Antiplatelet Therapy in Secondary Prevention in Patients with Ischaemic Peripheral Arterial Disease

Abstract

Introduction: Globally, peripheral arterial disease affects almost 200 million individuals at high risk of developing another type of cardiovascular disease with an annual incidence of cardiovascular events and cardiovascular mortality of 4-5% and a risk of acute limb ischaemia and amputation of 5%. All patients with clinical symptomatology of peripheral arterial disease should be treated with statins and antiplatelet drugs. Evidence Acquisition: The authors provide an overview, from the perspective of a clinical pharmacologist, of the pharmacokinetic properties of the antiplatelet agents available, mechanisms of their action, and differences among individual agents in side effects, efficacy and safety as well as a comparison of clinical trials. Evidence Synthesis: In a significant proportion of patients, therapy with clopidogrel is modified, with genetic polymorphism demonstrably preventing effective therapy in a proportion of patients. In cases where an antiplatelet agent other than aspirin is chosen, clopidogrel therapy is rational only if a genetic mutation resulting in ineffective therapy has been ruled out. Effective therapy can be accomplished using the more modern antiplatelet agents with balanced pharmacokinetic and pharmacodynamic properties. Conclusions: Several questions related to treatment of patients with peripheral arterial disease remain to be answered. Expert views on recommended antiplatelet therapy diverge. It would be unethical to ignore the fact that therapy may be ineffective in a proportion of clopidogrel-treated patients. Guidelines for the treatment and prevention of peripheral arterial disease should offer alternative antiplatelet drugs or recommendations to verify a patient´s genetic predisposition. Further clinical trials are warranted to assess the efficacy of individual antiplatelet agents and doses thereof in patients with peripheral arterial disease.