Importance: Although P2Y12 inhibitor monotherapy after a minimum period of dual antiplatelet therapy (DAPT) is a well-known way to reduce the risk of bleeding after percutaneous coronary intervention (PCI), data comparing long-term clinical outcomes between P2Y12 inhibitor monotherapy and extended DAPT in patients undergoing PCI have been unavailable.
Objective: To identify the long-term safety and efficacy of P2Y12 inhibitor monotherapy following 3 months of DAPT after PCI.
Design, setting, and participants: The Smart Angioplasty Research Team: Comparison Between P2Y12 Antagonist Monotherapy and Dual Antiplatelet Therapy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents (SMART-CHOICE) trial was an open-label, noninferiority, randomized clinical trial, enrolling patients who underwent PCI with drug-eluting stent at 33 hospitals in Korea from March 2014 through July 2017. Clinical follow-up was extended to 3 years and completed in August 2020.
Interventions: Patients were randomly assigned to either P2Y12 inhibitor monotherapy after 3 months of DAPT or DAPT for 12 months or longer.
Main outcomes and measures: The primary end point was major adverse cardiac and cerebrovascular events (a composite of all-cause death, myocardial infarction, or stroke) at 3 years. The secondary end points included the components of the primary end point, bleeding (defined as Bleeding Academic Research Consortium [BARC] types 2-5), and major bleeding (BARC types 3-5).
Results: In total, 2993 patients were randomly assigned to receive P2Y12 inhibitor monotherapy after 3 months of DAPT (1495 patients [50%]; mean [SD] age, 64.6 [10.7] years; 1087 [72.7%] male) or prolonged DAPT (1498 patients [50%]; mean [SD] age, 64.6 [10.7] years; 1111 [74.2%] male) after PCI. At 3 years, the primary end point occurred in 87 individuals (6.3%) in the P2Y12 inhibitor monotherapy group and 83 (6.1%) in the prolonged DAPT group (hazard ratio [HR], 1.06 [95% CI, 0.79-1.44]; P = .69). P2Y12 inhibitor monotherapy significantly reduced the risk of bleeding (BARC types 2-5: 112 [3.2%] vs 44 [8.2%]; HR, 0.39 [95% CI, 0.28-0.55]; P < .001) and major bleeding (BARC types 3-5; 17 [1.2%] vs 31 [2.4%]; HR, 0.56 [95% CI, 0.31-0.99]; P = .048), compared with prolonged DAPT. The landmark analyses between 3 months and 3 years and per-protocol analyses showed consistent results.
Conclusions and relevance: Among patients who underwent PCI and completed 3-month DAPT, P2Y12 inhibitor monotherapy was associated with a lower risk of clinically relevant major bleeding than prolonged DAPT. Although the 3-year risk of ischemic cardiovascular events was comparable between the 2 groups, this result should be interpreted with caution owing to the limited number of events and sample size.
Trial registration: ClinicalTrials.gov Identifier: NCT02079194.