Pharmacological prevention of atherothrombotic events in patients with peripheral arterial disease

Peripheral arterial disease (PAD) is strongly associated with atherosclerosis in the coronary and carotid arteries, leading to a highly increased incidence of myocardial infarction, ischaemic stroke and cardiovascular death. Fortunately, pharmacological interventions in large clinical trials have been as effective in subgroups of patients with PAD as in subjects with other atherosclerotic disease. Antiplatelet treatment is indicated in virtually all patients with PAD. Aspirin 75-325 mg day(-1) is considered as first-line treatment, and clopidogrel 75 mg day(-1) is an effective alternative. Statin therapy is indicated to achieve a target low-density lipoprotein cholesterol level of <= 2.5 mmol L-1 in patients with PAD and there is emerging evidence that even lower levels are beneficial. Lowering of plasma homocysteine by supplementing folic acid, vitamin B-12 and vitamin B-6 is not recommended in patients with mild to moderate hyperhomocysteinaemia in the 12-25 mu mol L-1 range, since it does not reduce the incidence of cardiovascular events. Antihypertensive treatment is indicated to achieve a goal blood pressure of <= 140/90 mmHg or <= 130/80 mmHg in the presence of diabetes or chronic kidney disease. All classes of antihypertensive drugs are acceptable for treatment of hypertension in patients with PAD, but angiotensin-converting enzyme inhibitors ramipril or perindopril are especially appropriate because they reduce the incidence of cardiovascular events beyond their blood pressure-lowering effects. Beta-blockers should not be used as first-line antihypertensive treatment. Diabetic patients with PAD should reduce their glycosylated haemoglobin to <= 7%. In conclusion, pharmacological secondary prevention of cardiovascular morbidity and mortality in patients with PAD should be as comprehensive as that in patients with established coronary or cerebrovascular disease.