Abstract 19408: Multiple Biomarker Approach Predicts Increasing Risk of Recurrent CV Events in Patients With Diabetes Mellitus in the EXAMINE Randomized Trial
Introduction: Patients with diabetes and recent acute coronary syndrome (ACS) have a significant but heterogeneous risk of recurrent cardiovascular (CV) events.
Hypothesis: We hypothesized that a multimarker approach, utilizing biomarkers of stress, injury, or fibrosis, could stratify patients by risk for recurrent CV events, in particular CV death or heart failure (CVD/HF).
Methods: The EXAMINE trial randomized 5380 patients with diabetes and ACS within the prior 15-90 days to alogliptin or placebo. Biomarkers were measured at baseline and were classified as elevated as follows: hs-TnI (≥26 ng/L), BNP (≥80 pg/ml), ST2 (≥35 ng/ml), GDF-15 (>1800 pg/ml), and FGF-23, adiponectin and galectin-3 (4th quartile). Two year KM rates of CVD/HF were evaluated by total risk, defined by the arithmetic sum of the number of elevated biomarkers.
Results: 5162 patients (96%) had values for all biomarkers with a 2y rate of CV death or HF of 7%. Each biomarker was an independent predictor of CVD/HF beyond the clinical characteristics of age, sex, time from ACS, prior HF, renal function, ACS type and body mass index without any interaction by treatment. Discrimination improved with the addition of biomarkers from a c-statistic of 0.75 for the clinical model to 0.79 for the multivariable model including biomarkers. After defining total risk for each patient based on biomarkers, 24% had 0 elevated biomarkers, 26% had 1, 22% had 2 and the remainder had 3 or more elevated biomarkers. The total biomarker score showed a significant gradient of risk for CVD/HF at 2 years (p-trend<0.0001) ranging from 1.3% with no elevated biomarkers to 43.9% with ≥6, translating to a more than 50 fold increased risk (Figure).
Conclusions: In patients with diabetes and recent ACS, a multimarker approach to defining risk identified a strong gradient of risk for CV death or HF.
Author Disclosures: E.A. Bohula: Consultant/Advisory Board; Modest; Merck. 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.B. White: Consultant/Advisory Board; Modest; Takeda, Ardea Biosciences, Astra Zeneca, Dendreon Group, Forest Research Institute, Roche Inc, St Judes Medical, Teva Pharmaceuticals. P. Jarolim: Research Grant; Significant; Abbott Laboratories, Amgen, Inc., AstraZeneca, LP, Beckman Coulter, Daiichi-Sankyo, Inc., GlaxoSmithKline, Merck & Co., Inc., Roche Diagnostics Corporation, Takeda Global Research and Development Cent. B.A. Bergmark: None. S. Kupfer: Employment; Significant; Takeda. M.P. Bonaca: Research Grant; Significant; Amgen, AstraZeneca, Daiichi Sankyo Co Ltd, Eli Lilly and Co, GlaxoSmithKline, Merck and Co. Consultant/Advisory Board; Modest; Merck and Co., AstraZeneca, Bayer, and Roche diagnostics. Y. Liu: None. 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. D.A. Morrow: Research Grant; Significant; Abbott, Amgen, AstraZeneca, Daiichi Sankyo Co Ltd, Eli Lilly and Co, GlaxoSmithKline, Merck and Co, Novartis Pharmaceuticals,Roche Diagnostics,Takeda. Consultant/Advisory Board; Modest; Abbott Laboratories, DiaDexus, Eli Lilly, Gilead, Merck, Roche Diagnostics.
- © 2016 by American Heart Association, Inc.