Prevalent and Incident Heart Failure in Cardiovascular Outcome Trials of Patients With Type 2 Diabetes

Abstract

Despite multiple examples of glucose-lowering therapies affecting heart failure (HF) risk, ascertainment of HF data in cardiovascular outcome trials of these medications has not been systematically characterized. In this review, large (n >1,000) published phase III and IV cardiovascular outcome trials evaluating glucose-lowering therapies through June 2017 were identified. Data were abstracted from publications, U.S. Food and Drug Administration advisory committee records, and U.S. Food and Drug Administration labeling documents. Overall, 21 trials including 152,737 patients were evaluated. Rates and definitions of baseline HF and incident HF were inconsistently provided. Baseline ejection fraction data were provided in 3 studies but not specific to patients with HF. No trial reported functional class, ejection fraction, or HF therapy at the time of incident HF diagnosis. HF hospitalization data were available in 15 trials, but only 2 included HF-related events within the primary composite endpoint. This systematic review highlights gaps in HF data capture within cardiovascular outcome trials of glucose-lowering therapies and outlines rationale and strategies for improving HF characterization.

Keywords: clinical trial; diabetes mellitus; heart failure; medication; outcomes.

Figure 1. PRISMA Flow Diagram of Search Strategy and Study Selection

Abbreviations: PRISMA= Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Central Illustration. Framework for Improving Characterization of Heart Failure in Cardiovascular Outcome Trials of Patients with Diabetes

DM, diabetes mellitus; ED, emergency department; EF, ejection fraction; HF, heart failure; IV, intravenous; NT-proBNP, N-terminal pro-B-type natriuretic peptide.