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
Authors: Hirotoshi Watanabe, Takeshi Morimoto, Masahiro Natsuaki, Ko Yamamoto, Yuki Obayashi, Manabu Ogita, Satoru Suwa, Tsuyoshi Isawa, Takenori Domei, Kyohei Yamaji, Shojiro Tatsushima, Hiroki Watanabe, Masanobu Ohya, Hideo Tokuyama, Tomohisa Tada, Hiroki Sakamoto, Hiroyoshi Mori, Hiroshi Suzuki, Tenjin Nishikura, Kohei Wakabayashi, Kiyoshi Hibi, Mitsuru Abe, Kazuya Kawai, Koichi Nakao, Kenji Ando, Kengo Tanabe, Yuji Ikari, Yoshihiro Morino, Kazushige Kadota, Yutaka Furukawa, Yoshihisa Nakagawa, Takeshi Kimura, Ken Kozuma, Keiichi Hanaoka, Saori Tezuka, Yumika Fujino, Risa Kato, Masayo Kitamura, Miyuki Tsumori, Miya Hanazawa, Misato Yamauchi, Itsuki Yamazaki, Mitsugu Hirokami, Nobuko Makiguchi, Yoichi Nozaki, Hirofumi Tomita, Masahiro Yagi, Tatsuya Komaru, Motoaki Higuchi, Takaaki Isshiki, Takahide Kodama, Atsushi Tosaka, Itaru Takamisawa, Hiroyuki Tanaka, Yoshiki Hata, Ryuichi Kato, Yoshihiro Akashi, Kazuhiko Yumoto, Kengo Tsukahara, Junya Ako, Yuko Onishi, Hiroyasu Uzui, Toshiyuki Noda, Itsuo Morishima, Minoru Yamada, Ruka Yoshida, Susumu Suzuki, Takuya Maeda, Takashi Tanigawa, Kazuaki Kaitani, Shunzo Matsuoka, Masaharu Akao, Takafumi Yokomatsu, Moriaki Inoko, Tsukasa Inada, Takashi Morita, Gaku Nakazawa, Shozo Ishihara, Makoto Kinoshita, Takanori Kusuyama, Kiyonori Togi, Toshihiro Tamura, Takashi Akasaka, Isao Tabuchi, Yasuki Kihara, Hironori Ueda, Yusuke Katayama, Takatoshi Wakeyama, Takeo Kaneko, Tetsuzo Wakatsuki, Koichi Kishi, Masayuki Doi, Hideki Okayama, Nobuhiro Suematsu, Shujiro Inoue, Masahiro Natsuaki, Kenichi Tsujita, Tomohiro Sakamoto, Hirofumi Kurokawa, Katsuro Kashima, Hiroki Uehara
Journal: JAMA Cardiology (2022)

<h3>Importance</h3> 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). <h3>Objective</h3> 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. <h3>Design, Setting, and Participants</h3> 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. <h3>Interventions</h3> 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). <h3>Main Outcomes and Measures</h3> 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. <h3>Results</h3> 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];<i>P</i>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]). <h3>Conclusions and Relevance</h3> 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. <h3>Trial Registration</h3> ClinicalTrials.gov Identifiers:NCT02619760andNCT03462498