Comparative Study of Bezafibrate and Pravastatin in Patients With Coronary Artery Disease and High Levels of Remnant Lipoprotein

Abstract

Background: Remnant lipoproteinemia is a strong risk factor for cardiovascular (CV) diseases. This study examined which of 2 common lipid-lowering drugs (fibrates and statins) is more effective in patients with remnant lipoproteinemia and if lowering remnant lipoprotein levels can reduce CV risk. Methods and Results:Remnant lipoprotein levels were measured by an immunoseparation method (remnantlike lipoprotein particles cholesterol: RLP-C) in 274 patients with coronary artery disease and high RLP-C levels (≥5.0 mg/dl). They were randomly assigned to receive bezafibrate (200-400 mg/day) or pravastatin (10-20 mg/day), and were prospectively followed-up for 1 year or until the occurrence of CV events. Complete follow-up data were obtained in 180 patients. RLP-C levels at 1 year of treatment were reduced more by bezafibrate than pravastatin (−37% and −25% from baseline, respectively). During follow-up, bezafibrate-treated patients had 3 CV events, compared with 12 events in pravastatin-treated patients (P<0.01). In multivariate logistic regression analysis, a decrease in RLP-C level was significantly associated with a reduction in CV events after adjustment for treatment group and changes in levels of other lipids. Conclusions:Bezafibrate therapy decreased RLP-C levels to a greater extent than pravastatin and a decrease in RLP-C level may be associated with a reduction in CV events in patients with high RLP-C levels. Effects of Fibrate and Statin on RLP-C Methods Study PatientsFrom 2003 December to 2005 March, 274 patients with CAD and high levels of RLP-C (≥5.0 mg/dl) at 17 hospitals (Appendix 1) were enrolled in this study. All patients met the following inclusion criteria: (1) total cholesterol (TC) level in fasting serum ≥180 mg/dl but <260 mg/dl; (2) TG level in fasting serum ≥150 mg/dl but <400 mg/dl; (3) presence of CAD based on angiographic evidence of organic diameter stenosis >50% of at least 1 major coronary artery, but patients were included if they had had a significant stenosis previously, which had been reduced to ≤50% after coronary revascularization; and (4) age 35-75 years. If lipid-lowering drugs were being administered at the time of enrollment, RLP-C, TC, high-density lipoprotein-cholesterol (HDL-C) and TG levels were measured after a wash-out period of more than 4 weeks. The exclusion criteria were: (1) acute coronary syndrome within 10 days prior to enrollment; (2) congestive heart failure (New York Heart Association class III or greater);

Combination Lipid Therapy on Lipid Profiles in Patients with Impaired Glucose Tolerance

“…It has also been shown that high levels of RLP cholesterol are an independent risk for cardiovascular events in patients with glucose intolerance [32]. Previous studies reported a significant association between reduced RLP cholesterol levels and a decrease in cardiovascular events [13,32]. The present study showed that bezafibrate treatment effectively reduced RLP cholesterol levels, while treatment with either rosuvastatin alone or bezafibrate plus rosuvastatin also resulted in a reduction in RLP cholesterol levels.…”

“…Previous studies have also reported that HDL cholesterol levels increase and fasting blood glucose concentrations decrease after administration of lipid-lowering agents, such as statins and fibrates [11,13]. As the present study included only a small number of patients and was of relatively short duration, further studies are required to clarify the effects of either statin plus fibrate, statin alone, or fibrate alone on HDL cholesterol and fasting blood glucose levels.…”

“…However, a simple and reliable technique for measuring levels of remnant like lipoprotein particles (RLP) cholesterol using an immunoseparation method has now been developed. It has been shown that this technique isolates mainly remnants of VLDL from fasting serum, with high RLP cholesterol levels predicting future coronary events in patients with coronary artery disease [13]. It has also been shown that high levels of RLP cholesterol are an independent risk for cardiovascular events in patients with glucose intolerance [32].…”

Fibrates are an essential part of modern anti-dyslipidemic arsenal: spotlight on atherogenic dyslipidemia and residual risk reduction

“…Only recently intermediate-size (274 patients) RCT have demonstrated that bezafibrate was significantly better than pravastatin (a relatively weak statin) in reduction of cardiovascular events [65]. Anyway, even intensive statin therapy does not eliminate the cardiovascular risk associated with low HDL or/and high triglycerides (atherogenic dyslipidemia)!…”

Determinants of Bezafibrate-induced Improvements in LDL Cholesterol in Dyslipidemic Patients with Diabetes

“…A comparison of statins and bezafibrate showed a mild improvement in remnant-like lipoprotein cholesterol (RLP-C) with statins versus bezafibrate 27) . In another study of patients with coronary artery disease complicated by high remnant lipoproteinemia, bezafibrate, but not pravastatin, significantly decreased the RLP-C levels and, during the one-year follow-up period, significantly decreased the incidence of cardiovascular events 28) . Bezafibrate is thus a therapeutic option in cases of dyslipidemia associated with diabetes mellitus, as statins normalize only the LDL-C level, leaving remnant lipoproteins and small dense LDL as residual risk factors.…”