BCPS Lecture Series:

Acute Coronary Syndromes

Kajal Jain, PharmD
Maddie Tompkins, PharmD
Objectives
▪Describe the epidemiology and pathophysiology of acute coronary
syndromes (ACS)
▪Develop a treatment plan for ACS using evidence-based
recommendations
▪Design a secondary prevention plan for patients that have experienced
an ACS event
 Epidemiology

▪Every 40 seconds an 57.9% 42.1%

American will have a mortality in mortality in
myocardial infarction (MI) males females

▪35% of people who

experience a coronary
event will die each year

Circulation. 2019;139(10):e56-e66.
 Pathophysiology
▪ Myocardial infarction is
myocardial cell death due to
prolonged ischemia
1. Atherothrombotic coronary
artery disease: dynamic
thrombus can lead to distal
embolization via plaque
rupture
2. Oxygen supply and demand
mismatch: insufficient blood
flow to ischemic myocardium

Eur Heart J. 2019;40(3):237-269.

Retrived from: https://www.heart.org/en/news/2019/04/0
4/proactive-steps-can-reduce-chances-of-second-heart-
attack
 Diagnosis: Electrocardiogram (ECG)

•ST-segment
elevation myocardial
STEMI infarction

•Non-ST-segment
elevation myocardial
NSTEMI infarction

Eur Heart J. 2019;40(3):237-269.

 Diagnosis: Troponins
▪Cardiac troponin I and T are
biochemical markers
released into the
bloodstream when
myocardial cells die
▪Myocardial injury: elevated
cardiac troponins within one
value above the 99th
percentile of the upper
reference limit
aNo myocardial injury = cTn values <_ 99th percentile URL or not
detectable bMyocardial injury = cTn values > 99th percentile URL

Eur Heart J. 2019;40(3):237-269.

 Clinical
suspicion

Diagnosis

ST segment No/Transient
elevation ECG changes

Positive Positive Negative

troponins troponins troponins

Unstable
STEMI NSTEMI angina
Eur Heart J. 2019;40(3):237-269.
 2018 Universal Definition of Myocardial Infarction

• Coronary athero-thrombosis
Type 1

• Oxygen supply and demand imbalance

Type 2

• Sudden cardiac death

Type 3

• Post-procedural
Type 4

• Post-coronary artery bypass grafting (CABG)

Type 5

Eur Heart J. 2019;40(3):237-269.

Patient Case
▪ JR is a 62 YOM presenting to the emergency department with a chief complaint of
nausea, vomiting, and squeezing chest pain that radiates to his jaw. An ECG and
blood samples are obtained with 10 minutes of arrival.

Lab 11/12 1214

cTnT 251 ng/L
Roche TnT Gen 5 STAT troponin assay has a 99th percentile of 19 ng/L

▪ What diagnosis is consistent with JR's presentation?

1. NSTEMI
2. STEMI
3. Unstable angina
 0-90 minutes

Relief of STEMI Symptoms

▪ Relief of pain, breathlessness, anxiety
▪ Titrated IV opioids can be considered
⎻ Morphine is commonly used but has slower uptake, delayed onset of action, and
diminished effects of oral antiplatelets
⎻ Meta-analysis from 2019 found an association with an increased risk of in-hospital
mortality with morphine
▪ Oxygen for hypoxemia (SaO2 < 90% or PaO2 <60 mmHg)
⎻ Deleterious effects have been described when used in normoxic patients
▪ NOTE: routine use of nitrates is no longer recommended due to lack of clinical benefit
▪ IV nitrates may be useful in the acute phase if a patient is hypertensive or has heart
failure
⎻ Do not use if there is hypotension, RV infarction, or recent use of
BMJ Open 2019;9:e025232. phosphodiesterase type 5 inhibitor
Eur Heart J. 2018;39(2):119-177.
 STEMI Care Logistics

Eur Heart J. 2018;39(2):119-177.

 Coronary Angiography
▪ A procedure which uses
contrast dye and x-ray imaging
to detect blockages in the
coronary arteries that are
caused by plaque buildup
▪ Identify target lesion and select
reperfusion method:
▪ Angioplasty
▪ Stenting
▪ Coronary artery bypass Retrieved from: https://www.emra.org/emresident/article/stemi-equivalents/

surgery

Eur Heart J. 2019;40(3):87-165.

 0-90 minutes

Percutaneous Coronary Intervention (PCI)

▪ Coronary stenting is the preferred PCI
method opposed to balloon angioplasty
alone
1. Bare metal stent (BMS)
2. Drug–eluting stent (DES)
- contain an antiproliferative drug
to inhibit restenosis (sirolimus,
everolimus, paclitaxel, etc)

Retrieved from: https://www.hopkinsmedicine.org/health/treatment-

tests-and-therapies/angioplasty-and-stent-placement-for-the-heart

Eur Heart J. 2018;39(2):119-177.

US Pharm. 2012;37(2):HS-4-HS-7.
 0-90 minutes

Periprocedural Antiplatelet Therapy

▪ Dual antiplatelet therapy (DAPT)
▪ Aspirin (non-enteric coated) 162-325mg + P2Y12 inhibitor
P2Y12 Loading Dose Peak Effect Pearls
Inhibitor
Ticagrelor* 180mg PO 2 hours Reversible
Transient dyspnea (14%)
Prasugrel* 60mg PO 4 hours Irreversible
CI: previous stroke/TIA
Avoid ≥ 75 years of age or <60 kg
Clopidogrel 600mg PO 6 hours Irreversible
Prodrug hydrolyzed by CYP2C19
Cangrelor 30mcg/kg IV bolus 2 minutes Reversible
then 4mcg/kg/min Do not administer PO antiplatelets
for duration of PCI until infusion is discontinued
Eur Heart J. 2018;39(2):119-177. *preferred agents
Lexi-Drugs. Lexi-Comp Online.
 COMMIT PLATO

TRITON- ISAR-
Review of STEMI Trials Supporting DAPT TIMI 28 REACT 5

▪ COMMIT: aspirin vs aspirin + clopidogrel ▪ PLATO: ticagrelor vs clopidogrel

▪ Reduction in death, reinfarction, or ▪ Reduction in composite of death from
stroke (9.2% vs 10.1%; p=0.002), vascular causes, myocardial infarction,
▪ TRITON-TIMI 28: prasugrel vs clopidogrel or stroke (9.8% vs 11.7%; p<0.001)

▪ Reduction in composite of the rate of ▪ No difference in rates of major bleeding

death from cardiovascular causes, (11.6% and 11.2%; P=0.43)
nonfatal myocardial infarction, or ▪ ISAR-REACT 5: prasugrel vs ticagrelor
nonfatal stroke (9.9% vs 12.1%; ▪ Reduction in composite of death, myocardial
p<0.001) infarction, or stroke at 1 year after
▪ Rate of life-threatening bleeding (1.4% randomization (6.9% vs 9.3%; p=0.006)
vs. 0.9%; P=0.01),and fatal bleeding ▪ No difference in major bleeding (4.8% vs
(0.4% vs. 0.1%; P=0.002) 5.4%; p=0.46)

Lancet. 2005. 366(9497):1607-21.

NEJM. 2007. 357(20):2001-2015.
NEJM. 2009. 361(11):1045-1057.
NEJM. 2019 Oct 17;381(16):1524-1534.
 0-90 minutes

Periprocedural Anticoagulation
Drug Dose Renal Dose Adjustment
UFH 70-100 IU/kg IV bolus or No renal adjustment required
50-70 IU/kg IV bolus with
GP IIb/IIIa inhibitor
Enoxaparin 0.5 mg/kg IV bolus If CrCl <30mL/min and age <75 YO, 30mg IV
bolus + 1mg/kg SQ
If CrCl <30mL/min and age ≥75 YO, omit IV
bolus and begin 1mg/kg SQ
Bivalirudin 0.75 mg/kg IV bolus then 1.75 If CrCl <30mL/min, decrease infusion rate to
mg/kg/hr for up to 4 hours 1 mg/kg/hr
post-procedure

▪ OASIS 6 trial: Use of fondaparinux in primary PCI was associated with potential harm
▪ Higher rate of guiding catheter thrombosis (0 vs. 22, P <0.001)
Eur Heart J. 2018;39(2):119-177.
Lancet 2011;378(9792):693–703.
▪ More coronary complications (225 vs 270, P = 0.04)
JAMA 2006;295(13):1519–1530.
 ATOLL MATRIX

Periprocedural Anticoagulation HEAT-

▪ ATOLL: enoxaparin vs UFH PPCI
▪ Enoxaparin arm had a reduction in the composite secondary endpoint of death, recurrent
MI/ACS, or urgent revascularization compared to UFH (7% vs 11%, P=0.015)
▪ HEAT-PPCI: UFH vs bivalirudin
▪ UFH arm had a reduction in the composite primary efficacy endpoint of all-cause mortality, CVA,
reinfarction, and unplanned target lesion revascularization compared to bivalirudin (5.7% vs
8.7%, P=0.01)
▪ No difference in primary safety endpoint of incidence of major bleeding (3.1% vs 3.5%, P=0.59)
▪ MATRIX: UFH vs. bivalirudin
▪ UFH was not associated with fewer major adverse cardiovascular events compared to
bivalirudin (16.8% vs 15.8%, P=0.28)
▪ No difference in adverse clinical events (18.4% vs 17%, P=0.91)
Eur Heart J. 2018;39(2):119-177.
Lancet. 2018 Sep 8;392(10150):835-848
Lancet. 2014 Nov 22;384(9957):1849-1858.
 0-90 minutes

Periprocedural GP IIb/IIIa Inhibitors

▪ No longer recommended for routine use in primary PCI
▪ GP IIb/IIIa inhibitors may be used for bailout therapy if there is no evidence of reflow or
a thrombotic complication occurs

Drug Dose Renal Dose Adjustment

Abciximab* 0.25 mg/kg IV bolus then 0.125 No renal adjustment required
mcg/kg/min (max 10 mcg/min)
for 12 hours
Eptifibatide 180 mcg/kg IV double bolus then If CrCl <50 mL/min, reduce
2.0 mcg/kg/min for 18 hours infusion by 50%
Tirofiban 25 mcg/kg IV bolus then 0.15 If CrCl ≤ 60 mL/min, reduce
mcg/kg/min for 18 hours infusion by 50%
*Removed from market. Last lot expired September 2019

Eur Heart J. 2018;39(2):119-177.

Lexi-Drugs. Lexi-Comp Online.
 0-24 hours

Lipid-Lowering Agents
▪Early and intensive statin therapy irrespective of cholesterol at
presentation
Atorvastation 40-80mg
Rosuvastatin 20-40mg

Improved Inflammation Inhibition of

endothelial reduction at platelet
function site of plaque aggregation

Eur Heart J. 2018;39(2):119-177.

Lancet 2010;376(9753):1670–1681.
 24 hours

Beta-Blockers
▪ Competitively inhibit the myocardial effects of circulating catecholamines and
reduce myocardial oxygen consumption
▪ Early parenteral beta-blockers followed by oral beta-blockers should be considered in
hemodynamically stable patients undergoing primary PCI
▪ METOCARD-CNIC: early IV metoprolol vs placebo
▪ Higher left ventricular ejection fraction (LVEF) at 6 months (48.7% vs
45.0%; p=0.025)
▪ Reduced composite of death, heart failure admission, reinfarction, and
malignant arrhythmias (10.8% vs 18.3%; p=0.065)
▪ EARLY-BAMI: early IV metoprolol vs placebo
▪ No benefit in reduction of infarct size or cardiac biomarker release
▪ Borderline reduction in malignant ventricular arrhythmias (3.6% vs 6.9%; p=0.05)
Eur Heart J. 2018;39(2):119-177.
J Am Coll Cardiol. 2014;63(22):2356-62.
J Am Coll Cardiol 2016;67(23):2705–2715.
 STEMI Care Logistics

Eur Heart J. 2018;39(2):119-177.

 0-10 minutes

Fibrinolysis
Fibrinolytic Dose Plasminogen
Alteplase (tPA) 15mg IV bolus then 0.75 mg/kg IV over 30
minutes (max 50 mg) then 0.5 mg/kg
IV over 60 minutes (max 35 mg)
Reteplase (rPA) 10 units + 10 units IV bolus, administered Plasmin
30 minutes apart
Tenecteplase 30 mg if <60 kg
(TNK-tPA) 35 mg if 60 to <70 kg
40 mg if 70 to <80 kg
Fibrin Degradation
45 mg if 80 to <90 kg Fibrin Clot Products
50 mg if ≥ 90 kg
Reduce to half-dose if patient > 75 years
of age

Eur Heart J. 2018;39(2):119-177.

 Fibrinolytic Therapy Contraindications
Absolute Contraindications Relative Contraindications
Previous ICH or stroke of unknown TIA in past 6 months
origin
Oral anticoagulant therapy
Ischemic stroke in past 6 months
Pregnancy or within 1 week postpartum
CNS damage, neoplasms or AVMs

Recent major surgery/trauma/head Refractory hypertension (SBP > 180 mmHg

injury within past month and/or DBP >110 mmHg)
GI bleed within past month Advanced liver disease
Known bleeding disorder Infective endocarditis
Aortic dissection Active PUD
Non-compressible punctures in past 24 Prolonged or traumatic resuscitation
hours
Eur Heart J. 2018;39(2):119-177.
 0-10 minutes

Antiplatelet and Anticoagulant Fibrinolytic Co-Therapies

Antiplatelet Loading Dose
Aspirin 162-325 mg PO
Clopidogrel 300mg PO
≥75 YO: 75 mg PO

Anticoagulant Dose
UFH 60 IU/kg IV bolus (max 4000 IU) then 12 IU/kg/h (max
1000 IU/h) for 24-48 hours
Enoxaparin <75 YO: 30 mg IV bolus then 1 mg/kg SQ Q12H
≥ 75 YO: 0.75 mg/kg SQ Q12H
▪ CLARITY-TIMI 28: aspirin vs aspirin + clopidogrel
▪ Reduction in death, reinfarction, or stroke (9.2% vs
10.1%; p=0.002)

Eur Heart J. 2018;39(2):119-177.

N Engl J Med. 2005. 352, 1179-1789.
Lancet 2001;358(9282):605–613.
Patient Case Continued
▪ JR has been diagnosed with a STEMI and preparations are underway to take him to the
IU Health cardiac catheterization lab for primary PCI. Which of the following medication
regimens represents the most appropriate treatment at this time?
1. Aspirin 81mg x4 (324mg) PO, clopidogrel 600mg PO, enoxaparin 0.5mg/kg IV bolus
2. Aspirin 81mg x4 (324mg) PO, clopidogrel 600mg PO, bivalirudin 0.75 mg/kg IV bolus
3. Aspirin 81mg x4 (324mg) PO, ticagrelor 180mg PO, fondaparinux 2.5mg IV once
4. Aspirin 81mg x4 (324mg) PO, ticagrelor 180mg PO, UFH 100 IU/kg IV bolus
 Clinical
suspicion

ST segment No/Transient
elevation ECG changes

Positive Positive Negative

troponins troponins troponins

Unstable
STEMI NSTEMI angina
Eur Heart J. 2019;40(3):237-269.
Goals of NSTE-ACS treatment

Decrease
myocardial
oxygen Increase
demand myocardial
oxygen
supply
 Ischemic Risk Assessment – GRACE score

GRACE score
•Direct estimation of mortality in the hospital, at 6 months, 1
year, and 3 years
•And risk of death/MI at 1 year
•Age, SBP, pulse, SCr, Killip class, cardiac arrest, cardiac
biomarkers, and ST deviation
Score interpretation
•Low: 1-108
•Intermediate: 109-140
•High: 141-372
Eur Heart J. 2015;37(3):281-307.
GRACE Risk Table
 Ischemic Risk Assessment – TIMI score
TIMI score
• Age ≥ 65 years old, ≥ CAD risk factors, known CAD, aspirin in the
past 7 days, severe angina, ST change ≥ 0.5 nm, positive cardiac
marker
Score Interpretation
• 0-1: 5% mortality risk
• 2: 8% mortality risk
• 3: 13% mortality risk
• 4: 20% mortality risk
• 5: 26% mortality risk
• 6-7: 41% mortality risk
Eur Heart J. 2015;37(3):281-307.
TIMI Risk Score for NSTEMI Calculator.
 PCI
▪ Reduce the risk of the target lesion associated infarction
▪ Timing is dependent on risk stratification

Risk Category Goal Time to PCI

Very high risk <2 hours
High risk <24 hours
Intermediate risk <72 hours

Eur Heart J. 2015;37(3):281-307.

J Am Coll Cardiol 2006;48:1319 –1325.
 Very High Risk Criteria

Mechanical Recurrent
Acute heart
complications dynamic ST-T
of MI failure wave changes

Recurrent or
Hemodynamic ongoing chest Life-
instability or pain refractory threatening
cardiogenic arrhythmias or
to medical
sock treatment cardiac arrest

Eur Heart J. 2015;37(3):281-307.

 High Risk Criteria

Rise or fall
in cardiac Dynamic
ST or T GRACE
troponins score >
compatible wave
changes 140
with MI

Eur Heart J. 2015;37(3):281-307

 Intermediate Risk Criteria

Early
LVEF <
Diabetes eGFR < post-
40% or
mellitus 60 infarction
CHF angina

GRACE
Prior PCI Recurrent
score 109-
or CABG 140 symptoms

Eur Heart J. 2015;37(3):281-307.

 Relief of NSTE-ACS symptoms

Oxygen Opiates Nitrates

• Oxygen • Signs of • No longer

saturation < ischemia even recommended
90% after beta
• Respiratory blockers
distress

Eur Heart J. 2015;37(3):281-307.

 Aspirin
▪ Loading dose of 162-325 mg

4 randomized CURRENT-
Meta-analysis
controlled trials OASIS 7
Compared aspirin
In unstable 46% odds 300-325mg/day
angina the reduction in to 75-100mg/day
incidence of MI or vascular events
death were when used for up
reduced to 2 years No benefit seen
with higher dose

Eur Heart J. 2015;37(3):281-307.

BMJ 2002;324:71 –86.
N Engl J Med 2010;363:930 –942.
 P2Y12 Inhibitors

Clopidogrel Prasugrel Ticagrelor

Inhibit P2Y12 which inhibits ADP-induced platelet aggregation
300-600 mg loading 60 mg loading dose 180 mg loading dose
dose then 75 mg daily then 10 mg daily then 90 mg BID
Faster onset and more More rapid and
inhibitory effect than consistent onset of
clopidogrel action than clopidogrel
CI: prior stroke or TIA

Eur Heart J. 2015;37(3):281-307.

JAMA 2002;288:2411 –2420
 P2Y12 Inhibitors Timing
▪ As soon as possible after diagnosis if conservative management
▪ Debated if pretreatment is needed with invasive management
▪ ACCOAST: prasugrel for pretreatment of PCI
⎻ No benefit seen (HR 1.02 (95% CI 0.84, 1.25), P = 0.81)
⎻ Increased bleeding (HR 1.90, (95% CI 1.19, 3.02), P = 0.006)
⎻ Do not use as pretreatment
▪ No studies on clopidogrel or ticagrelor

Eur Heart J. 2015;37(3):281-307.

N Engl J Med 2013; 369:999-1010
 >12
Duration of DAPT months
12
months
▪ 12 months for most patients
▪ If high bleeding risk, reduction to 6 months with 6
aspirin monotherapy months
▪ If high ischemic risk, > 12 months can be considered

Antiplatelet UA/NSTEMI UA/NSTEMI STEMI STEMI

- No PCI + PCI + Primary PCI + Fibrinolytic

Aspirin Aspirin Aspirin Aspirin Aspirin

P2Y12 inhibitor Clopidogrel 300mg Clopidogrel 600mg Clopidogrel 600mg Clopidogrel 300mg*
Ticagrelor 180mg Ticagrelor 180mg Ticagrelor 180mg
Prasugrel 60mg Prasugrel 60mg

*Switch to preferred agent (ticagrelor or

Eur Heart J. 2015;37(3):281-307. prasugrel) >48 h after fibrinolysis
 Glycoprotein IIb/IIIa Inhibitors
▪ Block platelet aggregation by inhibiting fibrinogen
▪ Meta-analysis
▪ 9% RRR in death or non-fatal MI when added to heparin with the greatest benefit in
those undergoing PCI
▪ Increase in major bleeding complications
▪ No significant increase in hemorrhage
▪ Reserve for bailout situations or thrombotic complications with PCI

Eur Heart J. 2015;37(3):281-307.

Eur Heart J 2002;23:1441 –1448.
 Beta Blockers
▪ Meta-analysis showed
▪ 13% RRR of mortality in the first week following MI
▪ 8% RRR for in-hospital mortality
▪ Avoid in patients that are risk of cardiogenic shock
▪ Age > 70 years, heart rate > 110 beats/min, systolic blood pressure < 120 mmHg
▪ Begin early in patients with ischemic symptoms and no contraindications
▪ Contraindications: coronary vasospasm or cocaine use

Eur Heart J. 2015;37(3):281-307.

JAMA 1988;260: 2088–2093.
Int J Cardiol 2013;168:915–921
 Unfractionated Heparin (UFH)
▪ Dose: 60–70IU/kg followed by 12–15 IU/kg/hr
▪ Monitor with aPTT
▪ Goal: 50–75 seconds
▪ PCI: give as an IV bolus
▪ ACT guidance: range of 250–350 s, or 200–250 s if a GPIIb/IIIa inhibitor is given
▪ Weight-adjusted manner: 70–100 IU/kg, or 50–70 IU/ kg in combination with a
GPIIb/IIIa inhibitor

Eur Heart J. 2015;37(3):281-307.

 Low molecular weight heparin
▪ Enoxaparin dose: 1mg/kg BID subcutaneously in eGFR > 30
▪ Routine monitoring not needed
▪ Anti-Xa levels if eGFR 15-30 or < 100 kg
▪ PCI: last dose ≥ 8 hours before PCI, bolus of 0.3mg/kg IV
▪ Meta-analysis comparing enoxaparin to UFH
▪ Reduction in death and MI at 30 days with enoxaparin (OR 0.90 (95% CI 0.81, 0.996), P =
0.043)
▪ No difference in major bleeds at day 7 (OR 1.13 (95% CI 0.84, 1.54))
▪ Based on studies, enoxaparin preferred over UFH in PCI due to:
▪ Reductions in death, MI, complications of MI, and major bleeds
▪ However controversial topic and based on provider preference and patient characteristics

Eur Heart J. 2015;37(3):281-307.

Eur Heart J 2007;28:2077 –2086
 Fondaparinux
▪ Dose: 2.5mg daily subcutaneously in eGFR > 20
▪ OASIS-5: fondaparinux versus enoxaparin
▪ Non-inferior in ischemic events (HR 1.01 (95% CI 0.90, 1.13), P = 0.007)
▪ Half in-hospital major bleeds and reduced mortality with fondaparinux (HR 0.45 (95% CI 0.34,
0.59), P < 0.001)
▪ PCI: bolus with UFH

Eur Heart J. 2015;37(3):281-307.

J Am Coll Cardiol 2009;54:468 –476.
 Bivalirudin
▪ Dose based on the ACUITY trial
▪ 0.1mg/kg bolus followed by 0.25 mg/kg/hour
▪ Undergoing PCI: additional 0.5 mg/kg bolus and then increased the infusion to
1.75 mg/kg/hour and then stop at the end of the procedure
▪ REPLACE-2: Bivalirudin and UFH with GPIIb/IIIa in patients undergoing PCI
▪ No difference in death, MI, urgent repeat revascularization and in-hospital major bleeding
at 30 days
▪ Reduction in rates of in-hospital major and minor bleeding with bivalirudin

Eur Heart J. 2015;37(3):281-307.

JAMA. 2003;289:853–63
 Lipid-Lowering Agents
▪ Meta-analysis: more-intensive vs less-intensive LDL-C lowering
▪ Reduced risk of cardiovascular death, non-fatal MI, ischemic stroke, and coronary
revascularization
▪ Every 1.0mmol/L reduction in LDL-C provides a proportional risk reduction

LDL-C Risk

Eur Heart J. 2018;39(2):119-177.

Lancet 2010;376(9753):1670–1681.
 Special Populations: Previous Oral Anticoagulant Use

Periprocedural

•Uninterrupted therapeutic parenteral anticoagulation regardless of last dose

of oral anticoagulant

Post-PCI

•Recommend oral anticoagulant in addition to antiplatelet therapy; triple

therapy
•Use the HAS-BLED score to assess bleeding risk
•Triple therapy for 6 months then discontinue aspirin or clopidogrel
•Consider limiting triple therapy to 4 weeks

Eur Heart J. 2015;37(3):281-307.

 HAS-BLED Score

HAS-BLED score ≥3

▪ Proceed with caution in continuing

oral anticoagulation in additional to
DAPT
Retrieved from: https://www.acc.org/latest-in-
cardiology/articles/2014/07/18/15/13/has-bled-tool-what-is-the-real-risk-of-
bleeding-in-anticoagulation
 Special Populations: Elderly and Renal Dysfunction

Elderly

•Tailor antithrombotic therapy to renal function and bodyweight

•Invasive strategy
•Weigh the risks/benefits, life expectancy, comorbidities, quality of life, frailty,
patient values/preferences

Renal Dysfunction

•Administer the same first-line antithrombotic treatment, but dose adjust for
renal function to minimize bleeding risk
•Consider UFH for anticoagulation if eGFR < 30
•Invasive strategy: hydration with isotonic saline and low- or iso-
osmolar contrast media
Eur Heart J. 2015;37(3):281-307.
 Special Populations: Diabetes and Left Ventricular Dysfunction
and Heart Failure

Diabetes

• Monitor BG to a target of < 180 mg/dL while preventing hypoglycemia

• Prasugrel and ticagrelor are the preferred P2Y12 inhibitors
• Invasive strategy recommended
• Monitor renal function for 2-3 days after invasive strategy

Left Ventricular Dysfunction and Heart Failure

• Emergency echocardiography to assess LV and valvular function

• Immediate coronary angiography when in acute HF with refractory angina, ST
deviation, or cardiogenic shock
• PCI recommended in cardiogenic shock if anatomy suitable
Eur Heart J. 2015;37(3):281-307.
 Special Populations: Atrial Fibrillation

Anticoagulant drugs

• All patients without contraindications

Patients with rapid ventricular rate (RVR)

• Electrical cardioversion in hemodynamically unstable patients

• Amiodarone to restore sinus rhythm non-urgently
• IV beta blockers in hemodynamically stable patients

Eur Heart J. 2015;37(3):281-307.

 Special Populations: Thrombocytopenia

Definition

• Platelets < 100,000 / µL or > 50% drop from baseline

IMMEDIATE

• Interrupt if GPIIb/IIIa inhibitor, UFH, LMWH, or other heparin products

Treatment with GP IIb/IIIa, platelet transfusion if:

• Major active bleeding

• Severe asymptomatic thrombocytopenia

Documented or suspected HIT

• Use non-heparin anticoagulant

Eur Heart J. 2015;37(3):281-307.
 Medications for Secondary Prevention
Lipid Lowering

• All patients as soon as possible after admission

• High intensity statin therapy unless history of intolerance: Atorvastatin 40-80mg
or Rosuvastatin 20-40mg
• Goal LDL of < 70 mg/dL

Antithrombotic therapy

• Aspirin + clopidogrel, prasugrel, or ticagrelor

• PPI if at high risk of GI bleed

ACE inhibitor or ARB

• Systolic left ventricular dysfunction

• Heart failure, hypertension, or diabetes

Eur Heart J. 2015;37(3):281-307.

 Medications for Secondary Prevention

Beta blockers

•Left ventricular ejection fraction (LVEF) < 40%

•Observational study: no association with lower risk of CV events or mortality
in patients with previous MI

Mineralocorticoid receptor antagonist

•LVEF < 40% (heart failure)

•Diabetes
•Eplerenone shown to reduce morbidity and mortality
•Eplerenone 25mg PO daily

Eur Heart J. 2015;37(3):281-307.

 Lifestyle Changes
Cardiac rehabilitation

• Enhance compliance to medical regimen

Exercise

• 30 minutes 3 or more times per week of aerobic exercise

• Sedentary patients: start light intensity exercise

Smoking cessation

• Reduce morbidity and mortality

Dietary changes

• Heart healthy diet

Eur Heart J. 2015;37(3):281-307.

Patient Case Continued
▪ JR is now ready for discharge
▪ PMH: Diabetes mellitus, hypertension, hypothyroidism
▪ Pertinent labs and vitals
A1c: 8.2% BP: 152/96 LDL: 159 eGFR: 52 LVEF: 52%
▪ Current medications: metformin 1000mg BID, amlodipine 10mg daily, levothyroxine
100 mcg daily, lisinopril 10mg daily
Based on this information, what medications does JR need at discharge?
A. Atorvastatin 40mg daily, aspirin 81mg daily, prasugrel 10 mg daily
B. Atorvastatin 40mg daily, prasugrel 10 mg daily, metoprolol succinate 50mg daily
C. Aspirin 81mg daily, prasugrel 10 mg daily
D. Atorvastatin 40mg daily, aspirin 81mg daily, clopidogrel 75mg
daily, hydrochlorothiazide 25mg daily
BCPS Lecture Series:
Acute Coronary Syndromes
Kajal Jain, PharmD
Maddie Tompkins, PharmD
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