{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T07:50:48Z","timestamp":1790495448080,"version":"4.1.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>Renin\u2013angiotensin aldosterone system (RAAS) inhibitors significantly improve outcome in heart failure (HF) patients with reduced ejection fraction (HFREF), irrespective of the occurrence of worsening renal function (WRF). However, in HF patients with preserved ejection fraction (HFPEF), RAAS inhibitors have not been shown to improve outcome but are still frequently prescribed.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              Random effect meta-analysis was performed to investigate the relationship between RAAS inhibitor therapy, WRF in both HF phenotypes, and mortality. Studies were selected based on literature search in MEDLNE and included randomized, placebo controlled trials of RAAS inhibitors in chronic HF. The primary outcome consisted of the interaction analysis for the association between RAAS inhibition\u2013induced WRF, HF phenotype and outcome. A total of 8 studies (6 HFREF and 2 HFPEF, including 28\u2009961 patients) were included in our analysis. WRF was more frequent in the RAAS inhibitor group, compared with the placebo group, in both HFREF and HFPEF. In HFREF, WRF induced by RAAS inhibitor therapy was associated with a less increased relative risk of mortality (relative risk, 1.19 (1.08\u20131.31);\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001), compared with WRF induced by placebo (relative risk, 1.48 (1.35\u20131.62);\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001;\n              <jats:italic>P<\/jats:italic>\n              for interaction 0.005). In contrast, WRF induced by RAAS inhibitor therapy was strongly associated with worse outcomes in HFPEF (relative risk, 1.78 (1.43\u20132.21);\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001), whereas placebo-induced WRF was not (relative risk, 1.25 (0.88\u20131.77);\n              <jats:italic>P<\/jats:italic>\n              =0.21;\n              <jats:italic>P<\/jats:italic>\n              for interaction 0.002).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>RAAS inhibitors induce renal dysfunction in both HFREF and HFPEF. However, in contrast to patients with HFREF where mortality increase with WRF is small, HFPEF patients with RAAS inhibitor\u2013induced WRF have an increased mortality risk, without experiencing improved outcome with RAAS inhibition.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.116.003588","type":"journal-article","created":{"date-parts":[[2017,2,17]],"date-time":"2017-02-17T02:10:33Z","timestamp":1487297433000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":113,"title":["Renin\u2013Angiotensin System Inhibition, Worsening Renal Function, and Outcome in Heart Failure Patients With Reduced and Preserved Ejection Fraction"],"prefix":"10.1161","volume":"10","author":[{"given":"Iris E.","family":"Beldhuis","sequence":"first","affiliation":[{"name":"From the Department of Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands (I.E.B., K.W.S., J.M.T.M., A.A.V., P.v.d.M., K.D.); Inserm, Centre d\u2019Investigations Cliniques-Plurith\u00e9matique 1433, Inserm U1116; CHRU Nancy, France (P.R.); Universit\u00e9 de Lorraine, F-CRIN INI-CRCT Network, Nancy, France (P.R.); and British Heart Foundation Cardiovascular Research Centre, University of Glasgow, United Kingdom (J.J.V.M.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koen W.","family":"Streng","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands (I.E.B., K.W.S., J.M.T.M., A.A.V., P.v.d.M., K.D.); Inserm, Centre d\u2019Investigations Cliniques-Plurith\u00e9matique 1433, Inserm U1116; CHRU Nancy, France (P.R.); Universit\u00e9 de Lorraine, F-CRIN INI-CRCT Network, Nancy, France (P.R.); and British Heart Foundation Cardiovascular Research Centre, University of Glasgow, United Kingdom (J.J.V.M.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jozine M.","family":"Ter Maaten","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands (I.E.B., K.W.S., J.M.T.M., A.A.V., P.v.d.M., K.D.); Inserm, Centre d\u2019Investigations Cliniques-Plurith\u00e9matique 1433, Inserm U1116; CHRU Nancy, France (P.R.); Universit\u00e9 de Lorraine, F-CRIN INI-CRCT Network, Nancy, France (P.R.); and British Heart Foundation Cardiovascular Research Centre, University of Glasgow, United Kingdom (J.J.V.M.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan A.","family":"Voors","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands (I.E.B., K.W.S., J.M.T.M., A.A.V., P.v.d.M., K.D.); Inserm, Centre d\u2019Investigations Cliniques-Plurith\u00e9matique 1433, Inserm U1116; CHRU Nancy, France (P.R.); Universit\u00e9 de Lorraine, F-CRIN INI-CRCT Network, Nancy, France (P.R.); and British Heart Foundation Cardiovascular Research Centre, University of Glasgow, United Kingdom (J.J.V.M.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"van der Meer","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands (I.E.B., K.W.S., J.M.T.M., A.A.V., P.v.d.M., K.D.); Inserm, Centre d\u2019Investigations Cliniques-Plurith\u00e9matique 1433, Inserm U1116; CHRU Nancy, France (P.R.); Universit\u00e9 de Lorraine, F-CRIN INI-CRCT Network, Nancy, France (P.R.); and British Heart Foundation Cardiovascular Research Centre, University of Glasgow, United Kingdom (J.J.V.M.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Rossignol","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands (I.E.B., K.W.S., J.M.T.M., A.A.V., P.v.d.M., K.D.); Inserm, Centre d\u2019Investigations Cliniques-Plurith\u00e9matique 1433, Inserm U1116; CHRU Nancy, France (P.R.); Universit\u00e9 de Lorraine, F-CRIN INI-CRCT Network, Nancy, France (P.R.); and British Heart Foundation Cardiovascular Research Centre, University of Glasgow, United Kingdom (J.J.V.M.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.V.","family":"McMurray","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands (I.E.B., K.W.S., J.M.T.M., A.A.V., P.v.d.M., K.D.); Inserm, Centre d\u2019Investigations Cliniques-Plurith\u00e9matique 1433, Inserm U1116; CHRU Nancy, France (P.R.); Universit\u00e9 de Lorraine, F-CRIN INI-CRCT Network, Nancy, France (P.R.); and British Heart Foundation Cardiovascular Research Centre, University of Glasgow, United Kingdom (J.J.V.M.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Damman","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands (I.E.B., K.W.S., J.M.T.M., A.A.V., P.v.d.M., K.D.); Inserm, Centre d\u2019Investigations Cliniques-Plurith\u00e9matique 1433, Inserm U1116; CHRU Nancy, France (P.R.); Universit\u00e9 de Lorraine, F-CRIN INI-CRCT Network, Nancy, France (P.R.); and British Heart Foundation Cardiovascular Research Centre, University of Glasgow, United Kingdom (J.J.V.M.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw128"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht386"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.13"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu320"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1313731"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2014.01.087"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.609"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hft089"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2012.07.048"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.028282"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.113.000792"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehl250"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.905"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d5928"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.326.7382.219"},{"key":"e_1_3_3_17_2","unstructured":"The Cochrane Collaboration. 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