Propionyl‐L‐carnitine for intermittent claudication

Background Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis. Intermittent claudication is a symptomatic form of PAD that is characterized by pain in the lower limbs caused by chronic occlusive arterial disease. This pain develops in a limb during exercise and is relieved with rest. Propionyl‐L‐carnitine (PLC) is a drug that may alleviate the symptoms of PAD through a metabolic pathway, thereby improving exercise performance. Objectives The objective of this review is to determine whether propionyl‐L‐carnitine is efficacious compared with placebo, other drugs, or other interventions used for treatment of intermittent claudication (e.g. exercise, endovascular intervention, surgery) in increasing pain‐free and maximum walking distance for people with stable intermittent claudication, Fontaine stage II. Search methods The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and the ClinicalTrials.gov trials register to July 7, 2021. We undertook reference checking and contact with study authors and pharmaceutical companies to identify additional unpublished and ongoing studies. Selection criteria Double‐blind randomized controlled trials (RCTs) in people with intermittent claudication (Fontaine stage II) receiving PLC compared with placebo or another intervention. Outcomes included pain‐free walking performance (initial claudication distance ‐ ICD) and maximal walking performance (absolute claudication distance ‐ ACD), analyzed by standardized treadmill exercise test, as well as ankle brachial index (ABI), quality of life, progression of disease, and adverse events. Data collection and analysis Two review authors independently selected trials, extracted data, and evaluated trials for risk of bias. We contacted study authors for additional information. We resolved any disagreements by consensus. We performed fixed‐effect model meta‐analyses with mean differences (MDs) and 95% confidence intervals (CIs). We graded the certainty of evidence according to GRADE. Main results We included 12 studies in this review with a total number of 1423 randomized participants. A majority of the included studies assessed PLC versus placebo (11 studies, 1395 participants), and one study assessed PLC versus L‐carnitine (1 study, 26 participants). We identified no RCTs that assessed