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Combined neprilysin and renin-angiotensin system inhibition in heart failure with reduced ejection fraction: A meta-analysis
Solomon, Scott D. Claggett, Brian L. McMurray, John J. V. Hernandez, Adrian F. Fonarow, Gregg C.
Solomon, Scott D.
Claggett, Brian L.
McMurray, John J. V.
Hernandez, Adrian F.
Fonarow, Gregg C.
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.
Keywords
heart failure, neprilysin, renin–angiotensin system, meta-analysis
Date
2016
Type
Journal article
Journal
European Journal of Heart Failure
Book
Volume
18
Issue
10
Page Range
1238-1243
Article Number
ACU Department
Collections
Relation URI
DOI
Source URL
Event URL
Open Access Status
License
File Access
Controlled