Antithrombotic Drugs in Peripheral Obliterative Arterial Diseases

Abstract

In the natural history of patients with peripheral obliterative arterial disease (POAD) the prognosis of the complaint “intermittent claudication” is relatively good and the amputation rate is presently only about 3%. However, POAD patients carry a high risk of cardiovascular events and their cumultative mortality rate within 10 years is as high as 40-50%. Atherothrombotic events in the coronary and, less frequently, cerebral arteries are by far the first cause of death and disability in these patients. The rationale for antithrombotic drugs in the treatment of POAD lies in the pivotal role of platelet activation and thrombin formation in the evolution of the atherothrombotic lesions, but also in the effect of some of these drugs on the regulation of microcirculatory responses. In acute thrombotic arterial occlusion, Heparin is the “first application” drug, especially in support of interventional revascularisation procedures. Regional thrombolysis often coupled with angioplasty (PTA), or systemic thrombolysis, are effective in revascularisation of especially infrainguinal-supra popliteal occlusions. However, controlled clinical trials are needed. In chronic POAD, intermittent claudication can be improved with a rational walking exercise programme, but, besides pentoxyphilline, especially ticlopidine significantly adds to the benefits of exercise. Regarding districtual progression of atherothrombosis and especially cardiovascular events, both aspirin and ticlopidine have been shown effective in single studies or meta-analyses. In a recent observational study of pooled data the cumulative endpoint including myocardial infarction, stroke and vascular death was reduced by 25 ± 10% in the generality of patients treated with anti-platelet drugs. Finally, in critical limbs ischemia (CLI), some prostanoid compounds as Iloprost and Prostaglandin El favourably influence rest pain and ulcer healing, but less evidence is available on their effects on hard events as amputation and death. In conclusion, following the general indication to “be conservative” in the treatment of these patients, it seems clear that antithrombotic drugs have become by far a key medication in all different phases of POAD.

lloprost delivered via the BREELIBTM nebulizer: a review of the clinical evidence for efficacy and safety

“…In the early 90s, iloprost was available on the pharmaceutical market as Ilomedin® Bayer Vital GmbH, Leverkusen, Germany, designated for the intravenous treatment of certain diseases of peripheral arteries. 27 The feasibility of safely delivering iloprost to the respiratory tract of patients by a conventional jet nebulizer initiated development of this stable prostacyclin analogue for aerosol therapy of PH. 28,29 The successful repurposing of iloprost was largely facilitated by the inherent advantages of the inhalative delivery, in particular by the pulmonary and intrapulmonary selectivity of the haemodynamic vasodilatory effects after pulmonary drug deposition.…”

Flow Cytometric Analysis of Platelet Function in Micro- and Macroangiopathy.

“…This assumption refers to data from coronary heart disease patients and to the clinical benefit of anti-platelet medication [30,31]. However, the literature is controversial.…”

Rationale for the use of platelet aggregation inhibitors in PAD patients

“…3 Moreover, the 10-year mortality rate for PAD patients is 40-50%, mostly due to CAD or CBVD. 4 to an active form with high affinity for fibrinogen. The active receptor binds fibrinogen, which in turn binds to another platelet, thus initiating thrombus formation and potentially leading to peripheral arterial occlusion, MI and IS.…”