Cholesterol treatment patterns and cardiovascular clinical outcomes associated with colesevelam HCl and ezetimibe.

INTRODUCTION: Pharmaceuticals are commonly used to help at-risk patients reduce low-density lipoprotein cholesterol (LDL-C) levels in an effort to prevent atherosclerotic coronary artery disease. Although both the cholesterol inhibitor ezetimibe and the newer generation bile acid sequestrant colesevelam hydrochloride (HCl) effectively reduce LDL-C levels in patients with hypercholesterolemia, real-world evidence based on clinical outcomes is lacking. METHODS: A retrospective analysis of healthcare insurance claims data from a large national healthcare payer was conducted to evaluate outcomes within 12 months among 2,067 patients with hypercholesterolemia after the initiation of treatment with colesevelam HCl (679 patients) as compared with ezetimibe (1,388 patients). Outcomes evaluated were (1) composite cardiovascular event which included myocardial infarction, stroke, angina, or revascularization and (2) macrovascular complication event which was a wider-encompassing measure that included all composite cardiovascular outcomes along with atherosclerosis, aneurysm, embolism, and peripheral vascular disease. RESULTS: An adjusted logistic regression model found lower odds of a composite cardiovascular event (odds ratio [OR] 0.54, 95 % confidence interval [CI] 0.30-0.97) within 12 months for subjects initiating treatment with colesevelam HCl compared with subjects initiating treatment with ezetimibe. The unadjusted OR was slightly lower (OR 0.52, 95 % CI 0.30-0.90). The odds ratio for the wider-encompassing macrovascular complication event occurring within 12 months of initiating treatment with colesevelam HCl or ezetimibe was not statistically significant (OR 0.821, 95 % CI 0.49-1.35). DISCUSSION: The evidence of lower risk for composite cardiovascular event rates for subjects treated with colesevelam HCl compared with those treated with ezetimibe suggests the potential need to consider risk of clinical outcomes, in addition to LDL-C levels, in real-world practice when choosing a pharmaceutical treatment.

Colesevelam hydrochloride for the treatment of type 2 diabetes mellitus.

BACKGROUND: Colesevelam hydrochloride is a bile acid sequestrant approved in January 2008 by the US Food and Drug Administration (FDA) for the treatment of adult patients with type 2 diabetes mellitus (DM) in combination with a sulfonylurea, metformin, and/or insulin therapy. OBJECTIVE: The purpose of this article was to review the pharmacology, pharmacokinetics, efficacy, adverse effects and tolerability, drug-drug interactions, contraindications/precautions, dosage and administration, pharmacoeconomics, and the overall role of colesevelam in the management of adult patients with type 2 DM. METHODS: A literature search using MEDLINE (1966-October 27, 2008), PubMed (1950-October 27, 2008), Science Direct (1994-October 27, 2008), Web of Science (1980-October 27, 2008), American Diabetes Association Scientific Abstracts (2004-2008), and International Pharmaceutical Abstracts (1970-October 27, 2008) was performed using the term colesevelam. English-language, original research and review articles were examined, and citations from these articles were assessed. Manufacturer prescribing information and the FDA review of the new drug application for colesevelam were also examined. RESULTS: Colesevelam is a hydrophilic, water-insoluble polymer, with negligible absorption and systemic distribution, that is excreted primarily in the feces. Through a mechanism still under investigation, colesevelam effectively lowers glycosylated hemoglobin (HbA(1c)) when used in combination with a sulfonylurea, metformin, and/or insulin therapy. Three completed, published Phase III clinical trials investigating colesevelam for the treatment of type 2 DM were evaluated for information, data, and conclusions. At dosing of 1.875 g BID or 3.75 g once daily in combination with one of the aforementioned agents versus placebo, reductions in HbA(1c) in all 3 Phase III clinical trials of colesevelam ranged from 0.5% to 0.7% (P < 0.02). In clinical trials, colesevelam was well tolerated, with hypoglycemia occurring in approximately 3% of studied patients. CONCLUSIONS: When used in combination with a sulfonylurea, metformin, and/or insulin therapy, colesevelam has been reported to significantly reduce HbA(1c) in adult patients with type 2 DM. Colesevelam's role in the management of type 2 DM remains undefined, however; further investigation into its mechanism of action and long-term efficacy and safety should be performed.