Ticagrelor monotherapy versus ticagrelor plus aspirin in patients with chronic coronary syndrome and high ischaemic risk: a post hoc analysis of the TWILIGHT trial.

Background: Short dual antiplatelet therapy (DAPT) followed by ticagrelor monotherapy may be a valuable therapeutic option for patients with chronic coronary syndrome (CCS) and high ischaemic risk (HIR) undergoing percutaneous coronary intervention (PCI).

Objective: We aimed to compare ticagrelor monotherapy with ticagrelor-based DAPT in CCS patients with and without HIR undergoing PCI.

Methods: The present analysis included the CCS cohort of the TWILIGHT trial, which randomised PCI patients to ticagrelor alone or in combination with aspirin for 12 months after 3 months of ticagrelor-based DAPT. Patients were stratified into HIR and non-HIR based on the 2019 European Society of Cardiology (ESC) CCS guidelines definition. Outcomes of interest were major adverse cardiac and cerebrovascular events (MACCE), a composite of death, myocardial infarction or stroke, and Bleeding Academic Research Consortium (BARC) Type 2-5 bleeding at 1 year.

Results: Of the 2,503 CCS patients who underwent randomisation, the ESC definition classified 1,264 (50.5%) as HIR and 1,239 (49.5%) as non-HIR. HIR patients displayed a higher risk of MACCE (3.9% vs 2.3%; p=0.015) and similar rates of BARC Type 2-5 bleeding (5.1% vs 5.7%; p=0.455) as compared to non-HIR patients. Ticagrelor monotherapy and ticagrelor-based DAPT were associated with similar risks of MACCE (HIR: 4.0% vs 3.8%, hazard ratio [HR] 1.06, 95% confidence interval [CI]: 0.60-1.85; non-HIR: 2.1% vs 2.6%, HR 0.80, 95% CI: 0.38-1.66, pinteraction=0.553) and bleeding (HIR: 4.7% vs 5.7%, HR 0.82, 95% CI: 0.50-1.33; non-HIR: 4.9% vs 6.7%, HR 0.71, 95% CI: 0.44-1.14; pinteraction=0.684) in both the HIR and non-HIR groups.

Conclusions: In a post hoc analysis of the TWILIGHT trial that included CCS patients undergoing PCI, ticagrelor monotherapy after 3 months of DAPT appeared to be safe and was not associated with increased risks of ischaemic or bleeding events, regardless of baseline HIR status, compared with standard ticagrelor-based DAPT. These findings suggest the potential to expand guideline recommendations for ticagrelor monotherapy in CCS.