Recurrent Events in Cardiovascular Trials: JACC State-of-the-Art Review

Area of Science:

• Cardiovascular Medicine
• Clinical Trials Methodology
• Biostatistics

Background:

• Randomized cardiovascular trials frequently observe recurrent nonfatal events during patient follow-up.
• Current standard practice often focuses on the time to the first event as the primary outcome, potentially overlooking valuable information.

Purpose of the Study:

• To evaluate the utility of analyses incorporating repeat events in cardiovascular trials.
• To determine if repeat event analyses improve understanding of treatment effects and total disease burden.
• To assess the impact of repeat event analyses on statistical power and their suitability as primary trial outcomes.

Main Methods:

• Comparison of statistical methods for analyzing repeat events, including Lin Wei Yang Ying, negative binomial, joint frailty, win ratio, and area under the curve.
• Illustration of method performance using data from five large cardiovascular trials.
• Benchmarking against traditional time-to-first-event analyses.

Main Results:

• Analyses including repeat events provide a more comprehensive understanding of treatment efficacy and disease progression.
• These methods can offer increased statistical power compared to time-to-first-event analyses.
• The study offers a guide to understanding and selecting appropriate statistical methods for repeat event data.

Conclusions:

• Incorporating repeat events into the analysis of cardiovascular trials enhances the evaluation of treatment effects and disease burden.
• The adoption of repeat event analyses as a primary outcome measure is recommended for future cardiovascular trials.
• Guidance is provided to facilitate the selection and application of appropriate statistical methodologies for repeat event data.