Prostanoids for critical limb ischaemia

Prostanoids appear to have small beneficial effects for rest-pain relief and ulcer healing compared to placebo, but they have no effect on the incidence of total amputations in critical limb ischaemia. Iloprost may have favourable results regarding amputations.

The quality of evidence is downgraded by study quality (unclear allocation concealment and high risk of attrition bias).

Summary

A Cochrane review included 33 studies with a total of 4 477 subjects. Twenty-one studies compared different prostanoids versus placebo, 7 compared prostanoids versus other agents, and 5 conducted head-to-head comparisons using 2 different prostanoids in patients with critical limb ischaemia, unsuitable for rescue or reconstructive intervention of the arteries.

Prostanoids relieved rest-pain (RR 1.30, 95% CI 1.06 to 1.59; 10 studies, n=1 179), and improved ulcer healing (RR 1.24, 95% CI 1.04 to 1.48; 11 studies, n=1 719) compared to placebo, but these effects were diluted when a sensitivity analysis that excluded studies at high risk of bias was performed. However, there was no effect on on the incidence of total amputations (RR 0.97, 95% CI 0.86 to 1.09; 12 studies, n=2 825) and cardiovascular mortality between prostanoids and placebo (RR 0.81, 95% CI 0.41 to 1.58; 3 studies, n=1 170). None of the included studies assessed quality of life. Adverse events were more frequent with prostanoids than with placebo (RR 2.11, 95% CI 1.79 to 2.50; 8 studies, n=655). The more frequently reported adverse events were headache, nausea, vomiting, diarrhoea, flushing, and hypotension.

Subgroup analysis by type of prostanoid revealed differences for total amputations owing to better results with iloprost against placebo (RR 0.82, 95% CI 0.69 to 0.97; 6 studies, n=1 205) than with the other prostanoids, which showed minimal or no effect.