Physicians' Academy for Cardiovascular Education

AQUARIUS: Aliskiren does not significantly reduce atheromavolume, but shows fewer MACE

News - Sep. 4, 2013

AQUARIUS: Effect of the Renin Inhibitor Aliskiren on Progression of Coronary Atherosclerosis: AQUARIUS Study Results

Presented at the ESC congress 2013 by: Stephen James NICHOLLS (Adelaide, AU)


A returning question in clinical practice is what is the ideal blood pressure to aim for in patients with coronary artery disease. Inhibiting the renin system is an attractive approach, since the RAAS system also has a role in the development of atherosclerosis. The Aliskiren Quantitative Atherosclerosis Regression Intravascular Ultrasound Study (AQUARIUS) was set up to assess development of atherosclerotic disease, as measured with intravascular ultrasound (IVUS), while treating with aliskiren, and to compare this to placebo treatment. Aliskiren was given in addition tot standard therapy in patients with coronary artery disease and a prehypertensive blood pressure (SBP: 125-139 mmHg, DBP <90 mmHg).

Main results

  • The primary endpoint of change in percentage atheroma volume (PAV) was not met, since the observed difference was not statistically significant. A strong trend was seen towards regression of the atheroma with aliskiren (-0.33 vs +0.11%, P=0.08).
  • The difference in total atheroma volume (TAV) did not reach statistical significance either (-4.1 mm3 after aliskiren, -2.1 mm3 after placebo, P=0.18).
  • Although the study had not been set up to detect a difference in clinical outcomes, a lower rate of major adverse clinical events (MACE) was seen after treatment with aliskiren (26/205), as compared to placebo treatment (50/308, P=0.004).
    Furthermore, significantly fewer myocardial infarcts occurred in the aliskiren group (n=1) as compared to the placebo group (n=8, P=0.02).
    A strong trend was seen towards lower mortality after aliskiren (n=1) as compared to placebo (n=6, P=0.07).


Although the primary endpoint was not met, a strong trend towards regression of the atherosclerotic plaque was observed in patients who were treated with aliskiren 300 mg. Significantly fewer MACE were seen in the aliskiren arm. This indicates that there is a potential benefit of further lowering of blood pressure in prehypertensive patients. More and larger studies will need to help define the target values for blood pressure in this patient group.
In the panel discussion at the ESC congress it was mentioned that the analysis to test for a relationship between blood pressure lowering and MACE had not been performed yet. However, since the decreases in blood pressure were relatively low, it might be that the effects of inhibition of the renin system with aliskiren go beyond lowering blood pressure, possibly by limiting progression of atherosclerotic disease. The lower MACE rate could be a consequence thereof.
Based on the results of the ALTITUDE study, the researchers had to take diabetic patients out of the study prematurely. It is possible that aliskiren does not have beneficial effects for plaque regression in this subgroup of patients.

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