Current and Emerging Therapies in Hypercholesterolemia: Focus on Colesevelam

Background: Statins are recommended as first line therapy for the prevention of cardiovascular disease. Some individuals are statin intolerant or may need additional cholesterol lowering to achieve their cholesterol targets. Purpose: To review the pharmacology, clinical efficacy and safety of colesevelam mono- and combination therapy in patients with hypercholesterolemia. Data source: English-language journals from PUBMED MEDLINE (without restriction of date) using key word colesevelam. Results: Trials of colesevelam as monotherpy or in combination had baseline LDL-c levels of 130 to 202 mg/dl and triglycerides levels of 114 to 230 mg/dl. Colesevelam monotherapy reduced LDL-c by 9%–20 % while increasing triglycerides 6%–25%. When added to low or moderate dose statin therapy, colesevelam decreased LDL-c an additional 6%–16%; when added to fenofibrate, cole-sevelam additionally decreased LDL-c by 17 % and non-HDL-c by 7%; and when added to statin + niacin 2 gr additionally decreased LDL-c by 10%. The hypertriglyceridemia observed with colesevelam monotherapy was largely attenuated when colesevelam was coadministered with statins, fenofibrate, or niacin 2 gr. Coadministration of colesevelam with ezetimibe provided variable additional LDL-c reductions ranging from 0 to 20 % over ezetimibe alone, and triglyceride responses were similarly variable. In diabetic individu-als with modest hypertriglyceridemia, colesevelam reduced hemoglobin A1c by 0.5%. Colesevelam has fewer drug interactions than older bile acid sequestrants and is well-tolerated when used in combination with other lipid-lowering medications as well as with ora