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Original Investigation
June 25, 2019

Effect of 1-Month Dual Antiplatelet Therapy Followed by Clopidogrel vs 12-Month Dual Antiplatelet Therapy on Cardiovascular and Bleeding Events in Patients Receiving PCI: The STOPDAPT-2 Randomized Clinical Trial

Author Affiliations
  • 1Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
  • 2Department of Cardiology, Kokura Memorial Hospital, Kitakyusyu, Japan
  • 3Department of Clinical Epidemiology, Hyogo College of Medicine, Nishinomiya, Japan
  • 4Department of Cardiovascular Medicine, Saga University, Saga, Japan
  • 5Department of Cardiovascular Medicine, Kobe City Medical Center General Hospital, Kobe, Japan
  • 6Department of Cardiology, Kurashiki Central Hospital, Kurashiki, Japan
  • 7Department of Cardiology, Juntendo University Shizuoka Hospital, Izunokuni, Japan
  • 8Department of Cardiology, Ogaki Municipal Hospital, Ogaki, Japan
  • 9Department of Cardiology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan
  • 10Department of Cardiology, Minamino Cardiovascular Hospital, Hachioji, Japan
  • 11Department of Cardiology, Sendai Cardiovascular Center, Sendai, Japan
  • 12Department of Cardiology, Saiseikai Fukuoka General Hospital, Fukuoka, Japan
  • 13Department of Cardiology, Mitsubishi Kyoto Hospital, Kyoto, Japan
  • 14Department of Cardiology, Sakakibara Heart Institute, Fuchu, Japan
  • 15Department of Cardiology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
  • 16Department of Cardiology, Gifu Prefectural General Medical Center, Gifu, Japan
  • 17Department of Cardiology, Ehime Prefectural Central Hospital, Matsuyama, Japan
  • 18Department of Cardiology, Hoshi General Hospital, Koriyama, Japan
  • 19Department of Cardiology, Shizuoka General Hospital, Shizuoka, Japan
  • 20Division of Cardiology, Yokohama City University Medical Center, Yokohama, Japan
  • 21Department of Cardiology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
  • 22Department of Cardiology, Chikamori Hospital, Kochi, Japan
  • 23Division of Cardiology, Saiseikai Kumamoto Hospital Cardiovascular Center, Kumamoto, Japan
  • 24Department of Cardiology, Mitsui Memorial Hospital, Tokyo, Japan
  • 25Department of Cardiology, Tokai University Hospital, Isehara, Japan
  • 26Hanaoka Seishu Memorial Cardiovascular Clinic, Sapporo, Japan
  • 27Department of Cardiology, Iwate Medical University Hospital, Morioka, Japan
  • 28Department of Cardiology, Teikyo University Hospital, Tokyo, Japan
  • 29Department of Cardiovascular Medicine, Shiga University of Medical Science, Otsu, Japan
JAMA. 2019;321(24):2414-2427. doi:10.1001/jama.2019.8145
Key Points

Question  In patients undergoing percutaneous coronary intervention, is 1 month of dual antiplatelet therapy (DAPT) followed by clopidogrel monotherapy noninferior to 12 months of DAPT with aspirin and clopidogrel for adverse cardiovascular and bleeding events?

Findings  In this randomized clinical trial that included 3045 patients, the 1-year cumulative incidence of a composite end point consisting of cardiovascular death, myocardial infarction, ischemic or hemorrhagic stroke, definite stent thrombosis, and major bleeding was 2.4% in the 1-month DAPT group and 3.7% in the 12-month DAPT group, a difference that met the noninferiority margin of a hazard ratio of 0.5, as well as superiority.

Meaning  These findings suggest that 1 month of DAPT followed by clopidogrel monotherapy provided benefit compared with 12 months of DAPT, although additional research is needed in other populations.

Abstract

Importance  Very short mandatory dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with a drug-eluting stent may be an attractive option.

Objective  To test the hypothesis of noninferiority of 1 month of DAPT compared with standard 12 months of DAPT for a composite end point of cardiovascular and bleeding events.

Design, Setting, and Participants  Multicenter, open-label, randomized clinical trial enrolling 3045 patients who underwent PCI at 90 hospitals in Japan from December 2015 through December 2017. Final 1-year clinical follow-up was completed in January 2019.

Interventions  Patients were randomized either to 1 month of DAPT followed by clopidogrel monotherapy (n=1523) or to 12 months of DAPT with aspirin and clopidogrel (n=1522).

Main Outcomes and Measures  The primary end point was a composite of cardiovascular death, myocardial infarction (MI), ischemic or hemorrhagic stroke, definite stent thrombosis, or major or minor bleeding at 12 months, with a relative noninferiority margin of 50%. The major secondary cardiovascular end point was a composite of cardiovascular death, MI, ischemic or hemorrhagic stroke, or definite stent thrombosis and the major secondary bleeding end point was major or minor bleeding.

Results  Among 3045 patients randomized, 36 withdrew consent; of 3009 remaining, 2974 (99%) completed the trial. One-month DAPT was both noninferior and superior to 12-month DAPT for the primary end point, occurring in 2.36% with 1-month DAPT and 3.70% with 12-month DAPT (absolute difference, −1.34% [95% CI, −2.57% to −0.11%]; hazard ratio [HR], 0.64 [95% CI, 0.42-0.98]), meeting criteria for noninferiority (P < .001) and for superiority (P = .04). The major secondary cardiovascular end point occurred in 1.96% with 1-month DAPT and 2.51% with 12-month DAPT (absolute difference, −0.55% [95% CI, −1.62% to 0.52%]; HR, 0.79 [95% CI, 0.49-1.29]), meeting criteria for noninferiority (P = .005) but not for superiority (P = .34). The major secondary bleeding end point occurred in 0.41% with 1-month DAPT and 1.54% with 12-month DAPT (absolute difference, −1.13% [95% CI, −1.84% to −0.42%]; HR, 0.26 [95% CI, 0.11-0.64]; P = .004 for superiority).

Conclusions and Relevance  Among patients undergoing PCI, 1 month of DAPT followed by clopidogrel monotherapy, compared with 12 months of DAPT with aspirin and clopidogrel, resulted in a significantly lower rate of a composite of cardiovascular and bleeding events, meeting criteria for both noninferiority and superiority. These findings suggest that a shorter duration of DAPT may provide benefit, although given study limitations, additional research is needed in other populations.

Trial Registration  ClinicalTrials.gov Identifier: NCT02619760

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