Influence of low HDL on progression of coronary artery disease and response to fluvastatin therapy

Background-Patients with coronary artery disease (CAD) commonly have low HD L cholesterol (I-IDL-C) and mildly elevated LDL cholesterol (LDL-C)I leadin g to uncertainty as to whether the appropriate goal of therapy should be lo wering LDL-C or raising HDL-C. Methods and Results-Patients in the Lipoprotein and Coronary Atherosclerosi s Study (LCAS) had mildly to moderately elevated LDL-C; many also had low H DL-CI providing an opportunity to compare angiographic progression and the benefits of the HMG-CoA reductase inhibitor fluvastatin in patients with lo w versus patients with higher HDL-C. Of the 339 patients with biochemical a nd angiographic data, 68 had baseline HDL-C <0.91 mmol/L (35 mg/dL), mean 0 .82+/-0.06 mmol/L (31.7+/-2.2 mg/dL), versus 1.23+/-0.29 mmol/L (47.4+/-11. 2 mg/dL) in patients with baseline HDL-C greater than or equal to 0.91 mmol /L. Among patients on placebo, those with low HDL-C had significantly more angiographic progression than those with higher HDL-C. Fluvastatin signific antly reduced progression among low-HDL-C patients: 0.065+/-0.036 mm versus 0.274+/-0.035 mm in placebo patients (P=0.0004); respective minimum lumen diameter decreases among higher-HDL-C patients were 0.036+/-0.021 mm and 0. 083+/-0.019 mm (P=0.09), The treatment effect of fluvastatin on minimum lum en diameter change was significantly greater among low-HDL-C patients than among higher-HDL-C patients (P=0.01); among low-HDL-C patients, fluvastatin patients had improved event-free survival compared with placebo patients. Conclusions-Although the predominant lipid-modifying effect of fluvastatin is to decrease LDL-C, patients with low HDL-C received the greatest angiogr aphic and clinical benefit.