{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T23:52:36Z","timestamp":1768780356033,"version":"3.49.0"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The association between angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) doses on outcomes in patients with heart failure (HF) with reduced ejection fraction is uncertain. The objective of this study was to investigate the effect of dose of ACEI and ARBs on outcomes and drug discontinuation in patients with HF with reduced ejection fraction.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p>\n              MEDLINE, Ovid SP, and Embase were searched from the inception of these databases till August 2016. Randomized controlled trials that compared high doses of ACEI or ARB against low doses among patients with HF with reduced ejection fraction were included. Pooled analysis was done using a random-effects model, and quality of the studies was assessed by JADAD scale. The main outcomes were all-cause mortality and drug discontinuation. A total of 6 studies (4841 patients in low-dose and 4330 patients in high-dose groups) were included. Compared with low dose, high-dose ACEI or ARBs decreased all-cause mortality modestly (relative risk, 0.94; 95% confidence interval (CI), 0.89\u20131.00;\n              <jats:italic>P<\/jats:italic>\n              =0.05;\n              <jats:italic>I<\/jats:italic>\n              <jats:sup>2<\/jats:sup>\n              =0%) and composite of HF hospitalizations and all-cause mortality (relative risk, 0.93; 95% CI, 0.87\u20131.00;\n              <jats:italic>P<\/jats:italic>\n              =0.04;\n              <jats:italic>I<\/jats:italic>\n              <jats:sup>2<\/jats:sup>\n              =39.8%). No significant difference was found between the 2 groups in HF hospitalizations (relative risk, 0.94; 95% CI, 0.70\u20131.26;\n              <jats:italic>P<\/jats:italic>\n              =0.68;\n              <jats:italic>I<\/jats:italic>\n              <jats:sup>2<\/jats:sup>\n              =52.8%) and all-cause hospitalizations (relative risk, 0.97; 95% CI, 0.85\u20131.11;\n              <jats:italic>P<\/jats:italic>\n              =0.67;\n              <jats:italic>I<\/jats:italic>\n              <jats:sup>2<\/jats:sup>\n              =31.7%) risk. Discontinuation rates were also not significantly different in both groups (odds ratio, 1.13; 95% CI, 0.92\u20131.39;\n              <jats:italic>P<\/jats:italic>\n              =0.25;\n              <jats:italic>I<\/jats:italic>\n              <jats:sup>2<\/jats:sup>\n              =32.6%).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>In patients with HF with reduced ejection fraction, compared with lower doses, higher doses of ACEI and ARB significantly though modestly improved the composite end point of all-cause mortality or HF hospitalization without significantly increasing the chances of discontinuation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.117.003956","type":"journal-article","created":{"date-parts":[[2017,8,9]],"date-time":"2017-08-09T00:50:28Z","timestamp":1502239828000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":60,"title":["Dose of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and Outcomes in Heart Failure"],"prefix":"10.1161","volume":"10","author":[{"given":"Muhammad Shahzeb","family":"Khan","sequence":"first","affiliation":[{"name":"From the John H. Stroger Jr Hospital of Cook County, Chicago, IL (M.S.K.); University of California Los Angeles (G.C.F.); Veterans Affairs Medical Center and George Washington University, DC (A.A.); Duke Clinical Research Institute and Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G.); Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (M.V.); Emory University, Atlanta, GA (H.K.); University of Georgia, Athens (C.M.); Northwestern University Feinberg School of..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregg C.","family":"Fonarow","sequence":"additional","affiliation":[{"name":"From the John H. Stroger Jr Hospital of Cook County, Chicago, IL (M.S.K.); University of California Los Angeles (G.C.F.); Veterans Affairs Medical Center and George Washington University, DC (A.A.); Duke Clinical Research Institute and Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G.); Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (M.V.); Emory University, Atlanta, GA (H.K.); University of Georgia, Athens (C.M.); Northwestern University Feinberg School of..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Ahmed","sequence":"additional","affiliation":[{"name":"From the John H. Stroger Jr Hospital of Cook County, Chicago, IL (M.S.K.); University of California Los Angeles (G.C.F.); Veterans Affairs Medical Center and George Washington University, DC (A.A.); Duke Clinical Research Institute and Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G.); Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (M.V.); Emory University, Atlanta, GA (H.K.); University of Georgia, Athens (C.M.); Northwestern University Feinberg School of..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen J.","family":"Greene","sequence":"additional","affiliation":[{"name":"From the John H. Stroger Jr Hospital of Cook County, Chicago, IL (M.S.K.); University of California Los Angeles (G.C.F.); Veterans Affairs Medical Center and George Washington University, DC (A.A.); Duke Clinical Research Institute and Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G.); Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (M.V.); Emory University, Atlanta, GA (H.K.); University of Georgia, Athens (C.M.); Northwestern University Feinberg School of..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muthiah","family":"Vaduganathan","sequence":"additional","affiliation":[{"name":"From the John H. Stroger Jr Hospital of Cook County, Chicago, IL (M.S.K.); University of California Los Angeles (G.C.F.); Veterans Affairs Medical Center and George Washington University, DC (A.A.); Duke Clinical Research Institute and Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G.); Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (M.V.); Emory University, Atlanta, GA (H.K.); University of Georgia, Athens (C.M.); Northwestern University Feinberg School of..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hassan","family":"Khan","sequence":"additional","affiliation":[{"name":"From the John H. Stroger Jr Hospital of Cook County, Chicago, IL (M.S.K.); University of California Los Angeles (G.C.F.); Veterans Affairs Medical Center and George Washington University, DC (A.A.); Duke Clinical Research Institute and Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G.); Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (M.V.); Emory University, Atlanta, GA (H.K.); University of Georgia, Athens (C.M.); Northwestern University Feinberg School of..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Marti","sequence":"additional","affiliation":[{"name":"From the John H. Stroger Jr Hospital of Cook County, Chicago, IL (M.S.K.); University of California Los Angeles (G.C.F.); Veterans Affairs Medical Center and George Washington University, DC (A.A.); Duke Clinical Research Institute and Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G.); Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (M.V.); Emory University, Atlanta, GA (H.K.); University of Georgia, Athens (C.M.); Northwestern University Feinberg School of..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihai","family":"Gheorghiade","sequence":"additional","affiliation":[{"name":"From the John H. Stroger Jr Hospital of Cook County, Chicago, IL (M.S.K.); University of California Los Angeles (G.C.F.); Veterans Affairs Medical Center and George Washington University, DC (A.A.); Duke Clinical Research Institute and Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G.); Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (M.V.); Emory University, Atlanta, GA (H.K.); University of Georgia, Athens (C.M.); Northwestern University Feinberg School of..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javed","family":"Butler","sequence":"additional","affiliation":[{"name":"From the John H. Stroger Jr Hospital of Cook County, Chicago, IL (M.S.K.); University of California Los Angeles (G.C.F.); Veterans Affairs Medical Center and George Washington University, DC (A.A.); Duke Clinical Research Institute and Division of Cardiology, Duke University Medical Center, Durham, NC (S.J.G.); Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (M.V.); Emory University, Atlanta, GA (H.K.); University of Georgia, Athens (C.M.); Northwestern University Feinberg School of..."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198706043162301"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199108013250501"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)02304-5"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14283-3"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.72.3_Suppl.S106"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hft134"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(96)00301-4"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.eurheartj.a060484"},{"key":"e_1_3_2_10_2","first-page":"S13","article-title":"Heterogeneity of angiotensin synthetic pathways and receptor subtypes: physiological and pharmacological implications.","volume":"11","author":"Dzau VJ","year":"1993","unstructured":"Dzau VJ, Sasamura H, Hein L. 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