Effect of Aliskiren on Progression of Coronary Disease in Patients With Prehypertension

Abstract

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 PARTICIPANTSA 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 MEASURESThe 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 mm 3 ; 95% CI, −6.27 to −1.94 mm 3 ) and placebo (−2.1 mm 3 ; 95% CI, −4.21 to 0.07 mm 3 ) (between-group difference, −2.04 mm 3 [95% CI, −5.03 to 0.95 mm 3 ]; 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

Advances in understanding the renin-angiotensin-aldosterone system (RAAS) in blood pressure control and recent pivotal trials of RAAS blockade in heart failure and diabetic nephropathy

“…In the ATMOSPHERE 26 trial (Aliskiren Trial to Minimize Outcomes in Patients with Heart failure), the addition of aliskiren to enalapril in patients with chronic heart failure was not associated with reduction in adverse outcomes (see “Recent clinical trials” section for details). Similarly, no improvement in coronary atherosclerosis in pre-hypertensive patients (AQUARIUS) 27 or improvement in cardiovascular outcomes in patients hospitalized with heart failure (ASTRONAUT) 28 was seen with aliskiren compared with placebo. Given the lack of demonstrated benefit and increased rates of adverse events such as hyperkalemia, hypotension, and renal impairment as seen in ASTRONAUT when combined with ACEIs or ARBs, the current use of aliskiren is limited 28 .…”

Effect of serial infusions of reconstituted high-density lipoprotein (CER-001) on coronary atherosclerosis: rationale and design of the CARAT study

“…In particular, serial application of intraarterial ultrasonography has evolved to assess the impact of medical therapies on disease progression (16,(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36). Serial IVUS imaging within an epicardial coronary artery enables precise quantitation of the volumetric burden of atherosclerotic plaque within an anatomically matched coronary segment, defined by the location of fiduciary side branches, after treatment.…”

Renin Inhibition with Aliskiren: A Decade of Clinical Experience

“…The proportion of patients demonstrating regression of percent atheroma volume was also similar in both groups. Thus no benefit was shown by the use of ALI in prehypertensive individuals with coronary atherosclerosis [103]. …”