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 E-1 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 mu g of prostaglandin E-1 in the form of alprostadil-alpha-cyclodextrine (n = 771) or no prostaglandin E-1 (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.

Objective: to evaluate the safety and efficacy of a stable prostaglandin E(1) added to the usual therapeutic practice (either invasive or not) in patients with chronic critical leg ischemia.Design: multicenter, controlled, randomised, open label trial.Setting: a representative sample (56 centers) of vascular and general surgery, angiology and general medicine departments of the Italian National Health Service.Patients: all patients suffering from leg ischemia considered as chronic and critical depending on the presence of persistently recurring rest pain for more than two weeks and/or foot ulceration or gangrene.Intervention: a daily i.v. infusion of 60 mu g of alprostadil alpha-cyclodextrine for the overall hospital stay, up to a maximum of 28 days (as an adjunct to the standard procedures adopted In each center) to patients randomly assigned to the experimental treatment.Measures: the primary evaluation of efficacy is based on the expected reduction of major amputations or persistence of critical leg ischemia at six months, The sum of these ''peripheral'' events, of death and of non-fatal myocardial infarction and stroke is used as a more comprehensive evaluation of the risk/benefit profile of the experimental treatment.Results: a reduction from 40% to 32% of the incidence of the primary end-points is the trial hypothesis, The recruitment of 1500 patients is required to verify this.Conclusions: this large-scale trial aims at providing a reliable estimate of the possibility of modifying hard end-points such as death and amputation in patients with critical leg ischemia.

Objective: To draw a picture of the different practices adopted for the diagnosis, specific treatment and general care of critical leg ischaemia (CLI) in the light of the recommendations of the recent Consensus Document.Design: Prospective observational study.Setting: A representative sample of vascular and general surgery, angiology, general medicine departments of the Italian National Health Service.Subjects: Patients with leg ischaemia considered as chronic and critical according to the definition and diagnostic criteria adopted in each centre.Chief outcome measures: Epidemiological profile of the standard population; prevalence of definition criteria and of diagnostic and therapeutic procedures; short and medium-term clinical outcome as well as of the general vascular morbidity and mortality.Main results: Over a 3 month period, 574 patients were recruited in 69 centres mainly on the basis of clinical findings of CLI (rest pain and/or trophic lesions). They had an adequate diagnostic assessment of their vascular lesions and a high cardiovascular risk in terms of prior morbidity and presence of risk factors, Over half of the patients underwent revascularisation and three quarters were given pharmacological treatments. At the end of the observation period, 50 patients had died (8.7%), three had had a myocardial infarction (0.5%), six a stroke (1.0%), 70 a major amputation (12.2%) and 103 had persistent CLI (17.9%).Conclusions: This survey confirms the dramatic prognosis of patients with CLI and provides an appropriate background and setting to conduct experimental clinical studies in this field.