Results of the TWILIGHT-ACS study revealed use of ticagrelor plus aspirin following coronary intervention in patients with acute coronary syndrome increased the risk of major bleeding.
Usman Baber, MD
New data has found dual platelet therapy with aspirin after coronary intervention for acute coronary syndrome was linked to an increased risk of bleeding and ischemic events compared to monotherapy.
Presented at the American Heart Association (AHA) 2019 Scientific Sessions in Philadelphia, the Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention for Acute Coronary Syndrome (TWILIGHT-ACS) study revealed treatment with ticagrelor monotherapy led to a 54% reduction in risk of major bleeding without increasing risk for ischemic event over a year compared to placebo.
TWILIGHT-ACS was designed with the intention of analyzing the effects of dual antiplatelet therapy in light of recent data suggesting maintenance of aspirin could increase the risk of bleeding and death in recent studies. The multicenter, international, double-blind, placebo-controlled trial assessed more than 9000 patients from 11 countries, of which 4614 were included in TWILIGHT-ACS.
For inclusion in the trial, patients needed to meet at least one clinical and one angiographic criterion established by investigators. Clinical criteria included being 65 or older, a female, troponin positive acute coronary syndrome, established vascular disease, diabetes mellitus treated with medications or insulin, and chronic kidney disease. Angiographic criteria included multivessel coronary artery disease, target lesion requiring a total stent length greater than 30 mm, thrombotic target lesion, bifurcation lesion with Medina X, 1, 1 classification requiring 2 or more stents, left main or proximal LAD lesion, and calcified target lesions requiring atherectomy.
Investigators noted exclusion criteria included STEMI, salvage percutaneous coronary intervention, need for chronic oral anticoagulation, and planned coronary revascularization.
The primary outcome measure of the study was BARC 2, 3, or 5 bleeding between 0 and 12 months after randomization. The secondary outcome measures of the study included non-fatal myocardial infarction, stroke, or all-cause death between 0 and 12 months after randomization.
In all, 2273 patients were randomized to receive ticagrelor plus placebo while the remaining 2341 received ticagrelor plus aspirin. At 15 months, 2236 (98.4%) patients remained in the ticagrelor plus placebo group and 2305 (98.5%) remained in the ticagrelor plus aspirin arm.
In the ticagrelor plus placebo group, the mean age was 64.2 years, 35.6% of patients had diabetes mellitus, 23.3% were classified as smokers, and 25.4% had a history of myocardial infarction. In the ticagrelor plus aspirin group, the mean age was 64.2 years, 34.3% had diabetes mellitus, 26.6% were smokers, and 25.2% had a history of myocardial infarction.
Upon analyses, investigators found the cumulative incidence of BARC 2, 3, or 5 bleeding was 7.6% in the ticagrelor plus aspirin group compared to 3.6% in the ticagrelor plus placebo arm at 360 days after randomization (HR 0.47, 95% CI: 0.47, 0.36-0.61; P<0.001). When examining more severe bleeding, investigsators noted ticagrelor alone decreased risk fo BARC 3 or 5 bleeding by 64% compared to ticagrelor plus aspirin (0.8% versus 2.1%, P<0.001).
Investigators also analyzed potential associations between the number of risk factors with the risk of BARC 2, 3, or 5 bleeding. In 3 different subgroups—1 to 3 risk factors, 4 or 5 risk factors, and 6 to 9 risk factors—ticagrelor plus aspirin was associated with a one-year rate nearly double that of the ticagrelor plus placebo group.
When examining rates of death, myocardial infarction, or stroke, investigators found similar rates at 360 days post-randomization. In those receiving ticagrelor and aspirin, 4.4% of patients experienced death, myocardial infarction, or stroke compared to 4.3% in the ticagrelor plus placebo group (HR 0.97, 95% CI: 0.74-1.28). In fact, data pointed to ticagrelor plus placebo leading to worse rates at one year in patients with 4 or 5 risk factors(4.4% versus 3.5%, respectively), but this was the only group where this effect was present.
This study, “Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention for Acute Coronary Syndrome,” was presented by Usman Baber, MD, at AHA 2019.