Study Summary

In the TWILIGHT study, ticagrelor monotherapy was compared with ticagrelor plus aspirin in patients who had undergone percutaneous coronary intervention (PCI) with drug-eluting stents and were at high risk of bleeding or ischemic events. “High-risk” patients were defined as those who had at least one clinical feature (i.e. age ≥65 years, female sex, etc.) and one angiographic feature (i.e. multivessel coronary artery disease, stent length >30 mm, etc.) associated with high risk of ischemic or bleeding events. The study was double-blinded, randomized, placebo-controlled, and took place at 187 sites across 11 countries. A total of 7,119 patients underwent randomization at 3 months post-PCI, after receiving aspirin plus ticagrelor without complication. The main exclusion criteria were presentation with ST-segment elevation myocardial infarction (MI), cardiogenic shock, long-term treatment with oral anticoagulants, or a contraindication to aspirin or ticagrelor. The primary endpoint was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding.

The primary endpoint occurred in 4.0% of patients receiving ticagrelor plus placebo and 7.1% of patient receiving ticagrelor plus aspirin (HR 0.56, 95% CI 0.45–0.68, P <0.001). The secondary endpoint (composite of death from any cause, nonfatal MI, and nonfatal stroke) occurred in 3.9% of patients in both groups (difference, -0.06 percentage points; HR 0.99, P <0.001 for noninferiority). The authors concluded that, among high-risk patients who underwent PCI and completed 3 months of dual antiplatelet therapy (DAPT), ticagrelor was associated with a lower incidence of clinically relevant bleeding than ticagrelor plus aspirin, with no higher risk of death, MI, or stroke.

Commentary

Study Strengths: The study was a randomized, placebo-controlled, double-blinded, international trial. The sample was large, including >9,000 high-risk patients most likely to benefit from reduced exposure to antiplatelet therapy. Approximately 37% of patients had diabetes mellitus, 16% had chronic kidney disease, 28% had a previous MI, 42% had previously undergone PCI, and 10% had previously undergone CABG.

Study Limitations: The trial lacked the power to detect differences in rare clinical events, such as stent thrombosis and stroke. The patients enrolled in this study were clinically and angiographically high-risk and, therefore, the results might not be generalizable to all patients who undergo PCI. The results of this study are also only applicable to patients who receive 3 months of DAPT. The incidence of the composite endpoint was lower than expected and could have biased the results towards the null.

Next Steps/Clinical Perspective: The TWILIGHT trial showed that ticagrelor monotherapy resulted in less bleeding without an increase in ischemic harm over a period of 1 year in patients who underwent PCI and received 3 months of DAPT. Future studies should evaluate the benefits of a shorter period of DAPT, and of prolonged monotherapy with ticagrelor beyond 1 year.

Trial Reference

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Mehran,  R. et al. Ticagrelor with or without aspirin in high-risk patients after PCI. N. Engl. J. Med. doi: 10.1056/NEJMoa1908419.
[PubMed: 31556978]