A re-examination of the BEST Trial using composite outcomes, including emergency department visits

Shen, L., Jhund, P. S. , Mogensen, U. M., Køber, L., Claggett, B., Rogers, J. K. and McMurray, J. J.V. (2017) A re-examination of the BEST Trial using composite outcomes, including emergency department visits. JACC: Heart Failure, 5(8), pp. 591-599. (doi:10.1016/j.jchf.2017.04.005) (PMID:28774394)

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Abstract

Objectives: The influence of choice of endpoint on trial size, duration, and interpretation of results was examined in patients with heart failure who were enrolled in BEST (Beta-blocker Evaluation of Survival Trial). Background: The choice of endpoints in heart failure trials has evolved over the past 3 decades. Methods: In the BEST trial, we used Cox regression analysis to examine the effect of bucindolol on the current standard composite of cardiovascular death or heart failure hospitalization (CVD/HFH) compared with the original primary mortality endpoint and the expanded composite that included emergency department (ED) visits. We also undertook an analysis of recurrent events primarily using the Lin, Wei, Ying, and Yang model. Results: Overall, 448 (33%) patients on placebo and 411 (30%) patients on bucindolol died (hazard ratio [HR]: 0.90; 95% confidence interval [CI]: 0.78 to 1.02; p = 0.11). A total of 730 (54%) patients experienced CVD/HFH on placebo and 624 (46%) on bucindolol (HR: 0.80; 95% CI: 0.72 to 0.89; p < 0.001). Adding ED visits increased these numbers to 768 (57%) and 668 (49%), respectively (HR: 0.81; 95% CI: 0.73 to 0.90; p < 0.001). A total of 568 (42%) patients on placebo experienced HFH compared with 476 (35%) patients on bucindolol (HR: 0.78; 95% CI: 0.69 to 0.89; p < 0.001), with a total of 1,333 and 1,124 admissions, respectively. With the same statistical assumptions, using the composite endpoint instead of all-cause mortality would have reduced the trial size by 40% and follow-up duration by 69%. The rate ratio for recurrent events (CVD/HFH) was 0.83 (95% CI: 0.73 to 0.94; p = 0.003). Conclusions: Choice of endpoint has major implications for trial size and duration, as well as interpretation of results. The value of broader composite endpoints and inclusion of recurrent events needs further investigation. (Beta Blocker Evaluation in Survival Trial [BEST]; NCT00000560)

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mogensen, Dr Ulrik and Jhund, Dr Pardeep and McMurray, Professor John and Kober, Professor Lars and Shen, Ms Li
Authors: Shen, L., Jhund, P. S., Mogensen, U. M., Køber, L., Claggett, B., Rogers, J. K., and McMurray, J. J.V.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:JACC: Heart Failure
Publisher:Elsevier
ISSN:2213-1779
ISSN (Online):2213-1787
Published Online:31 July 2017
Copyright Holders:Copyright © 2017 Elsevier
First Published:First published in JACC: Heart Failure 5(8):591-599
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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