Low-density lipoprotein cholesterol (LDL-C) reduction alone has consistently achieved a statistically significant 25–30% reduction in clinical events in multiple clinical trials. This degree of clinical benefit is inadequate, however, to stem the tide of coronary artery disease. A focus on low-density lipoprotein (LDL) reduction alone reduces the rate of coronary atherosclerosis progression but leaves a large number of patients experiencing clinical events despite adequate LDL-C control. One major contributor to coronary atherosclerosis that is not improved with LDL reduction is high-density lipoprotein (HDL) and reverse cholesterol transport.
Clinical trials funded by the US National Institutes of Health (NIH) have demonstrated that a combination of LDL reduction and HDL increase can achieve better clinical and arteriographic outcomes compared to LDL reduction alone. HDL heterogeneity helps to explain differences in the efficiency of reverse cholesterol transport. This process can be enhanced through appropriate diet, loss of excess body fat and physical activity. Nicotinic acid and fibric acid derivatives can enhance reverse cholesterol transport and have been used in multiple clinical trials. The combination of nicotinic acid and a statin drug are particularly beneficial in NIH-sponsored clinical trials. The HDL increase induced by nicotinic acid is primarily HDL2. By combining a two-staged LDL-C reduction and HDL-C raising strategy, improved clinical outcomes can be achieved for patients with coronary artery disease.