Doubling torcetrapib to its maximum tolerated dose more than doubles HDL cholesterol when combined with atorvastatin (Drugs Today 2006)

Epidemiological studies have identified both low-density lipoproteins (LDL) and high-density lipoproteins (HDL) as independent factors that modulate the risk of cardiovascular disease. Statins (HMG-CoA reductase inhibitors) that lower LDL and triglyceride levels are widely used for the treatment of hypercholesterolemia. Recently, a new class of drugs, cholesterol ester transfer protein (CETP) inhibitors, which significantly raise HDL and lower LDL, has been developed. Torcetrapib, a CETP inhibitor, has been shown to be effective, safe and well tolerated when used in combination with atorvastatin therapy. Torcetrapib has been shown to increase HDL cholesterol levels by 46% when given alone and by 61% when given in combination with atorvastatin, as well as to decrease LDL cholesterol levels by more than that achieved by atorvastatin alone. When the dosage of torcetrapib was doubled (at maximum tolerated dose), HDL increased by over 100%. Combination therapy appeared safe and well tolerated. Large trials evaluating the efficacy and safety of torcetrapib in combination therapy with atorvastatin are now in progress in order to establish whether CETP inhibition in combined therapy with statins will reduce the risk for atherosclerosis.