Hirotoshi Watanabe1, Takeshi Morimoto2, Masahiro Natsuaki3, Ko Yamamoto1, Yuki Obayashi1, Manabu Ogita4, Satoru Suwa4, Tsuyoshi Isawa5, Takenori Domei6, Kyohei Yamaji6, Shojiro Tatsushima7, Hiroki Watanabe7, Masanobu Ohya8, Hideo Tokuyama9, Tomohisa Tada10, Hiroki Sakamoto10, Hiroyoshi Mori11, Hiroshi Suzuki11, Tenjin Nishikura12, Kohei Wakabayashi12, Kiyoshi Hibi13, Mitsuru Abe14, Kazuya Kawai15, Koichi Nakao16, Kenji Ando6, Kengo Tanabe17, Yuji Ikari18, Yoshihiro Morino19, Kazushige Kadota8, Yutaka Furukawa20, Yoshihisa Nakagawa21, Takeshi Kimura1. 1. Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 2. Department of Clinical Epidemiology, Hyogo College of Medicine, Nishinomiya, Japan. 3. Department of Cardiovascular Medicine, Saga University, Saga, Japan. 4. Department of Cardiology, Juntendo University Shizuoka Hospital, Izunokuni, Japan. 5. Department of Cardiology, Sendai Kousei Hospital, Sendai, Japan. 6. Department of Cardiology, Kokura Memorial Hospital, Kitakyusyu, Japan. 7. Department of Cardiology, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan. 8. Department of Cardiology, Kurashiki Central Hospital, Kurashiki, Japan. 9. Department of Cardiology, Kawaguchi Cardiovascular and Respiratory Hospital, Kawaguchi, Japan. 10. Department of Cardiology, Shizuoka General Hospital, Shizuoka, Japan. 11. Showa University Fujigaoka Hospital, Yokohama, Japan. 12. Showa University Koto Toyosu Hospital, Tokyo, Japan. 13. Department of Cardiology, Yokohama City University Medical Center, Yokohama, Japan. 14. Department of Cardiology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan. 15. Department of Cardiology, Chikamori Hospital, Kochi, Japan. 16. Division of Cardiology, Saiseikai Kumamoto Hospital Cardiovascular Center, Kumamoto, Japan. 17. Division of Cardiology, Mitsui Memorial Hospital, Tokyo, Japan. 18. Department of Cardiology, Tokai University Hospital, Isehara, Japan. 19. Department of Cardiology, Iwate Medical University Hospital, Morioka, Japan. 20. Department of Cardiovascular Medicine, Kobe City Medical Center General Hospital, Kobe, Japan. 21. Department of Cardiovascular Medicine, Shiga University of Medical Science, Otsu, Japan.
Abstract
IMPORTANCE: Clopidogrel monotherapy after short dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) has not yet been fully investigated in patients with acute coronary syndrome (ACS). OBJECTIVE: To test the hypothesis of noninferiority of 1 to 2 months of DAPT compared with 12 months of DAPT for a composite end point of cardiovascular and bleeding events in patients with ACS. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, open-label, randomized clinical trial enrolled 4169 patients with ACS who underwent successful PCI using cobalt-chromium everolimus-eluting stents at 96 centers in Japan from December 2015 through June 2020. These data were analyzed from June to July 2021. INTERVENTIONS: Patients were randomized either to 1 to 2 months of DAPT followed by clopidogrel monotherapy (n = 2078) or to 12 months of DAPT with aspirin and clopidogrel (n = 2091). MAIN OUTCOMES AND MEASURES: The primary end point was a composite of cardiovascular (cardiovascular death, myocardial infarction [MI], any stroke, or definite stent thrombosis) or bleeding (Thrombolysis in MI major or minor bleeding) events at 12 months, with a noninferiority margin of 50% on the hazard ratio (HR) scale. The major secondary end points were cardiovascular and bleeding components of the primary end point. RESULTS: Among 4169 randomized patients, 33 withdrew consent. Of the 4136 included patients, the mean (SD) age was 66.8 (11.9) years, and 856 (21%) were women, 2324 (56%) had ST-segment elevation MI, and 826 (20%) had non-ST-segment elevation MI. A total of 4107 patients (99.3%) completed the 1-year follow-up in June 2021. One to 2 months of DAPT was not noninferior to 12 months of DAPT for the primary end point, which occurred in 65 of 2058 patients (3.2%) in the 1- to 2-month DAPT group and in 58 of 2057 patients (2.8%) in the 12-month DAPT group (absolute difference, 0.37% [95% CI, -0.68% to 1.42%]; HR, 1.14 [95% CI, 0.80-1.62]; P for noninferiority = .06). The major secondary cardiovascular end point occurred in 56 patients (2.8%) in the 1- to 2-month DAPT group and in 38 patients (1.9%) in the 12-month DAPT group (absolute difference, 0.90% [95% CI, -0.02% to 1.82%]; HR, 1.50 [95% CI, 0.99-2.26]). The major secondary bleeding end point occurred in 11 patients (0.5%) in the 1- to 2-month DAPT group and 24 patients (1.2%) in the 12-month DAPT group (absolute difference, -0.63% [95% CI, -1.20% to -0.06%]; HR, 0.46 [95% CI, 0.23-0.94]). CONCLUSIONS AND RELEVANCE: In patients with ACS with successful PCI, clopidogrel monotherapy after 1 to 2 months of DAPT failed to attest noninferiority to standard 12 months of DAPT for the net clinical benefit with a numerical increase in cardiovascular events despite reduction in bleeding events. The directionally different efficacy and safety outcomes indicate the need for further clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT02619760 and NCT03462498.
IMPORTANCE: Clopidogrel monotherapy after short dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) has not yet been fully investigated in patients with acute coronary syndrome (ACS). OBJECTIVE: To test the hypothesis of noninferiority of 1 to 2 months of DAPT compared with 12 months of DAPT for a composite end point of cardiovascular and bleeding events in patients with ACS. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, open-label, randomized clinical trial enrolled 4169 patients with ACS who underwent successful PCI using cobalt-chromium everolimus-eluting stents at 96 centers in Japan from December 2015 through June 2020. These data were analyzed from June to July 2021. INTERVENTIONS: Patients were randomized either to 1 to 2 months of DAPT followed by clopidogrel monotherapy (n = 2078) or to 12 months of DAPT with aspirin and clopidogrel (n = 2091). MAIN OUTCOMES AND MEASURES: The primary end point was a composite of cardiovascular (cardiovascular death, myocardial infarction [MI], any stroke, or definite stent thrombosis) or bleeding (Thrombolysis in MI major or minor bleeding) events at 12 months, with a noninferiority margin of 50% on the hazard ratio (HR) scale. The major secondary end points were cardiovascular and bleeding components of the primary end point. RESULTS: Among 4169 randomized patients, 33 withdrew consent. Of the 4136 included patients, the mean (SD) age was 66.8 (11.9) years, and 856 (21%) were women, 2324 (56%) had ST-segment elevation MI, and 826 (20%) had non-ST-segment elevation MI. A total of 4107 patients (99.3%) completed the 1-year follow-up in June 2021. One to 2 months of DAPT was not noninferior to 12 months of DAPT for the primary end point, which occurred in 65 of 2058 patients (3.2%) in the 1- to 2-month DAPT group and in 58 of 2057 patients (2.8%) in the 12-month DAPT group (absolute difference, 0.37% [95% CI, -0.68% to 1.42%]; HR, 1.14 [95% CI, 0.80-1.62]; P for noninferiority = .06). The major secondary cardiovascular end point occurred in 56 patients (2.8%) in the 1- to 2-month DAPT group and in 38 patients (1.9%) in the 12-month DAPT group (absolute difference, 0.90% [95% CI, -0.02% to 1.82%]; HR, 1.50 [95% CI, 0.99-2.26]). The major secondary bleeding end point occurred in 11 patients (0.5%) in the 1- to 2-month DAPT group and 24 patients (1.2%) in the 12-month DAPT group (absolute difference, -0.63% [95% CI, -1.20% to -0.06%]; HR, 0.46 [95% CI, 0.23-0.94]). CONCLUSIONS AND RELEVANCE: In patients with ACS with successful PCI, clopidogrel monotherapy after 1 to 2 months of DAPT failed to attest noninferiority to standard 12 months of DAPT for the net clinical benefit with a numerical increase in cardiovascular events despite reduction in bleeding events. The directionally different efficacy and safety outcomes indicate the need for further clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT02619760 and NCT03462498.
Authors: Davide Capodanno; Usman Baber; Deepak L Bhatt; Jean-Philippe Collet; George Dangas; Francesco Franchi; C Michael Gibson; Hyeon-Cheol Gwon; Adnan Kastrati; Takeshi Kimura; Pedro A Lemos; Renato D Lopes; Roxana Mehran; Michelle L O'Donoghue; Sunil V Rao; Fabiana Rollini; Patrick W Serruys; Philippe G Steg; Robert F Storey; Marco Valgimigli; Pascal Vranckx; Hirotoshi Watanabe; Stephan Windecker; Dominick J Angiolillo Journal: Nat Rev Cardiol Date: 2022-06-13 Impact factor: 32.419
Authors: Anna Falanga; Avi Leader; Chiara Ambaglio; Zsuzsa Bagoly; Giancarlo Castaman; Ismail Elalamy; Ramon Lecumberri; Alexander Niessner; Ingrid Pabinger; Sebastian Szmit; Alice Trinchero; Hugo Ten Cate; Bianca Rocca Journal: Hemasphere Date: 2022-07-13