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International Task Force for Prevention of
Coronary Heart Disease

CORONARY HEART DISEASE: REDUCING THE RISK

4.6 Drug treatment

Comment: This paper cites other reports of LE and polymyalgia rheumatica as rare side effects of statins

Comment: The improvement in endothelium-dependent vasomotion with cholesterol-lowering and antioxidant therapy may have important implications for the activity of myocardial ischaemia and may explain in part the reduced incidence of adverse coronary events that is known to result from cholesterol-lowering therapy

Comment: The Clopidogrel vs Aspirin in Patients at Risk of Ischaemic Events trial was designed to assess the relative efficacy of a daily dose of 75 mg clopidogrel compared to 325 mg aspirin per day in reducing the risk of ischaemic stroke, myocardial infarction, or vascular death. 19 185 patients, 72% male and 95% white, aged 62.5 ± 11.1 years (mean ± s.d.) from 384 centres in 16 countries were followed for an average of 1.9 years. Inclusion criteria were a recent stroke or focal neurological deficit (³ 1 week, but ²6 months before randomisation), recent myocardial infarction (²35 days before randomisation), or atherosclerotic peripheral vascular disease. The main exclusion criteria were youth (<21 years), severe stroke likely to lead to patient being bedridden or demented, carotid endarterectomy, severe comorbidity and uncontrolled hypertension. Women of childbearing age not using contraception were also excluded. Among patients receiving clopidogrel, the annual risk of the primary end-point cluster of ischaemic stroke, myocardial infarction or vascular death was 5.32% compared to 5.83% for patients on aspirin (RR 91.3%, p=0.043). No difference was seen in the secondary end points of: (a) ischaemic stroke, myocardial infarction, amputation of vascular death; (b) vascular death; (c) any stroke, myocardial infarction, or death from any cause; (d) death from any cause. The safety profiles of aspirin and clopidogrel were comparable, in particular neutropenia, a worrying side-effect of ticlopidine, was not seen with clopidogrel

Comment: This overview of all published randomised trials of statin drugs demonstrates large reductions in cholesterol and clear evidence of benefit on stroke and total mortality. There was, as expected, a large and significant decrease in CVD mortality, but there was no significant evidence for any increases in either non-CVD deaths or cancer incidence

Comment: This is the first report demonstrating a significant clinical benefit of lowering blood lipids with simvastatin in a diabetic population with coronary heart disease

Organization, Geneva, 1996