Maximizing coronary disease risk reduction using nicotinic acid combined with LDL-lowering therapy

Treatment with statins markedly reduces levels of LDL-cholesterol, and large, well-designed evaluations of these agents have demonstrated reductions in cardiovascular event rates of similar to 20-40%. Additional therapeutic strategies will be required to make further inroads into the substantial residual burden of cardiovascular disease in statin-treated patients. Epidemiological studies over several decades and outcome studies with agents that raise levels of this lipoprotein (nicotinic acid or fibrates) have established low HDL-cholesterol as an important therapeutic target. Combining agents which decrease LDL-cholesterol and increase HDL-cholesterol within a single regimen might provide a means of improving cardiovascular prognosis beyond that possible with statins atone. Six randomized clinical trials involving treatment with nicotinic acid in combination with a statins or bile acid sequestrant have demonstrated regression, or markedly slowed progression, of atherosclerosis in patients at high risk of a cardiovascular event. Three of these trials, the HDL-Atherosclerosis Treatment Study, the Familial Atherosclerosis Treatment Study, and the Armed Forces Regression Study, have associated these benefits with significant improvements in clinical outcomes. Correcting low HDL-cholesterol in statin-treated patients may provide a means to achieve the next leap forward in the management of cardiovascular disease.