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Existing and investigational combination drug therapy for high-density lipoprotein cholesterol
1Louisville Metabolic and Atherosclerosis Research Center, Louisville, Kentucky 40213, USA.
Insights
Lipid-altering drugs lower low-density lipoprotein (LDL) cholesterol but do not fully prevent or cure coronary artery disease (CAD). Combination therapy targeting multiple lipid risk factors, including high-density lipoprotein (HDL), may offer better CAD prevention.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
Background:
- Lipid-altering drugs have reduced coronary artery disease (CAD) risk for decades.
- However, monotherapy primarily targeting low-density lipoprotein (LDL) cholesterol has not cured or fully prevented CAD in many patients.
Purpose of the Study:
- To investigate the limitations of monotherapy lipid-altering drugs in CAD management.
- To explore the potential of combination therapy for a more comprehensive approach to CAD prevention.
Main Methods:
- Review of clinical outcomes trials of lipid-altering drugs.
- Analysis of the multifactorial nature of atherosclerosis and CAD risk factors.
Main Results:
- Monotherapy lipid-lowering drugs show benefits in a minority of patients.
- Atherosclerosis is a complex process influenced by multiple risk factors beyond LDL cholesterol.
- Low high-density lipoprotein (HDL) cholesterol is a significant CAD risk factor.
Conclusions:
- Predominant cholesterol-lowering drugs do not fully address the complexity of CAD.
- Combination therapy, potentially including agents that improve HDL cholesterol, may offer superior CAD risk reduction.
- A multidimensional approach to lipid management is crucial for effective CAD prevention.
Abstract:
For the past 3 to 4 decades, clinical outcomes trials have shown that drugs that favorably alter serum lipid levels reduce the risk of coronary artery disease (CAD) events. However, despite these successes, the reduction in serum low-density lipoprotein (LDL) cholesterol levels with monotherapy lipid-altering drugs does not "cure" CAD to the same degree that antibiotics "cure" many infections, nor do they "prevent" CAD in the same way that childhood immunizations "prevent" the onset of such conditions as measles, mumps, and rubella. Clinical outcome trials of monotherapy lipid-altering drugs have demonstrated a reduction in the relative risk of CAD in only a minority of patients. Thus, although safe and very effective in lowering serum LDL cholesterol levels, drugs that predominantly lower cholesterol do not "cure" atherosclerotic disease, nor have they been shown to "prevent" most CAD events in numerous clinical outcome trials. The reason for the suboptimal CAD outcomes benefits of monotherapy lipid-altering drugs is likely because atherosclerosis is a complex pathologic process with many important risk factors involved in the initiation and progression of atherosclerotic lesions and involved in the onset of the CAD event itself. An elevated serum LDL cholesterol level is an important CAD risk factor, but it is not the only lipid risk factor. A decreased serum high-density lipoprotein (HDL) cholesterol level is another important risk factor for CAD. Combination therapy through existing drugs (or possibly, in the future, through investigational lipid-altering drugs) may not only improve LDL cholesterol but also improve serum HDL cholesterol levels. This more global, multidimensional approach to lipid-altering drug treatment may provide the best chance to prevent CAD.