Cardiovascular Mortality in Patients With Type 2 Diabetes and Recent Acute Coronary Syndromes From the EXAMINE Trial.

Abstract

We evaluated the risk of cardiovascular (CV) death in all Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) study participants and in those who experienced an on-study, major nonfatal CV event. The study randomly assigned 5,380 patients with type 2 diabetes to alogliptin or placebo within 15 to 90 days of an acute coronary syndrome (ACS). Deaths and nonfatal CV events (myocardial infarction [MI], stroke, hospitalized heart failure [HHF], and hospitalization for unstable angina [UA]) were adjudicated. Patients were monitored until censoring or death, regardless of a prior postrandomized nonfatal CV event. Time-updated multivariable Cox models were used to estimate the risk of death in the absence of or after each nonfatal event. Rates of CV death were 4.1% for alogliptin and 4.9% for placebo (hazard ratio [HR] 0.85; 95% CI 0.66, 1.10). A total of 736 patients (13.7%) experienced a first nonfatal CV event (5.9% MI, 1.1% stroke, 3.0% HHF, and 3.8% UA). Compared with patients not experiencing a nonfatal event, the adjusted HR (95% CI) for death was 3.12 after MI (2.13, 4.58; P < 0.0001) 4.96 after HHF (3.29, 7.47; P < 0.0001), 3.08 after stroke (1.29, 7.37; P = 0.011), and 1.66 after UA (0.81, 3.37; P = 0.164). Mortality rates after a nonfatal event were comparable for alogliptin and placebo. In patients with type 2 diabetes and a recent ACS, the risk of CV death was higher after a postrandomization, nonfatal CV event, particularly heart failure, compared with those who did not experience a CV event. The risk of CV death was similar between alogliptin and placebo.