{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T17:01:45Z","timestamp":1788195705384,"version":"build-2803163510"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","funder":[{"DOI":"10.13039\/501100003197","name":"Agenzia Italiana del Farmaco, Ministero della Salute","doi-asserted-by":"publisher","award":["FARM 6WE4PP"],"award-info":[{"award-number":["FARM 6WE4PP"]}],"id":[{"id":"10.13039\/501100003197","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>Renin-angiotensin system (RAS) inhibitors reduce cardiovascular morbidity and mortality in patients with CKD. We evaluated the cardioprotective effects of the angiotensin-converting enzyme inhibitor ramipril in patients on maintenance hemodialysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, setting, participants, &amp; measurements<\/jats:title>\n                    <jats:p>In this phase 3, prospective, randomized, open-label, blinded end point, parallel, multicenter trial, we recruited patients on maintenance hemodialysis with hypertension and\/or left ventricular hypertrophy from 28 Italian centers. Between July 2009 and February 2014, 140 participants were randomized to ramipril (1.25\u201310 mg\/d) and 129 participants were allocated to non-RAS inhibition therapy, both titrated up to the maximally tolerated dose to achieve predefined target BP values. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the single components of the primary end point, new-onset or recurrence of atrial fibrillation, hospitalizations for symptomatic fluid overload, thrombosis or stenosis of the arteriovenous fistula, and changes in cardiac mass index. All outcomes were evaluated up to 42 months after randomization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At comparable BP control, 23 participants on ramipril (16%) and 24 on non-RAS inhibitor therapy (19%) reached the primary composite end point (hazard ratio, 0.93; 95% confidence interval, 0.52 to 1.64;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.80). Ramipril reduced cardiac mass index at 1 year of follow-up (between-group difference in change from baseline: \u221216.3 g\/m\n                      <jats:sup>2<\/jats:sup>\n                      ; 95% confidence interval, \u221229.4 to \u22123.1), but did not significantly affect the other secondary outcomes. Hypotensive episodes were more frequent in participants allocated to ramipril than controls (41% versus 12%). Twenty participants on ramipril and nine controls developed cancer, including six gastrointestinal malignancies on ramipril (four were fatal), compared with none in controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Ramipril did not reduce the risk of major cardiovascular events in patients on maintenance hemodialysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial registry name and registration number:<\/jats:title>\n                    <jats:p>ARCADIA, NCT00985322 and European Union Drug Regulating Authorities Clinical Trials Database number 2008\u2013003529\u201317.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2215\/cjn.12940820","type":"journal-article","created":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T17:30:17Z","timestamp":1617039017000},"page":"575-587","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":16,"title":["Ramipril and Cardiovascular Outcomes in Patients on Maintenance Hemodialysis"],"prefix":"10.2215","volume":"16","clinical-trial-number":[{"clinical-trial-number":"nct00985322","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Piero","family":"Ruggenenti","sequence":"first","affiliation":[{"name":"Department of Renal Medicine, Clinical Research Centre for Rare Diseases \u201cAldo e Cele Dacc\u00f2\u201d, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy"},{"name":"Unit of Nephrology and Dialysis, Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6684-2524","authenticated-orcid":false,"given":"Manuel Alfredo","family":"Podest\u00e0","sequence":"additional","affiliation":[{"name":"Department of Renal Medicine, Clinical Research Centre for Rare Diseases \u201cAldo e Cele Dacc\u00f2\u201d, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy"},{"name":"Unit of Nephrology and Dialysis, Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matias","family":"Trillini","sequence":"additional","affiliation":[{"name":"Department of Renal Medicine, Clinical Research Centre for Rare Diseases \u201cAldo e Cele Dacc\u00f2\u201d, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Perna","sequence":"additional","affiliation":[{"name":"Department of Renal Medicine, Clinical Research Centre for Rare Diseases \u201cAldo e Cele Dacc\u00f2\u201d, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobia","family":"Peracchi","sequence":"additional","affiliation":[{"name":"Department of Renal Medicine, Clinical Research Centre for Rare Diseases \u201cAldo e Cele Dacc\u00f2\u201d, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Rubis","sequence":"additional","affiliation":[{"name":"Department of Renal Medicine, Clinical Research Centre for Rare Diseases \u201cAldo e Cele Dacc\u00f2\u201d, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, 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