{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T01:25:08Z","timestamp":1768785908466,"version":"3.49.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2016,6,30]],"date-time":"2016-06-30T00:00:00Z","timestamp":1467244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The combined neprilysin\/renin\u2013angiotensin 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>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\u20130.97, P = 0.013. For the endpoint of all-cause mortality, the pooled HR was 0.88, 95% CI 0.80\u20130.98, 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.603","type":"journal-article","created":{"date-parts":[[2016,7,1]],"date-time":"2016-07-01T00:24:54Z","timestamp":1467332694000},"page":"1238-1243","source":"Crossref","is-referenced-by-count":61,"title":["Combined Neprilysin and Renin\u2013Angiotensin System Inhibition in Heart Failure with Reduced Ejection Fraction: A Meta-Analysis"],"prefix":"10.1093","volume":"18","author":[{"given":"Scott 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