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Eur J Heart Fail. 2018 Apr;20(4):760-768. doi: 10.1002/ejhf.1139. Epub 2018 Feb 12.

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).

Author information

1
BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
2
Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark.
3
Novartis Pharmaceutical Corporation, East Hanover, NJ, USA.
4
Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA.
5
Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, TX, USA.
6
Institut de Cardiologie de Montréal, Université de Montréal, Montréal, Canada.
7
Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden, and National Heart and Lung Institute, Imperial College, London, UK.
8
Medical University of South Carolina and Ralph H. Johnson Veterans Administration Medical Center, Charleston, SC, USA.
9
Novartis Pharma AG, Basel, Switzerland.

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; Neprilysin inhibitor; Recurrent events

PMID:
29431251
PMCID:
PMC6607507
DOI:
10.1002/ejhf.1139
[Indexed for MEDLINE]
Free PMC Article

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