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

Educational Objective
To understand the benefits and risks of dual antiplatelet therapy.
1 Credit CME
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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Article Information

Corresponding Author: Takeshi Kimura, MD, Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507 Japan (taketaka@kuhp.kyoto-u.ac.jp).

Accepted for Publication: May 23, 2019.

Author Contributions: Dr Kimura had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Domei, Morimoto, Natsuaki, Toyota, Ohya, Takagi, Suematsu, Yokomatsu, Takamisawa, Abe, Kawai, Nakao, Tanabe, Morino, Kozuma, Nakagawa, Kimura.

Acquisition, analysis, or interpretation of data: Watanabe, Domei, Morimoto, Natsuaki, Shiomi, Toyota, Ohya, Suwa, Nanasato, Hata, Yagi, Takamisawa, Doi, Noda, Okayama, Seino, Tada, Sakamoto, Hibi, Nakao, Ando, Tanabe, Ikari, Hanaoka, Morino, Kozuma, Kadota, Furukawa, Kimura.

Drafting of the manuscript: Watanabe, Domei, Toyota, Hata, Suematsu, Yokomatsu, Kawai, Hanaoka, Kadota, Kimura.

Critical revision of the manuscript for important intellectual content: Watanabe, Domei, Morimoto, Natsuaki, Shiomi, Toyota, Ohya, Suwa, Takagi, Nanasato, Yagi, Takamisawa, Doi, Noda, Okayama, Seino, Tada, Sakamoto, Hibi, Abe, Nakao, Ando, Tanabe, Ikari, Morino, Kozuma, Furukawa, Nakagawa, Kimura.

Statistical analysis: Watanabe, Morimoto, Shiomi, Toyota.

Obtained funding: Takagi, Kimura.

Administrative, technical, or material support: Watanabe, Morimoto, Natsuaki, Suwa, Nanasato, Doi, Noda, Okayama, Abe, Nakao, Tanabe, Hanaoka, Furukawa, Nakagawa, Kimura.

Supervision: Morimoto, Ohya, Sakamoto, Kawai, Ando, Tanabe, Ikari, Morino, Nakagawa, Kimura.

Conflict of Interest Disclosures: Dr Watanabe reported receipt of personal fees from Abbott Vascular Japan and Daiichi Sankyo. Dr Yagi reported receipt of personal fees from Otsuka Pharmaceutical, Daiichi Sankyo, and Kowa Pharmaceuticals. Dr Hibi reported receipt of personal fees from Abbott Vascular. Dr Nakao reported receipt of personal fees from Sanofi, Bayer, Daiichi-Sankyo, and Boehringer Ingelheim. Dr Tanabe reported receipt of personal fees from Abbott Vascular, AstraZeneca, Sanofi, Daiichi Sankyo, Terumo, Boston Scientific, Japan Lifeline, Bayer, and Medtronic and advisory board membership for Abbott Vascular and Terumo Japan. Dr Morino reported receipt of personal fees from Abbott Vascular and advisory board membership for Abbott Vascular and Terumo Japan. Dr Kozuma reported receipt of grants and personal fees from Abbott Vascular and advisory board membership for Abbott Vascular and Terumo Japan. Dr Furukawa reported receipt of personal fees from Daiichi Sankyo, Bayer, and Sanofi. Dr Nakagawa reported advisory board membership for Abbott Vascular. Dr Kimura reported receipt of personal fees from Abbott Vascular and grants from Abbott Vascular and Boston Scientific and advisory board membership for Abbott Vascular and Terumo Japan. No other disclosures were reported.

Funding/Support:Abbott Vascular funded the STOPDAPT-2 study but did not provide medications or coronary devices.

Role of the Funder/Sponsor: Abbott Vascular was involved in discussions regarding the study design but was not involved in the conduct of the study nor in the collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. The sponsor did not have the right to veto publication or to control the decision regarding to which journal the manuscript was submitted.

Data Sharing Statement: See Supplement 3.

Additional Contributions: We thank the study investigators for their efforts in enrolling patients and collecting data and the members of the Research Institute for Production Development for coordinating the study. Yusuke Yoshikawa, MD, Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, contributed to additional analyses in manuscript revision without receipt of compensation.

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