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

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.

Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure 1.. Participant Flow in the TICO Randomized Clinical Trial

aStudy sites were not required to provide screening logs. Data regarding reasons for ineligibility are not available. bOutcomes of patients who were lost to follow-up or withdrew consent were included to the point of final contact. Their time-to-event measure was censored at the last contact date.

Figure 2.. Time-to-Event Curves for the Primary Outcome and Landmark Analysis at 3 Months

A net adverse clinical event was defined as a composite of major bleeding by the Thrombolysis in Myocardial Infarction criteria or major adverse cardiac and cerebrovascular event. Between 3 and 12 months, the hazard ratio (HR) was 0.41 (95% CI, 0.25-0.68; P = .001). Reported HRs are for the patients with ticagrelor monotherapy after 3-month dual antiplatelet therapy (DAPT). The median observation periods were 365 days (interquartile range, 365-365) for both study groups.

Figure 3.. Subgroup Analyses for the Primary Outcome

Numbers and percentages shown are number of patients with event/number of patients at risk and incidences at 1 year. NSTEMI indicates non–ST-elevation myocardial infarction; STEMI, ST-elevation myocardial infarction. aP values for interaction were calculated using interaction terms in a Cox proportional hazard model. bChronic kidney disease was defined as an estimated glomerular filtration rate of less than 60 mL/min/1.73 m2 of body surface area. cCalculated as weight in kilograms divided by height in meters squared.