Colesevelam added to combination therapy with a statin and ezetimibe in patients with familial hypercholesterolemia: A 12-week, multicenter, randomized, double-blind, controlled trial

• Published in: Clinical therapeutics Vol. 32; no. 4; pp. 615 - 625
• Main Authors: Huijgen, Roeland, MD, Abbink, Evertine J., MD, PhD, Bruckert, Eric, MD, Stalenhoef, Anton F.H., MD, PhD, FRCP, Imholz, Ben P.M., MD, PhD, Durrington, Paul N., MD, FMedSci, Trip, M.D., MD, PhD, Eriksson, Mats, MD, PhD, Visseren, Frank L.J., MD, PhD, Schaefer, Juergen R., MD, Kastelein, John J.P., MD, PhD
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Bridgewater, NJ EM Inc USA 01.04.2010; Elsevier; Elsevier Limited
• Subjects: Adolescent; Adult; Aged; Allylamine - administration & dosage; Allylamine - adverse effects; Allylamine - analogs & derivatives; Allylamine - therapeutic use; Anticholesteremic Agents - administration & dosage; Anticholesteremic Agents - adverse effects; Anticholesteremic Agents - therapeutic use; Apolipoproteins; Apolipoproteins - blood; Atherosclerosis; Azetidines - administration & dosage; Azetidines - therapeutic use; bile acid sequestrant; Biological and medical sciences; Body Mass Index; Cardiology; Cardiovascular disease; Cholesterol; Cholesterol - blood; Clinical medicine; Colesevelam Hydrochloride; Disease prevention; Disorders of blood lipids. Hyperlipoproteinemia; Double-Blind Method; Drug Therapy, Combination; Ezetimibe; familial hypercholesterolemia; Female; Heart; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Hyperlipoproteinemia Type II - drug therapy; Internal Medicine; lipid-lowering therapy; Lipids; Male; Medical Education; Medical sciences; Medicin och hälsovetenskap; Medicine; Metabolic diseases; Middle Aged; Mortality; Pharmacology. Drug treatments; Smoking; Statins; Triglycerides - blood; Young Adult; Netherlands; bile acid sequestrant; lipid-lowering therapy; familial hypercholesterolemia; Multicenter study; Ezetimibe; Lipids; Hyperlipoproteinemia; Lipoprotein; Colesevelam; Randomization; Bile acid; Clinical trial; Dyslipemia; Human; Drug combination; Metabolic diseases; Polymer; Statin derivative; Cholesterol; Genetic disease; Hypercholesterolemia; Complexing agent; Double blind study; Combined treatment; Antilipemic agent
• ISSN: 0149-2918; 1879-114X; 1879-114X
• DOI: 10.1016/j.clinthera.2010.04.014

Abstract Background: Familial hypercholesterolemia (FH) has been associated with increased cardiovascular risk when untreated or when normal LDL-C concentrations are not reached. Some patients with FH do not reach LDL-C goals despite intensive combination therapy. Objective: This study assessed the efficacy and tolerability of colesevelam added to maximally tolerated, stable-dose combination treatment with a statin + ezetimibe. Methods: This Phase IV, multicenter, randomized, double-blind, placebo-controlled trial enrolled patients aged 18 to 75 years with FH and an LDL-C concentration >2.5 mmol/L who were receiving a maximally tolerated and stable regimen of a statin + ezetimibe. Patients were randomly assigned to receive colesevelam 3.75 g/d or placebo added to the statin + ezetimibe for 12 weeks. The primary efficacy outcome was the difference in LDL-C between the colesevelam and placebo groups after 6 weeks. Secondary efficacy outcomes were between-group differences in LDL-C, total cholesterol (TC), HDL-C, triglyceride (Tg), apolipoprotein (apo) B, and apoA-I concentrations, as well as apoB/apoA-I ratio after 12 weeks. Tolerability was assessed based on the prevalences of adverse events by organ system class in each treatment group. Results: Eighty-six patients were randomized (45 colesevelam, 41 placebo), of whom 84 (44 colesevelam, 40 placebo) were included in the primary analysis. The mean (SD) age of the participants was 52.8 (10.8) years, and 51 (59%) were men. The difference (95% CI) in LDL-C between colesevelam and placebo after 6 weeks was −18.5% (−25.3 to −11.8). Between-group differences in LDL-C, TC, HDL-C, Tg, and apoB/apoA-I ratio after 12 weeks were −12.0% (−17.8 to −6.3), −7.3% (−12.0 to −2.6), +3.3% (−2.4 to +9.0), +2.8% (−10.4 to +15.9), and −12.2% (−20.2 to −4.2), respectively. Colesevelam was generally well tolerated, with gastrointestinal adverse events in 12 of 45 patients (27%) versus 7 of 40 (18%) in the placebo group ( P = NS). Conclusion: In these patients with FH, colesevelam added to a combination of a statin + ezetimibe was associated with significantly improved LDL-C concentrations compared with placebo during the 12-week study period and was generally well tolerated.