Effects of aliskiren in diabetic and non-diabetic patients with coronary artery disease: Insights from AQUARIUS

Atherosclerosis. 2015 Dec;243(2):553-9. doi: 10.1016/j.atherosclerosis.2015.10.019. Epub 2015 Oct 20.

Abstract

Background: Aliskiren previously was found to have potentially harmful effects in diabetic individuals prescribed concomitant angiotensin converting enzyme inhibitors (ACEI) or angiotenisn receptor antagonists (ARB). We explored potential effects of aliskiren on coronary atheroma progression and major adverse cardiovascular events (MACE: death/non-fatal MI/non-fatal stroke/hospitalization for heart failure/hospitalization for ACS/arterial revascularization) in patients with and without diabetes mellitus (DM).

Methods: AQUARIUS employed serial intravascular ultrasound measures of coronary atheroma volume in coronary artery disease patients randomized to receive daily aliskiren 300 mg or placebo for 104 weeks. This post hoc analysis compared changes in plaque volume [percent atheroma volume (PAV) and total atheroma volume (TAV)] and MACE in patients with (n = 115) and without (n = 343) DM stratified by treatment allocation.

Results: In multivariable propensity-weighted analyses, which included controlling for baseline and concomitant ACEI/ARB therapy and duration of aliskiren therapy, aliskiren-treated non-DM patients demonstrated the greatest PAV and TAV regression, whereas aliskiren-treated DM patients demonstrated the greatest TAV progression and greater PAV. Aliskiren-treated non-DM patients appeared at significantly lower risk of MACE compared with their aliskiren-treated DM counterparts [HR 95% CI 0.28 (0.10, 0.80)]. Statistical interactions were noted between DM status and treatment allocation for both changes in PAV (p < 0.001), TAV (p = 0.010) and MACE (p = 0.057).

Conclusions: Aliskiren appears to be relatively anti-atherosclerotic in non-diabetic patients. Due to the limited number MACE and low numbers of diabetic patients in AQUARIUS, the pro-atherosclerotic effects of aliskiren in this population are inconclusive, and these results should be thus considered hypothesis generating. Further outcome studies are required in non-diabetic patients to confirm the possible favorable effects of aliskiren.

Trial registration: ClinicalTrials.gov NCT00853827.

Keywords: Aliskiren; Atherosclerosis; IVUS; Renin inhibition: diabetes mellitus.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amides / administration & dosage*
  • Amides / adverse effects
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Antihypertensive Agents / administration & dosage*
  • Antihypertensive Agents / adverse effects
  • Chi-Square Distribution
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / mortality
  • Coronary Vessels / diagnostic imaging
  • Coronary Vessels / drug effects*
  • Diabetic Angiopathies / diagnostic imaging
  • Diabetic Angiopathies / drug therapy*
  • Diabetic Angiopathies / mortality
  • Disease Progression
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Fumarates / administration & dosage*
  • Fumarates / adverse effects
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Myocardial Infarction / mortality
  • Plaque, Atherosclerotic
  • Prehypertension / diagnosis
  • Prehypertension / drug therapy*
  • Prehypertension / mortality
  • Propensity Score
  • Proportional Hazards Models
  • Risk Assessment
  • Risk Factors
  • Stroke / mortality
  • Time Factors
  • Treatment Outcome
  • Ultrasonography, Interventional

Substances

  • Amides
  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Fumarates
  • aliskiren

Associated data

  • ClinicalTrials.gov/NCT00853827