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PubMed1995

[Effectiveness, tolerance and safety of simvastatin in comparison with bezafibrate in treatment of hypercholesterolemia].

The efficacy, tolerability and safety of simvastatin was compared to that of bezafibrate in a randomized placebo controlled double-blind trial including 64 patients with primary hypercholesterolemia with total cholesterol levels above 240 mg/dl and low-density lipoprotein (LDL) cholesterol above 195 mg/dl. During a placebo period of four weeks patients were counselled for a diet low in cholesterol (< 300 mg/day) and saturated fat (< 10% of calories). This period was also used for randomization of the individuals into the bezafibrate and simvastatin group, respectively. Patients assigned to bezafibrate treatment took bezafibrate at 600 mg/day throughout the entire 12 weeks of active treatment. Patients assigned to simvastatin took simvastatin at 10 mg/day when LDL-cholesterol was below 195 mg/dl, and at 20 mg/day when LDL-cholesterol was above 195 mg. To compare the lipid lowering effect of both substances total cholesterol, LDL- and high-density lipoprotein (HDL)-cholesterol were measured as well as triglycerides, very low density lipoprotein (VLDL)-cholesterol and the concentrations of apolipoproteins (apo)-AI, apo-AII and apo-B, respectively. These variables were compared between the two study groups with respect to the percentage change from baseline levels obtained during the placebo period. After a 12 week treatment period mean percent reduction of total cholesterol in the simvastatin group was 24% and that of LDL-cholesterol was 36%, both more pronounced than the respective reductions (14% and 17%) observed in the bezafibrate group. The mean percent increase in HDL-cholesterol was similar in both treatment groups (simvastation by 20% vs. bezafibrate by 17%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1998

Bezafibrate and lovastatin decrease the oxidizability of low-density lipoproteins in heart transplant recipients with hyperlidemia.

BACKGROUND: Oxidized low-density lipoprotein plays an important role in the development of atherosclerosis. We evaluated the effect of two lipid-lowering drugs, bezafibrate and lovastatin, on the susceptibility of low-density lipoproteins for oxidation in vitro in 21 heart transplant recipients with hyperlipidemia. METHODS: Patients were given the same diet for 3 months, and after that they were randomized to lovastatin or bezafibrate for a period of 8 weeks and then crossed over to an additional 8 weeks of either bezafibrate or lovastatin. Baseline parameters were also compared with those of a control group of healthy subjects and after both periods of pharmacologic treatment. RESULTS: The low-density lipoproteins of transplant recipients presents a shorter lag time than in control subjects (64+/-3 vs 80+/-4 minutes, respectively). This parameter increases after both bezafibrate and lovastatin treatment (83+/-5 and 80+/-4 minutes, respectively). Moreover, we did observe a negative correlation between insulinemia and the lag time of oxidation after bezafibrate treatment (r = -0.5014, P < .021) and between the polyunsaturated fatty acids/monounsaturated fatty acids ratio in low-density lipoprotein cholesterol esters and lag time after lovastatin treatment (r = -0.4631, P < .04). CONCLUSIONS: Bezafibrate and lovastatin decrease the oxidizability of low-density lipoproteins in heart transplant recipients with hyperlipemia.

Bezafibrate↗
PubMed2001

Design and intermediate results of the Lower Extremity Arterial Disease Event Reduction (LEADER)* trial of bezafibrate in men with lower extremity arterial disease [ISRCTN4119421].

BACKGROUND: Raised levels of both triglycerides and fibrinogen, each of which are reduced by bezafibrate, may contribute to lower extremity arterial disease (LEAD). This condition is characterized by a particularly high incidence of coronary heart disease (CHD) and stroke, but is little studied thus far in randomised controlled trials. METHOD: Patients were recruited through 85 practices in the British Medical Research Council General Practice Research Framework and through nine hospital vascular clinics. The treatment regimen, which is double-blind and placebo-controlled, is bezafibrate 400 mg/day. The 1568 patients recruited represent 86% of those eligible at screening. RESULTS: None of the anticipated side effects (mainly gastrointestinal) differed between the two groups. Nearly 80% of the total person-years accrued at 3 years were spent on trial treatment. Bezafibrate significantly reduced total cholesterol by approximately 8.0% and low-density lipoprotein (LDL)-cholesterol by approximately 9.0%, and increased high-density lipoprotein (HDL)-cholesterol by approximately 11.0% initially, falling to about 6.0% at 3 years. Triglycerides were significantly reduced by about 23.0% and fibrinogen by about 14.0%. Plasma creatinine rose by approximately 11% in those on active treatment. All of these effects were highly significant (P < 0.0001). Bezafibrate had no effect on the level of C-reactive protein (CRP). CONCLUSION: The trial recruited an unusually high proportion of eligible patients, ensuring the general applicability of its results. The fibrinogen-lowering and lipid-modifying effects of bezafibrate were confirmed. Although bezafibrate lowers fibrinogen, it has no effect on CRP; this suggests that the reduction in fibrinogen is due to an effect on its metabolism rather than suppression of an inflammatory response.

Journal Article↗
PubMed1997

Comparison of bezafibrate and simvastatin in the treatment of dyslipidaemia in patients with NIDDM.

Fibrates and HMG CoA reductase inhibitors are commonly used in the treatment of diabetic dyslipidaemia. However, these two groups of drugs have not been compared in diabetic patients in a randomized controlled trial. Therefore, a multicentre study was performed in 73 subjects with non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) and combined hyperlipidaemia (serum cholesterol 6.2-10.0 mmol l(-1), serum triglycerides 2.3-10.0 mmol l(-1)), comparing the efficacy of 400 mg bezafibrate with 10 mg simvastatin in a double-blind fashion. Treatment with bezafibrate during 12 weeks reduced serum triglycerides significantly more than simvastatin (-41% vs -22%, p < 0.001) and increased HDL cholesterol more (bezafibrate: + 17% vs simvastatin: + 9%, p < 0.05). LDL cholesterol levels decreased by 14% (p < 0.001) during simvastatin and increased by 21% (p < 0.01) during bezafibrate. This increase in LDL cholesterol was positively correlated with fasting serum triglycerides (p < 0.001) and was associated with a reduction of the serum apolipoprotein B concentration, suggesting an increase in LDL particle size. Metabolic control of diabetes (fasting glycaemia; HbA1c) and insulin secretion (C-peptide levels) were unaffected by both treatments. The incidence of side-effects during treatment was similar for both drugs. Thus, 400 mg bezafibrate mainly increases HDL cholesterol and lowers serum triglycerides but at the expense of an increase in LDL cholesterol; 10 mg simvastatin lowers LDL cholesterin more effectively but has a smaller effect on HDL cholesterol and triglycerides.

Aged↗
PubMed1995

Influence of bezafibrate on hepatic cholesterol metabolism in gallstone patients: reduced activity of cholesterol 7 alpha-hydroxylase.

Bezafibrate is a hypolipidemic fibric acid derivative known to induce cholesterol supersaturation of bile. To characterize its effects on hepatic cholesterol metabolism, 31 normolipidemic, normal-weight patients with gallstones undergoing cholecystectomy were studied. Eleven patients (5 men) were randomized to treatment with bezafibrate, 200 mg three times daily for 4 weeks before operation; the remaining 20 patients (5 men) served as nontreatment controls. At operation, a liver biopsy specimen was obtained under standardized conditions and several important parameters of cholesterol metabolism were assayed. Bezafibrate treatment lowered total plasma cholesterol and triglycerides 30% and 37%, respectively. The hepatic cholesterol 7 alpha-hydroxylase activity was reduced by approximately 60% in the bezafibrate treated patients compared with the controls, whereas the acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity was similar in the two groups. The total 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity was increased twofold in the treated patients, whereas the active enzyme remained about the same as in the controls. The low-density lipoprotein (LDL) receptor binding activity was unaffected by the treatment. Bezafibrate treatment significantly reduces cholesterol 7 alpha-hydroxylase activity, and it is suggested that this may play an important role for the development of supersaturated bile during such therapy.

Adult↗
PubMed2000

Peroxisome proliferator-activated receptor alpha (PPARalpha) activators, bezafibrate and Wy-14,643, increase uncoupling protein-3 mRNA levels without modifying the mitochondrial membrane potential in primary culture of rat preadipocytes.

Uncoupling proteins (UCPs) are inner mitochondrial membrane transporters which act as pores for H(+) ions, dissipating the electrochemical gradient that develops during mitochondrial respiration at the expense of ATP synthesis. We have studied the effects of two fibrates, bezafibrate and Wy-14,643, on UCP-3 and UCP-2 mRNA levels in primary monolayer cultures of rat adipocytes and undifferentiated preadipocytes. Treatment with both PPARalpha activators for 24 h up-regulated UCP-3 mRNA levels. Thus, bezafibrate treatment resulted in an 8-fold induction in UCP-3 mRNA levels in preadipocytes compared with the 3.5-fold induction observed in adipocytes. Differences in the induction of UCP-3 between these cells correlated well with the higher expression of PPARalpha and RXRalpha mRNA values in preadipocytes compared to adipocytes. Wy-14,643 caused similar effects on UCP-3 mRNA expression. In contrast to UCP-3, UCP-2 mRNA levels were only slightly modified by bezafibrate in adipocytes. The induction in UCP-3 expression was not accompanied by changes in the mitochondrial membrane potential of rat primary preadipocytes after bezafibrate or Wy-14,643 treatment. Since it has been proposed that UCP-3 could be involved in the regulation of the use of fatty acids as fuel substrates, the UCP-3 induction achieved after bezafibrate and Wy-14, 643 treatment may indicate a higher oxidation of fatty acids, limiting their availability to be stored as triglycerides. This change may result in a reduced rate of conversion of preadipocytes to adipocytes, which directly affects fat depots.

Adipocytes↗
PubMed1994

The effects of clofibrate and bezafibrate on cholesterol metabolism in the liver of the male rat.

Fibric acid derivatives are used to treat hyperlipidemia and have wide ranging effects on lipid metabolism. The action of these compounds on cholesterol esterification, catalyzed by acyl-coenzyme A:cholesterol acyltransferase (ACAT), has been quite widely studied, but their effect on cholesteryl ester hydrolysis and the enzyme neutral cholesteryl ester hydrolase (nCEH) has been largely ignored. Male rats were therefore fed for 10 d on a standard chow diet supplemented with either clofibrate or bezafibrate, to study their effects on plasma lipid levels and hepatic cholesterol metabolism. Plasma triacylglycerols were not significantly altered by these diets, but bezafibrate significantly lowered plasma cholesterol levels (29.7%, P < 0.01). When expressed per unit weight of DNA, both fibrates reduced the hepatic content of triacylglycerol, cholesterol and cholesteryl esters (40, 18.7, 16.5 and 66.7, 28.6, 34.2% for clofibrate and bezafibrate, respectively). ACAT activity was significantly reduced by both drugs, but clofibrate (65% inhibition) was more effective than bezafibrate (35% inhibition). The most dramatic effect of the diets was a marked increase in the activity of both the microsomal and the cytosolic nCEH. When expressed on a whole liver basis, the effect of bezafibrate on the cytosolic enzyme (13.6-fold increase in activity) was much greater than that of clofibrate (4.8-fold increase). Increases in the activity of a cytosolic protein that inhibits the activity of nCEH were also noted, but these changes were relatively small. The results suggest that the activation of nCEH, in combination with the inhibition in ACAT activity, contributes to a decrease in the cholesteryl ester content of the liver which may influence the secretion of very low density lipoprotein.

Animals↗
PubMedDate not supplied

Biliary lipids, lithogenic index and biliary drug concentrations during etofibrate and bezafibrate treatment.

Hypolipidemic drugs like etofibrate and bezafibrate may induce lithogenic bile and increase the risk of gallstone formation. In this study, biliary lipids, lithogenic index and biliary drug concentrations were investigated in 6 hyperlipidemic patients after cholecystectomy. Patients were treated once daily for 5 days with either 500 mg/day etofibrate or 400 mg/day bezafibrate. Hepatic bile was collected for 6 days via T-drainage in 4 hourly aliquots. In the patients treated with etofibrate, the range of the lithogenic index remained stable with 0.89-1.69 before and 0.78-1.51 after 5 day drug therapy. In the bezafibrate group, the range of the lithogenic index rose from 0.81-1.40 to 1.26-1.66 mainly as a result of an increase of biliary cholesterol concentrations. Biliary drug concentrations were substantially higher under bezafibrate treatment than under etofibrate treatment. In conclusion, the fibrate drugs, etofibrate and bezafibrate, are different with regard to lithogenicity of bile and extent of biliary excretion. The safety profile of etofibrate may be preferably compared to other fibrate drugs.

Adult↗
PubMed2006

Bezafibrate may attenuate biliary damage associated with chronic liver diseases accompanied by high serum biliary enzyme levels.

BACKGROUND: Bezafibrate is a commonly used medicine for hyperlipidemia, and recently several reports have suggested the efficacy of bezafibrate for the treatment of primary biliary cirrhosis (PBC). To assess its efficacy for other liver diseases, we administered bezafibrate to patients with various categories of hepatobiliary impairment. METHODS: Bezafibrate (400 mg/day) was orally administered to 67 patients with chronic liver disease [22 with PBC, six with primary sclerosing cholangitis (PSC), 20 with chronic liver disease associated with hepatitis C virus (HCV) infection (CLD-C), seven with auto immune hepatitis (AIH), ten with alcoholic liver injury, and two with drug-induced liver injury]. RESULTS: The levels of biliary enzymes, such as alkaline phosphatase and gamma-glutamyltranspeptidase, decreased promptly and dramatically. The abnormally high level of alanine aminotransferase also showed a gradual decrease over 6 months in five of the eight PBC patients, all three PSC patients, eight of the 17 CLD-C patients, and all seven alcoholic liver injury patients. The level of immunoglobulin M showed a gradual decrease in 17 of the 22 PBC patients. CONCLUSIONS: Bezafibrate significantly reduced the level of biliary enzymes in various chronic liver diseases and may be useful for the treatment of certain liver disease subsets.

Aged↗
PubMed1992

Maxepa versus bezafibrate in hyperlipidemic cardiac transplant recipients.

Accelerated coronary artery disease is the most serious obstacle to long-term survival in cardiac transplant recipients. Lipid abnormalities are found frequently in these patients, and there is growing evidence that even minimally increased levels of cholesterol and triglycerides contribute to the development of accelerated coronary artery disease. However, the optimal lipid-lowering therapy after cardiac transplantation has not been defined. In an open, randomized study, the efficacy and safety of bezafibrate (400 mg/day) and fish oil (Maxepa) (10 g/day) for 3 months were compared in 87 cardiac transplant recipients with serum total cholesterol > 6.5 or triglycerides > 2.8 mmol/liter, or both. After 1 month, bezafibrate reduced total cholesterol by 13%, low-density lipoprotein cholesterol by 20% and apolipoprotein B by 13%. It also increased apolipoprotein A1 and high-density lipoprotein cholesterol by 12 and 20%, respectively, and significantly reduced fibrinogen at 3 months. Maxepa had no significant effect on these variables, but was as effective as bezafibrate in reducing triglycerides (36 and 31%, respectively). Both drugs increased lipoprotein (a) to a similar extent, and bezafibrate significantly increased serum creatinine. These results suggest that bezafibrate has better lipid-, apolipoprotein- and hemostatic modifying properties than does Maxepa, but its potentially adverse effect on renal function needs further investigation.

Apolipoprotein A-I↗
PubMed1989

Species differences in the effects of bezafibrate, a hypolipidemic agent, on hepatic peroxisome-associated enzymes.

The effects of bezafibrate on hepatic peroxisome-associated enzymes of rats, mice, guinea pigs, hamsters, rabbits, dogs and monkeys were examined. Dogs and monkeys were given bezafibrate orally at 30 mg/kg body wt daily for 2 weeks and at 125 mg/kg body wt daily for 13 weeks, respectively, and other species at 100 mg/kg daily for 2 weeks. In male rats, marked changes were observed in the activities of catalase (1.73-fold), D-amino acid oxidase (DAAO; 0.56-fold), fatty acyl-CoA oxidizing system (FAOS; 12.9-fold) and carnitine acetyltransferase (CAT; 35.8-fold); in female rats, the changes were less than in the males. In mice, there were no apparent sex differences in the responses of hepatic peroxisomal enzymes to bezafibrate and the increases in the activities of catalase, FAOS and CAT were 1.76-, 3.75- and 7.94-fold respectively. In guinea pigs, only slight increases in the activities of FAOS (3.00-fold) and CAT (2.83-fold) were observed. In hamsters, the increases in catalase, FAOS and CAT activities, were 1.23-, 2.19- and 2.77-fold respectively. Although rabbits and dogs showed slight increases in CAT activity, no significant response to the drug was observed in monkeys. Hepatomegaly and the increase of hepatic content of peroxisome proliferation-associated polypeptide (PPA-80), which has been recognized as a peroxisomal bifunctional protein in the fatty acid beta-oxidation pathway, were observed only in rats and mice. These results show that there were marked species differences in the effects of bezafibrate on hepatic peroxisomes, and that bezafibrate induced hepatic peroxisome proliferation in rodents, especially rats and mice.

Animals↗
PubMed1989

Inhibition of fatty acid biosynthesis by bezafibrate in different rat cells.

Bezafibrate is one of the main drugs used in the treatment of human hyperlipemic diseases. Its action on the biosynthesis of fatty acids has been studied and the following conclusions have been drawn: (1) Lipogenesis from glucose is inhibited in hepatocytes and adipocytes isolated from "refed" rats previously treated with bezafibrate. (2) Lipogenesis from glucose is inhibited by bezafibrate in hepatocytes and adipocytes isolated from "refed" rats. (3) Lipogenesis from glucose is also inhibited by bezafibrate in acini isolated from lactating rats. These results show that bezafibrate is an inhibitor of fatty acid synthesis.

Adipose Tissue↗
PubMed1986

Influence of bezafibrate on plasma lipoproteins, biliary lipids and fecal sterols in healthy men.

The effect of a 4-week treatment with 600 mg/day of bezafibrate in addition to a low-cholesterol, fat-modified diet on plasma lipids and lipoproteins and on biliary lipids and fecal sterols was investigated in 12 healthy men aged 25-39, and compared to the effect of the diet plus placebo, using a double-blind crossover design. The comparison of placebo and treatment values indicated that bezafibrate, beyond the effect of the diet, significantly lowered concentrations of circulating triglycerides (-25.5%), total cholesterol (-25.8%), LDL cholesterol (-19.5%), and apolipoprotein B (-19.9%), and increased apolipoprotein A-II concentrations in serum (+15.0%). There was a tendency towards lower biliary bile acid and cholesterol secretion rates with bezafibrate; lithogenic indices in fasting and stimulated bile were similar with the drug and placebo. Fecal bile acid excretion rate with diet plus bezafibrate was significantly less than with diet plus placebo. The data obtained are in accord with the hypothesis that bezafibrate exerts its effects on cholesterol and bile acid metabolism predominantly by decreasing VLDL secretion, possibly through an enhancement of fatty acid beta-oxidation in the liver.

Adult↗
PubMed1990

Effects of simvastatin, bezafibrate and gemfibrozil on the quantity and composition of plasma lipoproteins.

Simvastatin, 10-40 mg/d (n = 11), bezafibrate, 600 mg/d (n = 6), and gemfibrozil, 1200 mg/d (n = 5) were administered for 12 weeks after a 4-week placebo period to subjects with initial plasma levels (mg/100 ml. mean +/- SD) of cholesterol (346 +/- 77), and of triglycerides (180 +/- 54). Total LDL-C plasma concentration was lowered 32% by simvastatin and 35% by bezafibrate, but only bezafibrate diminished the triglyceride (41%) and increased HDL-C plasma levels (35%). Plasma lipoprotein fractions obtained by discontinuous gradient ultracentrifugation, namely, VLDL, lighter LDL (LDL-1), heavier LDL (LDL-2) and bulk HDL were chemically analyzed. Simvastatin and bezafibrate significantly diminished the quantity of VLDL and LDL-1 particles, although barely modifying their composition. Neither drug influenced the LDL-2 plasma concentration. Bezafibrate increased the total plasma HDL level little interfering with its chemical composition. Gemfibrozil was the least effective of all drugs but decreased the lipid and protein contents and their ratios in VLDL and LDL-2.

Adult↗
PubMed1990

The induction of adipose conversion by bezafibrate in 3T3-L1 cells. Synergism with dibutyryl-cAMP.

The induction of adipose conversion in 3T3-L1 cells by bezafibrate (Brandes, R., Hertz, R. Arad R., Naishtat S., Weil, S. and Bar-Tana, J. (1987) Life Sci., 40, 935-941) was enhanced by dibutyryl-cAMP as well as forskolin, theophylline or isobutylmethylxanthine added to the incubation medium together with the bezafibrate inducer. The synergistic effect of bezafibrate and dibutyryl-cAMP resulted in enhancing the expression of late markers of adipose conversion, e.g., lipid accumulation or glycerol-3-phosphate dehydrogenase activity and its mRNA. This enhanced expression of late markers was reflected in shortening the time period required for their first appearance as well as increasing their yield during the course of adipose conversion. By following the accumulation of glutamine synthetase mRNA serving as an early marker for adipose conversion, the synergistic effect of bezafibrate and dibutyryl-cAMP was already evident as early as 5 h following their addition to confluent 3T3-L1 cells. Hence, the induction of adipose conversion by bezafibrate in 3T3-L1 cells appears to involve an early event which is rate-limited by the availability of intracellular cAMP.

Adipose Tissue↗
PubMedDate not supplied

Long-term effects of bezafibrate on in vivo VLDL-triglyceride production in the rat.

Long-term effects of bezafibrate on in vivo production of VLDL-triglyceride were studied in the rat. Bezafibrate given at a daily dose of 30 mg/kg body weight for 14 days produced a decrease not only in triglyceride by 51% but in cholesterol by 28% and phospholipid by 18%. Despite a marked reduction in plasma triglyceride concentrations, there was no significant change in the rate of VLDL-triglyceride secretion from the liver into the circulation between bezafibrate-treated and control animals (1113 +/- 58 and 1234 +/- 63 micrograms/min, respectively). In addition, bezafibrate produced no change in lipid composition in VLDL. These results suggest that bezafibrate enhances triglyceride removal from the circulation, which leads to reduction in plasma triglyceride.

Animals↗
PubMed2004

High fasting glucose levels as a predictor of worse clinical outcome in patients with coronary artery disease: results from the Bezafibrate Infarction Prevention (BIP) study.

BACKGROUND: A high fasting glucose level may be a marker not only for microvascular complications, but also for macrovascular complications. We evaluated the clinical significance of a high fasting glucose level (> or =110 mg/dL), detected either at baseline or during follow-up, in the Bezafibrate Infarction Prevention (BIP) study. METHODS: The BIP study was a secondary prevention prospective double-blind study comparing bezafibrate to placebo. A total of 3122 patients with documented coronary artery heart disease who were aged 45 to 74 years and had a total cholesterol level between 180 and 250 mg/dL, low-density lipoprotein cholesterol level < or =180 mg/dL, a high-density lipoprotein cholesterol level < or =45 mg/dL, a triglyceride level < or =300 mg/dL, and a fasting glucose < or =160 mg/dL were randomized to receive 400 mg of bezafibrate daily or placebo. RESULTS: The primary end point of the BIP study was fatal myocardial infarction, non-fatal myocardial infarction, or sudden death. Secondary end points included hospitalization for unstable angina, percutaneous transluminal coronary angioplasty, and coronary artery bypass grafting. At baseline, 330 patients (11%) had diabetes mellitus, and 293 patients (9%) had an impaired fasting blood glucose level (IFG). During 6.2 years of follow-up, diabetes mellitus developed in 186 patients (6%), IFG developed in 366 patients (12%), and 62% of patients remained with normal fasting glucose levels (NFG). Patients with diabetes mellitus and IFG both at baseline or developing during follow-up had a significantly higher rate of secondary end points than paients with NFG (P <.0001). Bezafibrate treatment reduced secondary end points only in patients with NFG (P =.04). CONCLUSION: Diabetes mellitus and IFG were common in the BIP study and were predictive of a worse clinical outcome that was not attenuated with bezafibrate treatment.

Aged↗
PubMed2005

Relation between on-treatment increments in serum high-density lipoprotein cholesterol levels and cardiac mortality in patients with coronary heart disease (from the Bezafibrate Infarction Prevention trial).

This study evaluated the association between changes in serum levels of high-density lipoprotein (HDL) cholesterol that occur under bezafibrate therapy and cardiac mortality in patients with coronary heart disease (CHD) who were enrolled in the Bezafibrate Infarction Prevention trial. We compared serum levels of HDL cholesterol in 1,509 patients in tertiles of on-treatment increments with those of 1,517 patients in the placebo group. Long-term follow-up showed that cardiac mortality decreased significantly with increasing tertiles of on-treatment change in HDL cholesterol (9.5%, 6.6%, and 6.3% of patients tertiles 1, 2, and 3, respectively, died of cardiac causes, p for trend = 0.02). In multivariate analysis, the magnitude of on-treatment increment of HDL cholesterol was independently associated with a decreased risk of cardiac death (hazard ratio 1.05, 95% confidence interval 0.74 to 1.47, for tertile 1; hazard ratio 0.73, 95% confidence interval 0.50 to 1.07, for tertile 2; hazard ratio 0.65, 95% confidence interval 0.43 to 0.97, for tertile 3, compared with placebo-allocated patients, p for trend = 0.02). Analyzing the association with change in HDL cholesterol as a continuous variable showed that the risk of cardiac mortality was decreased by 27% for every 5-mg/dl increase in on-treatment change in HDL cholesterol (p <0.001). In conclusion, although a definite secondary prevention effect of bezafibrate could not be found when examining the intervention group as a whole, our findings are consistent with a possible independent association between an increase in HDL cholesterol with bezafibrate therapy and a decrease in cardiac mortality. In appropriately selected patients, monitoring short-term response to bezafibrate therapy through change in HDL cholesterol may indicate the potential long-term benefit of the drug.

Aged↗