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Original Investigation
June 16, 2020

Effect of Ticagrelor Monotherapy vs Ticagrelor With Aspirin on Major Bleeding and Cardiovascular Events in Patients With Acute Coronary Syndrome: The TICO Randomized Clinical Trial

Author Affiliations
  • 1Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea
  • 2Myongji Hospital, Hanyang University College of Medicine, Goyang, South Korea
  • 3Wonkwang University Hospital, Iksan, South Korea
  • 4Kangwon National University School of Medicine, Chuncheon, South Korea
  • 5Dankook University Hospital, Dankook University College of Medicine, Cheonan, South Korea
  • 6National Health Insurance Service Ilsan Hospital, Goyang-City, South Korea
  • 7Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, South Korea
  • 8Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, South Korea
  • 9Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
  • 10Department of Preventive Medicine and Biostatistics, Yonsei University College of Medicine, Seoul, South Korea
JAMA. 2020;323(23):2407-2416. doi:10.1001/jama.2020.7580
Visual Abstract. Effect of Ticagrelor Monotherapy vs Ticagrelor with Aspirin on Major Bleeding and Cardiovascular Events in Patients With Acute Coronary Syndrome: the TICO Randomized Clinical Trial.
Effect of Ticagrelor Monotherapy vs Ticagrelor with Aspirin on Major Bleeding and Cardiovascular Events in Patients With Acute Coronary Syndrome: the TICO Randomized Clinical Trial.
Key Points

Question  Does switching to ticagrelor monotherapy after 3 months of dual antiplatelet therapy reduce net adverse clinical events (a composite of major bleeding and major adverse cardiac and cerebrovascular events) among patients with acute coronary syndrome treated with drug-eluting stents?

Findings  In this randomized clinical trial that included 3056 patients with acute coronary syndrome, ticagrelor monotherapy after 3 months of dual antiplatelet therapy, compared with ticagrelor-based 12-month dual antiplatelet therapy, significantly reduced net adverse clinical events at 1 year (3.9% vs 5.9%).

Meaning  Among patients with acute coronary syndrome treated with new-generation drug-eluting stents, use of ticagrelor monotherapy after 3 months of dual antiplatelet therapy resulted in a modest but statistically significant reduction in a composite outcome of major bleeding and adverse cardiac and cerebrovascular events at 1 year.

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.

Trial Registration  ClinicalTrials.gov Identifier: NCT02494895

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