Effect of Ticagrelor Monotherapy vs Ticagrelor With Aspirin on Major Bleeding and Cardiovascular Events in Patients With Acute Coronary Syndrome

Abstract

IMPORTANCE 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). OBJECTIVE 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. DESIGN, SETTING, AND PARTICIPANTS 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. INTERVENTIONS 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). MAIN OUTCOMES AND MEASURES 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. RESULTS 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]; P = .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]; P = .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]; P = .09). CONCLUSIONS AND RELEVANCE 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.

2020 Korean Society of Myocardial Infarction Expert Consensus Document on Pharmacotherapy for Acute Myocardial Infarction

“…The difference between the groups was mainly driven by a reduced risk of major bleeding in the ticagrelor monotherapy group (0.2% vs. 1.6%, HR, 0.13; 95% CI, 0.04–0.44; p=0.001). 62) The Comparison Between P2Y 12 Antagonist Monotherapy and Dual Antiplatelet Therapy After DES (SMART-CHOICE) trial compared clinical benefits of aspirin plus a P2Y 12 receptor inhibitor for 3 months and thereafter P2Y 12 receptor inhibitor alone or DAPT for 12 months in Korean patients treated with drug-eluting stent (DES) (n=2,993, 58.2% of patients with ACS). 63) There were no significant differences in all-cause death (1.4% vs. 1.2%, HR, 1.18; 95% CI, 0.63–2.21; p=0.61), MI (0.8% vs. 1.2%, HR, 0.66; 95% CI, 0.31–1.40, p=0.28), or stroke (0.8% vs. 0.3%, HR, 2.23; 95% CI, 0.78–6.43, p=0.14) between the two groups.…”

Discontinuing Aspirin After Short Term Use Versus Continuous Use with a P2Y12 Inhibitor for the Treatment of Patients with Type 2 Diabetes Mellitus Following Percutaneous Coronary Intervention: A Meta-analysis

“…Among the full-text articles, 3 non-randomized trials, 2 case studies, 1 meta-analysis, 1 post hoc analysis and 24 repeated studies were eliminated. Finally, only five trials [9][10][11][12][13] were included in this analysis, as shown in Fig. 1.…”

Dual Antiplatelet Therapy in Coronary Artery Disease

“…The incidence of major adverse cardiac and cerebrovascular events was not significantly different between the two groups (2.3 vs. 3.4%, HR 0.69, p = 0.09). The study concluded that ticagrelor monotherapy after 3 months of DAPT offered modest but significant reduction in composite of major bleeding and cardiovascular events at 1 year compared to 12 months of DAPT [ 22 ].…”