Do angiotensin converting enzyme inhibitors improve walking distance in patients with symptomatic lower limb arterial disease? A systematic review and meta-analysis of randomised controlled trials

Abstract

Background: Several studies have reported the clinical effects of long-term treatment with cardioprotective medications in patients with lower limb peripheral arterial disease (PAD) in terms of reducing cardiovascular morbidity and mortality. A number of these studies investigated the clinical effect of angiotensin converting enzyme inhibitors (ACEIs) on walking distance in this group of patients.

Objective: To review the evidence regarding the effects of ACEIs in patients with symptomatic PAD of the lower limbs in terms of the effect on maximum and pain-free walking distances and ankle brachial pressure index (ABPI).

Methods: A systematic literature search of the medical literature from 1966 to 2010 on randomized placebo-controlled trials which assessed the effect of ACEIs on maximum and/or pain-free walking distances and/or ABPI in patients with symptomatic lower limbs PAD was performed. Data from included studies were pooled with use of random-effects model with standard mean differences. Heterogeneity across studies was assessed with calculation of I(2) statistic.

Results: From a total of 346 publications identified, 34 articles were selected for full review based on title and abstract. 4 RCTs comprising 576 patients (334(58%) males, mean age 60.7 years, age range (58-66)) met the inclusion criteria and were systematically reviewed. Of those, 137 (24%) patients suffered from symptomatic lower limb PAD. Maximum walking distances were pooled successfully from all 4 studies. After analysing these data, we found significant heterogeneity among the groups and no significant difference in the pooled treatment effect (standard mean difference = 0.46, 95% CI (-0.99-1.92), p = 0.53, I(2); = 95%). Pain-free walking distances and ankle brachial pressure indices were pooled successfully from 3 studies and showed an insignificant overall treatment effect (standard mean difference = 0.97, 95% CI (-0.24-2.18), p = 0.12 and 0.68, 95% CI (-0.70-2.06), p = 0.33, respectively).

Conclusion: The evidence regarding ACE inhibition efficacy on treadmill walking distance in patients with intermittent claudication is contradicting and lacked properly powered RCTs. However, based on this study, ACEIs did not improve treadmill walking distance and ABPI in patients with symptomatic lower limb arterial disease. Further research from properly powered RCTs is needed.