Abstract 17295: Cardiovascular Biomarkers and Long-term Outcomes in Patients with Type 2 Diabetes Mellitus Treated with Alogiptin vs. Placebo in the EXAMINE Trial

BACKGROUND: Thorough evaluation of the cardiovascular (CV) safety of new drugs for diabetes mellitus (DM) is now mandated by the US FDA. Alogliptin, a dipeptidyl-peptidase 4 inhibitor, is one of a new drug class for treatment of DM. CV biomarkers may provide useful insight with respect to CV safety of new treatments for DM. We evaluated the predictive value of baseline biomarkers for CV outcomes in a high risk population of DM patients (pts) in a large CV safety trial. METHODS: EXAMINE was a randomized, double-blind, placebo-controlled, multinational trial of alogliptin in pts with DM enrolled 15 to 90 days after an acute coronary syndrome (ACS). We measured B-type natriuretic peptide (BNP) and high sensitivity troponin I (hsTnI) at baseline (Abbott ARCHITECT). The primary endpoint was major adverse CV events (MACE) defined as CV death (CVD), myocardial infarction, or stroke. The composite of CV death or heart failure (HF) was also assessed as an exploratory endpoint. RESULTS: A total of 5230 pts with baseline biomarkers were followed for 18 mo (median). Baseline BNP and hsTnI showed a significant graded relationship with CV outcomes at 18 mo (Figure bars). BNP and hsTnI remained strongly and independently related to CV outcomes through the pts’ final visit after adjusting for age, sex, type of qualifying ACS, eGFR, & history of HF (Figure, adjusted HRs). The rates of MACE were similar with alogliptin vs. placebo in the highest risk pts identified by BNP (Group 4: 19.9 vs. 22.2%) or hsTnI (Group 4: 18.3 vs. 20.6%). Similar results were observed for CV death/HF based on BNP (17.5 vs. 19.4%) or hsTnI (14.3 vs. 14.9%). There was no evidence for heterogeneity in the effect of alogliptin on CV death/HF across BNP strata (p-interaction=0.71). CONCLUSIONS: Among pts with DM who were stable after a recent ACS, BNP & hsTnI identified pts at high risk of poor CV outcomes. In this study, the rates of MACE, including CV death or HF, were not increased with alogliptin vs. placebo even in these high risk pts. ![][1] [1]: /embed/graphic-1.gif