Angiotensin converting enzyme inhibition; a potential new therapy for intermittent claudication in peripheral arterial disease

Purpose: One third of patients with peripheral arterial disease (PAD) experience intermittent claudication, with the major consequence being loss of quality of life. We have previously reported that ramipril significantly improved walking distance in patients with PAD (n=40) (1), however applicability was constrained to patients with limiting infra-inguinal disease without diabetes. The current study was conducted in a larger more inclusive PAD population including patients with diabetes and patients with aorto-iliac as well as infra-inguinal disease, to examine the effects of ramipril on walking ability and quality of life. Methods: Two-hundred PAD patients (66±6 years (mean±SD); ramipril n=99, placebo n=101) were randomised to receive ramipril, 10mg once daily or placebofor 24 weeks in a randomised, double blind study. Pain free walking time (PFWT) and maximum walking time (MWT) were determined using a standard exercise treadmill test. Ankle-brachial index (ABI) was measured before and immediatelyfollowing the exercise test. The standard Walking Impairment Questionnaire (WIQ) and Short Form-36 (SF-36) questionnaire were administered to quantify walking ability and quality of life respectively. Results: Ramipril increased PFWT by 92% (Placebo 8.9±2 secs; Ramipril 87.2±65.8 secs; p less than 0.0001) and MWT by 139% (Placebo 14.4±32.9 secs; Ramipril 192.7±125.9 secs; p less than 0.0001). Ramipril also increased the resting ABI (Placebo -0.01±0.1; Ramipril 0.07±0.1; p less than 0.0001) and the ABI following exercise (Placebo-0.02±0.1; Ramipril 0.07±0.1; p less than 0.0001). Furthermore, the treatment group reported significantly higher scores on the distance (Placebo -3.4±7.0; Ramipril 12.4±9.5; p less than 0.0001), speed (Placebo -3.2±4.5; Ramipril 11.1±7.8; p less than 0.0001) and stair climbing (Placebo -7.1±10.5; Ramipril 23.8±18.7; p less than 0.0001) subscales of the WIQ. The treatment group also reported higher scores on the physical functioning subscale of the SF-36 (Placebo -0.1±0.9, Ramipril 2.1±2.8; p less than 0.0001). There were small, but significant reductions in blood pressure after ramipril therapy (systolic: Placebo 0.4±2.6 mmHg; Ramipril -2.6±1.8 mmHg; p less than 0.0001; diastolic: Placebo 0.7±2.7 mmHg; Ramipril -2.9±1.7 mmHg; p less than 0.0001). Conclusions: This is the first, adequately powered randomized trial demonstrating that ACE inhibition improves walking ability and quality of life in patients with PAD; an improvement substantially beyond that reported with conventional medical therapies