Effect of sacubitril/valsartan on recurrent events in the prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure trial (PARADIGM-HF)

Mogensen, U. M. et al. (2018) Effect of sacubitril/valsartan on recurrent events in the prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure trial (PARADIGM-HF). European Journal of Heart Failure, 20(4), pp. 760-768. (doi: 10.1002/ejhf.1139) (PMID:29431251)

Abstract

Aims: Recurrent hospitalizations are a major part of the disease burden in heart failure (HF), but conventional analyses consider only the first event. We compared the effect of sacubitril/valsartan vs. enalapril on recurrent events, incorporating all HF hospitalizations and cardiovascular (CV) deaths in PARADIGM-HF, using a variety of statistical approaches advocated for this type of analysis. Methods and results: In PARADIGM-HF, a total of 8399 patients were randomized and followed for a median of 27 months. We applied various recurrent event analyses, including a negative binomial model, the Wei, Lin and Weissfeld (WLW), and Lin, Wei, Ying and Yang (LWYY) methods, and a joint frailty model, all adjusted for treatment and region. Among a total of 3181 primary endpoint events (including 1251 CV deaths) during the trial, only 2031 (63.8%) were first events (836 CV deaths). Among a total of 1195 patients with at least one HF hospitalization, 410 (34%) had at least one further HF hospitalization. Sacubitril/valsartan compared with enalapril reduced the risk of recurrent HF hospitalization using the negative binomial model [rate ratio (RR) 0.77, 95% confidence interval (CI) 0.67–0.89], the WLW method [hazard ratio (HR) 0.79, 95% CI 0.71–0.89], the LWYY method (RR 0.78, 95% CI 0.68–0.90), and the joint frailty model (HR 0.75, 95% CI 0.66–0.86) (all P < 0.001). The effect of sacubitril/valsartan vs. enalapril on recurrent HF hospitalizations/CV death was similar. Conclusions: In PARADIGM-HF, approximately one third of patients with a primary endpoint (time-to-first) experienced a further event. Compared with enalapril, sacubitril/valsartan reduced both first and recurrent events. The treatment effect size was similar, regardless of the statistical approach applied.

• Item Type: Articles
• Additional Information: This work was supported by the Danish Heart Foundation [grant number 16-R107-A6786-22960] to U.M.M. PARADIGM-HF was funded by Novartis.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Shen, Dr Li and Jhund, Professor Pardeep and Mogensen, Dr Ulrik and McMurray, Professor John and Kober, Professor Lars
• Authors: Mogensen, U. M., Gong, J., Jhund, P. S., Shen, L., Køber, L., Desai, A. S., Lefkowitz, M. P., Packer, M., Rouleau, J. L., Solomon, S. D., Claggett, B. L., Swedberg, K., Zile, M. R., Mueller-Velten, G., and McMurray, J. J.V.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: European Journal of Heart Failure
• Publisher: Wiley
• ISSN: 1388-9842
• ISSN (Online): 1879-0844
• Published Online: 12 February 2018
• Copyright Holders: Copyright © 2018 The Authors
• First Published: First published in European Journal of Heart Failure 20(4): 760-768
• Publisher Policy: Reproduced under a Creative Commons License