Prostanoids for critical limb ischaemia.
BACKGROUND
Peripheral arterial occlusive disease (PAOD) is a common cause of morbidity and mortality due to cardiovascular diseases in the general population. While numerous treatments have been adopted for different disease stages, there is no option other than amputation for patients presenting with critical limb ischaemia (CLI), unsuitable for rescue or reconstructive intervention.


OBJECTIVE
To determine the effectiveness and safety of prostanoids in patients presenting with CLI.


METHODS
The Cochrane Peripheral Vascular Diseases Group searched their trials register (last searched October 2009) and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (last searched 2009, Issue 4) for publications describing randomised controlled trials (RCTs) of prostanoids for CLI. We ran additional searches in MEDLINE, EMBASE, LILACS, and SciSearch, and we also contacted pharmaceutical companies and experts, in order to identify unpublished data and trials still underway.


METHODS
Randomised controlled trials describing efficacy and safety of prostanoids compared with placebo or other pharmacological control treatments, in patients presenting with CLI, without chance of rescue or reconstructive intervention.


METHODS
Two authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data. Disagreements were resolved by consensus or by the third author.


RESULTS
We retrieved 532 citations which after the first screening resulted in 111 potential studies. Finally, after exclusion of studies of poor quality and a lack of sufficient information, 20 trials were included in the review.Prostanoids seem to have efficacy regarding rest-pain relief (risk ratio (RR) 1.32, 95% confidence interval (CI) 1.10 to 1.57; P = 0.003), and ulcer healing (RR 1.54, 95% CI 1.22 to 1.96). Iloprost also shows favourable results regarding major amputations (RR 0.69, 95% CI 0.52 to 0.93). The more frequently reported adverse events when using prostanoids were headache, facial flushing, nausea, vomiting and diarrhoea.


CONCLUSIONS
Despite some positive results regarding rest-pain relief, ulcer healing and amputations, there is no conclusive evidence based on this meta-analysis of the long-term effectiveness and safety of different prostanoids in patients with CLI. Further well-conducted, high quality randomised double-blinded trials should be performed.
Ruffolo
Antonio J
AJ
c/o Cochrane Peripheral Vascular Diseases Group, Public Health Sciences, The University of Edinburgh, Teviot Place, Edinburgh, UK, EH8 9AG.
Romano
Marina
M
Ciapponi
Agustín
A
D000527:Alprostadil / Q000627:therapeutic use; D000671:Amputation, Surgical; D011464:Epoprostenol / Q000627:therapeutic use; D006801:Humans; D016285:Iloprost / Q000627:therapeutic use; D007511:Ischemia / Q000188:drug therapy*; D007866:Leg / Q000098:blood supply* / Q000601:surgery; D007871:Leg Ulcer / Q000188:drug therapy; D016491:Peripheral Vascular Diseases / Q000188:drug therapy*; D011453:Prostaglandins / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D014665:Vasodilator Agents / Q000627:therapeutic use
D011453:Prostaglandins; D014665:Vasodilator Agents; D011464:Epoprostenol; D000527:Alprostadil; D016285:Iloprost