TOLERABILITY AND EFFICACY OF COMBINATION THERAPY WITH SIMVASTATIN PLUS GEMFIBROZIL IN TYPE IIB REFRACTORY FAMILIAL COMBINED HYPERLIPIDEMIA

Type IIb hyperlipidemia due to familial combined hyperlipidemia (FCH) is a common lipid metabolism disorder associated with a high incidence of coronary heart disease. Simvastatin and gemfibrozil are two drugs commonly used to treat this lipid abnormality. However, monotherapy wi th these drugs often fails to reduce serum cholesterol and triglycerid es to optimal levels. In this study the tolerability and efficacy of c ombined simvastatin plus gemfibrozil therapy was investigated over 18 months in 20 patients (15 men and five women, ages 42 to 71 years) at high risk for atherosclerosis affected by type IIb FCH. Patients were selected because they did not respond satisfactorily to monotherapy wi th simvastatin or gemfibrozil, taken for at least 6 months with no sid e effects, namely laboratory test alterations or subjective complaints . The administration protocol was designed as a three-phase open study . In the first phase (8 weeks) patients were assigned to take 10 mg/da y simvastatin plus 600 mg/day gemfibrozil; in the second phase (4 mont hs) variable doses of simvastatin [10 to 20 mg/day, depending on the d ecrease in low-density lipoprotein (LDL) cholesterol] and gemfibrozil (600 to 1200 mg/day, depending on serum triglyceride values) were pres cribed. In the follow-up period (phase 3) optimum therapy was maintain ed. No patient dropped out of the study, and no side effects were reco rded. Serum creatine phosphokinase remained within the normal range, a s did other hematochemical tolerability parameters. At the end of the follow-up, total (TC) and LDL cholesterol dropped by 35% (from 334 +/- 38 mg/dl to 218 +/- 27 mg/dl, P < 0.0001) and 39% (from 230 +/- 36 mg /dl to 141 +/- 29 mg/dl, P < 0.0001), respectively. Total serum trigly cerides decreased from 332 +/- 45 mg/dl to 166 +/- 44 mg/dl (-50% P < 0.0001), whereas high-density lipoprotein (HDL) cholesterol increased by 16% (from 38 +/- 7 mg/dl to 43 +/- 7 mg/dl, P < 0.0001). The TC to HDL cholesterol ratio decreased from 9.1 +/- 1.7 to 5.3 +/- 1 (P < 0.0 001). In six cases the therapy was able to normalize the lipoprotein p rofile and in others an obvious benefit of combination therapy versus monotherapy was evident. In conclusion, with the precaution of a caref ul selection of patients, simvastatin plus gemfibrozil administration may be a well-tolerated and effective therapy when drastic reduction o f atherogenic lipoproteins is needed in high-risk patients. However, w e do not recommend general use of such a combination, which must only be initiated under close medical supervision in a specialized center, since myopathy, rhabdomyolysis, and renal failure have been reported i n other studies.