Are high-density lipoprotein and triglyceride levels important in secondary prevention: impressions from the BIP and VA-HIT trials

Two major trials, the Bezafibrate Infarction Prevention Trial (BIP) and the Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (VA-HIT) were conducted to clarify the contribution of correcting diminished high density lipoprotein (HDL) (and lowering triglyceride, TG) levels to the risk of cardiovascular events in patients with coronary heart disease (CHD). In BIP, bezafibrate did not significantly reduce the risk of CHD. In contrast, in VA-HIT, gemfibrozil significantly reduced the risk of CHD (22% reduction in primary end point, P=0.006). These trials differ in several respects making direct comparisons difficult. For example, the placebo arm in VA-HIT had a greater prevalence of primary events than that in BIP (22 vs. 15%). The baseline mean LDL value in BIP was also higher compared to that in VA-HIT (148 vs. 112 mg/dl; 3.82 vs. 2.89 mmol/l). Other trials (e.g., AFCAPS and LIPID) showed that patients with LDL values similar to those in BIP benefited significantly from treatment with statins. Therefore, the BIP population may have been more effectively treated with a statin. In contrast, in VA-HIT the LDL level was close to those recommended in the USA and the UK for secondary prevention (100 and 115 mg/dl; 2.6 and 3.0 mmol/l, respectively). Guidelines emphasise that the LDL level is the main treatment target. However, BIP and VA-HIT suggest that correcting HDL and TG levels may be beneficial especially when the LDL level has reached the target value. We may have become too focused on LDL levels and the use of statins.