Prostanoids for chronic critical leg ischemia. A randomized, controlled, open-label trial with prostaglandin E1. The ICAI Study Group. Ischemia Cronica degli Arti Inferiori.

BACKGROUND

No effective pharmacologic intervention is available for critical leg ischemia, a severe clinical condition associated with high morbidity and mortality.

OBJECTIVE

To assess the safety and efficacy of prostaglandin E1 in improving the prognosis and quality of life in patients with critical leg ischemia.

DESIGN

Multicenter, centrally randomized, controlled, open-label trial.

SETTING

56 vascular surgery and angiology departments of the Italian National Health Service.

PATIENTS

1560 patients with chronic critical leg ischemia.

INTERVENTIONS

In addition to routine treatments practiced in each center, patients were randomly assigned to receive either a daily intravenous infusion of 60 microg of prostaglandin E1 in the form of alprostadil-alpha-cyclodextrine (n = 771) or no prostaglandin E1 (n = 789) during their hospital stay. The treatment period lasted for up to 28 days.

MEASUREMENTS

A combined end point consisting of death and peripheral and cardiocerebrovascular illness (major amputation or persistence of critical leg ischemia, acute myocardial infarction, or stroke) evaluated at hospital discharge and during 6 months of follow-up.

RESULTS

The incidence of the combined outcome measure was lower in the alprostadil group than in controls at hospital discharge (493 [63.9%] patients compared with 581 [73.6%] patients; relative risk, 0.87 [95% CI, 0.81 to 0.93]; P < 0.001) but differed only modestly at 6 months (348 of 661 [52.6%] patients compared with 387 of 673 [57.5%] patients; relative risk, 0.92 [CI, 0.83 to 1.01]; P = 0.074). Most of the observed benefit was due to recovery from critical leg ischemia.

CONCLUSIONS

Short-term treatment with alprostadil-alpha-cyclodextrine provides patients with critical leg ischemia clinical benefit that is apparent in the short term but decreases over time.