Cholesterol lowering for secondary prevention: what statin dose should we use?

Over the past decade, 17 large placebo-controlled trials have established that statin therapy lowers LDL cholesterol and prevents cardiovascular events and death in patients with coronary disease or at high risk for atherosclerotic events. Nine trials of higher dose vs. lower dose statins (reporting data from 29,853 patients with coronary artery disease and 486 patients with other indications for statin therapy) have established that higher dose statin therapy is more efficacious than lower dose therapy in reducing myocardial infarctions/coronary death (by 16%) and stroke (by 18%) in patients with coronary disease but only reduces all-cause mortality in patients at high risk for coronary death (such as patients immediately after acute coronary syndrome). Higher dose statins are associated with statistically significantly increased risks of myopathy and elevated transaminases compared to lower dose statins; while relative risks for these outcomes are 1.2 and 4.0, the absolute increases are small (0.5% and 1%). Secondary analyses of these trials using individual patient data and multivariate adjustment will be needed to appropriately examine the incremental benefits of different LDL targets, and trials are needed to determine whether combinations of low dose statins plus other lipid lowering agents may achieve better clinical outcomes than higher dose statin therapy alone.