The Roles of ACE Inhibitors in Lower Extremity Peripheral Artery Disease

Peripheral artery disease (PAD) is an age-dependent atherosclerotic disorder associated with an increased prevalence of cardiovascular morbidity and mortality. Approximately 35% of patients with PAD complain of lower extremity claudication, which may worsen to impair daily function. ACE inhibitors may possess vasoactive properties that improve symptoms of claudication. We designed a meta-analysis to quantify the effectiveness of ACE inhibitors on walking capacities in patients with lower extremity PAD. We reviewed MEDLINE and Cochrane databases from 1966 to 2013, in addition to relevant bibliographies to obtain our clinical trials. From the original findings, 4 randomized, placebo-controlled, double-blind studies qualified for inclusion. Using a random-effects model, ACE inhibitors were associated with an increase of 126 m [95% confidence interval (CI), -95 to 346] (P = 0.264) in maximal walking distance and a rise in Ankle-Brachial Index of 0.09 (95% CI, 0.024-0.205) (P = 0.12). However, pain-free walking distance was significantly increased by 86 m (95% CI, 13-156) (P = 0.021). Contradictions in study outcomes between more recent and earlier trials of ACE inhibitors in claudication impeded the interpretation of effectiveness. Early trials failed to demonstrate improvement in walking capacities, possibly because of omissions in patient enrollment criteria and inadequate sample size. Recent guidelines recommend consideration of ACE inhibitors in patients with PAD for cardioprotective effects. Although ACE inhibitors were well tolerated, vigilance for clinical predictors of renal arterial stenosis and renal instability after initiation will ensure safe administration in all patients with PAD.