A new subanalysis from the TWILIGHT trial found benefits of ticagrelor monotherapy remained consistent across both diabetics and nondiabetics.
Dominick Angiolillo, MD, PhD
A new analysis from the TWILIGHT trial found ticagrelor monotherapy in high-risk diabetics reduced bleeding without increasing risk of ischemic events when compared against use of ticagrelor with aspirin following percutaneous coronary intervention (PCI).
Presented at the American College of Cardiology’s Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC), results of the prespecified sub analysis indicated there was little difference in the efficacy and safety profile of ticagrelor seen in the overall TWILIGHT trial.
“Our primary goal was to ensure that dropping aspirin would reduce bleeding without increasing deaths, heart attacks or strokes,” said lead author Dominick Angiolillo, MD, PhD, professor of medicine at the University of Florida College of Medicine, in a statement. “That goal was met.”
The prespecified cohort analysis included 2620 individuals with diabetes mellitus from the original TWILIGHT trials. Of the 2620 patients with diabetes mellitus, 1319 were randomized to ticagrelor plus placebo and 1301 to ticagrelor plus aspirin.
Briefly, all TWILIGHT participants underwent 1:1 randomization to either ticagrelor plus placebo or ticagrelor plus aspirin and were followed for 1 year—all patients received therapy with aspirin before randomization for the first 3 months following PCI. Similarly to the TWILIGHT trial, the primary endpoint of the sub analysis was BARC 2, 3, or 5 bleeding and investigators also assessed for a composite ischemic endpoint of all-cause death, myocardial infarction (MI), or stroke.
Of those with diabetes, most (72.9%) had non-insulin treated diabetes mellitus. The mean age of the diabetes mellitus cohort was 64.8 years, 23.6% were female, and 61.6% presented with acute coronary syndrome (ACS). Of note, patients with diabetes mellitus were more likely to be from North America, of a non-white race, and have more risk factors than patients without diabetes mellitus.
Upon analysis, BARC 2, 3, or 5 bleeding occurred in 58 (4.5%) patients receiving ticagrelor plus placebo compared to 86 (6.7%) patients receiving ticagrelor plus aspirin (HR, 0.65; 95% CI, 0.47-0.91; P=.01). Results indicated 1-year BARC 3 or 5 bleeding rates were 1.1% and 3.1%, respectively, and the observed treatment effect was consistent across other bleeding scales, including TIMI, GUSTO, and ISTH.
The composite outcome of ischemic events occurred in 59 (4.6%) patients receiving ticagrelor plus placebo compared 75 (5.9%) patients receiving ticagrelor plus aspirin (HR 0.77; 95% CI, 0.55 to 1.09; P=.14). Investigators noted respective rates of 1.3% and 2.0% for all-cause death, 3.1% and 4.1% for MI, 0.6% and 0.4% for ischemic stroke, and 0.5% and 0.7% for stent thrombosis were similar between treatment groups (P >.1).
Additional analyses were performed by study investigators. Results of these analyses indicated the effect of monotherapy on primary and secondary outcomes was consistent among patients presenting with either an ACS or stable CAD and outcomes were also consistent irrespective of insulin use. An analysis assessing net adverse clinical events, which was a composite of BARC 3 or 5 bleeding, death, MI or stroke, significantly favored the use of ticagrelor monotherapy over ticagrelor plus aspirin (5.4% vs 8.7%; HR 0.61; 95% CI, 0.45 to 0.82; P=.001; P for interaction=.004).
“In patients with diabetes, treatment with ticagrelor alone significantly reduced clinically relevant bleeding compared with ticagrelor plus aspirin, without increasing the risk for additional heart attacks, strokes or death,” Angiolillo said in the aforementioned statement.
This study, “Ticagrelor with or without Aspirin in High-Risk Patients with Diabetes Mellitus undergoing Percutaneous Coronary Intervention,” was presented at ACC.20/WCC.