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)

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: Jhund, Professor Pardeep and Mogensen, Dr Ulrik and McMurray, Professor John and Shen, Ms Li and Kober, Professor Lars
• 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 > School of Cardiovascular & Metabolic Health
• 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