N-Terminal-pro-Brain Natriuretic Peptide Decreases Following Treatment with Alogliptin in Patients with Type 2 Diabetes and Recent Acute Coronary Syndromes: Results from EXAMINE

Introduction: In patients with type 2 diabetes (T2D) and recent acute coronary syndrome (ACS), EXAMINE showed that cardiovascular (CV) event rates, mortality and hospitalized heart failure (HHF) with the DPP-4 inhibitor alogliptin were not increased compared with placebo, including in patients with history of HF and elevated levels of brain natriuretic peptide (BNP). Hypothesis: In an on-treatment biomarker study, we investigated the effects of alogliptin on NT-pro-BNP. Methods: Patients with T2D who had an ACS within the previous 15-90 days were randomly assigned to alogliptin or placebo added to existing anti-hyperglycemic and cardiovascular therapies. Patients with compensated HF were included (28% at baseline). Among 5380 randomized patients, NT-pro-BNP was measured in a random sample of 1010 patients stratified for HF at baseline and 6 months post-randomization. Changes from baseline were assessed with an ANCOVA model controlling for treatment, geographic region, kidney function, and baseline NT-pro-BNP. Results: Patients’ characteristics of the random subgroup of 1010 patients were similar to the entire population. Levels of NT-pro-BNP were highest in patients with a history of HF at baseline. Alogliptin significantly reduced NT-pro-BNP at 6 months compared with placebo (Figure). Furthermore, alogliptin significantly reduced NT-pro-BNP compared with placebo in the highest baseline NT-pro-BNP quartile (LSMean change from baseline -1229 vs. -626 pg/ml, p=0.022). Subgroup analyses according to baseline NT-pro-BNP levels did not yield any significant interaction with the primary and secondary CV outcomes as well with the post hoc composite outcomes of CV death and HF hospitalization. Conclusions: Alogliptin reduces NT-pro-BNP in a post-ACS T2D population, consistent with the observation that alogliptin does not induce new onset HF or exacerbate HF outcomes even in patients with a prior history of HF and/or with high baseline NT-pro-BNP.