Prostanoids — Prostaglandin, prostacyclin, and their analogs improve blood flow through direct vasodilation, antiplatelet, and other rheologic effects and have anti-inflammatory effects as well. While some of these drugs remain under investigation, they have not been approved for treating the symptoms of PAD in the United States.
Agents previously investigated for the treatment of peripheral artery disease include prostaglandin E1 (alprostadil), the prostaglandin analog ecraprost, the prostacyclin epoprostenol (PGI2), as well as the prostacyclin analogs iloprost (inhalation, intravenous [IV] not available in the United States), beraprost (oral, not available in the United States), taprostene, and treprostinil (inhalation, oral, subcutaneous, IV). Prostaglandin E1 (PGE1) and epoprostenol (PGI2) are structurally unstable. Their stable analogs have a longer duration of action and a more specific effect (in general) than their endogenous equivalents.
● Claudication – A systematic review and meta-analysis (Cochrane) identified 18 trials. Four trials that compared PGE1 with placebo found significant improvements in treadmill exercise performance with PGE1 but not PGI2. However, the authors noted that the quality of individual trials was variable and results often unclear due to insufficient reporting information; the majority of trials did not report standard deviations for the primary outcomes.
● Chronic limb-threatening ischemia – In a systematic review and meta-analysis (Cochrane), 15 trials compared various preparations of prostacyclin analogues with placebo. No differences were seen for cardiovascular mortality or overall amputation risk (minor and major) for patients receiving prostanoids compared with placebo. However, prostanoids may reduce rest pain (risk ratio [RR] 1.30, 95% CI 1.06-1.59) and improve ulcer healing (RR 1.24, 95% CI 1.04-1.48) compared with placebo. Adverse events were more frequent with prostanoids.
