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Ramipril and Cardiovascular Outcomes in Patients on Maintenance Hemodialysis: The ARCADIA Multicenter Randomized
Piero Ruggenenti1,2, Manuel Alfredo Podestà1,2, Matias Trillini1
1Department of Renal Medicine, Clinical Research Centre for Rare Diseases "Aldo e Cele Daccò", Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy.
Insights
Ramipril, an ACE inhibitor, did not significantly lower major cardiovascular events in patients undergoing maintenance hemodialysis. The study found no reduction in cardiovascular death, heart attack, or stroke with ramipril compared to other therapies.
Area of Science:
- Nephrology
- Cardiology
- Clinical Trials
Background:
- Renin-angiotensin system (RAS) inhibitors are known to reduce cardiovascular risks in chronic kidney disease (CKD) patients.
- The cardioprotective effects of angiotensin-converting enzyme (ACE) inhibitors, specifically ramipril, were investigated in patients on maintenance hemodialysis.
Purpose of the Study:
- To evaluate the efficacy of ramipril in reducing major adverse cardiovascular events in patients undergoing maintenance hemodialysis.
- To assess the impact of ramipril on secondary cardiovascular outcomes and cardiac mass index in this patient population.
Main Methods:
- A phase 3, prospective, randomized, open-label, blinded end-point, parallel, multicenter trial (ARCADIA) was conducted.
- 140 patients on maintenance hemodialysis with hypertension and/or left ventricular hypertrophy received ramipril, while 129 received non-RAS inhibition therapy.
- The primary endpoint was a composite of cardiovascular death, myocardial infarction, or stroke, with follow-up up to 42 months.
Main Results:
- At comparable blood pressure control, ramipril did not significantly reduce the primary composite endpoint (16% vs. 19%, P=0.80).
- Ramipril led to a significant reduction in cardiac mass index at 1 year but did not impact other secondary outcomes.
- Hypotensive episodes were more frequent with ramipril, and a higher incidence of cancer, including fatal gastrointestinal malignancies, was observed.
Conclusions:
- Ramipril did not demonstrate a significant benefit in reducing major cardiovascular events for patients on maintenance hemodialysis.
- The study highlights potential safety concerns, including increased hypotension and cancer risk, associated with ramipril in this population.
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.
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