Psyllium for the reduction of cholestyramine-associated gastrointestinal symptoms in the treatment of primary hypercholesterolemia.

OBJECTIVE

To determine if the bulk-forming laxative, psyllium hydrophilic mucilloid (PHM), reduces the gastrointestinal side effects and enhances the cholesterol-lowering efficacy of cholestyramine resin in patients with primary hypercholesterolemia.

DESIGN

After a dietary lead-in period and 6 weeks of treatment with cholestyramine, the study followed a double-blinded, placebo-controlled, crossover format.

SETTING

Lipid clinic affiliated with a large metropolitan community hospital.

PARTICIPANTS

Twenty-seven randomly selected male and female patients with a diagnosis of primary hypercholesterolemia. Entry criteria required a fasting low-density lipoprotein cholesterol (LDL-C) concentration of 4.91 mmol/L (190 mg/dL) or greater and a triglyceride concentration of less than 2.26 mmol/L. Patients using steroids, beta-blockers, thiazide diuretics, and lipid-lowering agents, or having a history of allergy to psyllium or aspartame were excluded.

INTERVENTION

The study consisted of four interventional phases of 6 weeks' duration that included (1) dietary stabilization (National Cholesterol Education Program Step I Diet); (2) cholestyramine therapy (4 g twice daily); (3) cholestyramine with study medication (PHM [5.1 g twice daily] or placebo); and (4) cholestyramine with crossover to alternate study medication.

MAIN RESULTS

Following the 6-week dietary lead-in phase, four patients were eliminated from the study because their fasting LDL-C concentrations fell below 4.14 mmol/L (160 mg/dL), and one patient was eliminated because testosterone therapy was initiated by his internist. The remaining 22 patients entered the cholestyramine treatment phase. Four left the study within 2 weeks because of intolerable gastrointestinal tract symptoms. The 18 patients who completed this phase demonstrated significant reductions in their plasma total cholesterol (7.27 vs 6.67 mmol/L [281 vs 258 mg/dL]) and LDL-C (5.38 vs 4.63 mmol/L [208 vs 179 mg/dL]) concentrations compared with baseline levels. The addition of PHM to the cholestyramine regimen provided a tendency toward further reductions in total cholesterol and LDL-C levels (6.67 vs 6.46 mmol/L [258 vs 250 mg/dL] and 4.63 vs 4.29 mmol/L [179 vs 166 mg/dL], respectively), although statistical significance was not achieved. Psyllium hydrophilic mucilloid significantly reduced the frequency and severity of constipation, abdominal discomfort, and heartburn. No reports of new gastrointestinal tract symptoms or untoward effects were noted with the addition of PHM.

CONCLUSION

These data suggest that the addition of PHM to cholestyramine therapy may improve a patient's compliance by reducing the associated gastrointestinal tract side effects.