Note: This is a multi-article spread containing a shared

commentary. Please scroll down for the other article(s). CLINICAL IMPACT RATINGS
THERAPEUTICS GM C

After PCI and 1 mo of DAPT for ACS, ticagrelor alone vs.

continued DAPT for 11 mo reduced bleeding without increasing MACCE
Ge Z, Kan J, Gao X, et al; ULTIMATE-DAPT investigators. Ticagrelor alone versus ticagrelor plus aspirin from month 1 to month 12 after percutaneous coro-
nary intervention in patients with acute coronary syndromes (ULTIMATE-DAPT): a randomised, placebo-controlled, double-blind clinical trial. Lancet.
2024;403:1866-1878.

Question: After percutaneous coronary intervention (PCI) and 1 month of major bleeding or ischemic events. Key exclusions: DAPT discontinuation
dual antiplatelet therapy (DAPT) for acute coronary syndrome (ACS), does for >48 hours, stroke in the past 3 months, previous intracranial disease,
ticagrelor monotherapy vs. continued DAPT for 11 months reduce clinically previous coronary artery bypass grafting, estimated glomerular filtration rate
relevant bleeding? <20 mL/min/1.73 m2, or need for long-term oral anticoagulation.
Design: Randomized placebo-controlled trial (ULTIMATE-DAPT).
Interventions: Ticagrelor, 90 mg twice daily, plus aspirin placebo (n = 1700);
Blinding: Treatment allocation concealed; blinded (patients, treating physi- or continued DAPT (n = 1700) for 11 months.
cians and staff, researchers, and clinical events adjudication committee).*
Setting: 58 centers in China, Italy, Pakistan, and the UK. Funding: Chinese Society of Cardiology; National Natural Scientific
Foundation of China; Jiangsu Provincial & Nanjing Municipal Clinical Trial
Patients: 3400 patients aged ≥18 years (median age, 63 y; 74% men; Project.
88% Chinese) who had PCI for ACS followed by 1 month of DAPT (ticagre-
lor, 90 mg twice daily, plus enteric-coated aspirin, 100 mg/d) without *See Glossary.

Results: Ticagrelor monotherapy vs. continued DAPT for 11 mo after PCI and 1 mo of DAPT in adults with ACS (intention-to-treat analysis)

Outcomes Event rates At 11 mo

Ticagrelor monotherapy Continued DAPT RRR (95% CI)† NNT (CI)†
Bottom line:
After PCI and 1 month
Clinically relevant bleeding‡ 2.1% 4.6% 54% (33 to 70) 40 (32 to 65) of DAPT in adults with
MACCE§ 3.6% 3.7% 2% (–38 to 31) Not significantjj ACS, ticagrelor
monotherapy vs.
ACS = acute coronary syndrome; DAPT = dual antiplatelet therapy; MACCE = major adverse cardiovascular or cerebrovascular events; PCI = percutaneous coronary inter- continued DAPT
vention; other abbreviations defined in Glossary. Primary outcomes indicated by boldface. reduced clinically
†RRR, NNT, and CI calculated from risk ratios estimated using continued DAPT event rates and hazard ratios in article. relevant bleeding and
‡Bleeding Academic Research Consortium types 2, 3, or 5.
§Cardiac death, myocardial infarction, ischemic stroke, definite stent thrombosis, or clinically driven target vessel revascularization.
was noninferior for
jjP < 0.001 for noninferiority. MACCE at 11 months.

Commentary: DAPT with aspirin and a P2Y12 inhibitor is standard care af- DAPT and reduce overall bleeding. In the network meta-analysis by Park and
ter PCI to reduce major adverse cardiovascular events (MACE). Traditionally, colleagues including 14 trials in older adults treated with varying durations of
guidelines recommended 3 to 6 months of DAPT after elective PCI or 12 DAPT after PCI, abbreviated DAPT (1 to 3 mo) was associated with reduced
months of DAPT after PCI for ACS (1). The ischemic protection of DAPT bleeding and no difference in MACE.
comes with increased risk for bleeding, which is a major driver of morbidity ULTIMATE-DAPT and Park and colleagues’ meta-analysis should be inter-
and mortality after PCI. Initial trials with abbreviated DAPT found that 3 to
preted with caveats. First, only about 30% of ACS cases in ULTIMATE-DAPT
6 months of DAPT followed by aspirin monotherapy reduced major bleed-
and <30% in most studies in the meta-analysis had ST-segment elevation MI
ing but did not establish noninferiority for recurrent myocardial infarction
(MI) (2). This prompted trials of abbreviated DAPT followed by P2Y12 inhib- (STEMI), which carries the highest risk for MACE after PCI. Further, PCI com-
itor monotherapy to mitigate potentially increased rates of recurrent MI pre- plexity, a risk factor for post-PCI MACE, was low in ULTIMATE-DAPT. Therefore,
viously seen with aspirin monotherapy. the findings may not be generalizable to patients with STEMI or complex
PCI. In ULTIMATE-DAPT, MACCE rates were nonsignificantly increased in
ULTIMATE-DAPT found that 1 month of DAPT followed by ticagrelor mono- patients aged ≥65 years who were treated with abbreviated vs. longer-dura-
therapy reduced bleeding and achieved noninferiority for MACCE vs. 12 tion DAPT, whereas Park and colleagues' meta-analysis showed no difference
months of DAPT. The ACS-only population had heightened baseline ische- between DAPT durations for MACE in older patients. ULTIMATE-DAPT and
mic risk, whereas bleeding risk was low due to exclusion criteria. This
most studies in the meta-analysis enrolled primarily Asian patients, who may
double-blind trial replicated results of 2 open-label trials that found 1-
have elevated baseline risk for bleeding, thereby exaggerating the benefit of
or 3-month DAPT followed by ticagrelor monotherapy after PCI for ACS
abbreviated DAPT. They also used composite bleeding outcomes that included
reduced bleeding events and was noninferior for MACE (3, 4).
life-threatening and non–life-threatening bleeding. Reassuringly, ULTIMATE-
PCI is increasingly performed in older adults, who have higher risk for DAPT showed reductions with abbreviated DAPT for both composite and life-
MACE and bleeding after the procedure. A previous meta-analysis of trials threatening bleeding outcomes, implying benefit across the clinical spectrum
in older adults showed that 6 months of DAPT followed by aspirin mono- of bleeding, while being noninferior for overall MACCE.
therapy vs. 12 months of DAPT reduced bleeding with similar MACE rates (5).
However, P2Y12 inhibitor monotherapy step-down may permit shorter upfront continued on page JC87

This article was published at Annals.org on 6 August 2024. doi:10.7326/ANNALS-24-00968-JC ACP Journal Club is editorially independent from Annals of Internal Medicine.

JC86 Annals of Internal Medicine • Vol. 177 No. 8 • August 2024 © 2024 American College of Physicians
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 CLINICAL IMPACT RATINGS
THERAPEUTICS | REVIEW GM C

After PCI in older adults, DAPT for 3 vs. 6 or 12 mo reduces

bleeding without increasing NACE or MACE
Park DY, Hu JR, Jamil Y, et al. Shorter dual antiplatelet therapy for older adults after percutaneous coronary intervention: a systematic review and
network meta-analysis. JAMA Netw Open. 2024;7:e244000.

Question: After percutaneous coronary intervention (PCI) in older adults, Included studies: 14 RCTs with subgroup analyses of older adults (n = 19 102
how do different durations of dual antiplatelet therapy (DAPT) compare for aged ≥65 y; 63% to 83% men across all patients) met inclusion criteria. 4 RCTs
adverse clinical events? had low risk of bias for allocation concealment; incomplete outcome data;
and blinding of patients, study personnel, and outcome assessors (Cochrane Risk
Review methods: Multiple databases searched to Aug 2023 for English- of Bias tool).
language randomized controlled trials (RCTs) that compared different dura-
tions of DAPT (1, 3, 6, or 12 mo) after PCI in older adults and had follow-
up ≥9 months. Funding: No external funding.

Results: Network meta-analysis of shorter vs. longer DAPT duration after PCI in older adults

Outcomes* (number of trials analyzed) DAPT duration comparisons† RR (95% CI)‡

NACE (9) 1 mo vs. 12 mo 0.60 (0.33 to 1.07)
Bottom line:
After PCI in older
3 mo vs. 12 mo 0.77 (0.52 to 1.15) adults, DAPT for 3
6 mo vs. 12 mo 0.76 (0.49 to 1.17) months vs. 6 or 12
months, and 1 month
MACE (9) 1 mo vs. 12 mo 0.79 (0.61 to 1.01) vs. 6 months, reduces
3 mo vs. 12 mo 0.94 (0.73 to 1.20) bleeding. DAPT
6 mo vs. 12 mo 0.89 (0.70 to 1.13) durations of 1, 3, 6, or
12 months do not
Bleeding (6) 1 mo vs. 12 mo 0.78 (0.51 to 1.20) differ for NACE or
3 mo vs. 12 mo 0.57 (0.45 to 0.71) MACE.
6 mo vs. 12 mo 1.14 (0.71 to 1.84)
DAPT for 1 mo (RR, 0.68 [CI, 0.54 to 0.86]) or 3 mo (RR, 0.50 [CI, 0.29 to 0.84]) reduced bleeding vs. DAPT for 6 mo. Groups did not differ for
NACE, MACE, or bleeding for other DAPT duration comparisons.
DAPT = dual antiplatelet therapy; MACE = major adverse cardiovascular events; NACE = net adverse clinical events; PCI = percutaneous intervention; RCT = random-
ized controlled trial; RR = risk ratio; CI defined in Glossary. Primary outcome indicated by boldface.
*Outcome definitions varied across trials. Overall evidence quality was moderate (NACE) to high (MACE and bleeding) based on Grading of Recommendations
Assessment, Development, and Evaluation criteria.
†Cumulative event rates with 12 mo of DAPT: NACE, 5.40%; MACE, 5.76%; bleeding, 5.84%.
‡RR <1 favors shorter DAPT durations.

Commentary (continued from page JC86) Andrew T. Yan, MD

The trial was underpowered to exclude harm with respect to stent thrombo- St. Michael's Hospital and University of Toronto
sis, even though there was no interaction between DAPT duration and PCI Toronto, Ontario, Canada
features associated with ischemic events. Finally, Park and colleagues'
Disclosures: Disclosure forms are available with the article online.
meta-analysis did not use patient-level data or account for differences in
the antiplatelet monotherapy agent used after DAPT, which might have
affected clinical outcomes. References
ULTIMATE-DAPT and Park and colleagues' meta-analysis support current 1. Primary Panel; Bainey KR, Marquis-Gravel G, Belley-Côté E, et al. Canadian Cardiovascular
Society/Canadian Association of Interventional Cardiology 2023 focused update of the
guideline recommendations for 1 to 3 months of DAPT, with de-escalation guidelines for the use of antiplatelet therapy. Can J Cardiol. 2024;40:160-181.
to P2Y12 inhibitor monotherapy in selected patients (1). The results also 2. Andò G, De Santis GA, Greco A, et al. P2Y12 inhibitor or aspirin following dual antiplatelet
suggest there is no one-size-fits-all approach to DAPT after PCI. Clinicians therapy after percutaneous coronary intervention: a network meta-analysis. JACC Cardiovasc
managing DAPT should use validated tools to individually assess each Interv. 2022;15:2239-2249.
3. Hong SJ, Lee SJ, Suh Y, et al; T-PASS (Ticagrelor Monotherapy in Patients Treated With
patient's risk for thrombotic vs. bleeding events and consider patient prefer- New-Generation Drug-Eluting Stents for Acute Coronary Syndrome) Investigators.
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the ideal antiplatelet monotherapy agent after abbreviated DAPT. 4. Kim BK, Hong SJ, Cho YH, et al; TICO Investigators. Effect of ticagrelor monotherapy vs
ticagrelor with aspirin on major bleeding and cardiovascular events in patients with acute
coronary syndrome: the TICO randomized clinical trial. JAMA. 2020;323:2407-2416.
Cole Clifford, MD 5. Lee SY, Hong MK, Palmerini T, et al. Short-term versus long-term dual antiplatelet therapy
University of Toronto after drug-eluting stent implantation in elderly patients: a meta-analysis of individual
Toronto, Ontario, Canada participant data from 6 randomized trials. JACC Cardiovasc Interv. 2018:11:435-443.

This article was published at Annals.org on 6 August 2024. doi:10.7326/ANNALS-24-00961-JC ACP Journal Club is editorially independent from Annals of Internal Medicine.

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