Prostanoid drug therapy for peripheral arterial occlusive disease--the European experience

The most serious threat to a claudicant is not the possible future need for a major amputation, but rather that the medium-term mortality is two to three times that of the general age-matched population. In patients with more severe disease in the legs, approximately 45% will have had a major amputation or be dead within a year of developing rest pain, ulcers or gangrene. These are the challenges for pharmacotherapy in peripheral arterial occlusive disease. In the short and medium term, pharmacotherapy can only have a significant effect by modifying the microcirculatory response to the low perfusion pressure caused by the arterial disease. The microcirculatory changes in the leg in severe leg ischaemia are ill understood, but theoretically a number of pharmacological effects could be beneficial. In practice, the only type of drugs widely tested clinically in severe leg ischaemia are prostacyclin and its analogues. In the last 12 years the results of properly controlled randomized trials involving patients with chronic limb ischaemia have been carried out in approximately 2000 patients in Europe. The largest number were entered into trials using the prostacyclin analogue iloprost. Some of these trials have shown a significant benefit compared to placebo in terms of major amputation or death during the 6 months following a 2-4 week course of intravenous iloprost. The possible future indications for this type of therapy, as well as the use for prostaglandins in claudicants, is discussed.