Correlation of non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol with apolipoprotein B during simvastatin + fenofibrate therapy in patients with combined hyperlipidemia (a subanalysis of the SAFARI trial).

Guidelines have recommended non-high-density lipoprotein (non-HDL) cholesterol as a secondary target for therapy after the low-density lipoprotein (LDL) cholesterol goals have been met in patients with hypertriglyceridemia; non-HDL cholesterol is viewed as a surrogate for apolipoprotein (Apo)B, an alternate end point of treatment. The present analysis of the previously reported Simvastatin plus Fenofibrate for Combined Hyperlipidemia (SAFARI) trial assessed the associations of non-HDL cholesterol and LDL cholesterol with ApoB levels in patients with combined hyperlipidemia treated with combination simvastatin (20 mg) and fenofibrate (160 mg) or simvastatin monotherapy (20 mg). The correlations of these factors were analyzed in the overall modified intent-to-treat population (n = 594) and in patient subgroups stratified by triglyceride (TG) tertiles. Simvastatin plus fenofibrate and simvastatin alone significantly reduced LDL cholesterol, TG, non-HDL cholesterol and ApoB levels and non-HDL cholesterol/ApoB ratio (p < or =0.0004), regardless of the TG level. The greatest reductions occurred with combination treatment. The baseline levels of non-HDL cholesterol and LDL cholesterol correlated highly with ApoB and were stronger in the lower TG tertiles than in the higher TG tertiles. After 12 weeks, the correlations had changed little with simvastatin monotherapy but had increased substantially with combination therapy and were most improved at high TG levels. In conclusion, these results suggest that both non-HDL cholesterol and ApoB provide similar information in relation to treatment response in patients with combined hyperlipidemia and hypertriglyceridemia, and that non-HDL cholesterol is a good indicator of ApoB-containing lipoproteins, supporting its recommended use as a secondary therapeutic target in these patients.