{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:06:50Z","timestamp":1791295610622,"version":"4.1.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2013,12,11]],"date-time":"2013-12-11T00:00:00Z","timestamp":1386720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["546272"],"award-info":[{"award-number":["546272"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Impaired renal function is associated with worse clinical outcomes in patients with LV systolic dysfunction (LVSD) and heart failure. Renin\u2013angiotensin\u2013aldosterone system (RAAS) inhibitors provide clinical benefit in these settings and often worsen renal function. It is not clear whether worsening renal function (WRF) in patients exposed to these agents predicts a worse prognosis or merely reflects the pharmacological action of the drug on the kidney.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We performed a meta-analysis of all RAAS inhibitor LVSD trials reporting on outcomes according to WRF (as per individual study definition) in both active intervention and placebo groups. Five major studies (SOLVD, SAVE, RALES, Val-HeFT and EPHESUS) contributed, with 20\u2009573 patients. Compared with placebo, RAAS inhibitors reduced all-cause mortality overall [n\u2009=\u200920\u2009573, relative risk ratio (RR) 0.91, 95% confidence interval (CI) 0.86\u20130.95, P\u2009=\u20090.0003], in the group with no WRF (n\u2009=\u200918\u2009209, RR 0.91, 95% CI 0.83\u20130.99, P\u2009=\u20090.04), and in the WRF group (n\u2009=\u20092364, RR 0.72, 95% CI 0.62\u20130.84, P\u2009&amp;lt;\u20090.0001). Compared with no WRF, WRF was associated with increased all-cause mortality; however, this was less in the RAAS inhibitor group (n\u2009=\u20098905, RR 1.22, 95% CI 1.10\u20131.36, P\u2009=\u20090.0003) than in the placebo group (n\u2009=\u20099304, RR 1.52, 95% CI 1.37\u20131.69, P\u2009&amp;lt;\u20090.00001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>WRF shortly after randomization is associated with worsened outcomes compared with no WRF; however, the reduction in all-cause mortality associated with the use of RAAS inhibitors was significantly greater in the presence of WRF than in the no WRF group. Clinicians should not be deterred from using RAAS inhibitors in the setting of WRF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.13","type":"journal-article","created":{"date-parts":[[2014,1,2]],"date-time":"2014-01-02T11:04:35Z","timestamp":1388660675000},"page":"41-48","source":"Crossref","is-referenced-by-count":104,"title":["Worsening Renal Function During Renin\u2013Angiotensin\u2013Aldosterone System Inhibitor Initiation and Long-Term Outcomes in Patients with Left Ventricular Systolic Dysfunction"],"prefix":"10.1093","volume":"16","author":[{"given":"Hannah","family":"Clark","sequence":"first","affiliation":[{"name":"Centre of Cardiovascular Research & Education in Therapeutics, School of Public Health and Preventive Medicine, Monash University , Victoria, 3004 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Krum","sequence":"additional","affiliation":[{"name":"Centre of Cardiovascular Research & Education in Therapeutics, School of Public Health and Preventive Medicine, Monash University , Victoria, 3004 ,","place":["Australia"]},{"name":"Department of Clinical Pharmacology, The Alfred Hospital , Melbourne ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Hopper","sequence":"additional","affiliation":[{"name":"Centre of Cardiovascular Research & Education in Therapeutics, School of Public Health and Preventive Medicine, Monash University , Victoria, 3004 ,","place":["Australia"]},{"name":"Department of Clinical Pharmacology, The Alfred Hospital , Melbourne ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,12,11]]},"reference":[{"key":"2026011921105536200_ejhf13-bib-0001","doi-asserted-by":"crossref","first-page":"3667","DOI":"10.1161\/01.CIR.0000149806.01354.BF","article-title":"Chronic kidney disease, cardiovascular risk, and response 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