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

Study Questions:

What are the effects of renin inhibition with aliskiren on progression of coronary atherosclerosis in prehypertensive patients?


AQUARIUS (Aliskiren Quantitative Atherosclerosis Regression Intravascular Ultrasound Study) was a double-blind, randomized, multicenter trial (n = 613). Eligible participants had coronary artery disease (at least one 20% stenosis on clinically indicated coronary angiography and a target vessel for imaging with <50% obstruction), prehypertension (systolic blood pressure between 125 and 139 mm Hg and diastolic blood pressure <90 mm Hg), and two additional cardiovascular risk factors. Participants were randomized to receive 300 mg of aliskiren (n = 305) or placebo (n = 308) taken orally daily for 104 weeks. Following coronary angiography, baseline imaging of the target vessel was performed with intravascular ultrasound (IVUS); repeat examination was performed after at least 72 weeks of treatment. The primary efficacy parameter was the change in percent atheroma volume (PAV) from baseline to study completion.


The primary IVUS efficacy parameter, PAV, did not differ between participants treated with aliskiren (-0.33%; 95% confidence interval [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 = 0.08).


The authors concluded that aliskiren did not slow the progression of coronary atherosclerosis by IVUS in patients with prehypertension and nonobstructive coronary artery disease.


Findings from the AQUARIUS trial provide evidence against the use of direct renin inhibition for regression or prevention of progression of coronary atherosclerosis. Trials of add-on aliskiren therapy have also been disappointing in systolic heart failure and in patients with type 2 diabetes mellitus. The role of renin inhibition with aliskiren remains limited.

Clinical Topics: Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Novel Agents, Acute Heart Failure, Chronic Heart Failure, Interventions and Coronary Artery Disease, Interventions and Imaging, Interventions and Vascular Medicine, Angiography, Nuclear Imaging

Keywords: Coronary Artery Disease, Plaque, Atherosclerotic, Renin, Diabetes Mellitus, Type 2, Blood Pressure, Prehypertension, Risk Factors, Constriction, Pathologic, Angioplasty, Balloon, Coronary, Heart Failure, Systolic, Fumarates, Coronary Angiography, Confidence Intervals

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