Targeting Low HDL-Cholesterol to Decrease Residual Cardiovascular Risk in the Managed Care Setting

BACKGROUND: Most clinicians recognize the importance of reducinglow-density lipoprotein cholesterol (LDL-C) and, therefore, address thistherapeutic need to decrease cardiovascular disease risk. In addition to thecritical role that LDL-C plays, recent studies have shown the contribution ofother lipid fractions, such as high-density lipoprotein cholesterol (HDL-C)and triglycerides (TG), to overall cardiovascular health. Managed careinitiatives to reduce cardiovascular risk typically focus on highly effectivestatin therapies, which are primarily LDL-C-lowering agents and have lesserTG-lowering and HDL-C-raising effects. However, clinical and epidemiologicdata illustrate the need to expand the scope of therapies to reduce theresidual cardiovascular risk associated with low HDL-C levels and elevatedTG levels, even when LDL-C is managed successfully. OBJECTIVES: To address the value of treating beyond LDL-C level to improvepatient health outcomes and reduce health care-related costs. SUMMARY: Several large trials and meta-analyses have investigated the effects of lipid-lowering statin therapy and have consistently demonstrated that statin therapy significantly reduces LDL-C levels and incidence of cardiovascular events. In spite of the efficacy of statin therapy in these studies, statins did not eliminate cardiovascular risk. Rather, significant residual cardiovascular risk remains after treatment with statins, especially in high-risk patients such as those with diabetes. Residual cardiovascular risk stems, at least partially, from low HDL-C and elevated TG. Low HDL-Clevels have been identified as a significant, independent predictor of cardiovascular risk, and increases in HDL-C are associated with reductions in cardiovascular events. High TG levels are a significant risk factor for cardiovascular disease and are a marker for atherogenic remnant lipoproteins, such as very low-density lipoprotein cholesterol (VLDL-C). Additionally, with elevated TG levels, a combination of LDL-C with VLDL-Cin the measure of non-HDL-C may be a better predictor of cardiovascular risk than LDL-C alone. Recent national treatment guidelines suggest that combination therapymay be necessary to address multiple lipid targets (i.e., LDL-C, non-HDL-C,HDL-C, and TG); adding niacin or a fibrate to a statin is a therapeutic option that should be considered. As monotherapy agents, fibrates and niacin havebeen demonstrated to alter several lipid parameters and reduce cardiovascular events. Niacin appears to exert the greatest beneficial effects on the widest range of lipoprotein abnormalities, in addition to possessing an established safety profile. Moreover, niacin/statin combination therapy may provide greater benefits, as manifested through a correction of atherogenic lipid abnormalities, a slowing of atherosclerosis progression in coronaryheart disease (CHD) patients, and a reduction of residual cardiovascular risk. Pharmacoeconomic modeling studies have been used to describe the potential effects on both cardiovascular events and health care costs by the achievement of, or failure to achieve, combined optimal lipid values(OLVs). Achievement of OLVs is predicted to be associated with a reduced risk of cardiovascular events, in which greater magnitudes of risk reduction accompany the achievement of a greater number of lipid goals. Basedon patient baseline lipid values and product labeling information, mathematical models estimate that OLVs are achieved more frequently with extended-release niacin (niacin ER)/simvastatin combination therapy thanwith other high-potency agents. These modeling estimates were maintained in different patient groups, including those with diabetes or the metabolicsyndrome. Finally, these modeling studies estimated that a fixed-doseniacin ER/simvastatin combination therapy would reduce direct medical costs of CHD events more effectively than would high-dose simvastatin monotherapy. CONCLUSIONS: Statins are highly effective for lowering LDL-C levels and,consequently, cardiovascular event rates. However, statins do not eliminate cardiovascular risk. Even in the presence of tightly controlled LDL-C levels,evidence indicates that high TG and low HDL-C levels are independent cardiovascular risk factors. Treating lipid parameters beyond LDL-C may require the addition of niacin or a fibrate to statin therapy. Niacin is themost effective agent for raising HDL-C levels, and pharmacoeconomic modeling suggests that niacin ER/statin combination therapy may promote the cost-effective achievement of OLVs in several at-risk patientpopulations.