{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T17:23:47Z","timestamp":1788283427152,"version":"build-2803163510"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":27,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011725","name":"Servier","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To assess the impact of angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) on all-cause and cardiovascular (CV) mortality, as well as CV, cerebrovascular, and renal outcomes in patients at high\/very-high CV risk without heart failure by a systematic review and meta-analysis of placebo-controlled, double-blind, randomized trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>The CENTRAL, ClinicalTrials.gov, Ovid-MEDLINE, Ovid-Embase, Science Citation Index-Expanded, and WHO-ICTRP databases were searched between August and September 2023. Heart failure trials were excluded. The hypothesis of a homogeneous treatment effect between ACE-Is and ARBs was tested with a Cochran\u2019s Q statistic. The protocol for the systematic review was registered on PROSPERO (CRD42023452406) and the study reported as per PRISMA guidelines.<\/jats:p>\n                    <jats:p>17 trials (9 ACE-Is and 8 ARBs, total of 87 908 participants) were included. The event rates for all-cause mortality, CV mortality, and major CV events (MACEs) did not differ in the parallel placebo arms of ACE-I and ARB trials; however, compared to placebo, ACE-Is reduced the rate of CV mortality [hazard ratio (HR) 0.88; 95% confidence interval (CI) 0.78\u20130.99], all-cause mortality (HR 0.92; 95% CI 0.85\u20130.99) and myocardial infarction (HR 0.83; 95% CI 0.73\u20130.94), while ARBs did not. The rates of HF, stroke, and MACEs were significantly reduced by both drug classes. Angiotensin-converting enzyme inhibitors induced a greater reduction of CV mortality than ARBs (Q = 4.59; P-value = 0.03).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In patients at high\/very-high CV risk, ACE-Is were more protective against CV mortality than ARBs, supporting their preferential use for CV protection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ehjopen\/oeag119","type":"journal-article","created":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T11:37:54Z","timestamp":1783856274000},"source":"Crossref","is-referenced-by-count":2,"title":["Impact of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on cardiovascular and non-cardiovascular outcomes in patients at high\/very-high cardiovascular risk without heart failure: a systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7591-3686","authenticated-orcid":false,"given":"Stefano","family":"Masi","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa , Via Roma, 67, Pisa 56126 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7732-0887","authenticated-orcid":false,"given":"Gianluigi","family":"Savarese","sequence":"additional","affiliation":[{"name":"Department of Clinical Science and Education at S\u00f6dersjukhuset, Karolinska Institutet , Stockholm 171 77 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Orsini","sequence":"additional","affiliation":[{"name":"Department of Global Public Health, Karolinska Institutet , Norrbackagatan 4, Stockholm 171 76 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