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Original Investigation
September 18, 2013

Effect of Aliskiren on Progression of Coronary Disease in Patients With Prehypertension: The AQUARIUS Randomized Clinical Trial

Author Affiliations
  • 1South Australian Health and Medical Research Institute, Adelaide, Australia
  • 2Department of Medicine, ASH Comprehensive Hypertension Center, University of Chicago Medicine, Chicago, Illinois
  • 3Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands
  • 4Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio
  • 5Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, Ohio
  • 6National Institute for Health Research, University College London Hospitals Biomedical Research Centre, London, England
  • 7Novartis Pharmaceuticals, Basel, Switzerland
JAMA. 2013;310(11):1135-1144. doi:10.1001/jama.2013.277169

Importance  Blood pressure reduction and renin-angiotensin-aldosterone system inhibition are targets for treatment of atherosclerosis. The effect of renin inhibition on coronary disease progression has not been investigated.

Objective  To determine the effects of renin inhibition with aliskiren on progression of coronary atherosclerosis.

Design, Setting, and Participants  A double-blind, randomized, multicenter trial (Aliskiren Quantitative Atherosclerosis Regression Intravascular Ultrasound Study) comparing aliskiren with placebo in 613 participants with coronary artery disease, systolic blood pressure between 125 and 139 mm Hg (prehypertension range), and 2 additional cardiovascular risk factors conducted at 103 academic and community hospitals in Europe, Australia, and North and South America (enrollment from March 2009 to February 2011; end of follow-up: January 31, 2013).

Interventions  Participants underwent coronary intravascular ultrasound (IVUS) imaging and were randomized to receive 300 mg of aliskiren (n = 305) or placebo (n = 308) taken orally daily for 104 weeks. Disease progression was measured by repeat IVUS examination after at least 72 weeks of treatment.

Main Outcomes and Measures  The primary efficacy parameter was the change in percent atheroma volume (PAV) from baseline to study completion. Secondary efficacy parameters included the change in normalized total atheroma volume (TAV) and the percentage of participants with atheroma regression. Safety and tolerability were also assessed.

Results  Evaluable imaging data were available at baseline and follow-up for 458 participants (74.7%). The primary IVUS efficacy parameter, PAV, did not differ between participants treated with aliskiren (−0.33%; 95% CI, −0.68% to 0.02%) and placebo (0.11%; 95% CI, −0.24% to 0.45%) (between-group difference, −0.43% [95% CI, −0.92% to 0.05%]; P = .08). The secondary IVUS efficacy parameter, TAV, did not differ between participants treated with aliskiren (−4.1 mm3; 95% CI, −6.27 to −1.94 mm3) and placebo (−2.1 mm3; 95% CI, −4.21 to 0.07 mm3) (between-group difference, −2.04 mm3 [95% CI, −5.03 to 0.95 mm3]; P = .18). There were no significant differences in the proportion of participants who demonstrated regression of PAV (56.9% vs 48.9%; P = .08) and TAV (64.4% vs 57.5%; P = .13) in the aliskiren and placebo groups, respectively.

Conclusions and Relevance  Among participants with prehypertension and coronary artery disease, the use of aliskiren compared with placebo did not result in improvement or slowing of progression of coronary atherosclerosis. These findings do not support the use of aliskiren for regression or prevention of progression of coronary atherosclerosis.

Trial Registration  clinicaltrials.gov Identifier: NCT00853827.