Combined neprilysin and renin-angiotensin system inhibition in heart failure with reduced ejection fraction: a meta-analysis

Solomon, S. D., Claggett, B., McMurray, J. J.V. , Hernandez, A. F. and Fonarow, G. C. (2016) Combined neprilysin and renin-angiotensin system inhibition in heart failure with reduced ejection fraction: a meta-analysis. European Journal of Heart Failure, 18(10), pp. 1238-1243. (doi:10.1002/ejhf.603) (PMID:27364182)

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Abstract

Aims: The combined neprilysin/renin–angiotensin system (RAS) inhibitor sacubitril/valsartan reduced cardiovascular death or heart failure hospitalization, cardiovascular death, and all-cause mortality in a large outcomes trial. While sacubitril/valsartan is the only currently available drug in its class, there are two prior clinical trials in heart failure with omapatrilat, another combined neprilysin/RAS inhibitor. Using all available evidence can inform clinicians and policy-makers. Methods and results: We performed a meta-analysis using data from three trials in heart failure with reduced EF that compared combined neprilysin/RAS inhibition with RAS inhibition alone and reported clinical outcomes: IMPRESS (n = 573), OVERTURE (n = 5770), and PARADIGM-HF (n = 8399). We assessed the pooled hazard ratio (HR) for all-cause death or heart failure hospitalization, and for all-cause mortality in random-effects models, comparing combined neprilysin/RAS inhibition with ACE inhibition alone. The composite outcome of death or heart failure hospitalization was reduced numerically in patients receiving combined neprilysin/RAS inhibition in all three trials, with a pooled HR of 0.86, 95% confidence interval (CI) 0.76–0.97, P = 0.013. For the endpoint of all-cause mortality, the pooled HR was 0.88, 95% CI 0.80–0.98, P = 0.021. Combined neprilysin/RAS inhibition compared with ACE inhibition was associated with more hypotension, but less renal dysfunction and hyperkalaemia in all three trials. Conclusions: Pooled estimates from three trials with two separate drugs of combined neprilysin/RAS inhibition support the use of combined neprilysin/RAS inhibition in heart failure with reduced EF.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McMurray, Professor John
Authors: Solomon, S. D., Claggett, B., McMurray, J. J.V., Hernandez, A. F., and Fonarow, G. C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:European Journal of Heart Failure
Publisher:Wiley
ISSN:1388-9842
ISSN (Online):1879-0844
Published Online:30 June 2016

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