Advancing therapy for hypercholesterolemia.
BACKGROUND
Hypercholesterolemia holds a key role in the development and progression of atherosclerosis and is a causative factor of coronary artery disease. Current guidelines for cholesterol treatment target low-density cholesterol (LDL-C) as the primary goal of therapy. Despite advances in the pharmacotherapy of atherosclerosis, the most successful agents used to treat this disease--HMG CoA reductase inhibitors--remain ineffective for the primary or secondary prevention of myocardial infarction in 50-60% of patients. Advancing therapy for hypercholesterolemia with new-emerging drugs either as monotherapy or in combination will hopefully improve cardiovascular outcomes.


METHODS
The two major sources of cholesterol in the human body are: i) biosynthesis of cholesterol by the liver; and ii) absorption by the intestines. Both play a pivotal role in the overall balance of cholesterol. A recent and more effective therapeutic strategy is to treat both sources of cholesterol simultaneously with a complementary mechanism of action. The present article presents cholesterol metabolism and reviews new emerging lipid-lowering drugs and therapies that: i) lower LDL-C; ii) lower triglycerides; and iii) increase high-density lipoprotein cholesterol.


RESULTS
This review summarizes the pivotal role of both the liver and intestine in the overall balance of cholesterol in the body and describe the clinical impact and relevance of using new emerging lipid-lowering drugs either alone or co-administered with statins in controlling cholesterol levels.


CONCLUSIONS
An elevated concentration of LDL-C plays a causal role in the development of cardiovascular disease. The new aggressive cholesterol treatment goals call for a more advanced therapeutic approach to maximize the cardiovascular benefits associated with lower LDL-C levels.
Toutouzas
Konstantinos
K
Medical School of Athens University, Hippokration Hospital, First Department of Cardiology, Athens, Greece.
Drakopoulou
Maria
M
Skoumas
Ioannis
I
Stefanadis
Christodoulos
C
D001384:Azetidines / Q000627:therapeutic use; D001647:Bile Acids and Salts / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D002784:Cholesterol / Q000096:biosynthesis; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors; D008078:Cholesterol, LDL / Q000097:blood; D000069438:Ezetimibe; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000037:antagonists & inhibitors; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use; D011345:Fenofibrate / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy*; D007408:Intestinal Absorption; D009525:Niacin / Q000627:therapeutic use
D001384:Azetidines; D001647:Bile Acids and Salts; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008078:Cholesterol, LDL; D015525:Fatty Acids, Omega-3; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C106092:microsomal triglyceride transfer protein; D009525:Niacin; D002784:Cholesterol; D013186:Farnesyl-Diphosphate Farnesyltransferase; D000069438:Ezetimibe; D011345:Fenofibrate