September 27, 2019
TWILIGHT Study Supports Ticagrelor Monotherapy at 3 Months After PCI and DAPT
September 26, 2019—The Cardiovascular Research Foundation (CRF) announced that results from the TWILIGHT study were presented by investigator Roxana Mehran, MD, at TCT 2019, the 31st annual Transcatheter Cardiovascular Therapeutics scientific symposium, which is sponsored by CRF and held September 25–29 in San Francisco, California. The study was published simultaneously by Dr. Mehran et al in The New England Journal of Medicine.
According to CRF, the randomized, placebo-controlled TWILIGHT trial found that ticagrelor monotherapy—compared to ticagrelor plus aspirin—reduces bleeding events without increasing the risk of death, myocardial infarction, or stroke in high-risk patients who have undergone successful percutaneous coronary intervention (PCI) and completed 3 months of dual antiplatelet therapy (DAPT).
As summarized by CRF, the TWILIGHT study enrolled 9,006 patients between July 2015 and December 2017. The patients were those whom the treating clinician intended to discharge on ticagrelor plus aspirin upon completion of successful PCI with at least one locally approved drug-eluting stent. Trial inclusion also required the presence of at least one clinical and one angiographic feature associated with a high risk of ischemic or bleeding events.
After completing 3 months of DAPT, event-free patients were randomized to aspirin or placebo with continuation of ticagrelor for an additional 12 months. A total of 7,119 patients were randomized at 187 sites in 11 countries (23.8% female, 36.8% diabetes mellitus, 64.8% acute coronary syndrome). The primary endpoint was Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding. The secondary endpoint was the composite of all-cause death, myocardial infarction, or stroke.
Dr. Meharn reported that the TWILIGHT study demonstrated the following at 1 year:
- The incidence of major bleeding was 4.0% for patients randomized to ticagrelor plus placebo and 7.1% among patients who received ticagrelor plus aspirin (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.45 to 0.68; P < .001).
- The relative risk reduction was similar for BARC 3 or 5 bleeding (1.0% vs 2.0%; HR, 0.49; 95% CI, 0.33 to 0.74).
- Rates of all-cause death, myocardial infarction, or stroke were 3.9% for both groups (HR, 0.99; 95% CI, 0.78 to 1.25; Pnoninferiority < .001).
- The respective rates of all-cause death (1.0% vs 1.3%), myocardial infarction (2.7% vs 2.7%), and definite or probable stent thrombosis (0.4% vs 0.6%) were similar between groups.
- There were 16 ischemic strokes in the ticagrelor monotherapy group and eight ischemic strokes in the dual antiplatelet therapy group (0.5% vs. 0.2%).
- The effect of ticagrelor monotherapy on the key secondary outcome was consistent across predefined subgroups.
In the CRF announcement, Dr. Mehran commented, “Lowering bleeding risk while preserving ischemic benefit is critically important, especially in high risk patients. This study shows that among high-risk PCI patients who were treated with ticagrelor and aspirin for 3 months, an antiplatelet strategy of continuing ticagrelor alone, compared with ticagrelor plus aspirin, results in substantially less bleeding without incurring ischemic harm over 1 year. These results suggest that ticagrelor monotherapy may be a suitable antiplatelet strategy to lower bleeding while preserving ischemic benefit in this group of patients.”
Dr. Mehran concluded, “This landmark study unequivocally shows that withdrawal of aspirin in patients already on ticagrelor and acetylsalicylic acid for 3 months reduces bleeding significantly without incurring harm. This global collaboration with our colleagues was central to achieving the successful completion of this trial. For this I am most grateful. These are important questions for clinicians.”