Lower bleeding rates but no increase in risk of death, MI, or stroke topped results reported from the TWIGHLIGHT study which compared ticagrelor monotherapy at 3 months post-PCI vs ticarelor plus aspirin.
Discontinuing aspirin after 3 months of dual antiplatelet therapy (DAPT) with ticagrelor (Brilinta, Astra Zeneca) in high-risk patients who have undergone PCI with a drug eluting stent (DES) is associated with lower bleeding rates but not with increased risk of death, myocardial infarction (MI), or stroke, according to results of the double-blind, placebo-controlled TWILIGHT trial.
Results were announced today in San Francisco at Transcatheter Cardiovascular Therapeutics (TCT) 2019, the annual scientific conference of the Cardiovascular Research Foundation and simultaneously published in the New England Journal of Medicine.
Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, called the findings “groundbreaking” during her presentation in a late-breaking clinical trial session at TCT 2019. “Balancing ischemic and bleeding complications after a coronary intervention is a very important dilemma for us clinicians,” Mehran said during a TCT 2019 press conference. “The clinical imperative of lowering bleeding while preventing ischemic events requires a therapeutic strategy that decouples thrombotic from hemorrhagic risk."
The trial enrolled 9,006 patients who received open-label ticagrelor (90 mg twice daily) and aspirin (81-100 mg daily) for 3 months after a PCI between July 2015 and December 2017. The 7,119 patients that remained event-free of major bleeding or an ischemic event during the 3 months of treatment with DAPT were randomized to either double-blinded aspirin or placebo for an additional 12 months, with continuation of open-label ticagrelor.
Results of the phase 4 independent trial showed that in patients at high bleeding risk who underwent PCI with DES and completed 3 months of DAPT, ticagrelor monotherapy reduced the risk of BARC - Bleeding Academic Research Consortium - type 2, 3 or 5 bleeding vs ticagrelor plus low-dose aspirin after 12 months, according to an announcement from AstraZeneca. Ticagrelor monotherapy was associated with a 44% lower risk of BARC 2, 3 or 5 bleeding over 1 year, with an absolute risk reduction of 3.1%, compared to ticagrelor plus aspirin.
The incidence of the primary endpoint, time to first occurrence of BARC type 2, 3 or 5 bleeding between month 3 and 15, was 4.0% in patients treated with ticagrelor plus placebo vs 7.1% in patients treated with ticagrelor plus aspirin.
The incidence of BARC 3 or 5 bleeding was also lower with ticagrelor plus placebo vs ticagrelor plus aspirin. Rates of the composite of all-cause death, MI, or stroke, a key secondary endpoint, were similar between the two groups, 3.9% and 3.9%, respectively for ticagrelor plus placebo and ticagrelor plus aspirin.
TWIGHLIGHT is notable for being the largest study to date designed and powered specifically to demonstrate bleeding reductions with ticagrelor alone vs ticagrelor plus aspirin beyond 3 months post-procedure in a high-risk PCI population treated with DES. The study authors write in their conclusion: "The trial will provide novel insights with respect to the potential role of ticagrelor monotherapy as an alternative for long-term platelet inhibition in a broad population of patients undergoing PCI with DES."