Clinical and Biomarker Predictors of Expanded Heart Failure Outcomes in Patients With Type 2 Diabetes Mellitus After a Recent Acute Coronary Syndrome: Insights From the EXAMINE Trial

BACKGROUND: Improved heart failure (HF) risk stratification after a recent acute coronary syndrome may identify those who can benefit from therapies that reduce HF risk. We aimed to identify clinical and biomarker predictors for expanded HF outcomes in patients with type 2 diabetes mellitus after recent acute coronary syndrome. METHODS AND RESULTS: The EXAMINE (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) trial was a multicenter, non‐inferiority, double‐masked, placebo‐controlled study which randomized 5380 patients with type 2 diabetes mellitus after recent acute coronary syndrome to alogliptin or placebo. Baseline biomarkers were measured in 5154 patients: NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), high‐sensitivity troponin I, adiponectin, growth‐differentiation‐factor‐15, and galectin‐3. Our primary outcome was cardiovascular) death, HF hospitalization, elevated NT‐proBNP during follow‐up, or loop diuretics initiation. The association between clinical variables, biomarkers, and outcomes were assessed using Cox regression models. In the study population, the median age was 61.0 years, 67.7% were men, and 28.0% had baseline HF (median follow‐up was 18 months). In multivariable analyses, NT‐proBNP had the strongest association with the primary outcome (per log(2), hazard ratio 1.24; Wald χ(2) 67.4; P<0.0001) followed by a prior HF history (hazard ratio 1.42; Wald χ(2) 20.8; P<0.0001). A model with clinical variables and biomarkers allowed for risk prediction for expanded HF outcomes (C‐statistic=0.72). Discrimination results were similar for cardiovascular death or HF hospitalization. CONCLUSIONS: Among patients with type 2 diabetes mellitus after recent acute coronary syndrome, the use biomarkers such as N‐terminal pro‐B‐type natriuretic peptide and clinical variables enables risk stratification for expanded HF outcomes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00968708.