Combination Therapy with Colestipol and Psyllium Mucilloid in Patients with Hyperlipidemia

doi:10.1059/0003-4819-123-7-199510010-00003

Combination Therapy with Colestipol and Psyllium Mucilloid in Patients with Hyperlipidemia

From Victoria Hospital, University Hospital, Robarts Research Institute, and the University of Western Ontario, London, Ontario, Canada. Grant Support: The Upjohn Company of Canada, Toronto, Ontario, Canada, provided colestipol (Colestid) and funding. Searle Canada, Inc., Oakville, Ontario, Canada, provided bulk psyllium mucilloid (Metamucil). Requests for Reprints: J. David Spence, MD, Robarts and Siebens-Drake Research Institutes, Stroke Prevention and Atherosclerosis Research Centre, 1400 Western Road, London N6G 2V2, Ontario, Canada. Current Author Addresses: Drs. Spence and Munoz: Robarts and Siebens-Drake Research Institutes, Stroke Prevention and Atherosclerosis Research Centre, 1400 Western Road, London N6G 2V2, Ontario, Canada. Dr. Huff: Robarts Research Institute 416, University of Western Ontario, London N6C 3Y8, Ontario, Canada. Dr. Heidenheim: Room 137, Health Services Building, Victoria Hospital, SSC, London N6A 4G5, Ontario, Canada. Dr. Viswanatha: 47-5800 Osuna NE, Albuquerque, NM 87109. Dr. Lindsay: Nephrology Division, Room 474, Victoria Hospital, 375 South Street, London N6A 4G5, Ontario, Canada. Dr. Wolfe: 5-of-16 University Hospital, London N6A 5A5, Ontario, Canada. Dr. Mills: Drug Information, Pharmacy, Victoria Hospital, 375 South Street, London N6A 4G5, Ontario, Canada. Requests for details on the quality-of-life study should be directed to Dr. Heidenheim or Dr. Lindsay at the addresses given above.

Abstract

Objective: To test whether combining psyllium mucilloid with half the usual dose of colestipol reduces the adverse effects associated with colestipol and maintains or increases its efficacy in the treatment of hyperlipidemia. This strategy might make bile acid sequestrants, which are seldom used because they cause adverse effects such as bloating and constipation, more tolerable and less expensive.

Design: A randomized, parallel-group, double-blind, controlled trial.

Setting: An outpatient clinic in a tertiary care hospital.

Patients: 121 patients who had moderate primary hypercholesterolemia (total cholesterol level more than 6 mmol/L and less than 8 mmol/L; triglyceride level less than 3 mmol/L) after following a low-fat diet for 1 year (National Cholesterol Education Program Step Two diet).

Intervention: 5 g of cellulose placebo; 5 g of colestipol; 2.5 g of colestipol plus 2.5 g of psyllium; or 5 g of psyllium three times daily before meals for 10 weeks.

Main Outcome Measures: At baseline and at weeks 4 and 10, fasting blood lipid levels and apoprotein concentrations were measured and a quality-of-life instrument was completed.

Results: A combination of 2.5 g of psyllium and 2.5 g of colestipol was better tolerated than and as effective as either 5 g of colestipol alone or 5 g of psyllium alone. The combination therapy and colestipol alone did not differ significantly with respect to changes in individual lipid values. The ratio of total cholesterol to high-density lipoprotein cholesterol (HDL) was reduced by 18.2% (95% CI, 12.3% to 24%) with the combination therapy; by 10.6% (CI, 2.0% to 15.4%) with colestipol alone; by 6.1% (CI, 1.5% to 10.6%) with psyllium alone; and by 0.1% (CI, −4.8% to 7%) with placebo (P = 0.0002). Combination therapy reduced the ratio of total cholesterol to HDL significantly more than did colestipol alone or psyllium alone (P < 0.05).

Conclusions: These findings suggest that adding psyllium to half the usual dose of bile acid sequestrant resins maintains the efficacy and improves the tolerability of these resins.