Abstract 5068: A Prospective Randomized Comparative Trial of Bezafibrate and Pravastatin in Patients with Coronary Artery Disease and High Remnant Lipoprotein Levels

Abstract

Remnant lipoproteinemia is a strong risk factor for atherosclerotic cardiovascular diseases (CVD). However, it remains unclear whether the lowering of remnant lipoprotein levels can prevent CVD events, and it is uncertain which lipid-lowering drug is most effective in reducing remnant lipoprotein levels or CVD events. Thus, this study examined if lowering of remnant lipoprotein levels can reduce CVD risk and which of two common lipid-lowering drugs (fibrate or statin) is more effective. The serum levels of remnant lipoproteins were measured by an immunoseparation method (remnant-like lipoprotein particles cholesterol; RLP-C). This multi-center study recruited 202 patients with chronic coronary artery disease (CAD), high RLP-C levels (≥ 5.0 mg/dL), and mild hypercholesterolemia (≥ 180 and < 260 mg/dL). They were randomly assigned to receive bezafibrate (Beza, 200 ~ 400 mg/day, n = 101) or pravastatin (Prava, 10 ~ 20 mg/day, n = 101), and were prospectively followed-up for 1 year or until the occurrence of a CVD event: cardiac death, nonfatal myocardial infarction, unstable angina pectoris requiring unplanned revascularization, or ischemic stroke. The 2 groups had similar baseline levels of RLP-C (average in total patients, 9.8 ± 0.4 mg/dL), LDL-C (126 ± 6.0 mg/dL), HDL-C (43 ± 1.2 mg/dL), and triglycerides (212 ± 9.7 mg/dL). RLP-C levels at 1 year of treatment were reduced in Beza more than Prava (by - 30% and - 19% from baseline, respectively), whereas reduction of LDL-C levels was less in Beza than Prava (by - 7% and -15%). During follow up, CVD events occurred in 3 patients treated with Beza and in 11 patients with Prava (p = 0.03 by chi-square test) (cardiac death in 0 and 1, unstable angina in 2 and 10, and stroke in 1 and 0, respectively). In a multivariate Cox hazards analysis, reduction of 1-SD (38%) of percent change in RLP-C levels decreased risk of future CVD events by 36% independently of change in LDL-C and HDL-C levels (HR 0.64, 95% CI 0.46 – 0.90, p = 0.01). Bezafibrate therapy decreased RLP-C levels and CVD events to a greater extent than pravastatin in CAD patients with high RLP-C levels and mild hypercholesterolemia. Reduction of remnant lipoprotein levels may improve outcomes in CAD patients with high remnant lipoprotein levels.