{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T20:58:02Z","timestamp":1791579482927,"version":"4.3.4"},"reference-count":30,"publisher":"Oxford University Press (OUP)","funder":[{"name":"Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development","award":["I01HX002422"],"award-info":[{"award-number":["I01HX002422"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>In randomized controlled trials, target-dose angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) improved clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF), although the mortality reduction was not statistically significant. Target doses worsened kidney function, but kidney failure (KF) was not evaluated. We compared KF and mortality between below-target-dose and target-dose ACEIs and ARBs in patients with HFrEF, overall and stratified by advanced chronic kidney disease (CKD) status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Of the 154 945 Veterans with HFrEF (left ventricular ejection fraction \u2264 40%) and no baseline KF, 134 046 were initiated on ACEIs (target-dose, n = 37 667), and 20 899 were initiated on ARBs (target-dose, n = 4017) during 2000\u201318. While remaining blinded to study outcomes, we assembled two propensity score-matched cohorts: ACEI (N = 70 860; target-dose, n = 35 430) and ARB (N = 7900; target-dose, n = 3950), balanced on 76 baseline characteristics. Hazard ratios [95% confidence intervals (CIs)] associated with target doses were estimated for 5-year KF and 5-year all-cause mortality, through 31 December 2023.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the ACEI cohort, target-dose was associated with an 18% (95% CI, 11%\u201325%) lower risk of KF and a 6% (95% CI, 3%\u20138%) lower risk of death. Subgroup and spline analyses showed that the KF association was significant among those with baseline estimated glomerular filtration rate &amp;lt; 35\u2005mL\/min\/1.73\u2005m2, whereas the mortality association was significant among those with estimated glomerular filtration rate \u2265 35\u2005mL\/min\/1.73\u2005m2. Target-dose ACEIs were associated with a 3% (95% CI, 1%\u20136%) higher risk of heart failure hospitalization and a 7% (95% CI, 0%\u201314%) higher risk of hospitalization due to acute kidney injury. In the ARB cohort, target-dose had no association with outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Among patients with HFrEF, target-dose (vs below-target-dose) ACEIs, but not ARBs, were associated with a lower risk of KF (despite a higher risk of AKI), which was limited to those with advanced chronic kidney disease. The survival benefit was modest and limited to those without advanced chronic kidney disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejhf\/xuag076","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T12:38:04Z","timestamp":1772800684000},"source":"Crossref","is-referenced-by-count":6,"title":["Target-dose vs below-target-dose ACE inhibitors and lower risk of kidney failure and mortality in US Veterans with HFrEF"],"prefix":"10.1093","author":[{"given":"Amiya A","family":"Ahmed","sequence":"first","affiliation":[{"name":"Center for Data Science and Outcomes Research, Veterans Affairs Medical Center, Washington DC Veterans Affairs Medical Center , 50 Irving St. NW, Washington, DC 20422 ,","place":["USA"]},{"name":"Department of Internal Medicine, Yale University , New Haven, CT ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick","family":"Lu","sequence":"additional","affiliation":[{"name":"Center for Data Science and Outcomes Research, Veterans Affairs Medical Center, Washington DC Veterans Affairs Medical Center , 50 Irving St. NW, Washington, DC 20422 ,","place":["USA"]},{"name":"Department of Medicine, Brown University , Providence, RI ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Data Science and Outcomes Research, Veterans Affairs Medical Center, Washington DC Veterans Affairs Medical Center , 50 Irving St. NW, Washington, DC 20422 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkatesh K","family":"Raman","sequence":"additional","affiliation":[{"name":"Center for Data Science and Outcomes Research, Veterans Affairs Medical Center, Washington DC Veterans 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, Birmingham, AL ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Faselis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Veterans Affairs Medical Center , Palo Alto, CA ,","place":["USA"]},{"name":"Department of Medicine, Stanford School of Medicine , Palo Alto, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip H","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Medicine, Georgetown University , Washington, DC ,","place":["USA"]},{"name":"Department of Cardiology, MedStar Heart and Vascular Institute , Washington, DC ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregg C","family":"Fonarow","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California , Los Angeles, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A","family":"Heidenreich","sequence":"additional","affiliation":[{"name":"Department of Medicine, Veterans Affairs Medical Center , Palo Alto, CA ,","place":["USA"]},{"name":"Department of Medicine, Stanford School of Medicine , Palo Alto, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7596-4697","authenticated-orcid":false,"given":"Tariq","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale University , New Haven, CT ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0805-8683","authenticated-orcid":false,"given":"Stefan D","family":"Anker","sequence":"additional","affiliation":[{"name":"Department of Cardiology (CVK) of German Heart Center Charit\u00e9; German Centre for Cardiovascular Research (DZHK) Partner Site Berlin, Charit\u00e9 Universit\u00e4tsmedizin , Berlin 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