Chapter 7.1: Therapy (Randomized Trials)

CLINICAL SCENARIO A Patient With Peripheral Artery Disease: How Can I Improve Physical Function and Walking?

You are a general internist following up a 62-year-old man with a history of type 2 diabetes mellitus, hypertension, and hyperlipidemia who is taking oral hypoglycemics, a statin, and a thiazide-like diuretic. A vascular surgeon recently evaluated the patient for intermittent claudication and made a diagnosis of peripheral artery disease. The surgeon prescribed low-dose aspirin and pentoxifylline to reduce the patient's risk of vascular events and improve his ability to walk, citing 2 systematic reviews: a review of antiplatelet agents in peripheral artery disease that found a decrease in the odds of vascular events (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.63-0.96) and an increase in walking distance of 59 m (95% CI, 37-81 m) and another review of pentoxifylline in peripheral artery disease that increased maximum walking distance by 59 m (95% CI, 37-81 m).^1,2 Despite the new treatments, the patient is unable to walk more than 2 minutes without pain and finds his quality of life substantially impaired.

Listening to the patient's story of poor response to treatment and ongoing symptoms, you recall seeing an article that may be relevant. You ask him to return in a week for further review of his medications.

You formulate the relevant question for this individual: in a patient with debilitating peripheral vascular disease treated with antiplatelet therapy and not a candidate for surgery, how can we improve symptom-free walking? To conduct a rapid search focused on the most recent preappraised research (see chapter 5, Finding Current Best Evidence), you opt for ACP Journal Club, directly accessible through your institution (http://acpjc.acponline.org). Typing the terms “peripheral vascular disease” and “intermittent claudication” identifies 7 preappraised editorial summaries of studies, one of which turns out to be your target: Ramipril Improved Walking Times and QOL in Peripheral Artery Disease and Intermittent Claudication.³ You print a copy of the summary³ and the original full-text article that reports the results of the trial, Effect of Ramipril on Walking Times and Quality of Life Among Patients With Peripheral Artery Disease and Intermittent Claudication.⁴

This article describes a trial that includes 212 patients with peripheral artery disease and a history of stable intermittent claudication. Participants were randomly allocated to ramipril, 10 mg daily, or placebo for 24 weeks. The primary outcomes were pain-free walking time and maximum walking time.