Clinical relevance of statins: their role in secondary prevention

Five large randomized clinical trials show the benefits of lipid lowering with statins on cardiac morbidity and mortality. Three of these were secondary-prevention trials--the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study, Cholesterol and Recurrent Events (CARE), and Scandinavian Simvastatin Survival Study (4S). The CARE and LIPID studies, performed with pravastatin, comprise populations that are representative of the majority of patients with coronary disease in that they included subjects with 'average' cholesterol levels. The 4S study, using simvastatin, comprised a patient population with elevated lipid levels. Pooled data from three trials, CARE, LIPID, and the West of Scotland Coronary Prevention Study (WOSCOPS), were examined in the Pravastatin Pooling Project (PPP). Individual patient data from these three event trials were pooled into a single database, permitting subgroup analyses and providing increased power. In the PPP, pravastatin-treated patients had significantly lower all-cause mortality (7.9, vs. 9.8% in those receiving placebo, a relative risk reduction of 20%). Pravastatin treatment was associated with a significant 24% reduction in CHD mortality and a nonsignificant difference in other vascular deaths (17%) and noncardiovascular deaths (12%). However, the reductions in absolute risk were much larger in those with a history of coronary heart disease than in those without. In the combined analysis of CARE and LIPID, there was also a uniform relative risk reduction in both men and women. In high-risk groups such as diabetics, smokers, hypertensives, and the elderly, there were also significant risk reductions in clinical end points. Finally, in the 598 participants, who had a stroke (90% of which were non-fatal), CARE and LIPID individually demonstrated reductions in non-fatal and total stroke. These data confirm that benefits of treatment in secondary prevention of coronary heart disease encompasses prevention of stroke as well as coronary heart disease events. The benefits are found in those who have had unstable angina as well as myocardial infarction. These findings strengthen even further the case for much more widespread use of statins in secondary prevention.