Measuring B-type natriuretic peptide (BNP) and high-sensitivity troponin I (hsTnI) may help identify which patients with diabetes are at the highest risk for poor cardiovascular (CV) outcomes, new research presented at the American Heart Association’s Scientific Sessions 2014 suggests.

“Given the concern raised by some studies about a possible increase in heart failure with some DPP-4 inhibitors, understanding their safety in high-risk patients with cardiovascular disease is important,” lead study author David A. Morrow, MD, MPH, Associate Professor of Medicine at Harvard Medical School in Boston, told Endocrinology Advisor.

Dr. Morrow and his colleagues evaluated the predictive value of baseline biomarkers for CV outcomes in a high-risk population of patients with type 2 diabetes in a large CV safety trial that evaluated alogliptin, a DPP-4 inhibitor, for treatment of diabetes. 

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Known as EXAMINE (Cardiovascular Outcomes Study of Alogliptin in Patients With Type 2 Diabetes and Acute Coronary Syndrome), the trial was a randomized, double blind, placebo-controlled, multi-national trial of alogliptin in patients with type 2 diabetes. All of the patients were enrolled 15 to 90 days after an acute coronary syndrome (ACS).

The researchers measured BNP and hsTnI at baseline (Abbott ARCHITECT). The primary endpoint was major adverse CV events (MACE), which included CV death, myocardial infarction (MI) or stroke. A second, exploratory endpoint was a composite of CV death or heart failure.

For this investigation, 5,230 patients with baseline biomarkers were followed for a median of 18 months.

The researchers found a significant graded relationship between CV outcomes at 18 months and baseline BNP and hsTnI. The relationship remained strongly and independently related to CV outcomes through the patients’ final visit after adjusting for age, sex, type of qualifying ACS, estimated glomerular filtration rate (eGFR) and history of heart failure.

The study showed that the rates of MACE were similar among patients taking alogliptin and those taking placebo in the highest-risk patients identified by BNP or hsTnI. Similar results were observed for CV death and heart failure.

Mark A. Creager, MD, who is Director of the Vascular Center at Brigham and Women’s Hospital, Cardiovascular Division and Professor of Cardiovascular Medicine at Harvard Medical School, said this is an important study because it provides clinicians with additional insight. 

“This may lead to a better risk assessment and help us know which patients to target,” said Dr. Creager in an interview with Endocrinology Advisor. “This really confirms what we have seen in other settings, and this is particularly notable because all the patients have diabetes. It fine-tunes the data in this particular population. It adds new information and further indicates that there are further biomarkers that can help us.”


  1. Morrow DA et al. Abstract 17295. Presented at: American Heart Association’s Scientific Sessions 2014; Nov. 15-19, 2014; Chicago.