Alogliptin vs. Placebo and Heart Failure Outcomes: Reassuring Results, but Uncertainties Remain | Journal Scan

Mar 13, 2015
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Authors:
Zannad F, Cannon CP, Cushman WC, et al., on behalf of the EXAMINE Investigators.
Citation:
Heart Failure and Mortality Outcomes in Patients With Type 2 Diabetes Taking Alogliptin Versus Placebo in EXAMINE: A Multicentre, Randomised, Double-Blind Trial. Lancet 2015;Mar 9:[Epub ahead of print].
Summary By:
Prashant Vaishnava, MD, FACC

Study Questions:

In the EXAMINE trial (which demonstrated the noninferiority of the dipeptidyl peptidase 4 [DPP-4] inhibitor alogliptin to placebo on major adverse cardiac event [MACE] rates in patients with type 2 diabetes and recent acute coronary syndrome), did alogliptin increase the risk of heart failure outcomes?

Methods:

This was a post hoc analysis of the EXAMINE trial, a multicenter, randomized double-blind trial in which alogliptin was noninferior to placebo in type 2 diabetics with an acute coronary syndrome event within 15-90 days before randomization. Cardiovascular death and hospital admission for heart failure were analyzed.

Results:

A total of 5,380 patients were randomized. The MACE endpoint was observed in 433 (16.0%) patients assigned to alogliptin and in 441 (16.5%) patients assigned to placebo (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.86-1.12). Hospital admission for heart failure was the first event in 85 (3.1%) patients taking alogliptin compared with 79 (2.9%) taking placebo (HR, 1.07; 95% CI, 0.79-1.46).

Conclusions:

In a post hoc analysis of the EXAMINE trial, alogliptin did not increase hospital admission for heart failure.

Perspective:

This is a valuable study that stands in contrast to results of the SAVOR TIMI 53 trial, in which more patients in the saxagliptin group than in the placebo group were admitted to the hospital for heart failure. The mechanism of the discrepancy in results between SAVOR TIMI 53 and EXAMINE is uncertain. As the authors of this post hoc analysis posit, ‘SAVOR TIMI 53 analyses of the composite endpoint of all-cause death and hospital admission for heart failure…could be informative.’ For now, there are uncertainties about the use of DPP-4 inhibitors and the risk for heart failure outcomes; as written in an editorial accompanying this analysis, results of the TECOS trial (examining the use of sitagliptin in 14,724 patients with type 2 diabetes and escalated risk of cardiovascular events) will be informative.

Keywords: Heart Failure, Acute Coronary Syndrome, Diabetes Mellitus, Type 2, Dipeptidyl-Peptidase IV Inhibitors, Hospitalization, Risk, Metabolic Syndrome, Primary Prevention


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