FLUVASTATIN IN SEVERE HYPERCHOLESTEROLEMIA - ANALYSIS OF A CLINICAL-TRIAL DATABASE

Many patients with severe primary hypercholesterolemia-low density lip oprotein cholesterol (LDL-C) >240 mg/dL-have heterozygous familial hyp ercholesterolemia. In such familial hypercholesterolemic patients, the lipid-lowering efficacy of fluvastatin is related to genetic factors, and it is of interest whether the response to treatment differs from that in patients with more moderate hypercholesterolemia. Thus an expl oratory analysis of randomized, controlled clinical trials and their o pen-label extensions (12-78 weeks), conducted worldwide with fluvastat in greater than or equal to 20 mg/day (n = 1810) and placebo (n = 783) , assessed whether, apart from the potential differences between famil ial hypercholesterolemic and nonfamilial hypercholesterolemic patients , the response to 40 mg of fluvastatin is influenced by baseline plasm a lipid levels in relation to disease severity. Entry criteria include d LDL-C greater than or equal to 190 mg/dL with less than or equal to 1 risk factor and no coronary artery disease, or greater than or equal to 160 mg/dL with >1 risk factor or definite coronary artery disease. Of these patients, 591 (33%) given fluvastatin (20-40 mg/day) and 187 (24%) given placebo had severe hypercholesterolemia with baseline LDL -C >240 mg/dL. In controlled studies, the mean +/- SD duration of expo sure was 21.1 +/- 16.1 and 19.4 +/- 15.5 weeks for fluvastatin and pla cebo, respectively, whereas longterm efficacy was assessed after 55.3 +/- 21.7 weeks (fluvastatin) and 21.1 +/- 12.3 weeks (fluvastatin + ch olestyramine, after previous monotherapy). In summary, fluvastatin at 40 mg/day lowered LDL-C by 25-26% from baseline in controlled studies (n = 622), and by 27% in long-term studies (32-33% with fluvastatin cholestyramine; n = 386), irrespective of severity of cholesterolemia. High density lipoprotein cholesterol (HDL-C) and triglyceride respons es were enhanced, when at baseline HDL-C levels were low and triglycer ides raised, irrespective of baseline cholesterolemia, whereas the LDL -C response was unrelated to baseline in patients with LDL-C levels >2 40 mg/dL. In patients in the highest triglyceride tertile, fluvastatin plus cholestyramine apparently abolished the triglyceride increase ex pected with cholestyramine. This influence of baseline levels on fluva statin response can be considered beneficial, as hypercholesterolemic patients with low HDL-C and high triglyceride levels are at particular ly high cardiovascular risk.