Propionyl-L-carnitine fails to score over standard care for intermittent claudication: Study

Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis. Intermittent claudication is asymptomatic 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.

The objective of this review is to determine whether propionyl‐L‐carnitine is efficacious compared with placebo, other drugs, or other interventions used for the 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.

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 We undertook reference checking and contact with study authors and pharmaceutical companies to identify additional unpublished and ongoing studies.

The results were:

Researchers 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 PLC versus any other medication, exercise, endovascular intervention, or surgery. Participants received PLC 1 grams to 2 grams orally (9 studies) or intravenously (3 studies) per day or placebo.

For the comparison PLC versus placebo, there was a high level of both clinical and statistical heterogeneity due to study size, participants coming from different countries and centres, the combination of participants with and without diabetes, and use of different treadmill protocols. We found a high proportion of drug company‐backed studies. The overall certainty of the evidence was moderate.

For PLC compared with placebo, improvement in maximal walking performance (ACD) was greater for PLC than for placebo, with a mean difference in absolute improvement of 50.86 meters (95% CI 50.34 to 51.38; 9 studies, 1121 participants), or a 26% relative improvement (95% CI 23% to 28%). Improvement in pain‐free walking distance (ICD) was also greater for PLC than for placebo, with a mean difference in absolute improvement of 32.98 meters (95% CI 32.60 to 33.37; 9 studies, 1151 participants), or a 31% relative improvement (95% CI 28% to 34%). Improvement in ABI was greater for PLC than for placebo, with a mean difference in improvement of 0.09 (95% CI 0.08 to 0.09; 4 studies, 369 participants). Quality of life improvement was greater with PLC (MD 0.06, 95% CI 0.05 to 0.07; 1 study, 126 participants). Progression of disease and adverse events including nausea, gastric intolerance, and flu‐like symptoms did not differ greatly between PLC and placebo.

For the comparison of PLC with L‐carnitine, the certainty of evidence was low because this included a single, very small, cross‐over study. Mean improvement in ACD was slightly greater for PLC compared to L‐carnitine, with a mean difference in absolute improvement of 20.00 meters (95% CI 0.47 to 39.53; 1 study, 14 participants) or a 16% relative improvement (95% CI 0.4% to 31.6%). We found no evidence of a clear difference in the ICD (absolute improvement 4.00 meters, 95% CI ‐9.86 to 17.86; 1 study, 14 participants); or a 3% relative improvement (95% CI ‐7.4% to 13.4%). None of the other outcomes of this review were reported in this study.

Thus, researchers concluded that PLC might be considered as an alternative or an adjuvant to standard treatment when such therapies are found to be contraindicated or ineffective, there is no RCT evidence comparing PLC with standard treatment to directly support such use.

Reference:

Propionyl‐L‐carnitine for intermittent claudication by Victor Kamoen et al published in the Cochrane Database of Systematic Reviews

https://doi.org/10.1002/14651858.CD010117.pub2