Statin therapy secondary prevention trials

Elevated serum cholesterol levels and in particular LDL-cholesterol levels are strongly associated with cardiovascular mortality across the spectrum of epidemiologic studies and pharmacologic intervention studies in primary and secondary prevention trials (Ligure 4.4). In the Cholesterol Treatment Trialists Collaborators meta-analysis of >90,000 patients studied in 14 randomized trials of statin therapy, a reduction in LDL cholesterol of 1 mmol/L (39 mg/dL) was associated with a 12% proportional reduction in all-cause mortality, predominantly driven by a 19% proportional reduction in cardiovascular mortality (45). Among patients with pre-existing heart disease there were 14 fewer deaths per 1000 participants per mmol LDL cholesterol reduction, as well as an approximately 25% reduction in major adverse cardiac events. 

RCTs supporting the benefits of fibrate therapy is not consistent. Gemfibrozil was used in the Helsinki Heart Study, a primary prevention trial in men with raised non-HDL-cholesterol [55], and the Veterans Administration HDL Intervention Trial, VAHIT, a secondary CVD prevention trial in men with low HDL-cholesterol and relatively normal LDL [56], These studies showed significant positive benefit for the drug overall and in diabetic subgroups. However, the populations studied in these trials also respond well to statin therapy [43], In the Bezafibrate Infarction Prevention Trial, a CVD secondary prevention trial [57], there was a trend... 

Helsinki Heart Study (15) have all demonstrated the benefit of lipid lowering using various hypolipidemic agents for prevention of initial cardiac events. Secondary prevention trials have unequivocally shown that lipid lowering therapy not only reduces acute coronary events and other clinical endpoints, but also results in angiographic improvement. These studies have used different classes of drugs (statins, fibrates, niacin, bile acid resins—alone and in combination) in both hyper- and normo-cholesterolemic patients with established CAD. 

Note that a number of the large-scale trials of the use of lipid-regulating drugs in primary or secondary prevention of cardiovascular events included patients with diabetes. A review of these subgroups concluded that statins were the drug of choice for lipid-lowering therapy in patients with type 2 diabetes and known coronary artery disease or other cardiovascular risk factors. There was no evidence to recommend one statin over another. ... 

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