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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, Ulrik M. Gong, Jianjian Jhund, Pardeep Shen, Li Kober, Lars Desai, Akshay S. Lefkowitz, Martin P. Packer, Milton Rouleau, Jean L. Solomon, Scott
Mogensen, Ulrik M.
Gong, Jianjian
Jhund, Pardeep
Shen, Li
Kober, Lars
Desai, Akshay S.
Lefkowitz, Martin P.
Packer, Milton
Rouleau, Jean L.
Solomon, Scott
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.
Keywords
Heart failure, Hospitalization, Recurrent events, Neprilysin inhibitor
Date
2018
Type
Journal article
Journal
European Journal of Heart Failure
Book
Volume
20
Issue
4
Page Range
760-768
Article Number
ACU Department
Collections
Relation URI
Source URL
Event URL
Open Access Status
Open access
License
CC BY 4.0
File Access
Open