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

Area of Science:

• Cardiology
• Endocrinology
• Clinical Trials Methodology

Background:

• Glucose-lowering therapies have demonstrated effects on heart failure (HF) risk.
• Systematic characterization of HF data within cardiovascular outcome trials (CVOTs) for these therapies is lacking.

Purpose of the Study:

• To systematically evaluate the ascertainment and reporting of heart failure data in large-scale CVOTs of glucose-lowering therapies.
• To identify gaps in HF data collection and propose strategies for improvement.

Main Methods:

• Systematic review of published Phase III and IV CVOTs (n > 1,000) evaluating glucose-lowering therapies up to June 2017.
• Data abstraction from publications, FDA advisory committee records, and FDA labeling documents.
• Evaluation of 21 trials encompassing 152,737 patients.

Main Results:

• Inconsistent reporting of baseline and incident heart failure (HF) rates and definitions across trials.
• Limited availability of baseline ejection fraction data, often not specific to HF patients.
• Absence of data on functional class, ejection fraction, or HF therapy at the time of incident HF diagnosis.
• HF hospitalization data present in 15 trials, but only 2 included HF events in primary composite endpoints.

Conclusions:

• Significant gaps exist in the capture and reporting of heart failure data within CVOTs for glucose-lowering therapies.
• There is a critical need for standardized and comprehensive HF data ascertainment in future clinical trials.
• Improved HF characterization is essential for understanding the cardiovascular safety and efficacy of these medications.