{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T02:33:10Z","timestamp":1785551590432,"version":"3.56.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T00:00:00Z","timestamp":1626739200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2021,7,20]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Patients with left ventricular (LV) systolic dysfunction after myocardial infarction are at a high risk of developing heart failure. The addition of neprilysin inhibition to renin angiotensin system inhibition may result in greater attenuation of adverse LV remodeling as a result of increased levels of substrates for neprilysin with vasodilatory, antihypertrophic, antifibrotic, and sympatholytic effects.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>We performed a prospective, multicenter, randomized, double-blind, active-comparator trial comparing sacubitril\/valsartan 97\/103 mg twice daily with valsartan 160 mg twice daily in patients \u22653 months after myocardial infarction with a LV ejection fraction \u226440% who were taking a renin angiotensin system inhibitor (equivalent dose of ramipril \u22652.5 mg twice daily) and a \u03b2-blocker unless contraindicated or intolerant. Patients in New York Heart Association class \u2265II or with signs and symptoms of heart failure were excluded. The primary outcome was change from baseline to 52 weeks in LV end-systolic volume index measured using cardiac magnetic resonance imaging. Secondary outcomes included other magnetic resonance imaging measurements of LV remodeling, change in NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cardiac troponin I, and a patient global assessment of change questionnaire.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              From July 2018 to June 2019, we randomized 93 patients with the following characteristics: mean age, 60.7\u00b110.4 years; median time from myocardial infarction, 3.6 years (interquartile range, 1.2\u20137.2); mean LV ejection fraction, 36.8%\u00b17.1%; and median NT-proBNP, 230 pg\/mL (interquartile range, 124\u2013404). Sacubitril\/valsartan, compared with valsartan, did not significantly reduce LV end-systolic volume index; adjusted between-group difference, \u20131.9 mL\/m\n              <jats:sup>2<\/jats:sup>\n              (95% CI, \u20134.8 to 1.0);\n              <jats:italic>P<\/jats:italic>\n              =0.19. There were no significant between-group differences in NT-proBNP, high-sensitivity cardiac troponin I, LV end-diastolic volume index, left atrial volume index, LV ejection fraction, LV mass index, or patient global assessment of change.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>In patients with asymptomatic LV systolic dysfunction late after myocardial infarction, treatment with sacubitril\/valsartan did not have a significant reverse remodeling effect compared with 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: NCT03552575.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.121.054892","type":"journal-article","created":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T20:13:41Z","timestamp":1620936821000},"page":"199-209","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":52,"title":["Effect of Neprilysin Inhibition on Left Ventricular Remodeling in Patients With Asymptomatic Left Ventricular Systolic Dysfunction Late After Myocardial Infarction"],"prefix":"10.1161","volume":"144","clinical-trial-number":[{"clinical-trial-number":"nct03552575","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Kieran F.","family":"Docherty","sequence":"first","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre (K.F.D., R.T.C., K.J.M.B., R.L.G., T.H., A.M.J., M.M.Y.L., G.R., P.W., P.S.J., M.C.P., J.J.V.M.), University of Glasgow, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross T.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre (K.F.D., R.T.C., K.J.M.B., R.L.G., T.H., A.M.J., M.M.Y.L., G.R., P.W., P.S.J., M.C.P., J.J.V.M.), University of Glasgow, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katriona J.M.","family":"Brooksbank","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre (K.F.D., R.T.C., K.J.M.B., R.L.G., T.H., A.M.J., M.M.Y.L., G.R., P.W., P.S.J., M.C.P., J.J.V.M.), University of Glasgow, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8702-4520","authenticated-orcid":true,"given":"John G.","family":"Dreisbach","sequence":"additional","affiliation":[{"name":"Golden Jubilee National Hospital, Glasgow, United Kingdom (J.G.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3804-6795","authenticated-orcid":true,"given":"Paul","family":"Forsyth","sequence":"additional","affiliation":[{"name":"Pharmacy Services, National Health Service Greater Glasgow and Clyde, United Kingdom (P.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary L.","family":"Godeseth","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre (K.F.D., R.T.C., K.J.M.B., R.L.G., T.H., A.M.J., M.M.Y.L., G.R., P.W., P.S.J., M.C.P., J.J.V.M.), University of Glasgow, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey","family":"Hopkins","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre (K.F.D., R.T.C., K.J.M.B., R.L.G., T.H., A.M.J., M.M.Y.L., G.R., P.W., P.S.J., M.C.P., J.J.V.M.), University of Glasgow, United Kingdom."},{"name":"Glasgow Clinical Research Imaging Facility (T.H., G.R.), Queen Elizabeth University Hospital, United Kingdom (R.T.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice M.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre (K.F.D., R.T.C., K.J.M.B., R.L.G., T.H., A.M.J., M.M.Y.L., G.R., P.W., P.S.J., M.C.P., J.J.V.M.), University of Glasgow, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9213-2067","authenticated-orcid":true,"given":"Matthew M.Y.","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre (K.F.D., R.T.C., K.J.M.B., R.L.G., T.H., A.M.J., M.M.Y.L., G.R., P.W., P.S.J., M.C.P., J.J.V.M.), University of Glasgow, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"McConnachie","sequence":"additional","affiliation":[{"name":"Robertson Centre for Biostatistics, Institute of Health and Wellbeing (A.M., B.S.), University of Glasgow, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giles","family":"Roditi","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre (K.F.D., R.T.C., K.J.M.B., R.L.G., T.H., A.M.J., M.M.Y.L., G.R., P.W., P.S.J., M.C.P., J.J.V.M.), University of Glasgow, United Kingdom."},{"name":"Glasgow Clinical Research Imaging Facility (T.H., G.R.), Queen Elizabeth University Hospital, United Kingdom (R.T.C.)."},{"name":"Department of Radiology, Glasgow Royal Infirmary, United Kingdom (G.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain B.","family":"Squire","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester and National Institute for Health Research Biomedical Research Centre, Glenfield Hospital, United Kingdom (I.B.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3299-4014","authenticated-orcid":true,"given":"Bethany","family":"Stanley","sequence":"additional","affiliation":[{"name":"Robertson Centre for Biostatistics, Institute of Health and Wellbeing (A.M., B.S.), University of Glasgow, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7970-3643","authenticated-orcid":true,"given":"Paul","family":"Welsh","sequence":"additional","affiliation":[{"name":"Institute of 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