Measurement of end points in heart failure trials: jousting at windmills?

Area of Science:

• Cardiology
• Clinical Trials
• Heart Failure Research

Background:

• Congestive heart failure (CHF) incidence and prevalence are increasing globally.
• Randomized clinical trials (RCTs) are pivotal for advancing CHF treatments.
• The selection of appropriate end points in RCTs is critical for drug and device approval.

Purpose of the Study:

• To discuss the evolution and challenges of end point selection in CHF clinical trials.
• To highlight the impact of increasing trial subject numbers on end point design.
• To explore alternative end points, including combined and composite measures, and their limitations.

Main Methods:

• Review of end point selection strategies in major CHF randomized clinical trials.
• Analysis of challenges in trials for decompensated and diastolic heart failure.
• Discussion of issues encountered during and after trial completion.

Main Results:

• Advances in CHF treatment are linked to knowledge from RCTs.
• Increased survival improvements necessitate larger study populations.
• Development of combined and composite end points, often using mortality surrogates, is a response to these needs.

Conclusions:

• End point selection is a pivotal step in CHF drug and device approval.
• Alternative end points present specific limitations and challenges.
• Careful consideration of end points is essential for successful CHF clinical trials.