Effect of P2Y12 Inhibitor Monotherapy vs Dual Antiplatelet Therapy on Cardiovascular Events in Patients Undergoing Percutaneous Coronary Intervention: The SMART-CHOICE Randomized Clinical Trial

Abstract

Importance: Data on P2Y12 inhibitor monotherapy after short-duration dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention are limited.

Objective: To determine whether P2Y12 inhibitor monotherapy after 3 months of DAPT is noninferior to 12 months of DAPT in patients undergoing PCI.

Design, setting, and participants: The SMART-CHOICE trial was an open-label, noninferiority, randomized study that was conducted in 33 hospitals in Korea and included 2993 patients undergoing PCI with drug-eluting stents. Enrollment began March 18, 2014, and follow-up was completed July 19, 2018.

Interventions: Patients were randomly assigned to receive aspirin plus a P2Y12 inhibitor for 3 months and thereafter P2Y12 inhibitor alone (n = 1495) or DAPT for 12 months (n = 1498).

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 12 months after the index procedure. Secondary end points included the components of the primary end point and bleeding defined as Bleeding Academic Research Consortium type 2 to 5. The noninferiority margin was 1.8%.

Results: Among 2993 patients who were randomized (mean age, 64 years; 795 women [26.6%]), 2912 (97.3%) completed the trial. Adherence to the study protocol was 79.3% of the P2Y12 inhibitor monotherapy group and 95.2% of the DAPT group. At 12 months, major adverse cardiac and cerebrovascular events occurred in 42 patients in the P2Y12 inhibitor monotherapy group and in 36 patients in the DAPT group (2.9% vs 2.5%; difference, 0.4% [1-sided 95% CI, -∞% to 1.3%]; P = .007 for noninferiority). There were no significant differences in all-cause death (21 [1.4%] vs 18 [1.2%]; hazard ratio [HR], 1.18; 95% CI, 0.63-2.21; P = .61), myocardial infarction (11 [0.8%] vs 17 [1.2%]; HR, 0.66; 95% CI, 0.31-1.40; P = .28), or stroke (11 [0.8%] vs 5 [0.3%]; HR, 2.23; 95% CI, 0.78-6.43; P = .14) between the 2 groups. The rate of bleeding was significantly lower in the P2Y12 inhibitor monotherapy group than in the DAPT group (2.0% vs 3.4%; HR, 0.58; 95% CI, 0.36-0.92; P = .02).

Conclusions and relevance: Among patients undergoing percutaneous coronary intervention, P2Y12 inhibitor monotherapy after 3 months of DAPT compared with prolonged DAPT resulted in noninferior rates of major adverse cardiac and cerebrovascular events. Because of limitations in the study population and adherence, further research is needed in other populations.

Trial registration: ClinicalTrials.gov Identifier: NCT02079194.

Figure 1.. Randomization and Patient Flow in the Study Comparing P2Y12 Inhibitor Monotherapy vs Dual Antiplatelet Therapy in Patients Undergoing Percutaneous Coronary Intervention

Sites were not required to provide screening logs during the recruitment phase. Thus, the number of patients approached for participation is not available. Outcomes of patients who were lost to follow-up were included to the point of final contact. Their time-to-event measure was censored at the last contact date. There was no imputation of outcome events.

Figure 2.. Time-to-Event Curves for the Major Adverse Cardiovascular and Cerebrovascular Events and Landmark Analysis at 3 Months

A, Results of the analysis of the primary end point of major adverse cardiovascular and cerebrovascular events (a composite of death, myocardial infarction, or stroke) at 12 months. B, Results of the landmark analysis at 3 months (the point after which one group received P2Y12 inhibitor only and the other received DAPT) for the primary end point. Event rates were based on Kaplan-Meier estimates in time-to-first-event analyses. Hazard ratios are for the patients in the P2Y12 inhibitor monotherapy group. DAPT indicates dual antiplatelet therapy; HR, hazard ratio; MACCE, major adverse cardiac and cerebrovascular events. MACCE was defined as a composite of all-cause death, myocardial infarction, or stroke. The median length of patient follow-up was 365 days (25th and 75th percentile, 365 and 365) in the P2Y12 inhibitor monotherapy group and 365 days (25th and 75th percentile, 365 and 365) in the DAPT group.

Figure 3.. Time-to-Event Curves for the Bleeding and Landmark Analysis at 3 Months

A, Results of the analysis of the bleeding at 12 months. B, Results of the landmark analysis at 3 months (the point after which one group received P2Y12 inhibitor only and the other received DAPT) for bleeding. Event rates were based on Kaplan-Meier estimates in time-to-first-event analyses. Hazard ratios are for the patients in the P2Y12 inhibitor monotherapy group. DAPT indicates dual antiplatelet therapy; HR, hazard ratio.