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

Abstract

Objective: 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.

Research design and methods: 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.

Results: 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.

Conclusions: 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.

Trial registration: ClinicalTrials.gov NCT00968708.