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

Mar 28, 2022
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Abbott Medical Japan LLC
Date Presented:
11/05/2021
Date Published:
03/02/2022
Date Updated:
03/28/2022
Original Posted Date:
08/30/2021
References

Contribution To Literature:

Highlighted text has been updated as of March 28, 2022.

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 1-2 months followed by clopidogrel monotherapy for a total of 12 months (n = 2,078) or standard-duration DAPT with aspirin + clopidogrel for 12 months (n = 2,078). Aspirin dose was 100 mg/day, clopidogrel 75 mg/day, prasugrel 3.75 mg/day (switched to clopidogrel after 1-2 months).

  • Total number of enrollees: 4,169 (1,161 patients came from ACS subgroup of STOPDAPT-2 trial; 3,008 were newly enrolled)
  • 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): 57%, NSTEMI: 20%, unstable angina: 24%
  • Killip class IV: 3.2%, intra-aortic balloon pump: 4%
  • Prior myocardial infarction (MI): 6%, prior PCI: 11%
  • Total number of stents: 1.4

Principal Findings:

The primary outcome, cardiovascular death, MI, stroke, stent thrombosis, TIMI major or minor bleeding, for 1-2 months vs. 12 months of 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). Cardiovascular death was 0.5% vs. 0.5%.

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

  • Cardiovascular death/MI/stroke/stent thrombosis: 2.7% vs. 1.9% (HR 1.50, 95% CI 0.99-2.26)
  • 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: 0.5% 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)
  • TIMI major/minor bleeding: 0.5% vs. 1.2% (HR 0.46, 95% CI 0.23-0.94)

Combination STOPDAPT-2 and STOPDAPT-2 ACS trials (n = 5,997):

  • Primary endpoint: 2.8% in the 1-month DAPT group compared with 3.0% in the 12-month DAPT group (p for superiority = 0.68, p for noninferiority = 0.001) (p for interaction between ACS and stable coronary disease = 0.052, p for interaction between high-bleeding risk and non-high-bleeding risk = 0.95, p for interaction between complex and noncomplex PCI = 0.48)
  • TIMI major/minor bleeding: 0.5% in the 1-month DAPT group compared with 1.3% in the 12-month DAPT group (log rank p = 0.001) (p for interaction between ACS and stable coronary disease = 0.4, p for interaction between high-bleeding risk and non-high-bleeding risk = 0.36, p for interaction between complex and noncomplex PCI = 0.90)

Interpretation:

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

Among the total cohort of patients undergoing PCI for stable and unstable cardiovascular disease, 1 month of DAPT followed by clopidogrel monotherapy was noninferior to 12 months of DAPT followed by aspirin monotherapy at preventing net adverse clinical events. There was possible treatment interaction whereby there was a slight excess of net adverse ischemic events among ACS patients treated with 1 month of DAPT compared with 12 months of DAPT.

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 57% 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:

Watanabe H, Morimoto T, Natsuaki M, et al. Comparison of Clopidogrel Monotherapy After 1 to 2 Months of Dual Antiplatelet Therapy With 12 Months of Dual Antiplatelet Therapy in Patients With Acute Coronary Syndrome: The STOPDAPT-2 ACS Randomized Clinical Trial. JAMA Cardiol 2022;Mar 2:[Epub ahead of print].

Presented by Drs. Yuki Obayashi and Ko Yamamoto at the Transcatheter Cardiovascular Therapeutics (TCT) Conference, Orlando, FL, November 5, 2021.

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

Clinical Topics: Acute Coronary Syndromes, 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, TCT21, Transcatheter Cardiovascular Therapeutics


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