{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T22:06:52Z","timestamp":1770070012769,"version":"3.49.0"},"reference-count":16,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2008,2,1]],"date-time":"2008-02-01T00:00:00Z","timestamp":1201824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The efficacy and safety of adding an angiotensin receptor blocker (ARB) in heart failure (HF) patients already taking an angiotensin-converting enzyme-inhibitor (ACE-I) plus an aldosterone antagonist is uncertain (especially if taking a beta blocker as well). The CHARM-Added trial describes the largest experience of using multiple inhibitors of the renin\u2013angiotensin\u2013aldosterone system (RAAS) together.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>2548 HF patients, taking an ACE-I (936 no spironolactone\/no beta blocker; 1175 no spironolactone\/beta blocker; 199 spironolactone\/no beta blocker; 238 sprionolactone\/beta blocker), were randomized to placebo or candesartan and followed for 41 months (median). The primary outcome was cardiovascular death or HF hospitalization. In patients taking both a beta blocker and spironolactone (in addition to an ACE-I) at baseline, the candesartan:placebo hazard ratio was 0.85(95% CI 0.56, 1.29), compared to 0.85(95% CI 0.75, 0.96) in all randomized patients (interaction p value 0.49).<\/jats:p>\n                    <jats:p>The relative risk of discontinuation of candesartan (compared to placebo) because of hypotension, increased serum creatinine or hyperkalemia was not increased in patients taking spironolactone at baseline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>An ARB may provide added benefit, at acceptable risk, in HF patients already taking spironolactone as well as an ACE-I and beta blocker. These findings must be confirmed in a prospective randomized trial before this approach can be recommended, routinely.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.ejheart.2007.12.006","type":"journal-article","created":{"date-parts":[[2008,2,2]],"date-time":"2008-02-02T07:50:36Z","timestamp":1201938636000},"page":"157-163","source":"Crossref","is-referenced-by-count":23,"title":["Efficacy and Tolerability of Adding an Angiotensin Receptor Blocker in Patients with Heart Failure Already Receiving an Angiotensin-Converting Inhibitor Plus Aldosterone Antagonist, With or Without a Beta Blocker. Findings from the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM)-Added Trial"],"prefix":"10.1093","volume":"10","author":[{"given":"R.A.P.","family":"Weir","sequence":"first","affiliation":[{"name":"Department of Cardiology, Western Infirmary , Glasgow, G11 6NT ,","place":["United Kingdom"]},{"name":"Faculty of Medicine, University of Glasgow \u00a0","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John J.V.","family":"McMurray","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Western Infirmary , Glasgow, G11 6NT ,","place":["United Kingdom"]},{"name":"Faculty of Medicine, University of Glasgow \u00a0","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margareta","family":"Puu","sequence":"additional","affiliation":[{"name":"AstraZeneca R&D , M\u00f6lndal ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott D.","family":"Solomon","sequence":"additional","affiliation":[{"name":"Brigham & Women's Hospital , Boston, MA ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bertil","family":"Olofsson","sequence":"additional","affiliation":[{"name":"AstraZeneca R&D , M\u00f6lndal ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher B.","family":"Granger","sequence":"additional","affiliation":[{"name":"Duke University Medical Center , Durham, NC ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salim","family":"Yusuf","sequence":"additional","affiliation":[{"name":"HGM-McMaster Clinic , Hamilton, Ontario ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric L.","family":"Michelson","sequence":"additional","affiliation":[{"name":"AstraZeneca LP , Wilmington, DE ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl","family":"Swedberg","sequence":"additional","affiliation":[{"name":"Department of Medicine, Sahlgrenska University Hospital\/\u00d6stra , G\u00f6teborg ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc A.","family":"Pfeffer","sequence":"additional","affiliation":[{"name":"Brigham & Women's Hospital , Boston, MA ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"CHARM Investigators","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,1,13]]},"reference":[{"key":"2026020203434992400_ejhf2007-12-006-bib-0001","first-page":"1429","article-title":"Effects of enalapril on mortality in severe congestive heart failure. 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