Clopidogrel Monotherapy After 1-Month Dual Antiplatelet Therapy in Percutaneous Coronary Intervention: From the STOPDAPT-2 Total Cohort

Yuki Obayashi, Hirotoshi Watanabe, Takeshi Morimoto, Ko Yamamoto, Masahiro Natsuaki, Takenori Domei, Kyohei Yamaji, Satoru Suwa, Tsuyoshi Isawa, Hiroki Watanabe, Ruka Yoshida, Hiroki Sakamoto, Masaharu Akao, Yoshiki Hata, Itsuro Morishima, Hideo Tokuyama, Masahiro Yagi, Hiroshi Suzuki, Kohei Wakabayashi, Nobuhiro Suematsu, Tsukasa Inada, Toshihiro Tamura, Hideki Okayama, Mitsuru Abe, Kazuya Kawai, Koichi Nakao, Kenji Ando, Kengo Tanabe, Yuji Ikari, Yoshihiro Morino, Kazushige Kadota, Yutaka Furukawa, Yoshihisa Nakagawa, Takeshi Kimura, STOPDAPT-2 and STOPDAPT-2 ACS Investigators, Yuki Obayashi, Hirotoshi Watanabe, Takeshi Morimoto, Ko Yamamoto, Masahiro Natsuaki, Takenori Domei, Kyohei Yamaji, Satoru Suwa, Tsuyoshi Isawa, Hiroki Watanabe, Ruka Yoshida, Hiroki Sakamoto, Masaharu Akao, Yoshiki Hata, Itsuro Morishima, Hideo Tokuyama, Masahiro Yagi, Hiroshi Suzuki, Kohei Wakabayashi, Nobuhiro Suematsu, Tsukasa Inada, Toshihiro Tamura, Hideki Okayama, Mitsuru Abe, Kazuya Kawai, Koichi Nakao, Kenji Ando, Kengo Tanabe, Yuji Ikari, Yoshihiro Morino, Kazushige Kadota, Yutaka Furukawa, Yoshihisa Nakagawa, Takeshi Kimura, STOPDAPT-2 and STOPDAPT-2 ACS Investigators

Abstract

Background: The benefit of clopidogrel monotherapy after 1-month dual antiplatelet therapy (DAPT) compared with 12-month DAPT with aspirin and clopidogrel was demonstrated in the STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2), but not in the STOPDAPT-2 acute coronary syndrome (ACS); however, both trials were underpowered based on the actual event rates.

Methods: We obtained the prespecified pooled population of 5997 patients as the STOPDAPT-2 total cohort (STOPDAPT-2: N=3009/STOPDAPT-2 ACS: N=2988; ACS: N=4136/chronic coronary syndrome [CCS]: N=1861), comprising 2993 patients assigned to 1-month DAPT followed by clopidogrel monotherapy, and 3004 patients assigned to 12-month DAPT with aspirin and clopidogrel after percutaneous coronary intervention. The primary end point was the composite of cardiovascular (cardiovascular death, myocardial infarction, definite stent thrombosis, or any stroke) or bleeding (Thrombolysis in Myocardial Infarction major/minor) end points at 1 year.

Results: One-month DAPT was noninferior to 12-month DAPT for the primary end point (2.84% versus 3.04%; hazard ratio [HR], 0.94 [95% CI, 0.70-1.27]; Pnoninferiority=0.001; Psuperiority=0.68). There was no significant risk-difference for the cardiovascular end point between the 1- and 12-month DAPT groups (2.40% versus 1.97%; HR, 1.24 [95% CI, 0.88-1.75]; Pnoninferiority=0.14; Psuperiority=0.23). There was a lower risk of the bleeding end point with 1-month DAPT relative to 12-month DAPT (0.50% versus 1.31%; HR, 0.38 [95% CI, 0.21-0.70]; Psuperiority=0.002). One-month DAPT relative to 12-month DAPT was associated with a lower risk for major bleeding regardless of ACS or CCS (ACS: HR, 0.46 [95% CI, 0.23-0.94]; P=0.03, and CCS: HR, 0.26 [95% CI, 0.09-0.79]; P=0.02; Pinteraction=0.40), while it was associated with a numerical increase in cardiovascular events in ACS patients, but not in CCS patients, although not statistically significant and without interaction (ACS: HR, 1.50 [95% CI, 0.99-2.27]; P=0.053, and CCS: HR, 0.74 [95% CI, 0.38-1.45]; P=0.39; Pinteraction=0.08).

Conclusions: Clopidogrel monotherapy after 1-month DAPT compared with 12-month DAPT with aspirin and clopidogrel had a benefit in reducing major bleeding events without being associated with increase in cardiovascular events.

Registration: URL: https://www.

Clinicaltrials: gov; Unique identifiers: NCT02619760, NCT03462498.

Keywords: acute coronary syndrome; antiplatelet therapy; chronic coronary syndrome; coronary stent; percutaneous coronary intervention.

Figures

Figure 1.
Figure 1.
Study flow for the STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2) total cohort and acute coronary syndrome (ACS)/chronic coronary syndrome (CCS) subgroup analysis. DAPT indicates dual antiplatelet therapy.
Figure 2.
Figure 2.
Forrest plots for the effect of 1-month relative to 12-mo dual antiplatelet therapy (DAPT) for the primary and major secondary end points in the STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2) total cohort and in acute coronary syndrome (ACS)/chronic coronary syndrome (CCS) subgroups.
Figure 3.
Figure 3.
Cumulative incidence of the primary and major secondary end points in the STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2) total cohort: 1- vs 12-mo dual antiplatelet therapy (DAPT). Time-to-event curves during 1-y after index percutaneous coronary intervention (PCI): (A) for the primary end point, (B) for the major secondary cardiovascular end point, and (C) for the major secondary bleeding end point in the STOPDAPT-2 total cohort. TIMI indicates Thrombolysis in Myocardial Infarction.
Figure 4.
Figure 4.
Kaplan-Meier curves for the primary and major secondary end points stratified by acute coronary syndrome (ACS) and chronic coronary syndrome (CCS): 1- vs 12-mo dual antiplatelet therapy (DAPT). Time-to-event curves during 1-y after index percutaneous coronary intervention (PCI): (A) for the primary end point, (B) for the major secondary cardiovascular end point, and (C) for the major secondary bleeding end point stratified by ACS and CCS.

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