The AQUARIUS trial: Aliskiren does not slow progression of atherosclerosis

The renin-angiotensin-aldosterone system (RAAS) appears to have an important role in the development of atherosclerosis.  The Aliskiren Quantitative Atherosclerosis Regression Intravascular Ultrasound Study (AQUARIUS) sought to determine if direct renin inhibition with aliskiren slows atherosclerosis progression in patients with already controlled blood pressure.

The AQUARIUS study was a randomized, double-blinded trial comparing the effect of aliskiren versus placebo on atherosclerosis progression in coronary arteries as measured by intravascular ultrasound (IVUS) imaging. Eligible patients had at least one 20% stenosis on clinically indicated coronary angiography, controlled blood pressure (systolic blood pressure 125-139 mmHg and diastolic <90 mmHg), and 2 additional cardiovascular risk factors. Primary efficacy outcome was change in percent atheroma volume (PAV) and secondary efficacy outcome was change in normalized total atheroma volume (TAV) as assessed by IVUS.

Overall, 458 (74.7%) of randomized patients had evaluable IVUS data at baseline and follow-up. There were no significant differences in PAV (between group PAV difference = -0.43%, 95% CI -0.92% to 0.05%) or TAV (between group TAV difference= -2.04mm3, 95% CI -5.03 to 0.95mm3) outcomes in patients on aliskiren compared to placebo. In pre-specified exploratory analyses, treatment with aliskiren was associated with lower major adverse cardiovascular events (HR 0.50, 95% CI 0.31-0.81).

Conclusions: Treatment with aliskiren did not slow progression of atherosclerosis in patients without hypertension. While there was a lower incidence of major adverse cardiovascular events with aliskiren, this analysis was exploratory. Accordingly, current evidence does not support use of aliskiren for secondary prevention in patients with prehypertension and coronary artery disease.

  • ¬†Nicholls SJ, Bakris GL, Kastelein JJ,¬† et al. Effect of aliskiren on progression of coronary disease in patients with prehypertension: The aquarius randomized clinical trial. JAMA : the journal of the American Medical Association. 2013;310:1135-1144