{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:47:15Z","timestamp":1787165235297,"version":"build-2736575974"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":1135,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T00:00:00Z","timestamp":1666828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008272","name":"Novartis Pharmaceuticals Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008272","name":"Novartis Pharmaceuticals Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,1,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>As sacubitril\/valsartan may potentiate early natriuresis, expert consensus documents recommend diuretic dose reduction on first initiation. However, there are limited data on the effects of sacubitril\/valsartan on the background of varying diuretic regimens or on diuretic requirements over time in heart failure (HF) with preserved ejection fraction (HFpEF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>In this post hoc analysis of PARAGON-HF, of the 4796 patients, background diuretic therapy was distributed as follows: 341 (7%) on no diuretic, 698 (15%) on non-loop diuretic, and 3757 (78%) were on loop diuretics (1255, 1589, and 913 were on &amp;lt;40, 40 and &amp;gt;40\u2009mg furosemide equivalent doses, respectively). The primary composite outcome of total HF hospitalizations and cardiovascular death was analysed using semiparametric proportional rates methods. The cumulative incidence of the primary composite outcome (first events) was lowest in patients on no diuretic and highest in those on &amp;gt;40\u2009mg of loop diuretic (p\u2009&amp;lt;\u20090.001). The effects of sacubitril\/valsartan (vs. valsartan) on the primary composite outcome (recurrent events) did not significantly vary by baseline diuretic use (pinteraction = 0.65). Treatment effects on safety outcomes were similar across diuretic categories. Sacubitril\/valsartan reduced new loop diuretic initiations over the course of the trial (hazard ratio 0.83; 95% confidence interval 0.68\u20131.00, p = 0.055), with similar mean loop diuretic dose and rates of diuretic discontinuation between treatment groups in follow-up. Patients randomized to sacubitril\/valsartan experienced a slight early reduction in diuretic initiation or dose escalation at 30\u2009days after initiation (net reduction 1.7%, p = 0.02), but these differences were not sustained beyond this timepoint.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Patients with HFpEF on higher baseline diuretic doses were at heightened risk of HF events, but similarly benefited from sacubitril\/valsartan with a consistent safety profile across a range of diuretic doses. Initiation of sacubitril\/valsartan was associated with modestly lower new loop diuretic requirement in follow-up.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.2703","type":"journal-article","created":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T19:15:05Z","timestamp":1664651705000},"page":"87-94","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Sacubitril\/Valsartan and Loop Diuretic Requirement in Heart Failure with Preserved Ejection Fraction in the PARAGON-HF Trial"],"prefix":"10.1093","volume":"25","author":[{"given":"Safia","family":"Chatur","sequence":"first","affiliation":[{"name":"Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"Claggett","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orly","family":"Vardeny","sequence":"additional","affiliation":[{"name":"Minneapolis VA Center for Care Delivery and Outcomes Research, University of Minnesota , Minneapolis, MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karola","family":"Jering","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshay S.","family":"Desai","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc A.","family":"Pfeffer","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Lefkowitz","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation , East Hanover, NJ ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.V.","family":"McMurray","sequence":"additional","affiliation":[{"name":"BHF Cardiovascular Research Centre, University of Glasgow , Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Solomon","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muthiah","family":"Vaduganathan","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,10,27]]},"reference":[{"key":"2026010913080169300_ejhf2703-bib-0001","doi-asserted-by":"crossref","DOI":"10.3389\/fcvm.2021.754499","article-title":"Sacubitril-valsartan, clinical benefits and related mechanisms of action in heart failure with reduced ejection fraction. 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