Fibrates as highdensity lipoprotein cholesterolelevating agents

Several clinical studies have demonstrated that a reduction in CHD events is positively correlated with treatments that raised HDLc. The controlled Helsinki Heart Trial monitored coronary event rates in over 4000 asymptomatic middle-aged males with dyslipidemia for 5 years and showed that correcting low levels of HDLc with gemfibrozil led to a 34% decrease in coronary events.4'57 For each 1 mg dL _ 1 rise in HDLc among the study subjects, the average response was a 3% decrease in CHD risk.

Similarly, in the Veterans Affairs HDL Intervention Trial (VA-HIT), 2531 males with CHD having low HDLc (p40 mgdL _ 1), near-normal LDLc (p 140 mgdL _ 1), and elevated TG (p 300 mgdL _ 1) were treated for an average of 5 years with gemfibrozil.58 In this study, LDLc was not significantly altered, TG was lowered 31%, HDLc was raised 6%, and the combined number of CHD events was lowered 24% (a 2-3% decrease in CHD for every 1% rise in HDLc). In comparison, prospective statin trials showed only about a 1% reduction in CHD risk for every 1% decrease in LDLc (Table 4).34 However, attributing the event reductions observed in the VA-HIT trial exclusively to HDL elevations is confounded by the concomitant reductions in triglycerides. In contrast, no significant reductions in coronary events were observed in patients treated with bezafibrate 16 in the Bezafibrate Infarction Program (BIP) trial.

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