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

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.

Conflict of interest statement

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.

Figures

Figure 1.. Participant Flow in the STOPDAPT-2 Randomized Clinical Trial

CoCr-EES indicates cobalt-chromium everolimus-eluting stent. aA total of 183 patients had planned staged procedure and received other drug-eluting stents, so numbers are not mutually exclusive.

Figure 2.. One-Year Time to Events for the Primary and Major Secondary End Points

HR indicates hazard ratio; MI, myocardial infarction; PCI, percutaneous coronary intervention; TIMI, Thrombolysis in Myocardial Infarction. The median observation periods in the last data set were 400 (interquartile range, 368-732) days in the 1-month dual antiplatelet therapy (DAPT) group and 414 (interquartile range, 369-733) days in the 12-month DAPT group. The last day of data collection was day 365; patients with follow-up beyond 1 year were censored on day 366.

Figure 3.. Subgroup Analyses for the Effect of 1-Month DAPT on the Primary End Point

CREDO-Kyoto indicates Coronary Revascularization Demonstrating Outcome Study in Kyoto; HR, hazard ratio; PARIS, Patterns of Non-Adherence to Anti-Platelet Regimen in Stented Patients; STEMI, ST-segment elevation myocardial infarction. The vertical dashed line indicates the prespecified relative 50% noninferiority margin. Numbers and percentages shown are number of patients with event/number of patients at risk and incidences at 1 year. Acute coronary syndrome was the clinical presentation for the index percutaneous coronary intervention. Severe chronic kidney disease is defined as preprocedural estimated glomerular filtration rate less than 30 mL/min/1.73 m2 or undergoing maintenance dialysis. See Table 1 for definitions of PARIS and CREDO-Kyoto risk scores.