{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:26:26Z","timestamp":1792553186541,"version":"4.5.0"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"16","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Programme for Clinical Therapy Research in the Specialist Health Service","award":["2016205"],"award-info":[{"award-number":["2016205"]}]},{"DOI":"10.13039\/100008730","name":"Norwegian Cancer Society","doi-asserted-by":"crossref","award":["198136)"],"award-info":[{"award-number":["198136)"]}],"id":[{"id":"10.13039\/100008730","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007793","name":"Kristian.Gerhard Jebsen Foundation","doi-asserted-by":"crossref","award":["SKGJ-MED-024"],"award-info":[{"award-number":["SKGJ-MED-024"]}],"id":[{"id":"10.13039\/100007793","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2025,10,21]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Anthracycline- and trastuzumab-associated cardiotoxicity may lead to cardiac dysfunction and dose reduction or halt of potentially life-saving adjuvant cancer therapy. Whether angiotensin receptor\/neprilysin inhibitors can prevent cancer therapy\u2013related cardiac dysfunction and injury remains to be established.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>PRADA II (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) was a randomized, parallel-group, placebo-controlled, double-blind, multicenter trial conducted at 4 academic medical centers in Norway that evaluated the cardioprotective effect of sacubitril\/valsartan versus placebo administered concomitantly with anthracycline-containing breast cancer therapy and continued for 18 months. The target dose was 97\/103 mg BID. The primary outcome was change in left ventricular ejection fraction by cardiovascular magnetic resonance from prior to initiation of chemotherapy to 18 months thereafter. Secondary outcomes included change in echocardiographic global longitudinal strain, circulating cardiac troponins, and NT-proBNP (N-terminal pro-B-type natriuretic peptide).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      In total, 138 women (mean\u00b1SD age: 54.0\u00b19.4 years) were randomized. The overall decline in left ventricular ejection fraction from baseline to 18 months was 2.2 percentage points (95% CI, 1.1 to 3.3) in the placebo group and 1.1 percentage points (95% CI, \u22120.01 to 2.2) in the sacubitril\/valsartan group. The between-group difference was 1.1 percentage points (95% CI, \u22120.4 to 2.7;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.16). Left ventricular global longitudinal strain was normal and remained stable in the sacubitril\/valsartan group throughout the study (change from baseline to 18 months, \u22120.3 [95% CI, \u22120.80 to 0.2]). In contrast, there was a progressive decline in the placebo group (change from baseline to 18 months, 0.5 [95% CI, 0.05 to 1.0]). The between-group difference was \u22120.9 (95% CI, \u22121.5 to \u22120.2). The mean increases in NT-proBNP and cardiac troponin I concentrations from baseline to 18 months were greater in the placebo group than in the sacubitril\/valsartan group (log difference, 0.3 [95% CI, 0.05 to 0.6] for NT-proBNP and 0.5 [95% CI, 0.1to 1.0] for cardiac troponin I).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Anthracycline-based treatment for early breast cancer was associated with a reduction in left ventricular ejection fraction that was not significantly attenuated by sacubitril\/valsartan.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>REGISTRATION:<\/jats:title>\n                    <jats:p>\n                      URL:\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: NCT03760588.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.125.076616","type":"journal-article","created":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T06:30:06Z","timestamp":1756535406000},"page":"1136-1145","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":43,"title":["Sacubitril\/Valsartan and Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy: The PRADA II Randomized Clinical Trial"],"prefix":"10.1161","volume":"152","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6452-0369","authenticated-orcid":true,"given":"Torbj\u00f8rn","family":"Omland","sequence":"first","affiliation":[{"name":"K.G. Jebsen Centre for Cardiac Biomarkers, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway (T.O., S.L.H., M.N.G., V.V.-J., G.G.)."},{"name":"Departments of Cardiology (T.O., A.M.L., V.V.-J.), Akershus University Hospital, L\u00f8renskog, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5430-1613","authenticated-orcid":true,"given":"Siri Lagethon","family":"Heck","sequence":"additional","affiliation":[{"name":"K.G. Jebsen Centre for Cardiac Biomarkers, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway (T.O., S.L.H., M.N.G., V.V.-J., G.G.)."},{"name":"Diagnostic Imaging (S.L.H.), Akershus University Hospital, L\u00f8renskog, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Espen","family":"Holte","sequence":"additional","affiliation":[{"name":"Departments of Circulation and Medical Imaging (E.H.), NTNU-Norwegian University of Science and Technology, Trondheim, Norway."},{"name":"Clinics of Cardiology (E.H., M.N.G.), St. Olavs Hospital, Trondheim, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albulena Mecinaj","family":"Lilleaasen","sequence":"additional","affiliation":[{"name":"Departments of Cardiology (T.O., A.M.L., V.V.-J.), Akershus University Hospital, L\u00f8renskog, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8623-7911","authenticated-orcid":true,"given":"Mari Nordb\u00f8","family":"Gynnild","sequence":"additional","affiliation":[{"name":"K.G. Jebsen Centre for Cardiac Biomarkers, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway (T.O., S.L.H., M.N.G., V.V.-J., G.G.)."},{"name":"Clinics of Cardiology (E.H., M.N.G.), St. Olavs Hospital, Trondheim, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4535-5043","authenticated-orcid":true,"given":"Morten Wang","family":"Fagerland","sequence":"additional","affiliation":[{"name":"Oslo Center for Biostatistics and Epidemiology, Research Support Services (M.W.F.), Oslo University Hospital, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Vinje-Jakobsen","sequence":"additional","affiliation":[{"name":"K.G. Jebsen Centre for Cardiac Biomarkers, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway (T.O., S.L.H., M.N.G., V.V.-J., G.G.)."},{"name":"Departments of Cardiology (T.O., A.M.L., V.V.-J.), Akershus University Hospital, L\u00f8renskog, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Katrine Lislegaard","family":"N\u00e6s","sequence":"additional","affiliation":[{"name":"Surgery (A.-K.L.N.), St. Olavs Hospital, Trondheim, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Egil St\u00f8re","family":"Blix","sequence":"additional","affiliation":[{"name":"Department of Oncology, University Hospital of North Norway, Troms\u00f8, Norway (E.S.B.)."},{"name":"Department of Clinical Medicine, UiT The Arctic University of Norway, Troms\u00f8, Norway (E.S.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9141-0499","authenticated-orcid":true,"given":"Alf Inge","family":"Larsen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Stavanger University Hospital, Stavanger, Norway (A.I.L.)."},{"name":"Institute of Clinical Science, University of Bergen, Bergen, Norway (A.I.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6239-3856","authenticated-orcid":true,"given":"J\u00fcrgen","family":"Geisler","sequence":"additional","affiliation":[{"name":"Oncology (J.G.), Akershus University Hospital, L\u00f8renskog, Norway."},{"name":"Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway (J.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1316-8676","authenticated-orcid":true,"given":"Geeta","family":"Gulati","sequence":"additional","affiliation":[{"name":"K.G. 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