Aortic Aneurysmal Regression of Dilation: Value of ACE-Inhibition on RisK - AARDVARK

Description:

The goal of the trial was to assess the efficacy of perindopril compared with amlodipine and placebo in slowing growth in small abdominal aortic aneurysms (AAAs).

Contribution to the Literature: Perindopril is not superior to amlodipine or placebo in slowing AAA growth in patients with small AAAs, despite a greater reduction in blood pressure.

Study Design

Patients were randomized in a 1:1:1 fashion to either perindopril 10 mg once daily (n = 73), amlodipine 5 mg (n = 72), or placebo (n = 79).

  • Total number of enrollees: 224
  • Duration of follow-up: 2 years
  • Mean patient age: 71 years
  • Percentage female: 5%

Inclusion criteria:

  • Age ≥55 years
  • AAA diameter 3.0-5.4 cm
  • Systolic blood pressure <150 mm Hg

Exclusion criteria:

  • Already on angiotensin-converting enzyme inhibitor (ACEi)/angiotensin-receptor blocker (ARB)/calcium channel blocker (except amlodipine 5 mg)
  • Known renal artery stenosis
  • Serum creatinine >2 mg/dl
  • Life expectancy <2 years

Other salient features/characteristics:

  • Systolic blood pressure: 130 mm Hg
  • External AAA diameter at baseline: 4.04 cm

Principal Findings:

The primary outcome, estimated average annual AAA growth for perindopril, amlodipine, and placebo: 1.77 mm vs. 1.81 mm vs. 1.68 mm (p = 0.78 for perindopril vs. placebo)

Secondary outcomes for perindopril vs. amlodipine vs. placebo:

  • Reduction in systolic blood pressure at 12 months: -9.5 mm Hg vs. -6.7 mm Hg vs. -0.5 mm Hg; p < 0.001 for both medications vs. placebo)
  • Reduction in diastolic blood pressure at 12 months: -5.8 mm Hg vs. -4.7 mm Hg vs. -0.2 mm Hg; p < 0.001 for both medications vs. placebo
  • Proportion that reached 5.5 cm or referred for/undergoing surgery for AAA repair: 13.7% vs. 15.3% vs. 13.9%, p > 0.05
  • No aortic ruptures

Interpretation:

The results of this trial indicate that perindopril is not superior to amlodipine or placebo in slowing AAA growth in patients with small AAAs, despite a greater reduction in blood pressure. This trial was designed as a pilot trial to power a larger trial comparing ACEi to placebo with clinical endpoints. The utility of both ACEi and ARBs in reducing aortic aneurysmal growth remains controversial, with several recent trials showing no clinical benefit despite experimental evidence to the contrary.

References:

Bicknell CD, Kiru G, Falaschetti E, Powell JT, Poulter NR, on behalf of the AARDVARK Collaborators. An evaluation of the effect of an angiotensin-converting enzyme inhibitor on the growth rate of small abdominal aortic aneurysms: a randomized placebo-controlled trial (AARDVARK). Eur Heart J 2016;Jul 1:[Epub ahead of print].


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