Hahn JY, et al. - This study incorporated a scrutiny of the possibility of non-inferiority of a 6-month duration of dual antiplatelet therapy (DAPT) to the conventional 12-month or longer duration of DAPT in subjects with acute coronary syndrome undergoing percutaneous coronary intervention. Owing to the increased risk of myocardial infarction with 6-month DAPT and the wide non-inferiority margin, safety of short-term DAPT could not be demonstrated in these patients with current-generation drug-eluting stents (DES). Data recommended prolonged DAPT in patients with acute coronary syndrome without excessive risk of bleeding as the standard of care.

Methods

• A randomized, open-label, non-inferiority trial was performed at 31 centres in South Korea.
• Eligible candidates included subjects having unstable angina, non-ST-segment elevation myocardial infarction, or ST-segment elevation myocardial infarction, and who underwent percutaneous coronary intervention.
• Using a web-based system by computer-generated block randomization, they were randomly allocated to either the 6-month DAPT group or to the 12-month or longer DAPT group, with stratification by site, clinical presentation and diabetes.
• Herein, assessors were masked to treatment allocation.
• A composite of all-cause death, myocardial infarction, or stroke at 18 months after the index procedure in the intention-to-treat population served as the primary endpoint.
• Secondary endpoints included the individual components of the primary endpoint; definite or probable stent thrombosis as defined by the Academic Research Consortium; and Bleeding Academic Research Consortium (BARC) type 2-5 bleeding at 18 months after the index procedure.
• An analysis was performed of the primary endpoint per protocol.

Results

• A total of 2,712 patients were randomly assigned between Sept 5, 2012 and Dec 31, 2015; 1,357 to the 6-month DAPT group and 1,355 to the 12-month or longer DAPT group.
• During this study, clopidogrel was used as a P2Y12 inhibitor for DAPT in 1,082 (79.7%) patients in the 6-month DAPT group and in 1,109 (81.8%) patients in the 12-month or longer DAPT group.
• The occurrence of primary endpoint was noted in 63 subjects in the 6-month DAPT group and in 56 individuals in the 12-month or longer DAPT group (cumulative event rate 4.7% vs 4.2%; absolute risk difference 0.5%; upper limit of one-sided 95% CI 1.8%; p_{non-inferiority}=0.03 with a predefined non-inferiority margin of 2.0%).
• No prominent variation was discovered in the all-cause mortality between the 6-month DAPT group and the 12-month or longer DAPT group (35 [2.6%] patients vs 39 [2.9%]; hazard ratio [HR] 0.90 [95% CI 0.57-1.42]; p=0.90) and neither did stroke (11 [0.8%] patients vs 12 [0.9%]; 0.92 [0.41-2.08]; p=0.84).
• Nevertheless, findings disclosed a more frequent occurrence of myocardial infarction in the 6-month DAPT group compared to the 12-month or longer DAPT group (24 [1.8%] patients vs 10 [0.8%]; 2.41 [1.15-5.05]; p=0.02).
• In the 6-month DAPT group, 15 (1.1%) patients had stent thrombosis compared with 10 (0.7%) in the 12-month or longer DAPT group (HR 1.50 [95% CI 0.68-3.35]; p=0.32).
• As per the outcomes, the rate of BARC type 2-5 bleeding was 2.7% (35 patients) in the 6-month DAPT group and 3.9% (51 patients) in the 12-month or longer DAPT group (HR 0.69 [95% CI 0.45-1.05]; p=0.09).
• Similar results yielded from the per-protocol analysis and from the intention-to-treat analysis.