Abstract 15319: 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.
Author Disclosures: F. Zannad: Consultant/Advisory Board; Modest; Servier, Resmed, Janssen, Novartis, Air Liquide, Cardiorenal diagnostics, CVCT, Biotronik, St. Jude, Boston Scientific. Consultant/Advisory Board; Significant; Takeda, Pfizer. C.P. Cannon: Research Grant; Significant; Takeda, Accumetrics, Arisaph, Astra Zeneca, Boehringer-Ingelheim, GlaxoSmithKline, Janssen, Merck, Regeneron, Sanofi. Consultant/Advisory Board; Modest; CSL Behring, Essentials, Takeda. W.C. Cushman: Research Grant; Significant; Merck, Lilly, National Heart, Lung and Blood Institute. G.L. Bakris: Research Grant; Significant; Takeda, Medtronic, Relypsa. Consultant/Advisory Board; Modest; Abbvie, CVRx, Janssen, Eli Lilly, Medtronic, Novartis, GSK, Bayer. S.E. Nissen: Research Grant; Significant; Takeda. D.A. Morrow: Research Grant; Significant; Abbott, Amgen, AstraZeneca, Beckman Coulter, BG Medicine, BRAHMS, Bristol Meyers Squibb, Critical Diagnostics, CV Therapeutics, Daiichi Sankyo Co Ltd, Eli Lilly and Co, GlaxoSmithKline, Johnson & Johnson, Merck and Co, Novartis Pharmaceuticals, Roche Diagnostics, Sanofi-Aventis, Singulex, Takeda. Consultant/Advisory Board; Modest; Abbott Laboratories, DiaDexus, Eli Lilly, Gilead, Instrumentation Laboratory, Konica Minolta, Johnson & Johnson, Merck, Roche Diagnostics, Servier. S.K. Heller: Research Grant; Significant; Takeda, NovoNordisk, Eli Lilly, Sanofi Aventis. Consultant/Advisory Board; Modest; Takeda, NovoNordisk, Eli Lilly. R.M. Bergenstal: Consultant/Advisory Board; Modest; Abbott Diabetes Care, Amylin, AstraZeneca, Bayer, Takeda, Becton Dickinson, Calibra, Eli Lilly, Halozyme, Johnson and Johnson, Medronic, NovoNordisk, Resmed, Roche, Sanofi. A.T. Perez: Employment; Significant; Takeda. P.R. Fleck: Employment; Significant; Takeda. C.R. Mehta: None. S. Kupfer: Employment; Significant; Takeda. H. Lam: Employment; Significant; Takeda. C. Wilson: Employment; Significant; Takeda. W.B. White: Consultant/Advisory Board; Modest; Takeda, Ardea Biosciences, Astra Zeneca, Dendreon Group, Forest Research Institute, Roche Inc, St Judes Medical, Teva Pharnaceuticals.
- © 2014 by American Heart Association, Inc.