Results from the late-breaking TWILIGHT trial suggest that, among high-risk patients who have undergone percutaneous coronary intervention (PCI) and completed three months of dual antiplatelet therapy (DAPT), it’s safer to continue treatment with ticagrelor alone rather than add aspirin to that cocktail.
TWILIGHT, a double-blind trial that pitted ticagrelor alone against ticagrelor plus aspirin in a population of high-bleeding-risk patients for one year, was presented at TCT 2019 in San Francisco in September and published simultaneously in the New England Journal of Medicine. It was clear before the study launched that DAPT plus aspirin and a P2Y12 inhibitor like ticagrelor yielded more favorable outcomes in post-PCI patients compared to aspirin alone, but even with DAPT, the adverse event rate among patients who suffer from diabetes or other CV comorbidities “remains unacceptably high.”
“The use of more potent P2Y12 inhibitors or extension of the duration of DAPT lowers residual ischemic risk among such patients but increases bleeding,” co-first author R. Mehran, of the Icahn School of Medicine at Mount Sinai, and colleagues wrote in NEJM. “Although previously considered relatively benign, post-PCI bleeding has been shown to be associated with a substantial and durable risk of death, approximating or even exceeding that associated with myocardial infarction.”
Mehran et al. enrolled 9,006 patients in their study who’d undergone both PCI and DAPT. After three months of treatment with ticagrelor plus aspirin, patients who hadn’t experienced a major bleeding or ischemic event continued to take ticagrelor and were randomized to receive either aspirin or a placebo for an additional year.
After three months, 7,119 people—nearly 80% of the study population—were randomly assigned to continue ticagrelor with aspirin or a placebo. Between randomization and one year, the incidence of the team’s primary endpoint of Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding was 4% in patients assigned to ticagrelor plus placebo and 7.1% among patients assigned to ticagrelor plus aspirin.
The difference in risk between the two groups was similar for BARC 3 or 5 bleeding—1% in the ticagrelor plus placebo cohort and 2% in the ticagrelor plus aspirin cohort—and the incidence of death from any cause, nonfatal MI or nonfatal stroke was 3.9% in both groups.
“The treatment effect with respect to both bleeding and ischemic endpoints was consistent across subgroups,” Mehran and colleagues said. “In aggregate, these results show that a transition to an antiplatelet strategy of treatment with ticagrelor alone after a three-month course of DAPT in high-risk patients who had undergone PCI provided a clinical benefit of less bleeding without ischemic harm.”