Researchers writing in the New England Journal of Medicine report that a combination treatment of ticagrelor and aspirin leads to improved cardiovascular disease outcomes in patients with stable coronary artery disease and diabetes mellitus.
Diabetes patients are at high risk for developing platelet-mediated thrombosis. The standard therapy is aspirin, but it doesn’t always provide a sufficient protective effect. Ticagrelor (a reversible antagonist of the platelet P2Y12 receptor) together with aspirin has been shown to have protective cardiovascular effects in patients with acute coronary syndromes and in high-risk patients with previous myocardial infarction despite the presence or absence of diabetes.
Because patients with stable coronary artery disease and diabetes mellitus have higher rates of negative cardiovascular events, researchers led by P. Gabriel Steg, M.D., Harvard Medical School, conducted a randomized, double-blind trial of ticagrelor plus aspirin as compared to placebo plus aspirin.
The trial included 19,220 patients (median age 66 years, 31.4 percent were women) with stable coronary artery disease and type 2 diabetes mellitus, but no history of myocardial infarction or stroke.
After a median follow-up of 39.9 months, patients in the treatment group had a lower incidence of ischemic cardiovascular events but a higher incidence of major bleeding than those in the placebo plus aspirin group.
Cardiovascular death, myocardial infarction or stroke―which was the primary efficacy outcome―was lower in the treatment group as compared to the placebo group (7.7% vs. 8.5%; HR, 0.90; 95% CI, 0.81 to 0.99; P=0.04). But the incident of major bleeding―which was the primary safety outcome―was 2.2 percent higher in the treatment group compared to 1 percent in the placebo aspirin treatment group (HR, 2.32; 95% CI, 1.82 to 2.94; P<0.001). Also, more common in the treatment group was the incidence of intracranial hemorrhage (0.7% vs. 0.5%; HR, 1.71; 95% CI, 1.18 to 2.48; P=0.005).
There were no significant differences in the rates of fatal bleeding. The incidence of an exploratory composite outcome of death from any cause, myocardial infarction, stroke, fatal bleeding, or intracranial hemorrhage, was similar in the ticagrelor group and the placebo group (10.1% vs. 10.8%; HR, 0.93; 95% CI, 0.86 to 1.02).
P. Gabriel Steg, M.D., Deepak L. Bhatt, M.D., M.P.H., et al. "Ticagrelor in Patients with Stable Coronary Disease and Diabetes," NEJM, Oct. 3, 2019. DOI: 10.1056/NEJMoa1908077