CORONARY-HEART-DISEASE RISK-FACTORS AND LDL-CHOLESTEROL-LOWERING EFFICACY OF FIBRATES AND SIMVASTATIN

The objective of this study was to assess the low-density lipoprotein cholesterol (LDL-C) lowering efficacy of fibric acid derivatives (fibr ates) and simvastatin as a function of coronary heart disease (CHD) ri sk status, stratified according to National Cholesterol Education Prog ram guidelines. Two independent databases were analysed retrospectivel y The first data set originated from a consecutive sample of 6340 pati ents with primary hypercholesterolaemia who completed the diet plus fi brate treatment phase of the Belgian General Practitioners Trial, an o pen-label, prospective study conducted in a primary care setting. The second data set was derived from 782 participants in five randomised, double-blind studies that each compared a specific fibrate with simvas tatin. The main outcome measures were percentage of subjects reaching LDL-C treatment goal, and mean percentage reduction in LDL-C across 5 (first data set) or 3 (second data set) CHD risk strata. In the Belgia n General Practitioners Trial LDL-C lowering efficacy of fibrates was inversely related to CHD risk status as 15.0% of patients with prior C HD reached the LDL-C goal < 4.13 mmol/L (< 160 mg/dl) vs 30.2% of thos e without CHD and no other risk factor (p < 0.0001 after adjustment fo r baseline LDL-C and triglycerides). Adjusted mean percentage reductio ns in LDL-C were 15.1 and 18.2 in these strata, respectively (p < 0.05 ). Younger age, male gender, high blood pressure, low high-density lip oprotein cholesterol, and history of prior CHD were significant (p < 0 .05) negative deter minants of both outcome measures in multivariate a nalyses that adjusted for other risk factors. In the pooled analysis o f five randomised trials, the percentage of fibrate-treated patients w ith prior atherosclerotic disease reaching LDL-C goal < 4.20 mmol/L (< 162 mg/dl) was significantly lower when compared with those without C HD and no risk factor other than LDL-C (adjusted odds ratio = 0.46; p = 0.009), while simvastatin efficacy was similar across CHD risk strat a. In conclusion, our results, derived from two independent databases, suggest that the LDL-C lowering efficacy of fibrates, but not of simv astatin, is inversely related to CHD risk status. This exploratory ana lysis must be confirmed by future prospective studies.