Background

People with severely blocked arteries of the leg suffer from pain, ulcers (areas showing loss of skin that do not heal easily), or gangrene (areas showing dead tissues resulting from loss of blood supply). This condition is usually associated with several risk factors, such as diabetes, smoking, high cholesterol, high blood pressure, obesity, and unhealthy lifestyle. The main treatments for people with this condition are surgical procedures performed to unblock the arteries. However, in some situations, surgical unblocking is not possible and amputation of part of the leg is required.

Prostanoids make up a family of medicines that could increase blood supply to the legs when taken orally or by injection. Prostanoids expand and open up small blood vessels and reduce the activity of inflammatory cells and platelets, preventing blood clots. We wanted to discover the benefits and harms of prostanoids for people whose leg arteries are severely blocked with no chance for surgical unblocking.

Review question

In this review, we studied the effect of prostanoids in people with severely blocked leg arteries who are not able to undergo any surgical unblocking procedure.

Study characteristics

We searched published and unpublished studies up to January 2017. We found 33 clinical trials with a total of 4477 participants; most were published in the 1980s and 1990s and were carried out in European countries. Eleven out of 33 studies received funding from pharmaceutical companies. Most studies included patients over 60 years old who had severe blocking of arteries of the leg; many also had diabetes. Follow-up was usually less than 1 year.

Key results

We found that, when compared with placebo, prostanoids provided a small beneficial effect by alleviating pain in the leg at rest and improving ulcer healing. Prostanoids did not reduce deaths or the need for an amputation. We found that no studies evaluated the quality of life of people with this condition. We found insufficient evidence to compare effects of prostanoids against those of other medications or other prostanoids.

Our findings suggest that taking prostanoids does cause harm. When 1000 patients are treated with prostanoids, on average 674 (572 to 798) will experience adverse events, compared with 319 given placebo. Adverse events usually include nausea, vomiting, diarrhoea, headache, dizziness, and flushing. More severe adverse events include low blood pressure, chest pain, and abnormalities in heart rhythm.

Quality of the evidence

When evaluating effects of prostanoids on rest-pain, ulcer healing, and adverse events, researchers provided moderate-quality evidence; review authors downgraded this in most cases because of loss of participants to follow-up. Evaluating cardiovascular mortality yielded evidence of low quality related to loss of participants to follow-up and small numbers of reported events. On the other hand, the quality of evidence on risk of amputation was high.