RT Journal Article SR Electronic T1 Ramipril and Cardiovascular Outcomes in Patients on Maintenance Hemodialysis JF Clinical Journal of the American Society of Nephrology JO CLIN J AM SOC NEPHROL FD American Society of Nephrology SP 575 OP 587 DO 10.2215/CJN.12940820 VO 16 IS 4 A1 Ruggenenti, Piero A1 Podestà, Manuel Alfredo A1 Trillini, Matias A1 Perna, Annalisa A1 Peracchi, Tobia A1 Rubis, Nadia A1 Villa, Davide A1 Martinetti, Davide A1 Cortinovis, Monica A1 Ondei, Patrizia A1 Condemi, Carmela Giuseppina A1 Guastoni, Carlo Maria A1 Meterangelis, Agnese A1 Granata, Antonio A1 Mambelli, Emanuele A1 Pasquali, Sonia A1 Genovesi, Simonetta A1 Pieruzzi, Federico A1 Bertoli, Silvio Volmer A1 Del Rosso, Goffredo A1 Garozzo, Maurizio A1 Rigotti, Angelo A1 Pozzi, Claudio A1 David, Salvatore A1 Daidone, Giuseppe A1 Mingardi, Giulio A1 Mosconi, Giovanni A1 Galfré, Andrea A1 Romei Longhena, Giorgio A1 Pacitti, Alfonso A1 Pani, Antonello A1 Hidalgo Godoy, Jorge A1 Anders, Hans-Joachim A1 Remuzzi, Giuseppe A1 , YR 2021 UL http://cjasn.asnjournals.org/content/16/4/575.abstract AB Background and objectives 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.Design, setting, participants, & measurements 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 (1.25–10 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.Results 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; P=0.80). Ramipril reduced cardiac mass index at 1 year of follow-up (between-group difference in change from baseline: −16.3 g/m2; 95% confidence interval, −29.4 to −3.1), 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.Conclusions Ramipril did not reduce the risk of major cardiovascular events in patients on maintenance hemodialysis.Clinical Trial registry name and registration number: ARCADIA, NCT00985322 and European Union Drug Regulating Authorities Clinical Trials Database number 2008–003529–17.