Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2 Acute Coronary Syndrome - STOPDAPT-2 ACS

Contribution To Literature:

The STOPDAPT-2 ACS trial showed that 1-month DAPT followed by clopidogrel monotherapy for 11 months did not meet criteria for noninferiority compared with standard 12-month duration DAPT for the composite ischemic/bleeding endpoint among patients undergoing ACS PCI with a CoCr DES.

Description:

The goal of the trial was to compare the safety and efficacy of a short-duration dual antiplatelet therapy (DAPT) (1 month) followed by clopidogrel monotherapy compared with standard-duration DAPT (12 months) among patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS).

Study Design

Eligible patients were randomized in a 1:1 open-label fashion to either DAPT with aspirin and clopidogrel for 1 month followed by clopidogrel monotherapy for 11 months (n = 2,078) or standard-duration DAPT with aspirin + clopidogrel for 12 months (n = 2,078). Aspirin dose was 100 mg/day; clopidogrel at 75 mg/day.

  • Total number of enrollees: 4,169 (1,161 patients came from ACS subgroup of STOPDAPT-2 trial)
  • Duration of follow-up: 12 months
  • Mean patient age: 67 years
  • Percentage female: 21%

Inclusion criteria:

  • PCI for ACS with cobalt-chromium everolimus-eluting stent (CoCr-EES)

Exclusion criteria:

  • Oral anticoagulants
  • Prior intracranial hemorrhage
  • Contraindication to aspirin or clopidogrel
  • Serious in-hospital complication (reinfarction, stroke, bleeding)

Other salient features/characteristics:

  • ST-segment elevation MI (STEMI): 56%, NSTEMI: 20%, unstable angina: 24%
  • Killip class IV: 3.2%, intra-aortic balloon pump: 4%
  • Prior myocardial infarction (MI): 6%, prior PCI: 11%
  • Target lesions: 1.3

Principal Findings:

The primary outcome, cardiovascular death, MI, stroke, stent thrombosis, TIMI major or minor bleeding, for 1-month vs. 12-month DAPT, was 3.2% vs. 2.8% (hazard ratio [HR] 1.14, 95% confidence interval [CI] 0.80-1.62, p for noninferiority = 0.06).

Secondary outcomes for 1-month vs. 12-month DAPT:

  • Cardiovascular death/MI/stroke/stent thrombosis: 2.8% vs. 1.9% (HR 1.50, 95% CI 0.99-2.26)
  • TIMI major/minor bleeding: 0.5% vs. 1.2% (HR 0.46, 95% CI 0.23-0.94)
  • All-cause mortality: 1.4% vs. 0.9%
  • MI: 1.6% vs. 0.9% (HR 1.91, 95% CI 1.06-3.44, p < 0.05)
  • Definite stent thrombosis: 0.45% vs. 0.2%
  • Bleeding academic research consortium (BARC) 3/5 bleeding:  0.5% vs. 1.3% (HR 0.41, 95% CI 0.20-0.83)

Interpretation:

The results of this trial indicate that 1-month DAPT followed by clopidogrel monotherapy for 11 months did not meet criteria for noninferiority compared with standard-duration 12-month DAPT for the composite ischemic/bleeding endpoint among patients undergoing ACS PCI with a CoCr DES. In fact, the composite ischemic endpoint trended towards harm in the 1-month DAPT arm, with a significant nearly 2-fold increase in the risk of MI. Both major and minor bleeding events were lower with 1-month DAPT. One caveat is that these were all East Asian patients, and clopidogrel resistance was not assessed.

These are interesting findings, and add to the body of literature on the optimal duration and type of antiplatelet agent post-PCI. Contrary to the current trial, short-duration followed by clopidogrel monotherapy was noninferior to standard 12-month duration DAPT in the SMART-CHOICE (3 months) and STOPDAPT-2 (1 month) trials. These two trials included <50% of patients with ACS, and an even smaller number with STEMI. The current trial included all-comers with STEMI (including shock); these patients comprised 56% of all patients enrolled. Similar to the current trial, SMART-DATE included ACS patients undergoing PCI and found a higher risk of MI with 6 months of DAPT (clopidogrel being the P2Y12 inhibitor of choice in ~80%) compared with 12 months of DAPT. Other trials such as TWILIGHT and TICO demonstrated noninferiority for ticagrelor monotherapy after 3 months compared with standard 12-month duration, with a lower risk of bleeding. TWILIGHT trial did not include STEMI patients.

References:

Presented by Dr. Hirotoshi Watanabe at the European Society of Cardiology Virtual Congress, August 30, 2021.

Clinical Topics: Acute Coronary Syndromes, Cardiovascular Care Team, Invasive Cardiovascular Angiography and Intervention, Interventions and ACS

Keywords: ESC Congress, ESC21, Acute Coronary Syndrome, Aspirin, Drug-Eluting Stents, Hemorrhage, Myocardial Infarction, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors, Stents, Stroke, Thrombosis


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