Psyllium for the reduction of cholestyramine-associated gastrointestinal symptoms in the treatment of primary hypercholesterolemia
J. J. Maciejko, R. Brazg, A. Shah, S. Patil and M. Rubenfire
Department of Medicine, Sinai Hospital, Detroit, Mich.
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.
