title: Prostanoids in patients with peripheral arterial disease: A meta-analysis of placebo-controlled randomized clinical trials.
abstract: OBJECTIVE
  Prostanoids are indicated in the treatment of peripheral arterial disease (PAD). Available trials suggest that these compounds could reduce the symptoms of intermittent claudication, even though the quality of studies is poor. The present meta-analysis is aimed at verifying the effects of prostanoids on amputation rate and ulcer healing in patients with lower limb PAD.
  
  
  METHODS
  The review protocol was published on http://www.crd.york.ac.uk/prospero (CRD42015020258). A comprehensive search for published and unpublished trials comparing iloprost, alprostadil, prostaglandin-E1, epoprostenol, or taprostene with placebo/no therapy on amputation rate in patients with PAD and ulcer healing rate in patients with concomitant foot ulcers. Mantel-Haenzel odds ratio (MH-OR) was calculated with random effect models for the chosen endpoints.
  
  
  RESULTS
  A total of 18 trials, enrolling 3,077 and 2,763 patients in the prostanoid and comparator groups, respectively were included in the analysis. Only 11 and 10 of those trials reported data on total and major amputations, respectively. Prostanoids were associated with a significantly lower risk of major (MH-OR [95% confidence interval] was 0.77 [0.63; 0.93], p=0.007), but not total, amputations. Healing rate (available only in 7 trials) was not significantly augmented by prostanoid treatment.
  
  
  CONCLUSIONS
  Available data are not sufficient to support an extensive use of prostanoids in patients with critical limb ischemia, as an adjunct to revascularization or as an alternative to major amputation in cases which cannot undergo revascularization.
authors.affiliation: Diabetology, Careggi Teaching Hospital, Via delle Oblate 4, 50141 Florence, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Vitale
authors.affiliation: Division of Geriatric Cardiology and Medicine, Careggi Teaching Hospital. Electronic address: mmonami@libero.it.
authors.forename: Matteo
authors.initials: M
authors.lastname: Monami
authors.affiliation: Diabetology, Careggi Teaching Hospital, Via delle Oblate 4, 50141 Florence, Italy. Electronic address: edoardo.mannucci@unifi.it.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Mannucci
mesh_terms: D000527:Alprostadil / Q000009:adverse effects / Q000627:therapeutic use; D000671:Amputation, Surgical / Q000009:adverse effects; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy / Q000009:adverse effects; D017719:Diabetic Foot / Q000188:drug therapy* / Q000601:surgery; D011464:Epoprostenol / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D016285:Iloprost / Q000009:adverse effects / Q000627:therapeutic use; D016491:Peripheral Vascular Diseases / Q000188:drug therapy* / Q000601:surgery; D011459:Prostaglandins E, Synthetic / Q000009:adverse effects / Q000627:therapeutic use; D011465:Prostaglandins, Synthetic / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D014945:Wound Healing / Q000187:drug effects
chemical_list: D002317:Cardiovascular Agents; D011459:Prostaglandins E, Synthetic; D011465:Prostaglandins, Synthetic; C039188:taprostene; D011464:Epoprostenol; D000527:Alprostadil; D016285:Iloprost
keywords: Foot ulcers; Lower limb amputations; Meta-analysis; Peripheral artery disease; Prostanoids