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

Gregson, JORCID logo; Stone, GW; Bhatt, DL; Packer, M; Anker, SD; Zeller, C; Redfors, B; Pocock, SJ and (2023) Recurrent Events in Cardiovascular Trials: JACC State-of-the-Art Review. Journal of the American College of Cardiology, 82 (14). pp. 1445-1463. ISSN 0735-1097 DOI: 10.1016/j.jacc.2023.07.024
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Many randomized trials in cardiovascular disease have repeat nonfatal events (such as hospitalizations) occurring during patient follow-up; yet, it remains common practice to have time-to-first event as the primary outcome. We explore the value of analyses that include repeat events. Do they help us understand the effect of treatment and total disease burden? Do they enhance statistical power? Should they become a trial's primary analysis? It may also be difficult to choose which of the various statistical methods for analyzing repeat events to use, and we provide a nontechnical guide to what each method is doing. We compare several methods for repeat events: Lin Wei Yang Ying, negative binomial, joint frailty, win ratio, and area under the curve. We illustrate their performance in 5 large cardiovascular trials and compare them with time-to-first-event analyses. We review their use in recently published heart failure trials and make recommendations for their use in future trials.


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This is an author accepted manuscript version of an article accepted for publication and following peer review. Please be aware that minor differences may exist between this version and the final version if you wish to cite from it.
Available under Creative Commons: Attribution-NonCommercial-No Derivative Works 4.0

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