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Gemfibrozil in familial combined hyperlipidaemia: effect of added low‐dose cholestyramine on plasma and biliary lipids
Author(s) -
ÖDMAN B.,
ERICSSON S.,
LINDMARK M.,
BERGLUND L.,
ANGELIN B.
Publication year - 1991
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.1991.tb01380.x
Subject(s) - gemfibrozil , cholestyramine , medicine , cholesterol , endocrinology , chemistry
. Gemfibrozil is frequently used for lipid‐lowering in familial combined hyperlipidaemia (FCHL) and in other forms of combined hyperlipidaemia. This therapy increases biliary cholesterol saturation, enhancing the risk for gallstone formation. Furthermore, in hypertriglyceridaemia, LDL cholesterol levels often tend to rise. We have explored the possibility that addition of a low dose of cholestyramine to gemfibrozil therapy obliterates these phenomena. Eighteen gallstone‐free patients with definite ( n = 5) or probable ( n = 10) FCHL, or combined hyperlipoproteinaemia ( n = 3) were randomized to a 6 week treatment with gemfibrozil, 600 mg b.i.d., or gemfibrozil 600 mg b.i.d.plus 4 g cholestyramine o.d. After 6 weeks the patients were crossed over to the alternative treatment. Plasma lipoproteins and biliary lipids were determined at baseline and at the end of each period. Institution of gemfibrozil treatment resulted in a decrease in plasma cholesterol by 15% ( P < 0.05) and in plasma triglycerides by 47% ( P < 0.05); HDL cholesterol increased by 18% ( P < 0.05). Addition of cholestyramine further decreased plasma and LDL total cholesterol by 9% ( P < 0.05). Total triglycerides and HDL cholesterol did not change. Gemfibrozil treatment was associated with a rise in the relative biliary concentration of cholesterol from 5.6 ± 0.4 to 6.9 ± 0.5 molar percent ( P < 001), and a parallel decrease in the relative concentration of bile acids, resulting in an increased cholesterol saturation of the bile, from 77.5 to 90.6% ( P < 0.05). This change was not observed during the combined therapy (mean cholesterol saturation, 82.4%). It is concluded that the addition of a low dose of cholestyramine neutralizes the negative effects on biliary lipid composition induced by gemfibrozil and strengthens some of the positive effects on plasma lipoprotein levels.