Effect of Ticagrelor Monotherapy vs Ticagrelor With Aspirin on Major Bleeding and Cardiovascular Events in Patients With Acute Coronary Syndrome
Authors: Byeong-Keuk Kim, Sung-Jin Hong, Yun-Hyeong Cho, Kyeong Ho Yun, Yong Hoon Kim, Yongsung Suh, Jae Young Cho, Ae-Young Her, Sungsoo Cho, Dong Woon Jeon, Sang-Yong Yoo, Deok-Kyu Cho, Bum-Kee Hong, Hyuckmoon Kwon, Chul-Min Ahn, Dong-Ho Shin, Chung-Mo Nam, Jung-Sun Kim, Young-Guk Ko, Donghoon Choi, Myeong-Ki Hong, Yangsoo Jang
Journal: JAMA (2020)

<h3>Importance</h3> Discontinuing aspirin after short-term dual antiplatelet therapy (DAPT) was evaluated as a bleeding reduction strategy. However, the strategy of ticagrelor monotherapy has not been exclusively evaluated in patients with acute coronary syndromes (ACS). <h3>Objective</h3> To determine whether switching to ticagrelor monotherapy after 3 months of DAPT reduces net adverse clinical events compared with ticagrelor-based 12-month DAPT in patients with ACS treated with drug-eluting stents. <h3>Design, Setting, and Participants</h3> A randomized multicenter trial was conducted in 3056 patients with ACS treated with drug-eluting stents between August 2015 and October 2018 at 38 centers in South Korea. Follow-up was completed in October 2019. <h3>Interventions</h3> Patients were randomized to receive ticagrelor monotherapy (90 mg twice daily) after 3-month DAPT (n = 1527) or ticagrelor-based 12-month DAPT (n = 1529). <h3>Main Outcomes and Measures</h3> The primary outcome was a 1-year net adverse clinical event, defined as a composite of major bleeding and adverse cardiac and cerebrovascular events (death, myocardial infarction, stent thrombosis, stroke, or target-vessel revascularization). Prespecified secondary outcomes included major bleeding and major adverse cardiac and cerebrovascular events. <h3>Results</h3> Among 3056 patients who were randomized (mean age, 61 years; 628 women [20%]; 36% ST-elevation myocardial infarction), 2978 patients (97.4%) completed the trial. The primary outcome occurred in 59 patients (3.9%) receiving ticagrelor monotherapy after 3-month DAPT and in 89 patients (5.9%) receiving ticagrelor-based 12-month DAPT (absolute difference, −1.98% [95% CI, −3.50% to −0.45%]; hazard ratio [HR], 0.66 [95% CI, 0.48 to 0.92];<i>P</i> = .01). Of 10 prespecified secondary outcomes, 8 showed no significant difference. Major bleeding occurred in 1.7% of patients with ticagrelor monotherapy after 3-month DAPT and in 3.0% of patients with ticagrelor-based 12-month DAPT (HR, 0.56 [95% CI, 0.34 to 0.91];<i>P</i> = .02). The incidence of major adverse cardiac and cerebrovascular events was not significantly different between the ticagrelor monotherapy after 3-month DAPT group (2.3%) vs the ticagrelor-based 12-month DAPT group (3.4%) (HR, 0.69 [95% CI, 0.45 to 1.06];<i>P</i> = .09). <h3>Conclusions and Relevance</h3> Among patients with acute coronary syndromes treated with drug-eluting stents, ticagrelor monotherapy after 3 months of dual antiplatelet therapy, compared with ticagrelor-based 12-month dual antiplatelet therapy, resulted in a modest but statistically significant reduction in a composite outcome of major bleeding and cardiovascular events at 1 year. The study population and lower than expected event rates should be considered in interpreting the trial. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT02494895