. The three-armed COMPASS trial randomized 18
Among ACS patients, trials of de-escalation from ticagrelor or prasu 278 patients with CCS and/or PAD (mean 68 ± 8 years) to either DPI
grel to clopidogrel or low-dose prasugrel have shown noninferior or with aspirin 100 mg daily plus rivaroxaban 2.5 mg twice daily, rivaroxaban
superior safety compared to no de-escalation (generally regardless of 5 mg twice daily alone, or aspirin alone; DPI compared to aspirin alone
age), although underpowered for efficacy (Table 4).68,108–110,115,119,120 reduced the composite of cardiovascular death, MI or stroke over a
Although recent evidence indicates improved outcomes with guided mean follow-up of 23 months, while increasing modified International
compared to non-guided choices,31,120,121 platelet function or genetic Society on Thrombosis and Haemostasis-defined major bleeding, but
testing to guide P2Y12-inhibitor escalation/de-escalation has not yet be not ICH or fatal bleeding. There was no significant interaction between
come routine practice. age and treatment effects, although the benefit-to-risk ratio of DPI was
The HOST-EXAM trial randomized 5438 East Asian CCS patients numerically less favourable among the 21% ≥75 years compared to the
(mean 63 ± 11 years), who had uneventfully completed 6–18 months younger strata,122 suggesting the need for carefully individualized deci
of DAPT after PCI, to clopidogrel 75 mg daily or aspirin 100 mg daily sions (Table 1, Figure 1). Of note, patients <65 years required additional
Table 4 Recent trials of abbreviated or de-escalated dual antiplatelet therapy after percutaneous coronary intervention, with analyses by age
270
Trial name (design) No. of Pt type % Mean age Experimental Control Follow-up Safety events Ischaemic events Combined adverse Analyses by age
pts ACS (% older) arm (Exp.) arm (Ctrl) Exp. vs. Ctrl Exp. vs. Ctrl events
Exp. vs. Ctrl
...................................................................................................................................................................................................................................................
Abbreviated DAPT followed by P2Y12 inhibitor or aspirin monotherapy
GLOBAL LEADERS51,107 (open) 15 968 PCI 47 65 y (16% >75) 1 mo Tic + Asa → 23 mo Tic 12 mo DAPT →12 24 mo BARC bleed 3 or 5: Death, new Q-wave MI: Death, stroke, MI, BARC bleed Int-P between age ≤ or >75
90 bid mo Asa 2.0% vs. 2.1% (RR 3.8% vs. 4.4% (RR 0.87, 3 or 5: 7.72% vs. 8.17% (RR and treatment strategy =
0.97, 95% CI 95% CI 0.75–1.01; P = 0.95, 95% CI 0.85–1.06; P = 0.06 for safety and 0.23
0.78–1.20; P = 0.073) 0.34) for ischaemic events51,107
0.77)
76
TWILIGHT (double-blind) 7119 PCI 71 65 y (52% ≥65) 12 mo Tic 90 bid + placebo 12 mo Tic + Asa 12 mo BARC bleed 2, 3 or 5: Death, MI, stroke: 3.9% vs. No significant interaction
(after 3 mo uneventful (after 3 mo 4.0% vs. 7.1% (HR 3.9% (HR 0.99, 95% CI between age < or ≥65
Tic-based DAPT) uneventful Tic- 0.56, 95% CI 0.78–1.25; P for NI < (or ARC HBR status) and
based DAPT) 0.45–0.68; P < 0.001) treatment strategy for
0.001) safety and ischaemic
events76,116
SMART-CHOICE111 (open) 2993 PCI 58 65 y (51% ≥65) 3 mo DAPT → 12 mo DAPT 12 mo BARC bleed 2–5: MACCE: 2.9% vs. 2.5% MACCE plus BARC bleed 2–5: Int-P between age < or ≥65
9 mo Clo 2.0% vs. 3.4% (HR (difference 0.4%, 1-sided 4.5% vs. 5.6% (HR 0.81, 95% and treatment strategy =
0.58; 95% CI, 95% CI −∞ to 1.3; P for CI 0.58–1.12; P = 0.2) 0.10 for safety and = 0.90
0.36–0.92; P = NI = 0.007) for ischaemic events111
0.02)
STOPDAPT-2112 (open) 3045 PCI 38 69 y (32% ≥75) 1 mo DAPT → 12 mo DAPT 12 mo BARC bleed 3 or 5: CV death, MI, definite ST, CV death, MI, definite ST, Int-P between age < or ≥75
11 mo Clo 0.54% vs. 1.81% ischaemic or ischaemic or haemorrhagic and treatment strategy =
(HR 0.30, 95% CI haemorrhagic stroke: stroke, TIMI major or minor 0.20 for combined
0.13–0.65; P = 1.96% vs. 2.51% (HR bleed: 2.4% vs. 3.7% (HR adverse events112
0.003) 0.79, 95% CI 0.49–1.29; 0.64; 95% CI 0.42–0.98; P =
P = 0.34) 0.04)
TICO (open)113 3056 PCI 100 61 y (39% ≥65) 3 mo Tic + Asa → 9 mo Tic 12 mo Tic + Asa 12 mo TIMI major bleed: MACCE: 2.3% vs. 3.4% (HR Death, MI, stroke, definite or Int-P between age ≥64 and
90 bid 1.7% vs. 3.0% (HR 0.69, 95% CI −0.45 to probable ST, TV revasc, benefit of Exp. vs. Ctrl =
0.56, 95% CI 1.06; P = 0.09) TIMI major bleed: 3.9% vs. 0.036 for combined
0.34–0.91; P = 5.9% (HR 0.66, 95% CI adverse events118
0.02) 0.48–0.92; P = 0.01)
MASTER DAPT75 (open) 4579 HBR PCI (33% 37 76 y (69% ≥75) 11 mo P2Y12i or Asa after 1 ≥2 mo DAPT 11 mo BARC 2, 3, 5: 6.5% vs. Death, stroke, MI: Death, stroke, MI, BARC bleed No significant interaction
AF) mo uneventful DAPT after 1 mo 9.4% (P < 0.001) 6.1% vs. 5.9% 3 or 5: 7.5% vs. 7.7% (P for between age < or ≥75
uneventful (P for NI = 0.001) NI < 0.001) and treatment strategy
DAPT for safety, ischaemic or
combined adverse
events75
STOPDAPT-2 ACS114 (open) 4136 PCI 100 67 y 1 mo DAPT → 11 mo Clo 12 mo DAPT 12 mo Any TIMI bleed: CV death, MI, definite ST, CV death, MI, definite ST, Int-P between age ≤ or >75
0.54% vs. 1.17% stroke: 2.76% vs. 1.86% stroke, TIMI bleed: 3.2% vs. and treatment strategy =
(P < 0.05) (P > 0.05) 2.8% (P for NI = 0.06) 0.47 for safety, 0.75 for
ischaemic, and 0.46 for
combined adverse
events114
De-escalation from newer P2Y12 inhibitor to clopidogrel or low-dose prasugrel

TROPICAL-ACS108 (open) 2610 PCI 100 59 y (14% >78) PFT-Clo + Asa or Pra + Asa 12 mo Pra + Asa 12 mo BARC bleed ≥2: 5% CV death, MI, stroke: 3% vs. CV death, MI, stroke, BARC Int-P between age as
at 2 weeks → 12 mo vs. 6% (HR 0.82, 3% (HR 0.77, 95% CI bleed ≥2: 7% vs. 9% (HR continuous variable and
Continued
F. Andreotti et al.

Table 4 Continued
Trial name (design) No. of Pt type % Mean age Experimental Control Follow-up Safety events Ischaemic events Combined adverse Analyses by age
pts ACS (% older) arm (Exp.) arm (Ctrl) Exp. vs. Ctrl Exp. vs. Ctrl events
Exp. vs. Ctrl
...................................................................................................................................................................................................................................................
95% CI 0.59– 0.48–1.21; P for NI = 0.81, 95% CI 0.62–1.06; P treatment strategy =
1.13; P = 0.23) 0.0115) for NI = 0.0004; P = 0.12) 0.027 (safety and
ischaemic combined
endpoint benefit of Exp.
vs. Ctrl ≤70 y)119
120
POPular-Genetics (open) 2488 PCI 100 62 y (15% >75) Clo in CYP 2C19*2 or *3 12 mo Tic (91%)/ 12 mo PLATO major or CV death, MI, definite ST, Any death, MI, definite ST, Int-P between age < or ≥75
non carriers + Asa → 12 Pra + Asa minor bleed: 9.8% stroke: 2.7% vs. 3.3% stroke, PLATO major bleed: and treatment strategy =
Antithrombotic therapy in the elderly
mo vs. 12.5% (HR (HR 0.83, 95% CI 0.53– 5.1% vs. 5.9% (P for NI < 0.88 for safety and 0.72
0.78, 95% CI 1.31) 0.001) for combined adverse
0.61–0.99; P = events120
0.04)
68
POPular-AGE (open) 1002 PCI 100 77 y (100% Clo + Asa at 26 days → 12 12 mo Tic (95%)/ 12 mo PLATO major or Death, MI, stroke: 12.8% vs. Death, MI, stroke, PLATO All patients ≥70 y
≥70, 35% mo Pra + Asa minor bleed: 12.5% (HR 1.02, 95% CI major or minor bleed: 27.3%
≥80) 17.6% vs. 23.1% 0.72–1.45; P = 0.91) vs. 30.7%; P for NI = 0.06)
(HR 0.74, 95% CI
0.56–0.97; P =
0.03)
TOPIC109 (open) 646 PCI 100 60 y 1 mo Tic (44%)/Pra + Asa 12 mo Tic (41%)/ 12 mo BARC bleed ≥2: Any ischaemic event: 9.3% CV death, urgent revasc, stroke, Not available
→11 mo Clo + Asa Pra + Asa 4.0% vs. 14.9% vs. 11.5% (HR 0.80, 95% BARC bleed ≥2: 13.4% vs.
(HR 0.30, 95% CI CI 0.50–1.29; P = 0.36) 26.3% (HR 0.48, 95% CI
0.18–0.50; P < 0.34–0.68; P < 0.01)
0.01)
HOST-REDUCE-POLYTECH- 2338 PCI 100 59 y (0.1% 1 mo Pra 10 + Asa → 11 mo 12 mo Pra 10 + Asa 12 mo BARC bleed ≥ 2: CV death, MI, ST, ischaemic Death, MI, ST, ischaemia-driven Int-P between age < or ≥65
ACS110 (open) ≥75) Pra 5 + Asa 2.9% vs. 5.9% (HR stroke: 1.4% vs. 1.8% revasc, stroke, BARC bleed and treatment strategy =
0.48, 95% CI (HR 0.76, 95% CI 0.40– ≥2: 7.2% vs. 10.1% (HR 0.70, 0.68 for combined
0.32–0.73; P = 1.45; P = 0.40) 95% CI 0.52–0.92; P < adverse events110
0.0007) 0.012)
TALOS-AMI115 (open) 2697 PCI 100 60 y (27% ≥75) 1 mo Tic + Asa → 11 mo 12 mo Tic + Asa 12 mo BARC ≥ 2: 3.0% vs. CV death, MI, stroke: 2.1% CV death, MI, stroke, BARC Int-P between age < or ≥75
Clo + Asa 5.6% (HR 0.52, vs. 3.1% (P = 0.15) bleed ≥2: 4.6% vs. 8.2% (P and treatment strategy =
95% CI 0.35– for NI < 0.001, P = 0.0001) 0.98 for combined
0.77; P = 0.0012) adverse events115
ACS, acute coronary syndrome; ARC, Academic Research Consortium; Asa, aspirin once daily; BARC, Bleeding Academic Research Consortium; bid, twice daily; CI, confidence interval; Clo, clopidogrel once daily; Ctr, control; CV, cardiovascular;
DAPT, dual antiplatelet therapy; Exp., experimental; HBR, high bleeding risk; HR, hazard ratio; i, inhibitor; int-P, P for interaction; MACCE, major adverse cardiac and cerebrovascular events; MI, myocardial infarction; mo, month; NI, noninferiority; PCI,
percutaneous coronary intervention; PFT, platelet function testing; PLATO, Study of Platelet Inhibition and Patient Outcomes; Pra, prasugrel; Pt, patient; revasc, revascularisation; RR, rate ratio; ST, stent thrombosis; Tic, ticagrelor; TIMI, Thrombolysis
in Myocardial Infarction; TV, target vessel; vs., versus; y, years; 5, 5 mg; 10, 10 mg; 60, 60 mg; 90, 90 mg.
271

ischaemic risk factors for enrolment.122 Models estimating individual life clopidogrel during or after, rather than before, PCI, and (iii) unreported
time benefit and bleeding risk may help select older patients for adjunct intervals between receipt of study drug and PCI for the 63% of patients
ive low-dose rivaroxaban.123,124 In the VOYAGER-PAD trial of 6564 receiving clopidogrel before the procedure.138
patients with recent lower extremity revascularization [median (inter Most trials evaluating the intravenous glycoprotein IIb/IIIa inhibi
quartile range) 67(61–73) years], a rivaroxaban 2.5 mg twice daily plus tors (GPIs) abciximab, eptifibatide and tirofiban in ACS or PCI pa
aspirin strategy vs. aspirin alone reduced the rate of major cardiovascular tients preceded the era of early DAPT and newer P2Y12-inhibitor
events and limb ischaemia over a median of 2.3 years, without significantly loading.140,141 Today, given unproven benefits on ischaemic events
increasing TIMI major bleeding.125 The 20% of patients ≥75 years when added to DAPT, and a clear increase in bleeding, ESC guidelines
showed a particularly favourable benefit-to-risk ratio.125 recommend intravenous GPIs only for no-reflow or ‘bailout’ throm
botic complications during PCI, or as a bridge before surgery in pa
Managing atrial fibrillation patients with concomitant tients at very high-ischaemic risk.30,31,40,41,140 In patients ≥70 years,
coronary artery disease particularly those at HBR, the net benefit is even more uncertain, sup
porting restricted use.
Meta-analyses of six randomized trials of AF patients with concomitant

ACS or undergoing PCI (mean age 70) indicate that triple antithrombo
tic therapy (TAT with either VKA or NOAC plus aspirin and clopido
grel) causes increased major or clinically relevant bleeding compared to Heparins, the pentasaccharide
double antithrombotic therapy (DAT with OAC and clopidogrel), but fondaparinux, and bivalirudin
reduces stent thrombosis and MI events.39,126,127 Each trial was indi
In the young as in the elderly, parenteral unfractionated heparin (UFH)
vidually underpowered for ischaemic events or for robust information
or the low-molecular-weight heparin (LMWH) enoxaparin is recom
on the use of ticagrelor or prasugrel. For these patients, ESC guidelines
mended by ESC guidelines for patients undergoing PCI in the setting
recommend an initial 1-week course of TAT, whereas meta-analyses
of ST-elevation MI (STEMI), NSTE-ACS, or CCS.31,32,41,142,143 In
support TAT duration up to 1 month.24,39,128–130 Early DAT may be
NSTE-ACS patients (mean 67 ± 11 years), fondaparinux halved major
preferred in patients not undergoing PCI, given the lack of stent throm
bleeds and reduced 6-month mortality compared to enoxaparin, with
bosis risk.24,31,39,128,131,132 Non-vitamin K antagonist oral anticoagulants
similar ischaemic event rates.144,145 The findings were consistent for
are preferable to VKAs given their superior safety profile.24,31,39,131–133
≥65 and <65 years.144 Additional UFH (60–85 U/kg), however, needs
Among 2236 Japanese AF patients with CCS and prior PCI (mean 74
to be given to invasively managed NSTE-ACS patients on fondaparinux
± 8 years), rivaroxaban monotherapy showed lower rates of ischaemic
to prevent catheter thrombus formation.146 As per EMA, enoxaparin’s
events, major bleeds, haemorrhagic strokes, and all-cause death vs. riv
therapeutic dose should be halved when CrCl is <30 mL/min and is
aroxaban plus an antiplatelet agent at a 23 month follow-up, regardless
contraindicated when <15 mL/min,147 whereas fondaparinux is
of age < or ≥75.134 Among 696 AF patients with CCS (out of 2000
contraindicated with CrCl <20 mL/min.148 Reduced bleeding rates
planned, mean 75 ± 8 years), OAC monotherapy (VKA or NOAC)
with peri-PCI intravenous bivalirudin vs. UFH or LMWH with or
vs. OAC plus an antiplatelet agent showed similar rates of combined is
without GPIs have not been borne out in meta-analyses comparing
chaemic and major bleeding events after 2.5 years, although the primary
bivalirudin to UFH alone.149 Moreover, stent thrombosis rates
noninferiority endpoint for ischaemic events was not met.135
are increased with bivalirudin vs. UFH, with or without GPIs.149 In
For elderly AF-ACS/AF-PCI patients, in line with current guide
the subgroup of 1592 MI patients ≥75 years enrolled in the
lines31,32 and with the MASTER DAPT trial of HBR patients (36%
VALIDATE-SWEDEHEART trial, however, no difference in 180-day
taking OAC; mean 73 ± 9 years),75 our consensus supports DAT
ischaemic and bleeding outcomes were reported for bivalirudin vs.
with a NOAC (at the recommended dose for stroke prevention)
heparin monotherapy.150 Prolonged high-dose infusion of bivalirudin
and an antiplatelet agent (preferably clopidogrel) after a short per
(1.75 mg/kg/h for 3–4 h) may attenuate the stent thrombosis risk.151
iod of TAT (1–2 weeks from the acute event). Triple antithrombo
Bivalirudin and fondaparinux may be used in the setting of
tic therapy can be prolonged if high-ischaemic risk or other
heparin-induced thrombocytopenia.140
anatomical/procedural characteristics outweigh the bleeding risk,
followed by DAT up to 1 year and (N)OAC monotherapy there
after (Table 1, Figure 1).
Fibrinolysis
Parenteral antithrombotic drugs in Irrespective of age, intravenous fibrinolysis vs. placebo improves sur
vival when administered to STEMI patients within 12 h of symptom on
older adults set, despite an early hazard of ICH.152 If delay to treatment is similar,
primary PCI, however, is a better reperfusion strategy than fibrinolysis
Cangrelor and glycoprotein IIb/IIIa in terms of early and longterm survival,153 a superiority that has been
inhibitors confirmed in older patients.154 Intravenous fibrinolysis followed by res
Intravenous cangrelor, a rapid, reversible, direct P2Y12 inhibitor, has cue PCI as needed is still an alternative to primary PCI if the latter is un
been compared to oral clopidogrel, started either before or at available within 120 min from STEMI diagnosis.41,155 Advanced age,
PCI.136–138 In both younger and older (≥75) patients, the largest trial138 lower body weight, female sex, previous cerebrovascular disease, and
showed significantly reduced rates of ischaemic events at 48 h with can hypertension on admission are significant predictors of ICH during fi
grelor vs. a 600 or 300 mg loading dose of clopidogrel, without increas brinolysis.156 For patients ≥75 years receiving tenecteplase, ESC guide
ing severe bleeding.139 Transfer of trial data to contemporary practice, lines recommend halving the dose of the fibrinolytic agent, avoiding the
however, may be limited by: (i) 25% of patients assigned to clopidogrel loading dose of clopidogrel and enoxaparin, and reducing the enoxapar
receiving a 300 mg loading dose; (ii) 37% of patients receiving in maintenance dose by 25% to reduce the excess risk of ICH.41,155,157
Periprocedural antithrombotic for higher risks of death, thromboembolism and bleeding in the rivarox
aban 10 mg daily plus aspirin arm vs. clopidogrel plus aspirin arm.182
regimens in older adults The ENVISAGE-AF trial of 1426 AF TAVI patients (mean 82 years)
demonstrated noninferior net clinical benefit but increased gastro
Invasive vs. conservative management of intestinal bleeds with edoxaban 60/30 mg daily vs. VKA at a median
older non-ST-elevation acute coronary of 1.5 years.183 The ATLANTIS trial of 1500 TAVI patients (mean
syndrome patients 82 years) with or without a clear indication for OAC demonstrated
For biomarker-positive NSTE-ACS patients, an invasive strategy is similar 1-year major bleeding rates with apixaban 5 mg twice daily vs.
superior to a conservative one to prevent ischaemic events, with usual care, regardless of OAC indication.184,185 Apixaban vs. antiplatelet
the greatest benefit in high-risk groups, including those ≥70 and therapy markedly reduced valve thrombosis at 3–6 months, but with
≥80 years.158–160 Regardless of the acute setting, age ≥80 tends to fa a signal for increased noncardiovascular death.184,185 The recent
vour coronary revascularization by PCI over bypass surgery.40,161–163 ADAPT-TAVR trial randomized 229 patients without a clear indication
The role of conservative vs. invasive management in elderly for OAC (mean 80 years) to edoxaban 60/30 mg daily or DAPT.172 At
6 months, subclinical valve thromboses were numerically lower, but the

NSTE-ACS patients is being further investigated in the SENIOR-RITA
trial (ClinicalTrials.gov NCT03052036). For periprocedural antithrom number of patients with new brain lesions numerically higher in the
botic regimens, see above. NOAC group.172 In line with guideline indications, the above data sug
Medical management of NSTE-ACS is not uncommon among the gest that a NOAC may be considered over VKA but not over antiplate
elderly (67% >80 years vs. 33% <70 years in the GRACE registry)164 let therapy post-TAVI.166,182–184 Because superiority over VKA therapy
owing to unsuitable coronary anatomy, contraindications to angiog of apixaban184 or edoxaban183 was not shown, with increased major
raphy/PCI or, less often, lack of obstructive coronary stenoses.71,128 (gastrointestinal) bleeds for the latter,183 careful evaluation when
DAPT as per current ESC guidelines is warranted in medically managed choosing OAC type after TAVI is encouraged. Non-vitamin K antagon
older NSTE-ACS patients in association with short-term parenteral an ist oral anticoagulants are favoured by guidelines over VKAs for long
ticoagulation (fondaparinux or enoxaparin).31,71 However, the relative term stroke prevention in older AF patients, except in those with
net benefit of different types and durations of antithrombotic regimens clinically significant mitral stenosis or mechanical heart valves.166,183,184
in the elderly in this setting is still undefined.165
Left atrial appendage closure (LAAC)
Transcatheter aortic valve implantation The main indication for left atrial appendage closure (LAAC) is stroke
prevention in AF HBR patients in whom lifelong OAC is contraindi
For patients ≥75 years with severe aortic stenosis, transcatheter aortic
cated.186,187 Preliminary data indicate that percutaneous LAAC in the
valve implantation (TAVI) is a lifesaving procedure, preferable to sur
elderly is effective and reasonably safe.187–190 However, individualized
gery when performed transfemorally.166,167 Patients undergoing TAVI
weighing of potential benefits against risks (stroke, bleeding,
are on average aged ≥80;168–172 40–50% have concomitant AF, chronic
procedure-/device-related adverse events) is advised. A review of
kidney disease168,169 or CCS.170 Bleeding complications are common
10 154 patients undergoing catheter-based LAAC with imaging during
(up to three times more frequent than ischaemic stroke) and impact
follow-up (mean 73 ± 9 years) reported device-related thrombosis in
survival.173 To predict bleeding events at 30 days, a risk score and
3.8% (≤90 days in 42%, at 90–365 days in 57%, and >1 year in
web calculator (comprising low haemoglobin, small femoral artery
1%).191 While further trials are ongoing (NCT03463317 Closure-AF
diameter, low CrCl, DAPT, OAC, and—optionally—low serum iron)
and NCT03642509 Occlusion-AF), a recent meta-analysis of 1516 ran
has been developed using artificial intelligence and validated in over
domized patients followed for 3 years (mean 73 ± 8 years) supports
10 000 TAVI patients.35
percutaneous LAAC vs. OAC (warfarin or apixaban) in terms of safety
Defining optimal antithrombotic therapy for TAVI has been challen
(significantly fewer ICH and nonprocedural major bleeds) and a favour
ging, with early recommendations based on small randomized stud
able signal on cardiovascular mortality.192 Procedural complications,
ies174,175 or experience from PCI. Intraprocedural anticoagulation
however, were not accounted for in the safety profile.192 Conceptual
with UFH, achieving an activated clotting time (ACT) of 200–300 s, is
support for LAAC comes from the recent LAAOS III trial that rando
commonly used in trials, registries and routine practice. Whether
mized 4770 anticoagulated AF patients with CHA2DS2-VASc ≥2
ACT-guided antagonization with protamine sulfate improves safety is
undergoing cardiac surgery (mean 71 ± 8 years) to either surgical
pending.176 After the procedure, guidelines166,167 recommend either
LAAC or none: at 3.8 years, ischaemic stroke/systemic embolism oc
(i) antiplatelet monotherapy (usually aspirin)173,177 lifelong or (ii)
curred in 4.8% vs. 7.0% (P = 0.001, number needed to treat = 37), with
OAC lifelong (for patients with other indications for anticoagula
out significant differences in rates of bleeding, heart failure or death.
tion).178 Aspirin vs. aspirin plus clopidogrel resulted in fewer major
The effect was greatest among those ≥72 years.193
bleeds, fewer combined bleeding and ischaemic events, and noninfer
Periprocedural anticoagulation during percutaneous LAAC is man
iority for ischaemic events in the POPular-TAVI trial cohort A (665 pa
datory. After the procedure, antithrombotic therapy usually includes
tients, mean 80 years).177 In patients with a clear indication for OAC,
short-term anticoagulation (e.g. 45 days) when the Watchman device
OAC monotherapy caused fewer total bleeds than OAC plus clopido
is used, or DAPT with aspirin and clopidogrel over 1–6 months (until
grel, without a significant increase in ischaemic events (313 patients, co
complete endothelialization of the thrombogenic foreign surface), fol
hort B, mean 81 years).178
lowed by single antiplatelet or no antithrombotic therapy.194
Registry data of NOACs vs. VKA in TAVI patients who need OAC
have yielded contrasting findings in terms of survival, safety, and ischae
mic events.179–181 Four randomized trials have since tested NOACs vs. Cardiac and noncardiac surgery
usual care in TAVI patients.172,182–184 The GALILEO trial of 1644 sinus Surgery is common in the elderly.10 Perioperative aspirin vs. no aspirin
rhythm TAVI patients (mean 81 years) was interrupted after 17 months in noncardiac surgery (NCS) results in similar mortality, reduced risk of
venous thromboembolism, but increased major bleeding in patients bleeding risk assessment and bleeding-avoidance measures (e.g. PPI,
with coronary artery disease, PAD, prior stroke, or multiple CVD abbreviated or de-escalated DAPT), particularly among HBR patients
risk factors, including older age.195–200 In one RCT, the subgroup (Graphical Abstract, Tables 1–4, Figure 1). While robust evidence to re
with prior PCI (mean 68 years) benefited from perioperative aspirin.201 fine antithrombotic therapy in older adults is increasing, powered
In patients at HBR or refusing blood transfusions, ESC guidelines rec dedicated studies are still needed.
ommend preoperative discontinuation of aspirin or clopidogrel for
5 days, of ticagrelor for 3–5 days, and of prasugrel for 7 days.30,199,200
In patients on DAPT following recent PCI, postponement of NCS is ad Funding
vised.30,199,200 When NCS is undeferrable, temporary discontinuation None declared.
of oral P2Y12 inhibition, with or without bridging with a rapid, reversible Conflict of interest: The authors declare that none received specific
intravenous GPI (tirofiban, eptifibatide) or cangrelor (Table 3) is reason funding in relation to the work: ‘Acute, periprocedural and longterm antith
able, depending on the patient- and surgery-related bleeding and ischae rombotic therapy in older adults: 2022 Update by the ESC Working Group
mic risk.30,138,139,199 on Thrombosis’ by Felicita Andreotti, Tobias Geisler, Jean-Philippe Collet,
For patients on warfarin, ESC guidelines recommend preoperative Bruna Gigante, Diana A Gorog, Sigrun Halvorsen, Gregory YH Lip, Joao

reduction of the international normalized ratio (INR) <1.5.199,202 If Morais, Eliano Pio Navarese, Carlo Patrono, Bianca Rocca, Andrea
the thromboembolic risk is very high (e.g. AF with CHA2DS2-VASc Rubboli, Dirk Sibbing, Robert F. Storey, Freek W.A. Verheugt, and
≥4, mechanical heart valve, recent mitral valve repair, previous venous Gemma Vilahur.
thromboembolism, or thrombophilia), it is reasonable to stop warfarin
3–5 days preoperatively, with daily INR monitoring and bridging with Data availability
therapeutic LMWH doses, adapted to renal function (Table 3).36,199,202
No original data were generated or analysed for this manuscript.
Measuring anti-FXa activity with a target of 0.5–1.0 U/mL at peak,
or diluted thrombin time or ecarin clotting time to assess residual
anti-Xa or anti-IIa levels, is advisable when managing mechanical References
heart valves or severe obesity.36,199,202 In patients taking NOACs, 1. http://ec.europa.eu/eurostat/statistics-explained/index.php/Population_structure_and_
LMWH bridging is not advocated given NOACs’ reversible pharma ageing
2. https://www.who.int/ageing/ageism/en/
codynamics and short half-life.93,203 For moderate or HBR surgery, 3. Vetrano DL, Palmer K, Marengoni A, Marzetti E, Lattanzio F, Roller-Wirnsberger R,
discontinuation of dabigatran is advised 24–48 or 48–96 h before, et al. Frailty and multimorbidity: a systematic review and meta-analysis. J Gerontol A
respectively, and of FXa inhibitors 24 or 48 h before, depending Biol Sci Med Sci 2019;74:659–666.
4. Dagenais GR, Leong DP, Rangarajan S, Lanas F, Lopez-Jaramillo P, Gupta R, et al.
on renal function.93,203 For low bleeding risk surgery (e.g. cataract
Variations in common diseases, hospital admissions, and deaths in middle-aged adults
or minor skin or dental surgery), no OAC interruption is needed ac in 21 countries from five continents (PURE): a prospective cohort study. Lancet 2020;
cording to ESC guidelines, with INR levels in patients on warfarin 395:785–794.
maintained in the lower therapeutic range.200 The above applies 5. Wilkins JT, Ning H, Berry J, Zhao L, Dyer AR, Lloyd-Jones DM. Lifetime risk and years
lived free of total cardiovascular disease. JAMA 2012;308:1795–1801.
to all age strata.30,199,200,203 6. Chao T-F, Wang K-L, Liu C-J, Lin Y-J, Chang S-L, Lo L-W, et al. Age threshold for in
creased stroke risk among patients with atrial fibrillation: a nationwide cohort study
from Taiwan. J Am Coll Cardiol 2015;66:1339–1347.
Future challenges and needs 7. Costa F, van Klaveren D, James S, Heg D, Räber L, Feres F, et al. Derivation and valid
ation of the predicting bleeding complications in patients undergoing stent implant
Efforts to improve drug adherence and to ascertain the effectiveness of ation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled
analysis of individual-patient datasets from clinical trials. Lancet 2017;389:1025–1034.
deprescribing in older adults are encouraged. Application of new and 8. Li L, Geraghty OC, Mehta Z, Rothwell PM. Age-specific risks, severity, time course, and
existing scores weighing bleeding vs. thrombotic risks to old and very outcome of bleeding on long-term antiplatelet treatment after vascular events: a
old cohorts, with the help of artificial intelligence and in silico modelling, population-based cohort study. Lancet 2017;390:490–499.
is encouraged.204 As risks increase continuously with age, quantitative 9. Kodali SK, Velagapudi P, Hahn RT, Abbott D, Leon MB. Valvular heart disease in pa
tients ≥80 years of age. J Am Coll Cardiol 2018;71:2058–2072.
rather than qualitative scores are likely preferable.34 By the same token, 10. Ellison EC, Pawlik TM, Way DP, Satiani B, Williams TE. The impact of the aging popu
to determine critical age ranges in clinical trials, analyses by continuous lation and incidence of cancer on future projections of general surgical workforce
rather than arbitrary cut-off values are encouraged. Randomized con needs. Surgery 2018;163:553–559.
11. Andreotti F, Rocca B, Husted S, Ajjan RA, ten Berg J, Cattaneo M, et al. Antithrombotic
trolled trials powered to assess the efficacy and safety of single or com
therapy in the elderly: expert position paper of the European Society of Cardiology
bined antithrombotic regimens in old and very old adults with acute or Working Group on Thrombosis. Eur Heart J 2015;36:3238–3249.
chronic CVD and/or AF are needed. Novel antithrombotic therapies 12. Selak V, Kerr A, Poppe K, Wu B, Harwood M, Grey C, et al. Annual risk of major bleed
with potentially favourable safety profiles (e.g. FXI/XIa inhibitors) ing among persons without cardiovascular disease not receiving antiplatelet therapy.
JAMA 2018;319:2507–2520.
should be tested particularly in the elderly. 13. Ho PM, Bryson CL, Rumsfeld JS. Medication adherence: its importance in cardiovascu
lar outcomes. Circulation 2009;119:3028–3035.
14. Cramer JA, Roy A, Burrell A, Fairchild CJ, Fuldeore MJ, Ollendorf DA, et al. Medication
Conclusions compliance and persistence: terminology and definitions. Value Health 2008;11:44–47.
15. Pasina L, Brucato AL, Falcone C, Cucchi E, Bresciani A, Sottocorno M, et al. Medication
Net benefits of antithrombotic therapies and interventions remain largely non-adherence among elderly patients newly discharged and receiving polypharmacy.
Drugs Aging 2014;31:283–289.
favourable in elderly patients with CVD or AF, achieving greater absolute 16. Polymeris AA, Traenka C, Hert L, Seiffge DJ, Peters N, De Marchis GM, et al.
effects compared to younger patients.11,37–39,48,49,82,99,100,104,125,139,166,167 Frequency and determinants of adherence to oral anticoagulants in stroke patients
Choosing optimal regimens for older adults, although challenging, is with atrial fibrillation in clinical practice. Eur Neurol 2016;76:187–193.
17. Browning JA, Tsang CCS, Dong X, Wan JY, Chisholm-Burns MA, Finch CK, et al.
possible on the basis of individual characteristics (Tables 2 and 3)
Effects of medicare comprehensive medication review on racial/ethnic disparities in
and the multiple treatment options summarized in this document nonadherence to statin medications among patients with Alzheimer’s disease: an ob
(Table 1). We encourage deprescribing, polypill use, systematic servational analysis. BMC Health Serv Res 2022;22:159.
18. Page AT, Clifford RM, Potter K, Schwartz D, Etherton-Beer CD. The feasibility and 41. Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, et al. 2017 ESC
effect of deprescribing in older adults on mortality and health: a systematic review guidelines for the management of acute myocardial infarction in patients presenting
and meta-analysis. Br J Clin Pharmacol 2016;82:583–623. with ST-segment elevation. Eur Heart J 2018;39:119–177.
19. Huffman MD, Xavier D, Perel P. Uses of polypills for cardiovascular disease and evi 42. Sotomi Y, Hikoso S, Nakatani D, Dohi T, Mizuno H, Okada K, et al. Practical assess
dence to date. Lancet 2017;389:1055–1065. ment of the tradeoff between fatal bleeding and coronary thrombotic risks using
20. Rankin A, Cadogan CA, Patterson SM, Kerse N, Cardwell CR, Bradley MC, et al. the academic research consortium for high bleeding risk criteria. J Atheroscler
Interventions to improve the appropriate use of polypharmacy for older people. Thromb 2022;29:1236–1248.
Cochrane Database Syst Rev 2018;9:CD008165. 43. Urban P, Gregson J, Owen R, Mehran R, Windecker S, Valgimigli M, et al. Assessing the
21. Krishnaswami A, Steinman MA, Goyal P, Zullo AR, Anderson TS, Birtcher KK, et al. risks of bleeding vs thrombotic events in patients at high bleeding risk after coronary
Deprescribing in older adults with cardiovascular disease. J Am Coll Cardiol 2019;73: stent implantation: the ARC-high bleeding risk trade-off model. JAMA Cardiol 2021;6:
2584–2595. 410–419.
22. Bahiru E, de Cates AN, Farr MR, Jarvis MC, Palla M, Rees K, et al. Fixed-dose combin 44. Capodanno D, Bhatt DL, Gibson CM, James S, Kimura T, Mehran R, et al. Bleeding
ation therapy for the prevention of atherosclerotic cardiovascular diseases. Cochrane avoidance strategies in percutaneous coronary intervention. Nat Rev Cardiol 2022;
Database Syst Rev 2017;2017:CD009868. 19:117–132.
23. Joseph P, Roshandel G, Gao P, Pais P, Lonn E, Xavier D, et al. Fixed-dose combination 45. Halvorsen S, Storey RF, Rocca B, Sibbing D, ten Berg J, Grove EL, et al. Management of
therapies with and without aspirin for primary prevention of cardiovascular disease: an antithrombotic therapy after bleeding in patients with coronary artery disease and/or
individual participant data meta-analysis. Lancet 2021;398:1133–1146. atrial fibrillation: expert consensus paper of the European Society of Cardiology

24. Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomström-Lundqvist C, et al. 2020 Working Group on Thrombosis. Eur Heart J 2016;38:1455–1462.
ESC guidelines for the diagnosis and management of atrial fibrillation developed in col 46. Scally B, Emberson JR, Spata E, Reith C, Davies K, Halls H, et al. Effects of gastropro
laboration with the European Association of Cardio-Thoracic Surgery (EACTS). Eur tectant drugs for the prevention and treatment of peptic ulcer disease and its compli
Heart J 2021;42:373–498. cations: a meta-analysis of randomised trials. Lancet Gastroenterol Hepatol 2018;3:
25. Hijazi Z, Lindbäck J, Alexander JH, Hanna M, Held C, Hylek EM, et al. The ABC (age, 231–241.
biomarkers, clinical history) stroke risk score: a biomarker-based risk score for pre 47. Moayyedi P, Eikelboom JW, Bosch J, Connolly SJ, Dyal L, Shestakovska O, et al.
dicting stroke in atrial fibrillation. Eur Heart J 2016;37:1582–1590. Pantoprazole to prevent gastroduodenal events in patients receiving rivaroxaban
26. Yeh RW, Secemsky EA, Kereiakes DJ, Normand S-LT, Gershlick AH, Cohen DJ, et al. and/or aspirin in a randomized, double-blind, placebo-controlled trial.
Development and validation of a prediction rule for benefit and harm of dual antipla Gastroenterology 2019;157:403–412.
telet therapy beyond 1 year after percutaneous coronary intervention. JAMA 2016; 48. Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, et al. Aspirin in the
315:1735–1749. primary and secondary prevention of vascular disease: collaborative meta-analysis of
27. Garay A, Ariza-Solé A, Formiga F, Raposeiras-Roubín S, Abu-Assi E, Sánchez-Salado JC, individual participant data from randomised trials. Lancet 2009;373:1849–1860.
et al. Prediction of post-discharge bleeding in elderly patients with acute coronary syn 49. Patrono C, García Rodríguez LA, Landolfi R, Baigent C. Low-dose aspirin for the pre
dromes: insights from the BleeMACS registry. Thromb Haemost 2018;118:929–938. vention of atherothrombosis. N Engl J Med 2005;353:2373–2383.
28. Urban P, Mehran R, Colleran R, Angiolillo DJ, Byrne RA, Capodanno D, et al. Defining 50. Han Y, Liao Z, Li Y, Zhao X, Ma S, Bao D, et al. Magnetically controlled capsule endos
high bleeding risk in patients undergoing percutaneous coronary intervention: a con copy for assessment of antiplatelet therapy-induced gastrointestinal injury. J Am Coll
sensus document from the Academic Research Consortium for High Bleeding Risk. Eur Cardiol 2022;79:116–128.
Heart J 2019;40:2632–2653. 51. Tomaniak M, Chichareon P, Modolo R, Takahashi K, Chang CC, Kogame N, et al.
29. Cao D, Mehran R, Dangas G, Baber U, Sartori S, Chandiramani R, et al. Validation of Ticagrelor monotherapy beyond one month after PCI in ACS or stable CAD in elderly
the academic research consortium high bleeding risk definition in contemporary PCI patients aged above 75 years: a prespecified analysis of the randomized GLOBAL
patients. J Am Coll Cardiol 2020;75:2711–2722. LEADERS trial. EuroIntervention 2020;15:e1605–e1614.
30. Valgimigli M, Bueno H, Byrne RA, Collet J-P, Costa F, Jeppsson A, et al. 2017 ESC fo 52. Johnston SC, Amarenco P, Albers GW, Denison H, Easton JD, Evans SR, et al.
cused update on dual antiplatelet therapy in coronary artery disease developed in col Ticagrelor versus aspirin in acute stroke or transient ischemic attack. N Engl J Med
laboration with EACTS. Eur Heart J 2018;39:213–260. 2016;375:35–43.
31. Collet J-P, Thiele H, Barbato E, Barthélémy O, Bauersachs J, Bhatt DL, et al. 2020 ESC 53. Chiarito M, Sanz-Sánchez J, Cannata F, Cao D, Sturla M, Panico C, et al. Monotherapy
guidelines for the management of acute coronary syndromes in patients presenting with a P2Y12 inhibitor or aspirin for secondary prevention in patients with established
without persistent ST-segment elevation. Eur Heart J 2021;42:1289–1367. atherosclerosis: a systematic review and meta-analysis. Lancet 2020;395:1487–1495.
32. Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C, et al. 2019 54. Koo B-K, Kang J, Park KW, Rhee T-M, Yang H-M, Won K-B, et al. Aspirin versus clo
ESC guidelines for the diagnosis and management of chronic coronary syndromes. Eur pidogrel for chronic maintenance monotherapy after percutaneous coronary inter
Heart J 2019;41:407–477. vention (HOST-EXAM): an investigator-initiated, prospective, randomised,
33. Wester A, Mohammad MA, Olivecrona G, Holmqvist J, Yndigegn T, Koul S. Validation open-label, multicentre trial. Lancet 2021;397:2487–2496.
of the 4-item PRECISE-DAPT score: a SWEDEHEART study. J Am Heart Assoc 2021; 55. Ikeda Y, Shimada K, Teramoto T, Uchiyama S, Yamazaki T, Oikawa S, et al. Low-dose
10:e020974. aspirin for primary prevention of cardiovascular events in Japanese patients 60 years or
34. Bor WL, Chan Pin Yin DRPP, Brouwer J, Nijenhuis VJ, Peper J, Timmers L, et al. older with atherosclerotic risk factors: a randomized clinical trial. JAMA 2014;312:
Assessment of the Academic Research Consortium for high bleeding risk criteria in 2510–2520.
patients undergoing TAVR. JACC Cardiovasc Interv 2021;14:1265–1267. 56. Sugawara M, Goto Y, Yamazaki T, Teramoto T, Oikawa S, Shimada K, et al. Low-dose
35. Navarese EP, Zhang Z, Kubica J, Andreotti F, Farinaccio A, Bartorelli AL, et al. aspirin for primary prevention of cardiovascular events in elderly Japanese patients
Development and validation of a practical model to identify patients at risk of bleeding with atherosclerotic risk factors: subanalysis of a randomized clinical trial (JPPP-70).
after TAVR. JACC Cardiovasc Interv 2021;14:1196–1206. Am J Cardiovasc Drugs 2019;19:299–311.
36. Rocca B, Fox KAA, Ajjan RA, Andreotti F, Baigent C, Collet J-P, et al. Antithrombotic 57. McNeil JJ, Wolfe R, Woods RL, Tonkin AM, Donnan GA, Nelson MR, et al. Effect of
therapy and body mass: an expert position paper of the ESC Working Group on aspirin on cardiovascular events and bleeding in the healthy elderly. N Engl J Med
Thrombosis. Eur Heart J 2018;39:1672–1686f. 2018;379:1509–1518.
37. Friberg L, Rosenqvist M, Lip GYH. Net clinical benefit of warfarin in patients with atrial 58. Halvorsen S, Andreotti F, ten Berg JM, Cattaneo M, Coccheri S, Marchioli R, et al.
fibrillation: a report from the Swedish atrial fibrillation cohort study. Circulation 2012; Aspirin therapy in primary cardiovascular disease prevention: a position paper of
125:2298–2307. the European Society of Cardiology Working Group on Thrombosis. J Am Coll
38. Patti G, Lucerna M, Pecen L, Siller-Matula JM, Cavallari I, Kirchhof P, et al. Cardiol 2014;64:319–327.
Thromboembolic risk, bleeding outcomes and effect of different antithrombotic strat 59. Arora S, Shemisa K, Vaduganathan M, Qamar A, Gupta A, Garg SK, et al. Premature
egies in very elderly patients with atrial fibrillation: a sub-analysis from the PREFER in ticagrelor discontinuation in secondary prevention of atherosclerotic CVD. J Am Coll
AF (PRE vention oF Thromboembolic Events– European Registry in Atrial Fibrillation). J Cardiol 2019;73:2454–2464.
Am Heart Assoc 2017;6:e005657. 60. Fontana P, Ibberson M, Stevenson B, Wigger L, Daali Y, Niknejad A, et al. Contribution
39. Galli M, Andreotti F, Porto I, Crea F. Intracranial haemorrhages vs. stent thromboses of exome sequencing to the identification of genes involved in the response to clopi
with direct oral anticoagulant plus single antiplatelet agent or triple antithrombotic dogrel in cardiovascular patients. J Thromb Haemost 2020;18:1425–1434.
therapy: a meta-analysis of randomized trials in atrial fibrillation and percutaneous cor 61. Erlinge D, Gurbel PA, James S, Lindahl TL, Svensson P, ten Berg JM, et al. Prasugrel 5 mg
onary intervention/acute coronary syndrome patients. Europace 2020;22:538–546. in the very elderly attenuates platelet inhibition but maintains noninferiority to prasu
40. Neumann F-J, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, et al. grel 10 mg in nonelderly patients: the GENERATIONS trial, a pharmacodynamic and
2018 ESC/EACTS guidelines on myocardial revascularization. Eur Heart J 2019;40: pharmacokinetic study in stable coronary artery disease patients. J Am Coll Cardiol
87–165. 2013;62:577–583.
62. Denninger MH, Necciari J, Serre-Lacroix E, Sissmann J. Clopidogrel antiplatelet activity 85. Sardar P, Chatterjee S, Chaudhari S, Lip GYH. New oral anticoagulants in elderly
is independent of age and presence of atherosclerosis. Semin Thromb Hemost 1999;25: adults: evidence from a meta-analysis of randomized trials. J Am Geriatr Soc 2014;62:
41–45. 857–864.
63. Dobesh PP, Oestreich JH. Ticagrelor: pharmacokinetics, pharmacodynamics, clinical 86. Silverio A, Di Maio M, Prota C, De Angelis E, Radano I, Citro R, et al. Safety and efficacy
efficacy, and safety. Pharmacotherapy 2014;34:1077–1090. of non-vitamin K antagonist oral anticoagulants in elderly patients with atrial fibrillation:
64. Teng R. Pharmacokinetic, pharmacodynamic and pharmacogenetic profile of the oral systematic review and meta-analysis of 22 studies and 440 281 patients. Eur Heart J
antiplatelet agent ticagrelor. Clin Pharmacokinet 2012;51:305–318. Cardiovasc Pharmacother 2021;7:f20–f29.
65. Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, et al. 87. Shen N-N, Wu Y, Wang N, Kong L-C, Zhang C, Wang J-L, et al. Direct oral anticoa
Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J gulants vs. vitamin-K antagonists in the elderly with atrial fibrillation: a systematic re
Med 2007;357:2001–2015. view comparing benefits and harms between observational studies and randomized
66. Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, et al. Ticagrelor controlled trials. Front Cardiovasc Med 2020;7:132.
versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009;361: 88. Gujjarlamudi H. Polytherapy and drug interactions in elderly. J Midlife Health 2016;7:
1045–1057. 105–107.
67. Husted S, James S, Becker RC, Horrow J, Katus H, Storey RF, et al. Ticagrelor versus 89. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. Dabigatran
clopidogrel in elderly patients with acute coronary syndromes: a substudy from the versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139–1151.
90. Eikelboom JW, Wallentin L, Connolly SJ, Ezekowitz M, Healey JS, Oldgren J, et al. Risk
prospective randomized PLATelet inhibition and patient outcomes (PLATO) trial.
of bleeding with 2 doses of dabigatran compared with warfarin in older and younger
Circ Cardiovasc Qual Outcomes 2012;5:680–688.

patients with atrial fibrillation: an analysis of the randomized evaluation of long-term
68. Gimbel M, Qaderdan K, Willemsen L, Hermanides R, Bergmeijer T, de Vrey E, et al.
anticoagulant therapy (RE-LY) trial. Circulation 2011;123:2363–2372.
Clopidogrel versus ticagrelor or prasugrel in patients aged 70 years or older with
91. Reilly PA, Lehr T, Haertter S, Connolly SJ, Yusuf S, Eikelboom JW, et al. The effect of
non-ST-elevation acute coronary syndrome (POPular AGE): the randomised, open-
dabigatran plasma concentrations and patient characteristics on the frequency of is
label, non-inferiority trial. Lancet 2020;395:1374–1381.
chemic stroke and major bleeding in atrial fibrillation patients. J Am Coll Cardiol
69. Szummer K, Montez-Rath ME, Alfredsson J, Erlinge D, Lindahl B, Hofmann R, et al.
2014;63:321–328.
Comparison between ticagrelor and clopidogrel in elderly patients with an acute cor
92. https://www.ema.europa.eu/en/documents/product-information/pradaxa-epar-
onary syndrome: insights from the SWEDEHEART registry. Circulation 2020;142: product-information_en.pdf
1700–1708. 93. Steffel J, Collins R, Antz M, Cornu P, Desteghe L, Haeusler KG, et al. 2021 European
70. Savonitto S, Ferri LA, Piatti L, Grosseto D, Piovaccari G, Morici N, et al. Comparison of Heart Rhythm Association practical guide on the use of non-vitamin K antagonist oral
reduced-dose prasugrel and standard-dose clopidogrel in elderly patients with acute anticoagulants in patients with atrial fibrillation. Europace 2021;23:1612–1676.
coronary syndromes undergoing early percutaneous revascularization. Circulation 94. Pollack CV, Reilly PA, van Ryn J, Eikelboom JW, Glund S, Bernstein RA, et al.
2018;137:2435–2445. Idarucizumab for dabigatran reversal—full cohort analysis. N Engl J Med 2017;377:
71. Roe MT, Goodman SG, Ohman EM, Stevens SR, Hochman JS, Gottlieb S, et al. Elderly 431–441.
patients with acute coronary syndromes managed without revascularization: insights 95. Glund S, Stangier J, van Ryn J, Schmohl M, Moschetti V, Haazen W, et al. Effect of age
into the safety of long-term dual antiplatelet therapy with reduced-dose prasugrel ver and renal function on idarucizumab pharmacokinetics and idarucizumab-mediated re
sus standard-dose clopidogrel. Circulation 2013;128:823–833. versal of dabigatran anticoagulant activity in a randomized, double-blind, crossover
72. Menichelli M, Neumann F-J, Ndrepepa G, Mayer K, Wöhrle J, Bernlochner I, et al. Age- phase Ib study. Clin Pharmacokinet 2017;56:41–54.
and weight-adapted dose of prasugrel versus standard dose of ticagrelor in patients 96. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus
with acute coronary syndromes: results from a randomized trial. Ann Intern Med warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883–891.
2020;173:436–444. 97. Granger CB, Alexander JH, McMurray JJV, Lopes RD, Hylek EM, Hanna M, et al.
73. Schüpke S, Neumann F-J, Menichelli M, Mayer K, Bernlochner I, Wöhrle J, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365:
Ticagrelor or prasugrel in patients with acute coronary syndromes. N Engl J Med 981–992.
2019;381:1524–1534. 98. Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, et al.
74. Navarese EP, Khan SU, Kołodziejczak M, Kubica J, Buccheri S, Cannon CP, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013;369:
Comparative efficacy and safety of oral P2Y12 inhibitors in acute coronary syndrome: 2093–2104.
network meta-analysis of 52 816 patients from 12 randomized trials. Circulation 2020; 99. Halvorsen S, Atar D, Yang H, De Caterina R, Erol C, Garcia D, et al. Efficacy and safety
142:150–160. of apixaban compared with warfarin according to age for stroke prevention in atrial
75. Valgimigli M, Frigoli E, Heg D, Tijssen J, Jüni P, Vranckx P, et al. Dual antiplatelet therapy fibrillation: observations from the ARISTOTLE trial. Eur Heart J 2014;35:1864–1872.
after PCI in patients at high bleeding risk. N Engl J Med 2021;385:1643–1655. 100. Kato ET, Giugliano RP, Ruff CT, Koretsune Y, Yamashita T, Kiss RG, et al. Efficacy and
76. Mehran R, Baber U, Sharma SK, Cohen DJ, Angiolillo DJ, Briguori C, et al. Ticagrelor safety of edoxaban in elderly patients with atrial fibrillation in the ENGAGE AF–TIMI
with or without aspirin in high-risk patients after PCI. N Engl J Med 2019;381: 48 trial. J Am Heart Assoc 2016;5:e003432.
2032–2042. 101. Halperin JL, Hankey GJ, Wojdyla DM, Piccini JP, Lokhnygina Y, Patel MR, et al. Efficacy
77. Bonaca MP, Bhatt DL, Cohen M, Steg PG, Storey RF, Jensen EC, et al. Long-term use of and safety of rivaroxaban compared with warfarin among elderly patients with non
ticagrelor in patients with prior myocardial infarction. N Engl J Med 2015;372: valvular atrial fibrillation in the rivaroxaban once daily, oral, direct factor Xa inhibition
compared with vitamin K antagonism for prevention of stroke and embolism trial in
1791–1800.
atrial fibrillation (ROCKET AF). Circulation 2014;130:138–146.
78. Yeh RW, Kereiakes DJ, Steg PG, Windecker S, Rinaldi MJ, Gershlick AH, et al. Benefits
102. Caldeira D, Nunes-Ferreira A, Rodrigues R, Vicente E, Pinto FJ, Ferreira JJ. Non-vitamin
and risks of extended duration dual antiplatelet therapy after PCI in patients with and
K antagonist oral anticoagulants in elderly patients with atrial fibrillation: a systematic
without acute myocardial infarction. J Am Coll Cardiol 2015;65:2211–2221.
review with meta-analysis and trial sequential analysis. Arch Gerontol Geriatr 2019;81:
79. Mauri L, Kereiakes DJ, Yeh RW, Driscoll-Shempp P, Cutlip DE, Steg PG, et al. Twelve
209–214.
or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med 2014;
103. Okumura K, Akao M, Yoshida T, Kawata M, Okazaki O, Akashi S, et al. Low-dose edox
371:2155–2166.
aban in very elderly patients with atrial fibrillation. N Engl J Med 2020;383:1735–1745.
80. Storey RF, Angiolillo DJ, Bonaca MP, Thomas MR, Judge HM, Rollini F, et al. Platelet
104. Hylek EM, Held C, Alexander JH, Lopes RD, De Caterina R, Wojdyla DM, et al. Major
inhibition with ticagrelor 60 mg versus 90 mg twice daily in the PEGASUS-TIMI 54 trial.
bleeding in patients with atrial fibrillation receiving apixaban or warfarin. J Am Coll
J Am Coll Cardiol 2016;67:1145–1154. Cardiol 2014;63:2141–2147.
81. Hilkens NA, Algra A, Diener HC, Bath PM, Csiba L, Hacke W, et al. Balancing benefits 105. Connolly SJ, Crowther M, Eikelboom JW, Gibson CM, Curnutte JT, Lawrence JH, et al.
and risks of long-term antiplatelet therapy in noncardioembolic transient ischemic at Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors. N
tack or stroke. Stroke 2021;52:3258–3265. Engl J Med 2019;380:1326–1335.
82. Mant J, Hobbs FDR, Fletcher K, Roalfe A, Fitzmaurice D, Lip GYH, et al. Warfarin ver 106. Ansell J, Bakhru S, Laulicht BE, Tracey G, Villano S, Freedman D. Ciraparantag reverses
sus aspirin for stroke prevention in an elderly community population with atrial fibril the anticoagulant activity of apixaban and rivaroxaban in healthy elderly subjects. Eur
lation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a Heart J 2022;43:985–992.
randomised controlled trial. Lancet 2007;370:493–503. 107. Vranckx P, Valgimigli M, Jüni P, Hamm C, Steg PG, Heg D, et al. Ticagrelor plus aspirin
83. Chao T-F, Liu C-J, Lin Y-J, Chang S-L, Lo L-W, Hu Y-F, et al. Oral anticoagulation in very for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopi
elderly patients with atrial fibrillation: a nationwide cohort study. Circulation 2018;138: dogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months
37–47. after implantation of a drug-eluting stent: a multicentre, open-label, randomised super
84. Bai Y, Guo S-D, Deng H, Shantsila A, Fauchier L, Ma C-S, et al. Effectiveness and safety iority trial. Lancet 2018;392:940–949.
of oral anticoagulants in older patients with atrial fibrillation: a systematic review and 108. Sibbing D, Aradi D, Jacobshagen C, Gross L, Trenk D, Geisler T, et al. Guided de-
meta-regression analysis. Age Ageing 2018;47:9–17. escalation of antiplatelet treatment in patients with acute coronary syndrome
undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, percutaneous coronary intervention: a network meta-analysis of randomized con
open-label, multicentre trial. Lancet 2017;390:1747–1757. trolled trials. JAMA Cardiol 2019;4:747–755.
109. Cuisset T, Deharo P, Quilici J, Johnson TW, Deffarges S, Bassez C, et al. Benefit of 128. Windecker S, Lopes RD, Massaro T, Jones-Burton C, Granger CB, Aronson R, et al.
switching dual antiplatelet therapy after acute coronary syndrome: the TOPIC (timing Antithrombotic therapy in patients with atrial fibrillation and acute coronary syn
of platelet inhibition after acute coronary syndrome) randomized study. Eur Heart J drome treated medically or with percutaneous coronary intervention or undergoing
2017;38:3070–3078. elective percutaneous coronary intervention: insights from the AUGUSTUS trial.
110. Kim H-S, Kang J, Hwang D, Han J-K, Yang H-M, Kang H-J, et al. Prasugrel-based de- Circulation 2019;140:1921–1932.
escalation of dual antiplatelet therapy after percutaneous coronary intervention in pa 129. Rubboli A, Lip GYH. Algorithm for the management of antithrombotic therapy in atrial
tients with acute coronary syndrome (HOST-REDUCE-POLYTECH-ACS): an open- fibrillation patients undergoing percutaneous coronary intervention: an updated pro
label, multicentre, non-inferiority randomised trial. Lancet 2020;396:1079–1089. posal based on efficacy considerations. Eur Heart J Cardiovasc Pharmacother 2020;6:
111. Hahn J-Y, Song YB, Oh J-H, Chun WJ, Park YH, Jang WJ, et al. Effect of P2Y12 inhibitor 197–198.
monotherapy vs dual antiplatelet therapy on cardiovascular events in patients under 130. Gargiulo G, Cannon CP, Gibson CM, Goette A, Lopes RD, Oldgren J, et al. Safety and
going percutaneous coronary intervention: the SMART-CHOICE randomized clinical efficacy of double vs. Triple antithrombotic therapy in patients with atrial fibrillation
trial. JAMA 2019;321:2428–2437. with or without acute coronary syndrome undergoing percutaneous coronary inter
112. Watanabe H, Domei T, Morimoto T, Natsuaki M, Shiomi H, Toyota T, et al. Effect of vention: a collaborative meta-analysis of non-vitamin K antagonist oral anticoagulant-
1-month dual antiplatelet therapy followed by clopidogrel vs 12-month dual antiplate based randomized clinical trials. Eur Heart J Cardiovasc Pharmacother 2021;7:f50–f60.
let therapy on cardiovascular and bleeding events in patients receiving PCI: the 131. Lip GYH, Collet J-P, Haude M, Byrne R, Chung EH, Fauchier L, et al. 2018 Joint

STOPDAPT-2 randomized clinical trial. JAMA 2019;321:2414–2427. European consensus document on the management of antithrombotic therapy in atrial
113. Kim B-K, Hong S-J, Cho Y-H, Yun KH, Kim YH, Suh Y, et al. Effect of ticagrelor mono fibrillation patients presenting with acute coronary syndrome and/or undergoing per
therapy vs ticagrelor with aspirin on major bleeding and cardiovascular events in pa cutaneous cardiovascular interventions: a joint consensus document of the European
tients with acute coronary syndrome: the TICO randomized clinical trial. JAMA Heart Rhythm Association (EHRA), European Society of Cardiology Working Group
2020;323:2407–2416. on Thrombosis, European Association of Percutaneous Cardiovascular Interventions
114. Watanabe H, Morimoto T, Natsuaki M, Yamamoto K, Obayashi Y, Ogita M, et al. (EAPCI), and European Association of Acute Cardiac Care (ACCA) endorsed by the
Comparison of clopidogrel monotherapy after 1 to 2 months of dual antiplatelet ther Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), Latin
apy with 12 months of dual antiplatelet therapy in patients with acute coronary syn America Heart Rhythm Society (LAHRS), and Cardiac Arrhythmia Society of
drome: the STOPDAPT-2 ACS randomized clinical trial. JAMA Cardiol 2022;7:
Southern Africa (CASSA). Europace 2019;21:192–193.
407–417. 132. Angiolillo DJ, Goodman SG, Bhatt DL, Eikelboom JW, Price MJ, Moliterno DJ, et al.
115. Kim CJ, Park M-W, Kim MC, Choo E-H, Hwang B-H, Lee KY, et al. Unguided de-
Antithrombotic therapy in patients with atrial fibrillation treated with oral anticoagu
escalation from ticagrelor to clopidogrel in stabilised patients with acute myocardial
lation undergoing percutaneous coronary intervention: a north American perspec
infarction undergoing percutaneous coronary intervention (TALOS-AMI): an
tive–2018 update. Circulation 2018;138:527–536.
investigator-initiated, open-label, multicentre, non-inferiority, randomised trial.
133. Lopes RD, Heizer G, Aronson R, Vora AN, Massaro T, Mehran R, et al. Antithrombotic
Lancet 2021;398:1305–1316.
therapy after acute coronary syndrome or PCI in atrial fibrillation. N Engl J Med 2019;
116. Escaned J, Cao D, Baber U, Nicolas J, Sartori S, Zhang Z, et al. Ticagrelor monotherapy
380:1509–1524.
in patients at high bleeding risk undergoing percutaneous coronary intervention:
134. Yasuda S, Kaikita K, Akao M, Ako J, Matoba T, Nakamura M, et al. Antithrombotic ther
TWILIGHT-HBR. Eur Heart J 2021;42:4624–4634.
apy for atrial fibrillation with stable coronary disease. N Engl J Med 2019;381:
117. Giacoppo D, Matsuda Y, Fovino LN, D’Amico G, Gargiulo G, Byrne RA, et al. Short
1103–1113.
dual antiplatelet therapy followed by P2Y12 inhibitor monotherapy vs. Prolonged
135. Matsumura-Nakano Y, Shizuta S, Komasa A, Morimoto T, Masuda H, Shiomi H, et al.
dual antiplatelet therapy after percutaneous coronary intervention with second-
Open-label randomized trial comparing oral anticoagulation with and without single
generation drug-eluting stents: a systematic review and meta-analysis of randomized
antiplatelet therapy in patients with atrial fibrillation and stable coronary artery disease
clinical trials. Eur Heart J 2021;42:308–319.
beyond 1 year after coronary stent implantation: OAC-ALONE study. Circulation
118. Kim BG, Hong S-J, Kim B-K, Lee S-J, Ahn C-M, Shin D-H, et al. Age-dependent effect of
2019;139:604–616.
ticagrelor monotherapy versus ticagrelor with aspirin on major bleeding and cardio
136. Harrington RA, Stone GW, McNulty S, White HD, Lincoff AM, Gibson CM, et al.
vascular events: a post hoc analysis of the TICO randomized trial. J Am Heart Assoc
Platelet inhibition with cangrelor in patients undergoing PCI. N Engl J Med 2009;
2021;10:e022700.
119. Sibbing D, Gross L, Trenk D, Jacobshagen C, Geisler T, Hadamitzky M, et al. Age and 361:2318–2329.
137. Bhatt DL, Lincoff AM, Gibson CM, Stone GW, McNulty S, Montalescot G, et al.
outcomes following guided de-escalation of antiplatelet treatment in acute coronary
syndrome patients undergoing percutaneous coronary intervention: results from Intravenous platelet blockade with cangrelor during PCI. N Engl J Med 2009;361:
the randomized TROPICAL-ACS trial. Eur Heart J 2018;39:2749–2758. 2330–2341.
120. Claassens DMF, Vos GJA, Bergmeijer TO, Hermanides RS, van ‘t Hof AWJ, van der 138. Bhatt DL, Stone GW, Mahaffey KW, Gibson CM, Steg PG, Hamm CW, et al. Effect of
Harst P, et al. A genotype-guided strategy for oral P2Y12 inhibitors in primary PCI. platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med 2013;
N Engl J Med 2019;381:1621–1631. 368:1303–1313.
121. Galli M, Benenati S, Capodanno D, Franchi F, Rollini F, D’Amario D, et al. Guided versus 139. Cavender MA, Bhatt DL, Stone GW, Steg PG, Gibson CM, Hamm CW, et al.
standard antiplatelet therapy in patients undergoing percutaneous coronary interven Cangrelor in older patients undergoing percutaneous coronary intervention: findings
tion: a systematic review and meta-analysis. Lancet 2021;397:1470–1483. from CHAMPION PHOENIX. Circ Cardiovasc Interv 2017;10:pii: e005257.
122. Eikelboom JW, Connolly SJ, Bosch J, Dagenais GR, Hart RG, Shestakovska O, et al. 140. Roffi M, Patrono C, Collet J-P, Mueller C, Valgimigli M, Andreotti F, et al. 2015 ESC
Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med guidelines for the management of acute coronary syndromes in patients presenting
2017;377:1319–1330. without persistent ST-segment elevation: task force for the management of acute cor
123. de Vries TI, Eikelboom JW, Bosch J, Westerink J, Dorresteijn JAN, Alings M, et al. onary syndromes in patients presenting without persistent ST-segment elevation of
Estimating individual lifetime benefit and bleeding risk of adding rivaroxaban to aspirin the European Society of Cardiology (ESC). Eur Heart J 2016;37:267–315.
for patients with stable cardiovascular disease: results from the COMPASS trial. Eur 141. Rubboli A, Patti G. What is the role for glycoprotein IIB/IIIA inhibitor use in the cath
Heart J 2019;40:3771–3778a. eterization laboratory in the current era? Curr Vasc Pharmacol 2018;16:451–458.
124. Darmon A, Ducrocq G, Jasilek A, Feldman L, Sorbets E, Ferrari R, et al. Use of risk 142. Liu Z, Silvain J, Kerneis M, Barthélémy O, Payot L, Choussat R, et al. Intravenous en
scores to identify lower and higher risk subsets among COMPASS-eligible patients oxaparin versus unfractionated heparin in elderly patients undergoing primary percu
with chronic coronary syndromes. Insights from the CLARIFY registry. Clin Cardiol taneous coronary intervention: an analysis of the randomized ATOLL trial. Angiology
2020;44:58–65. 2017;68:29–39.
125. Krantz MJ, Debus SE, Hsia J, Patel MR, Anand SS, Nehler MR, et al. Low-dose rivarox 143. Montalescot G, Zeymer U, Silvain J, Boulanger B, Cohen M, Goldstein P, et al.
aban plus aspirin in older patients with peripheral artery disease undergoing acute limb Intravenous enoxaparin or unfractionated heparin in primary percutaneous coronary
revascularization: insights from the VOYAGER PAD trial. Eur Heart J 2021;42: intervention for ST-elevation myocardial infarction: the international randomised
4040–4048. open-label ATOLL trial. Lancet 2011;378:693–703.
126. Gargiulo G, Goette A, Tijssen J, Eckardt L, Lewalter T, Vranckx P, et al. Safety and ef 144. Yusuf S, Mehta SR, Chrolavicius S, Afzal R, Pogue J, Granger CB, et al. Comparison of
ficacy outcomes of double vs. triple antithrombotic therapy in patients with atrial fib fondaparinux and enoxaparin in acute coronary syndromes. N Engl J Med 2006;354:
rillation following percutaneous coronary intervention: a systematic review and 1464–1476.
meta-analysis of non-vitamin K antagonist oral anticoagulant-based randomized clinical 145. Szummer K, Oldgren J, Lindhagen L, Carrero JJ, Evans M, Spaak J, et al. Association be
trials. Eur Heart J 2019;40:3757–3767. tween the use of fondaparinux vs low-molecular-weight heparin and clinical outcomes
127. Lopes RD, Hong H, Harskamp RE, Bhatt DL, Mehran R, Cannon CP, et al. Safety and in patients with non–ST-segment elevation myocardial infarction. JAMA 2015;313:
efficacy of antithrombotic strategies in patients with atrial fibrillation undergoing 707–716.
146. Mehta SR, Boden WE, Eikelboom JW, Flather M, Steg PG, Avezum A, et al. 167. Otto CM, Nishimura RA, Bonow RO, Carabello BA, Erwin JP, Gentile F, et al. 2020
Antithrombotic therapy with fondaparinux in relation to interventional management ACC/AHA guideline for the management of patients with valvular heart disease: ex
strategy in patients with ST- and non-ST-segment elevation acute coronary syn ecutive summary: a report of the American College of Cardiology/American Heart
dromes: an individual patient-level combined analysis of the Fifth and Sixth Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 2021;
Organization to Assess Strategies in Ischemic Syndromes (OASIS 5 and 6) randomized 77:450–500.
trials. Circulation 2008;118:2038–2046. 168. Lüders F, Kaier K, Kaleschke G, Gebauer K, Meyborg M, Malyar NM, et al. Association
147. https://www.ema.europa.eu/en/medicines/human/EPAR/inhixa of CKD with outcomes among patients undergoing transcatheter aortic valve implant
148. https://www.ema.europa.eu/en/medicines/human/EPAR/arixtra ation. Clin J Am Soc Nephrol 2017;12:718–726.
149. Navarese EP, Schulze V, Andreotti F, Kowalewski M, Kołodziejczak M, Kandzari DE, 169. Rodés-Cabau J, Urena M, Nombela-Franco L, Amat-Santos I, Kleiman N,
et al. Comprehensive meta-analysis of safety and efficacy of bivalirudin versus heparin Munoz-Garcia A, et al. Arrhythmic burden as determined by ambulatory continuous
with or without routine glycoprotein IIb/IIIa inhibitors in patients with acute coronary cardiac monitoring in patients with new-onset persistent left bundle branch block fol
syndrome. JACC Cardiovasc Interv 2015;8:201–213. lowing transcatheter aortic valve replacement. JACC Cardiovasc Interv 2018;11:
150. Wester A, Attar R, Mohammad MA, Isma N, James S, Omerovic E, et al. Bivalirudin 1495–1505.
versus heparin monotherapy in elderly patients with myocardial infarction: a prespe 170. Faroux L, Guimaraes L, Wintzer-Wehekind J, Junquera L, Ferreira-Neto AN, del Val D,
cified subgroup analysis of the VALIDATE-SWEDEHEART trial. Circ Cardiovasc Interv et al. Coronary artery disease and transcatheter aortic valve replacement. J Am Coll
2020;13:e008671. Cardiol 2019;74:362–372.
151. Fahrni G, Wolfrum M, De Maria GL, Banning AP, Benedetto U, Kharbanda RK. 171. Kumar N, Khera R, Fonarow GC, Bhatt DL. Comparison of outcomes of transfemoral

Prolonged high-dose bivalirudin infusion reduces major bleeding without increasing versus transapical approach for transcatheter aortic valve implantation. Am J Cardiol
stent thrombosis in patients undergoing primary percutaneous coronary intervention: 2018;122:1520–1526.
novel insights from an updated meta-analysis. J Am Heart Assoc 2016;5:e003515. 172. Park D-W, Ahn J-M, Kang D-Y, Kim KW, Koo HJ, Yang DH, et al. Edoxaban versus dual
152. Fibrinolytic Therapy Trialists’ (FTT) Collaborative Group. Indications for fibrinolytic antiplatelet therapy for leaflet thrombosis and cerebral thromboembolism after
therapy in suspected acute myocardial infarction: collaborative overview of early mor TAVR: the ADAPT-TAVR randomized clinical trial. Circulation 2022;146:466–479.
tality and major morbidity results from all randomised trials of more than 1000 pa 173. ten Berg J, Sibbing D, Rocca B, Van Belle E, Chevalier B, Collet J-P, et al. Management of
tients. Lancet 1994;343:311–322. antithrombotic therapy in patients undergoing transcatheter aortic valve implantation:
153. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic a consensus document of the ESC Working Group on Thrombosis and the European
therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Association of Percutaneous Cardiovascular Interventions (EAPCI), in collaboration
Lancet 2003;361:13–20.
with the ESC Council on Valvular Heart Disease. Eur Heart J 2021;42:2265–2269.
154. Bueno H, Betriu A, Heras M, Alonso JJ, Cequier A, Garcia EJ, et al. Primary angioplasty
174. Ussia GP, Scarabelli M, Mulè M, Barbanti M, Sarkar K, Cammalleri V, et al. Dual antipla
vs. fibrinolysis in very old patients with acute myocardial infarction: TRIANA
telet therapy versus aspirin alone in patients undergoing transcatheter aortic valve im
(TRatamiento del Infarto Agudo de miocardio eN Ancianos) randomized trial and
plantation. Am J Cardiol 2011;108:1772–1776.
pooled analysis with previous studies. Eur Heart J 2011;32:51–60.
175. Rodés-Cabau J, Masson J-B, Welsh RC, Garcia del Blanco B, Pelletier M, Webb JG, et al.
155. Armstrong PW, Gershlick AH, Goldstein P, Wilcox R, Danays T, Lambert Y, et al.
Aspirin versus aspirin plus clopidogrel as antithrombotic treatment following trans
Fibrinolysis or primary PCI in ST-segment elevation myocardial infarction. N Engl J
catheter aortic valve replacement with a balloon-expandable valve. JACC Cardiovasc
Med 2013;368:1379–1387.
Interv 2017;10:1357–1365.
156. Simoons M, de Jaegere P, van Domburg R, Boersma E, Maggioni A, Franzosi M, et al.
176. Al-Kassou B, Kandt J, Lohde L, Shamekhi J, Sedaghat A, Tabata N, et al. Safety and ef
Individual risk assessment for intracranial haemorrhage during thrombolytic therapy.
ficacy of protamine administration for prevention of bleeding complications in patients
Lancet 1993;342:1523–1528.
undergoing TAVR. JACC Cardiovasc Interv 2020;13:1471–1480.
157. White HD, Braunwald E, Murphy SA, Jacob AJ, Gotcheva N, Polonetsky L, et al.
177. Brouwer J, Nijenhuis VJ, Delewi R, Hermanides RS, Holvoet W, Dubois CLF, et al.
Enoxaparin vs. unfractionated heparin with fibrinolysis for ST-elevation myocardial in
Aspirin with or without clopidogrel after transcatheter aortic-valve implantation. N
farction in elderly and younger patients: results from ExTRACT-TIMI 25. Eur Heart J
Engl J Med 2020;383:1447–1457.
2007;28:1066–1071.
178. Nijenhuis VJ, Brouwer J, Delewi R, Hermanides RS, Holvoet W, Dubois CLF, et al.
158. O’Donoghue M, Boden WE, Braunwald E, Cannon CP, Clayton TC, de Winter RJ, et al.
Anticoagulation with or without clopidogrel after transcatheter aortic-valve implant
Early invasive vs conservative treatment strategies in women and men with unstable
angina and non–ST-segment elevation myocardial infarction: a meta-analysis. JAMA ation. N Engl J Med 2020;382:1696–1707.
179. Seeger J, Gonska B, Rodewald C, Rottbauer W, Wöhrle J. Apixaban in patients with
2008;300:71–80.
159. Fox KAA, Clayton TC, Damman P, Pocock SJ, de Winter RJ, Tijssen JGP, et al. atrial fibrillation after transfemoral aortic valve replacement. JACC Cardiovasc Interv
Long-term outcome of a routine versus selective invasive strategy in patients with 2017;10:66–74.
non–ST-segment elevation acute coronary syndrome. J Am Coll Cardiol 2010;55: 180. Jochheim D, Barbanti M, Capretti G, Stefanini GG, Hapfelmeier A, Zadrozny M, et al.
2435–2445. Oral anticoagulant type and outcomes after transcatheter aortic valve replacement.
160. Kaura A, Sterne JAC, Trickey A, Abbott S, Mulla A, Glampson B, et al. Invasive versus JACC Cardiovasc Interv 2019;12:1566–1576.
non-invasive management of older patients with non-ST elevation myocardial infarc 181. Kawashima H, Watanabe Y, Hioki H, Kozuma K, Kataoka A, Nakashima M, et al. Direct
tion (SENIOR-NSTEMI): a cohort study based on routine clinical data. Lancet 2020; oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation after
396:623–634. TAVR. JACC Cardiovasc Interv 2020;13:2587–2597.
161. Wongcharoenkiat N, Tresukosol D, Laksanabunsong P, Udompunturak S. A compari 182. Dangas GD, Tijssen JGP, Wöhrle J, Søndergaard L, Gilard M, Möllmann H, et al. A con
son of outcomes between percutaneous coronary intervention versus coronary ar trolled trial of rivaroxaban after transcatheter aortic-valve replacement. N Engl J Med
tery bypass surgery in octogenarian patients. J Med Assoc Thai 2012; 95 Suppl 2: 2020;382:120–129.
S154–S164. 183. Van Mieghem NM, Unverdorben M, Hengstenberg C, Möllmann H, Mehran R,
162. Chang M, Lee CW, Ahn J-M, Cavalcante R, Sotomi Y, Onuma Y, et al. Predictors of López-Otero D, et al. Edoxaban versus vitamin K antagonist for atrial fibrillation after
long-term outcomes after bypass grafting versus drug-eluting stent implantation for TAVR. N Engl J Med 2021;385:2150–2160.
left main or multivessel coronary artery disease. Catheter Cardiovasc Interv 2017;90: 184. Collet J-P, Van Belle E, Thiele H, Berti S, Lhermusier T, Manigold T, et al. Apixaban vs.
177–185. standard of care after transcatheter aortic valve implantation: the ATLANTIS trial. Eur
163. Giacoppo D, Colleran R, Cassese S, Frangieh AH, Wiebe J, Joner M, et al. Percutaneous Heart J 2022;43:2783–2797.
coronary intervention vs coronary artery bypass grafting in patients with left main cor 185. Andreotti F, Massetti M, ten Berg J. Defining optimal antithrombotic therapy
onary artery stenosis: a systematic review and meta-analysis. JAMA Cardiol 2017;2: post-TAVI: the contribution of ATLANTIS. Eur Heart J 2022;43:2798–2800.
1079–1088. 186. Tilz RR, Potpara T, Chen J, Dobreanu D, Larsen TB, Haugaa KH, et al. Left atrial ap
164. Devlin G, Gore JM, Elliott J, Wijesinghe N, Eagle KA, Avezum A, et al. Management and pendage occluder implantation in Europe: indications and anticoagulation post-
6-month outcomes in elderly and very elderly patients with high-risk non-ST-elevation implantation. Results of the European Heart Rhythm Association Survey. Europace
acute coronary syndromes: the global registry of acute coronary events. Eur Heart J 2017;19:1737–1742.
2007;29:1275–1282. 187. Andreotti F, Crea F. Defining the role of left atrial appendage closure in atrial fibrilla
165. Galli M, Andreotti F, D’Amario D, Vergallo R, Vescovo GM, Giraldi L, et al. tion. Rev Esp Cardiol (Engl Ed) 2013;66:79–82.
Antithrombotic therapy in the early phase of non-ST-elevation acute coronary syn 188. Gafoor S, Franke J, Bertog S, Boehm P, Heuer L, Gonzaga M, et al. Left atrial appendage
dromes: a systematic review and meta-analysis. Eur Heart J Cardiovasc Pharmacother occlusion in octogenarians: short-term and 1-year follow-up. Catheter Cardiovasc Interv
2020;6:43–56. 2014;83:805–810.
166. Vahanian A, Beyersdorf F, Praz F, Milojevic M, Baldus S, Bauersachs J, et al. 2021 ESC/ 189. Freixa X, Gafoor S, Regueiro A, Cruz-Gonzalez I, Shakir S, Omran H, et al. Comparison
EACTS guidelines for the management of valvular heart disease. Eur Heart J 2022;43: of efficacy and safety of left atrial appendage occlusion in patients aged <75 to ≥75
561–632. years. Am J Cardiol 2016;117:84–90.
190. Davtyan KV, Kalemberg AA, Topchyan AH, Simonyan GY, Bazaeva EV, Shatahtsyan 198. Gherli R, Mariscalco G, Dalén M, Onorati F, Perrotti A, Chocron S, et al. Safety of pre
VS. Left atrial appendage occluder implantation for stroke prevention in elderly pa operative use of ticagrelor with or without aspirin compared with aspirin alone in pa
tients with atrial fibrillation: acute and long-term results. J Geriatr Cardiol 2017;14: tients with acute coronary syndromes undergoing coronary artery bypass grafting.
590–592. JAMA Cardiol 2016;1:921–928.
191. Alkhouli M, Busu T, Shah K, Osman M, Alqahtani F, Raybuck B. Incidence and clinical 199. Sousa-Uva M, Head SJ, Milojevic M, Collet J-P, Landoni G, Castella M, et al. 2017
impact of device-related thrombus following percutaneous left atrial appendage occlu EACTS guidelines on perioperative medication in adult cardiac surgery. Eur J
sion. JACC Clin Electrophysiol 2018;4:1629–1637. Cardiothorac Surg 2018;53:5–33.
192. Turagam MK, Osmancik P, Neuzil P, Dukkipati SR, Reddy VY. Left atrial appendage 200. Kristensen SD, Knuuti J, Saraste A, Anker S, Bøtker HE, Hert SD, et al. 2014 ESC/ESA
closure versus oral anticoagulants in atrial fibrillation: a meta-analysis of randomized guidelines on non-cardiac surgery: cardiovascular assessment and management: the
trials. J Am Coll Cardiol 2020;76:2795–2797.
joint task force on non-cardiac surgery: cardiovascular assessment and management
193. Whitlock RP, Belley-Cote EP, Paparella D, Healey JS, Brady K, Sharma M, et al. Left at
of the European Society of Cardiology (ESC) and the European Society of
rial appendage occlusion during cardiac surgery to prevent stroke. N Engl J Med 2021;
Anaesthesiology (ESA). Eur Heart J 2014;35:2383–2431.
384:2081–2091.
201. Graham MM, Sessler DI, Parlow JL, Biccard BM, Guyatt G, Leslie K, et al. Aspirin in pa
194. Glikson M, Wolff R, Hindricks G, Mandrola J, Camm AJ, Lip GYH, et al. EHRA/EAPCI
tients with previous percutaneous coronary intervention undergoing noncardiac sur
expert consensus statement on catheter-based left atrial appendage occlusion—an
update. EuroIntervention 2020;15:1133–1180. gery. Ann Intern Med 2018;168:237–244.
195. Mantz J, Samama CM, Tubach F, Devereaux PJ, Collet J-P, Albaladejo P, et al. Impact of 202. Denas G, Testa S, Quintavalla R, Guazzaloca G, Padayattil Jose S, Zoppellaro G, et al. A

preoperative maintenance or interruption of aspirin on thrombotic and bleeding bridging protocol in high-thrombotic risk mechanical valve bearers undergoing surgery
events after elective non-cardiac surgery: the multicentre, randomized, blinded, or invasive procedures. J Am Coll Cardiol 2016;68:2714–2715.
placebo-controlled, STRATAGEM trial. Br J Anaesth 2011;107:899–910. 203. Douketis JD, Spyropoulos AC, Duncan J, Carrier M, Le Gal G, Tafur AJ, et al.
196. Devereaux PJ, Mrkobrada M, Sessler DI, Leslie K, Alonso-Coello P, Kurz A, et al. Perioperative management of patients with atrial fibrillation receiving a direct oral anti
Aspirin in patients undergoing noncardiac surgery. N Engl J Med 2014;370:1494–1503. coagulant. JAMA Intern Med 2019;179:1469–1478.
197. Wolff G, Navarese EP, Brockmeyer M, Lin Y, Karathanos A, Kołodziejczak M, et al. 204. Andreotti F, Iervolino A, Navarese EP, Maggioni AP, Crea F, Scambia G. Precision phe
Perioperative aspirin therapy in non-cardiac surgery: a systematic review and nomapping of acute coronary syndromes to improve patient outcomes. J Clin Med
meta-analysis of randomized controlled trials. Int J Cardiol 2018;258:59–67. 2021;10:1755.

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European Heart Journal (2023) 44, 262–279 SPECIAL ARTICLE

Acute, periprocedural and longterm

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syndrome patients fibrillation patients

* Corresponding authors. Emails: felicita.andreotti@unicatt.it; tobias.geisler@med.uni-tuebingen.de

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Introduction to preventable cardiovascular outcomes.13–16 In older adults with CVD,

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Table 1 Key consensus points on antithrombotic therapy in older adults

Clinical scenario and strategy Key point

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1 MAJOR 2 MINOR FEATURES

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Table 3 European Medicines Agency-approved antithrombotic regimens for older adults

Drug and dose Indication Age, weight or renal EMA-approved considerations

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Drug and dose Indication Age, weight or renal EMA-approved considerations

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Patient ≥75 yrs treated with PCI

High bleeding risk evaluation

HBR yes HBR no

Indication for OAC ? Up to 1 yr ASA + prasugrel or ASA + ticagrelor

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De-escalation from newer P2Y12 inhibitor to clopidogrel or low-dose prasugrel

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