A study has found that among patients with prehypertension and coronary artery disease, use of the renin (an enzyme secreted by the kidneys) inhibitor aliskiren, compared with placebo, did not result in improvement or slowing in the progression of coronary atherosclerosis. The study was study published by JAMA. The study is being released early online to coincide with its presentation at the European Society of Cardiology Congress 2013.
"Guidelines recommend blood pressure reduction in patients with hypertension with a treatment goal of 140 mm Hg for systolic and 90 mm Hg diastolic blood pressure for most individuals. The benefit of additional blood pressure lowering agents in patients who have reached treatment goals has not been established. However, few trials have examined the benefits and risks of further intensifying blood pressure treatment in patients with established coronary artery disease (CAD), who are in the prehypertension range. Preclinical data demonstrate that renin-angiotensin-aldosterone system (RAAS) activation plays an important role in atherosclerosis and that RAAS inhibition may have a direct beneficial effect on the artery wall," according to background information in the article. "Blood pressure reduction and RAAS inhibition are targets for treatment of atherosclerosis. The effect of renin inhibition on coronary disease progression has not been investigated."
Stephen J. Nicholls, M.B.B.S., Ph.D., of the South Australian Health and Medical Research Institute, Adelaide, Australia, and colleagues conducted a study to determine if renin inhibition with aliskiren would slow progression of coronary atherosclerosis in patients whose blood pressure was considered optimally controlled to current treatment targets. The randomized, multicenter trial compared 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. The trial was 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 was January 2013).
Participants underwent coronary intravascular ultrasound (IVUS) imaging and were randomized to receive 300 mg of aliskiren (n = 305) or placebo (n = 308) daily for 104 weeks. Disease progression was measured by repeat IVUS examination after at least 72 weeks of treatment, with evaluable imaging data available at follow-up in 74.7 percent of patients (225 in the aliskiren group and 233 in the placebo group). The primary efficacy parameter was the change in percent atheroma (a fatty deposit) volume (PAV) from baseline to study completion.
The researchers found that there was no difference between the treatment groups with respect to measures of atheroma burden at baseline. The primary efficacy measure, PAV, decreased by 0.33 percent in the aliskiren group and increased by 0.11 percent in the placebo group (between-group difference, -0.43 percent). There were no significant differences in the proportion of participants who demonstrated regression of PAV (56.9 percent vs. 48.9 percent) and total atheroma volume (64.4 percent vs. 57.5 percent) in the aliskiren and placebo groups, respectively.
A greater number of discontinuations of participation due to adverse events were observed in the aliskiren group compared with the placebo group (8.2 percent vs. 4.5 percent, respectively).
"These findings do not support the use of aliskiren for regression or prevention of progression of coronary atherosclerosis," the authors conclude.