Prostaglandin E1 for peripheral arterial occlusive disease
Clinical bottom line
Prostaglandin E1 appears to be effective in treating intermittent claudication and peripheral arterial occlusive disease.
Reference
A Creutzig et al. Meta-analysis of randomised controlled prostaglandin E1 studies in peripheral arterial occlusive disease stages III and IV. Vasa 2004 33: 137-144.
K Amendt. PGE1 and other prostaglandins in the treatment of intermittent claudication: a meta-analysis. Angiology 2005 56: 409-415.
P Petronella et al. Prostaglandin E1 versus lumbar sympathectomy in the treatment of peripheral arterial occlusive disease: randomised study of 86 patients. Nutrition and Metabolism in Cardiovascular Diseases 2004 14: 186-192.
Background
The mechanisms of anti-ischemic effects of PGE1 in patients with peripheral arterial occlusive disease are probably complex and clearly not limited to a direct vasodilator action. In addition to the known effects on blood flow, viscosity, fibrinolysis and platelet aggregation, the compound also inhibits monocyte and neutrophil function, suggesting that PGE1 will also have anti-inflammatory effects. Several randomised trials have now been completed, and combined in a meta-analysis. PGE1 is usually given as a slow intravenous infusion, once a day or more, for up to 28 days.
Systematic review (Creutzig)
- Date review completed: 2004
- Number of trials included: 7
- Number of patients: 643, but 254 in placebo-controlled trials
- Control group: placebo, other treatments
- Main outcomes: ulcer healing, pain, response rates
Results
In the placebo-controlled trials, PGE1 had significantly better results:
- For response (ulcer healing or pain) PGE1 was better than placebo (48% vs 25%, implying a number needed to treat for response of about 5.
- Major amputation or death by six months was 23% for PGE1 and 34% for placebo, a NNT of 10.
- Pooled results for response were 60% for PGE1, 25% for placebo, and 54% for iloprost.
- Pooled adverse event rates were 40% for PGE1, 15% for placebo, and 74% for iloprost.
A randomised trial (Petronella 2004) compared PGE1 with lumbar sympathectomy in 86 patients and found a 60% complete remission rate, similar to sympathectomy.
Systematic review (Amendt)
- Date review completed: 2004
- Number of trials included: 9 with PGE1, 4 with other prostaglandins
- Number of patients: 344 with PGE1, 402 other prostaglandins (beraprost, iloprost, AS-013)
- Control groups: placebo, other treatments
- Main outcomes: pain free walking distance, maximum walking distance
Results
PGE1 and other prostaglandins substantially increased pain free walking distance more than other prostaglandins or placebo. There were also fewer adverse events with PGE1 (14%) than with other prostaglandins (31%).
Comment
Intravenous PGE1 has significant beneficial effects over placebo, not just for pain, but for patients surviving with both legs. It is also better than other prostaglandins in intermittent claudication, on the basis of limited information.