Ulrik M. Mogensen
Akshay S. Desai
Martin P. Lefkowitz
Jean L. Rouleau
Brian L. Claggett
Michael R. Zile
John McMurray, Australian Catholic UniversityFollow
Mogensen, U. M, Gong, J., Jhund, P., Shen, L., Kober, L., Desai, A. S, Lefkowitz, M. P, Packer, M., Rouleau, J. L, Solomon, S., Claggett, B. L, Sweberg, K., Zile, M. R, Mueller-Velten, G. & McMurray, J. (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), M. Metra. 760-768. United Kingdom: John Wiley & Sons. Retrieved from https://doi.org/10.1002/ejhf.1139
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.
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.
Mary MacKillop Institute for Health Research
Open Access Journal Article
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