ESC Report 2013 – Alogliptin treatment shows no increase cardiovascular risk in Acute Coronary Syndrome

by Bruce Sylvester – Alogliptin treatment of patients with type 2 diabetes and with high cardiovascular risk due to recent acute coronary syndromes has led to similar rates of cardiovascular events as placebo treatment,  according to results of the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) trial presented in Amsterdam on Sept 2, 2013 at the European Society of Cardiology Congress.

“Compared with placebo, treatment with alogliptin resulted in similar rates of the primary endpoint, which was a composite of cardiovascular death, myocardial infarction, and stroke ,” said lead investigator William B. White, MD , professor of medicine, University of Connecticut School of Medicine in Farmington, Connecticut, USA.

“The findings could guide clinicians to choose among the many anti-diabetic agents available when treating patients with type 2 diabetes and very high cardiovascular risk,” White added.

EXAMINE was designed to test the non-inferiority of alogliptin to placebo for the designated endpoint. It was undertaken to fulfill U.S. Food and Drug Administration required evaluation of cardiovascular risks in drugs in development.

“It represents the first cardiovascular safety trial of an anti-diabetic drug in patients with acute coronary syndromes. Hence, for those who are likely candidates for the drug in clinical practice with elevated CV risk, including those with a recent acute coronary syndrome, it is reassuring that alogliptin does not increase cardiovascular morbidity or mortality,” said Dr. White. “However, EXAMINE does not rule out longer-term benefits or risks of alogliptin with respect to cardiovascular end points as the median duration of the trial was approximately 18 months,” he added.

The investigators enrolled 5,380 subjects from 898 centers in 49 countries. They randomized the subjects to alogliptin or placebo, administered in a double-blind fashion along with standard-of-care treatment for type 2 diabetes mellitus and for cardiovascular risk factors.

Accounting for renal clearance, alogliptin dosing was modified, with 71.4% of patients receiving 25 mg, 25.7% receiving 12.5 mg, and 2.9% receiving 6.25 mg daily.

The researchers found that, after a median follow-up of 18 months (up to 40 months), the primary composite endpoint occurred at similar rates in alogliptin and placebo-treated subjects (11.3% vs 11.8% respectively; P <0.001 for non-inferiority).

Endpoint glycated hemoglobin levels were significantly lower in subjects on alogliptin than placebo, showing a mean change from baseline of -0.33% and +0.03% respectively.

Rates of hypoglycemia, malignancy, pancreatitis, and dialysis were similar for both groups.

“There is a need for safe glucose lowering therapies in patients with diabetes who are at an elevated risk for cardiovascular disease,” White said. “Given the EXAMINE study design and high risk patient population evaluated, these results provide key insights to clinicians treating diabetes patients with cardiovascular disease.”

The study was funded by Takeda Development Center Americas, Inc.