{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:56:51Z","timestamp":1790823411144,"version":"4.1.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T00:00:00Z","timestamp":1642464000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Heart Fail"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Patients with heart failure are at higher risk of progression to end\u2010stage renal disease (ESRD), regardless of ejection fraction (EF). We assessed the renal effects of angiotensin\u2013neprilysin inhibition in a pooled analysis of 13\u2009195 patients with heart failure with reduced and preserved EF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      We combined data from PARADIGM\u2010HF (EF \u226440%;\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a08399) and PARAGON\u2010HF (EF \u226545%;\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a04796) in a pre\u2010specified pooled analysis. We assessed the effect of treatment (sacubitril\/valsartan vs. enalapril or valsartan) on a composite of either \u226550% reduction in estimated glomerular filtration rate (eGFR), ESRD, or death from renal causes, in addition to changes in eGFR slope. We assessed whether baseline renal function or EF modified the effect of therapy on renal outcomes. At randomization, eGFR was 68\u2009\u00b1\u200920\u2009ml\/min\/1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      in PARADIGM\u2010HF and 63\u2009\u00b1\u200919\u2009ml\/min\/1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      in PARAGON\u2010HF. The composite renal outcome occurred in 70 of 6594 patients (1.1%) in the sacubitril\/valsartan group and in 123 of 6601 patients (1.9%) in the valsartan or enalapril group (hazard ratio 0.56, 95% confidence interval [CI] 0.42\u20130.75;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). The mean eGFR change was \u22121.8 (95% CI \u22121.9 to \u22121.7) ml\/min\/1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      \/year for the sacubitril\/valsartan group, compared with \u22122.4 (95% CI \u22122.5 to \u22122.2) ml\/min\/1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      \/year for the valsartan or enalapril group. The treatment effect on the composite renal endpoint was not modified by categories of baseline eGFR (\n                      <jats:italic>p<\/jats:italic>\n                      \u2010interaction\u00a0=\u00a00.64), but was most pronounced in those with baseline EF between 30% and 60% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2010interaction\u00a0=\u00a00.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In patients with heart failure, sacubitril\/valsartan reduced the risk of serious adverse renal outcomes and slowed decline in eGFR, compared with valsartan or enalapril, independent of baseline renal function.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.2421","type":"journal-article","created":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T22:23:38Z","timestamp":1641421418000},"page":"1591-1598","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["<scp>Angiotensin\u2013neprilysin<\/scp>\n                    inhibition and renal outcomes across the spectrum of ejection fraction in heart failure"],"prefix":"10.1093","volume":"24","author":[{"given":"Finnian R.","family":"Mc Causland","sequence":"first","affiliation":[{"name":"Renal Division, Department of Medicine, Brigham and Women's Hospital  Boston MA USA"},{"name":"Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin P.","family":"Lefkowitz","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals  East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Claggett","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston MA USA"},{"name":"Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milton","family":"Packer","sequence":"additional","affiliation":[{"name":"Baylor Heart and Vascular Institute Baylor University Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Senni","sequence":"additional","affiliation":[{"name":"Cardiology Division, Cardiovascular Department, Azienda Ospedaliera Papa Giovanni XXIII Hospital  Bergamo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Gori","sequence":"additional","affiliation":[{"name":"Cardiology Division, Cardiovascular Department, Azienda Ospedaliera Papa Giovanni XXIII Hospital  Bergamo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pardeep S.","family":"Jhund","sequence":"additional","affiliation":[{"name":"British Heart Foundation Cardiovascular Research Centre University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina M.","family":"McGrath","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Brigham and Women's Hospital  Boston MA USA"},{"name":"Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean L.","family":"Rouleau","sequence":"additional","affiliation":[{"name":"Institut de Cardiologie de Montr\u00e9al Universit\u00e9 de Montr\u00e9al  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Shi","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals  East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Swedberg","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Medicine University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muthiah","family":"Vaduganathan","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston MA USA"},{"name":"Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Inserm CIC1433, CHRU de Nancy  Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc A.","family":"Pfeffer","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston MA USA"},{"name":"Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Zile","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina  Charleston SC USA"},{"name":"Ralph H. 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