{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:36:01Z","timestamp":1791920161855,"version":"4.3.4"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2020,2,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Unlike heart failure with reduced ejection fraction, there is no approved treatment for heart failure with preserved ejection fraction, the predominant phenotype in women. Therefore, there is a greater heart failure therapeutic deficit in women compared with men.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>In a prespecified subgroup analysis, we examined outcomes according to sex in the PARAGON-HF trial (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction), which compared sacubitril-valsartan and valsartan in patients with heart failure with preserved ejection fraction. The primary outcome was a composite of first and recurrent hospitalizations for heart failure and death from cardiovascular causes. We also report secondary efficacy and safety outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Overall, 2479 women (51.7%) and 2317 men (48.3%) were randomized. Women were older and had more obesity, less coronary disease, and lower estimated glomerular filtration rate and NT-proBNP (N-terminal pro\u2013B-type natriuretic peptide) levels than men. For the primary outcome, the rate ratio for sacubitril-valsartan versus valsartan was 0.73 (95% CI, 0.59\u20130.90) in women and 1.03 (95% CI, 0.84\u20131.25) in men (\n                      <jats:italic>P<\/jats:italic>\n                      interaction = 0.017). The benefit from sacubitril-valsartan was attributable to reduction in heart failure hospitalization. The improvement in New York Heart Association class and renal function with sacubitril-valsartan was similar in women and men, whereas the improvement in Kansas City Cardiomyopathy Questionnaire clinical summary score was less in women than in men. The difference in adverse events between sacubitril-valsartan and valsartan was similar in women and men.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>As compared with valsartan, sacubitril-valsartan seemed to reduce the risk of heart failure hospitalization more in women than in men. Whereas the possible sex-related modification of the effect of treatment has several potential explanations, the present study does not provide a definite mechanistic basis for this finding.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration:<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      . Unique identifier: NCT01920711.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.119.044491","type":"journal-article","created":{"date-parts":[[2019,11,17]],"date-time":"2019-11-17T10:45:18Z","timestamp":1573987518000},"page":"338-351","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":350,"title":["Effects of Sacubitril-Valsartan Versus Valsartan in Women Compared With Men With Heart Failure and Preserved Ejection Fraction"],"prefix":"10.1161","volume":"141","author":[{"given":"John J.V.","family":"McMurray","sequence":"first","affiliation":[{"name":"BHF Cardiovascular Research Centre, University of Glasgow, UK (J.J.V.M., A.M.J., P.S.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice M.","family":"Jackson","sequence":"additional","affiliation":[{"name":"BHF Cardiovascular Research Centre, University of Glasgow, UK (J.J.V.M., A.M.J., P.S.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn S.P.","family":"Lam","sequence":"additional","affiliation":[{"name":"National Heart Center Singapore and Duke\u2013National University of Singapore (C.S.P.L.)."},{"name":"Department of Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands (C.S.P.L., D.J.v.V.)."},{"name":"The George Institute for Global Health, Newtown, Australia (C.S.P.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret M.","family":"Redfield","sequence":"additional","affiliation":[{"name":"Mayo Clinic, Rochester, MN (M.M.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inder S.","family":"Anand","sequence":"additional","affiliation":[{"name":"University of Minnesota, Minneapolis (I.S.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbo","family":"Ge","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Cardiovascular Diseases, China (J.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marty P.","family":"Lefkowitz","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals, East Hanover, NJ (M.P.L., A.R.R., S.V.S., V.C.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldo P.","family":"Maggioni","sequence":"additional","affiliation":[{"name":"National Association of Hospital Cardiologists Research Center, Florence, Italy (A.P.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Martinez","sequence":"additional","affiliation":[{"name":"National University of Cordoba, Argentina (F.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milton","family":"Packer","sequence":"additional","affiliation":[{"name":"Baylor University Medical Center, Dallas, TX (M.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc A.","family":"Pfeffer","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (M.A.P., A.M.S., B.C., S.D.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burkert","family":"Pieske","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiology, German Center for Cardiovascular Research Partner Site Berlin, Germany (B.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adel R.","family":"Rizkala","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals, East Hanover, NJ (M.P.L., A.R.R., S.V.S., V.C.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini V.","family":"Sabarwal","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals, East Hanover, NJ (M.P.L., A.R.R., S.V.S., V.C.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amil M.","family":"Shah","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (M.A.P., A.M.S., B.C., S.D.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjiv J.","family":"Shah","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor C.","family":"Shi","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals, East Hanover, NJ (M.P.L., A.R.R., S.V.S., V.C.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk J.","family":"van Veldhuisen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands (C.S.P.L., D.J.v.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"INSERM Centre d\u2019Investigation Clinic 1433 and Universite de Lorraine, Centre Hospitalier Regional et Universitaire, Nancy, France (F.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Zile","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina and the Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston (M.R.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Cikes","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, University of Zagreb School of Medicine and University Hospital Centre Zagreb, Croatia (M.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Goncalvesova","sequence":"additional","affiliation":[{"name":"Department of Heart Failure\u2013Transplantation, National Cardiovascular Institute, Bratislava, Slovakia (E.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzvetana","family":"Katova","sequence":"additional","affiliation":[{"name":"Clinic of Cardiology, National Cardiology Hospital, Sofia, Bulgaria (T.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anamaria","family":"Kosztin","sequence":"additional","affiliation":[{"name":"Heart and Vascular Center, Semmelweis 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