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Solomon Behar - One of the best experts on this subject based on the ideXlab platform.

  • Long-term Benefit of High-Density Lipoprotein Cholesterol–Raising Therapy With Bezafibrate: 16-Year Mortality Follow-up of the Bezafibrate Infarction Prevention Trial
    Archives of internal medicine, 2009
    Co-Authors: Ilan Goldenberg, Solomon Behar, Valentina Boyko, Alexander Tennenbaum, David Tanne, Victor Guetta
    Abstract:

    Background Major randomized trials of fibrate therapy demonstrate an inverse relationship between on-treatment high-density lipoprotein cholesterol (HDL-C) increments and clinical outcome. We hypothesized that the degree of HDL-C response to Bezafibrate is independently associated with subsequent long-term mortality. Methods The risk of death at 16 years of follow-up among 3026 patients with coronary heart disease allocated to the original Bezafibrate (n = 1509) and placebo (n = 1517) arms of the Bezafibrate Infarction Prevention (BIP) trial was related to HDL-C response to Bezafibrate therapy, categorized as upper-tertile (>8 mg/dL) or lower-tertile (≤8 mg/dL) on-treatment HDL-C change. Results Multivariate analysis demonstrated that patients allocated to Bezafibrate therapy experienced a significant 11% reduction ( P  = .06) in the risk of long-term mortality compared with placebo-allocated patients. Mortality reduction among Bezafibrate-allocated patients was related to a significant 22% ( P  = .008) reduction in the risk of death in patients with an upper-tertile HDL-C response to therapy, whereas among patients with a lower HDL-C response, the risk of death was similar to that of the placebo group (hazard ratio, 0.95; P  = .43). Accordingly, the cumulative probability of death at 16 years was significantly lower among Bezafibrate-allocated patients with an upper-tertile HDL-C response (32.1%) compared with the placebo group (37.9%; P  = .02), whereas patients with a lower HDL-C response to treatment displayed a mortality rate (36.8%) similar to the placebo group ( P  = .57). Conclusion Our findings suggest that HDL-C level–raising therapy with Bezafibrate is associated with long-term mortality reduction that may be related to the degree of HDL-C response to treatment.

  • long term benefit of high density lipoprotein cholesterol raising therapy with Bezafibrate 16 year mortality follow up of the Bezafibrate infarction prevention trial
    JAMA Internal Medicine, 2009
    Co-Authors: Ilan Goldenberg, Solomon Behar, Valentina Boyko, Alexander Tennenbaum, David Tanne, Victor Guetta
    Abstract:

    Background Major randomized trials of fibrate therapy demonstrate an inverse relationship between on-treatment high-density lipoprotein cholesterol (HDL-C) increments and clinical outcome. We hypothesized that the degree of HDL-C response to Bezafibrate is independently associated with subsequent long-term mortality. Methods The risk of death at 16 years of follow-up among 3026 patients with coronary heart disease allocated to the original Bezafibrate (n = 1509) and placebo (n = 1517) arms of the Bezafibrate Infarction Prevention (BIP) trial was related to HDL-C response to Bezafibrate therapy, categorized as upper-tertile (>8 mg/dL) or lower-tertile (≤8 mg/dL) on-treatment HDL-C change. Results Multivariate analysis demonstrated that patients allocated to Bezafibrate therapy experienced a significant 11% reduction ( P  = .06) in the risk of long-term mortality compared with placebo-allocated patients. Mortality reduction among Bezafibrate-allocated patients was related to a significant 22% ( P  = .008) reduction in the risk of death in patients with an upper-tertile HDL-C response to therapy, whereas among patients with a lower HDL-C response, the risk of death was similar to that of the placebo group (hazard ratio, 0.95; P  = .43). Accordingly, the cumulative probability of death at 16 years was significantly lower among Bezafibrate-allocated patients with an upper-tertile HDL-C response (32.1%) compared with the placebo group (37.9%; P  = .02), whereas patients with a lower HDL-C response to treatment displayed a mortality rate (36.8%) similar to the placebo group ( P  = .57). Conclusion Our findings suggest that HDL-C level–raising therapy with Bezafibrate is associated with long-term mortality reduction that may be related to the degree of HDL-C response to treatment.

  • Long-term effects of peroxisome proliferator-activated receptor ligand Bezafibrate on N-terminal pro-B type natriuretic peptide in patients with advanced functional capacity impairment
    Cardiovascular Diabetology, 2009
    Co-Authors: Koichi Node, Enrique Z Fisman, Teruo Inoue, Valentin Boyko, Ilan Goldberg, Yehuda Adler, Ehud Schwammenthal, Zipora Matas, Solomon Behar, Alexander Tenenbaum
    Abstract:

    Background The effects of pan-peroxisome proliferator-activated receptor (PPAR) ligand Bezafibrate on N-terminal pro-B type natriuretic peptide (ProBNP) level in patients with coronary artery disease (CAD) is unknown. The current study aimed to investigate the long-term effects of Bezafibrate on ProBNP level in patients with pre-existing CAD and advanced functional capacity impairment. Methods Metabolic and inflammatory parameters were analyzed from stored frozen serum samples obtained from 108 patients enrolled in the Bezafibrate Infarction Prevention (BIP) Study. They presented with New York Heart Association (NYHA) functional class III, comprising 58 patients in the Bezafibrate group and 50 in the placebo groups, and completed a 2-year prospective, double-blind, placebo-controlled follow-up. Results During follow-up ProBNP level did not change significantly in the placebo group, whereas it increased slightly in the Bezafibrate group, which was older and with lower baseline ProBNP values. No significant differences between the groups were found for ProBNP levels after 2 year of follow-up. Analysis-of-covariance (ANCOVA) -taking into account age and baseline ProBNP level- showed that Bezafibrate was not associated with longitudinal ProBNP changes during the follow-up period (p = 0.3). Conclusion Long-term treatment by Bezafibrate was not associated with longitudinal ProBNP changes in patients with pre-existing CAD and advanced functional capacity impairment.

  • attenuation of progression of insulin resistance in patients with coronary artery disease by Bezafibrate
    JAMA Internal Medicine, 2006
    Co-Authors: Alexander Tenenbaum, Enrique Z Fisman, Zipora Matas, Valentina Boyko, David Tanne, Michael Motro, Michal Benderly, Moti Haim, Solomon Behar
    Abstract:

    Background: Development of insulin resistance (IR) may be important in the pathogenesis of both metabolic syndrome and type 2 diabetes mellitus. Few data are available regarding the short-term efficacy of the peroxisome proliferator–activated receptor ligand Bezafibrate on IR, and its long-term effect is unknown. The present analysis aimed to investigate the effect of Bezafibrate on IR in patients with coronary artery disease enrolled in the Bezafibrate Infarction Prevention Study. Methods: Metabolic and inflammatory parameters were analyzed from stored frozen plasma samples obtained from patients who completed a 2-year, randomized, doubleblind, placebo-controlled study. The homeostatic indexes of IR (HOMA-IRs) were calculated according to the homeostasis model of assessment. Results: Both the patients taking Bezafibrate (n = 1262) and those taking placebo (n = 1242) displayed similar baseline characteristics. The HOMA-IRs significantly correlated at baseline and during follow-up with glucose (r=0.35 and 0.31, respectively) and triglycerides (r=0.16 and 0.19, respectively). In a subgroup of 351 patients with diabetes, HOMA-IR at baseline was 88% higher than in their counterparts with normal glucose levels (P.001). In the placebo group, during follow-up there was a significant 34.4% rise in HOMA-IR. In contrast, in the Bezafibrate group there was only a nonsignificant 6.6% change in HOMA-IR. The intergroup differences in percentage changes of HOMA-IR were in favor of Bezafibrate (P.001). Conclusions: In patients with coronary artery disease enrolled in our study, as represented by the placebo group, HOMA-IR increased over time. During the 2 years of the follow-up, Bezafibrate significantly attenuated this process. Arch Intern Med. 2006;166:737-741

  • effect of Bezafibrate on incidence of type 2 diabetes mellitus in obese patients
    European Heart Journal, 2005
    Co-Authors: Alexander Tenenbaum, Enrique Z Fisman, Yehuda Adler, Ehud Schwammenthal, Valentina Boyko, David Tanne, Michael Motro, Joseph Shemesh, Jonathan Leor, Solomon Behar
    Abstract:

    Aims To assess the effect of fibric acid derivative Bezafibrate on incidence of type 2 diabetes in obese patients over a median 6.3 years follow-up period. Methods and results The study sample comprised 339 non-diabetic obese patients (body mass index ≥30.0 kg/m2) aged 42–74. Patients received either Bezafibrate retard 400 mg (178 patients) or placebo (161 patients) once daily. Development of new diabetes was recorded in 98 patients: in 56 (37.0%) from the placebo group vs. 42 (27.1%) from the Bezafibrate group, ( P log-rank=0.01). The median time (interquartile range) until onset of new diabetes was significantly delayed in patients on Bezafibrate when compared with those on placebo: 4.0 (2.1–5.0) vs. 2.0 (0.5–3.5) years, P =0.002. Multivariable analysis identified Bezafibrate treatment as an independent predictor of reduced risk of new diabetes with hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.39–0.91]. Other significant variables associated with future overt type 2 diabetes in obese patients were triglycerides (50 mg/dL increment) with HR 1.15 (95% CI 1.02–1.28) and fasting glucose (10 mg/dL increment) with HR 2.27 (95% CI 1.83–2.81). Conclusion Bezafibrate, when compared with placebo, reduced the incidence and delayed the onset of type 2 diabetes in obese patients over a long-term follow-up period.

Alexander Tenenbaum - One of the best experts on this subject based on the ideXlab platform.

  • Bezafibrate for the treatment of dyslipidemia in patients with coronary artery disease 20 year mortality follow up of the bip randomized control trial
    Cardiovascular Diabetology, 2016
    Co-Authors: Yaron Arbel, Robert Klempfner, Aharon Erez, Ilan Goldenberg, Sagit Benzekry, Nir Shlomo, Enrique Z Fisman, Alexander Tenenbaum
    Abstract:

    Recent data support the renewed interest in hypertriglyceridemia as a possible important therapeutic target for cardiovascular risk reduction. This study was designed to address the question of all-cause mortality during extended follow-up of the BIP trial in patients stratified by baseline triglyceride levels. In the BIP trial 3090 patients with proven coronary artery disease were randomized to Bezafibrate 400 mg/day or placebo. All-cause mortality data after 20 years of follow-up, were obtained from the National Israeli Population Registry. Patients with hypertriglyceridemia (triglycerides ≥200 mg/dL, n = 458) were equally distributed among the study groups (15 % in both placebo and Bezafibrate groups). During follow-up 1869 patients died (952 in placebo vs. 917 in Bezafibrate group). Following multivariate adjustment allocation to Bezafibrate was associated with small but significant 10 % mortality risk reduction (HR 0.90; 95 % CI 0.82–0.98, p = 0.026). Variables associated with significantly increased mortality risk were history of a past MI, NYHA class, diabetes, age, higher BMI and glucose level. In patients with hypertriglyceridemia multivariate analysis demonstrated a 25 % all-cause mortality risk reduction associated with allocation to Bezafibrate (HR 0.75, CI 95 % 0.60–0.94; p = 0.012). In patients without hypertriglyceridemia Bezafibrate had no significant effect on long-term mortality. During long-term follow-up Bezafibrate-allocated patients experienced a modest but significant 10 % reduction in the adjusted risk of mortality. This effect of Bezafibrate was more prominent among patients with baseline hypertriglyceridemia (25 % mortality risk reduction).

  • balanced pan ppar activator Bezafibrate in combination with statin comprehensive lipids control and diabetes prevention
    Cardiovascular Diabetology, 2012
    Co-Authors: Alexander Tenenbaum, Enrique Z Fisman
    Abstract:

    All fibrates are peroxisome proliferators-activated receptors (PPARs)-alpha agonists with ability to decrease triglyceride and increase high density lipoprotein- cholesterol (HDL-C). However, Bezafibrate has a unique characteristic profile of action since it activates all three PPAR subtypes (alpha, gamma and delta) at comparable doses. Therefore, Bezafibrate operates as a pan-agonist for all three PPAR isoforms. Selective PPAR gamma agonists (thiazolidinediones) are used to treat type 2 diabetes mellitus (T2DM). They improve insulin sensitivity by up-regulating adipogenesis, decreasing free fatty acid levels, and reversing insulin resistance. However, selective PPAR gamma agonists also cause water retention, weight gain, peripheral edema, and congestive heart failure. The expression of PPAR beta/ delta in essentially all cell types and tissues (ubiquitous presence) suggests its potential fundamental role in cellular biology. PPAR beta/ delta effects correlated with enhancement of fatty acid oxidation, energy consumption and adaptive thermogenesis. Together, these data implicate PPAR beta/delta in fuel combustion and suggest that pan-PPAR agonists that include a component of PPAR beta/delta activation might offset some of the weight gain issues seen with selective PPAR gamma agonists, as was demonstrated by Bezafibrate studies. Suggestively, on the whole body level all PPARs acting as one orchestra and balanced pan-PPAR activation seems as an especially attractive pharmacological goal. Conceptually, combined PPAR gamma and alpha action can target simultaneously insulin resistance and atherogenic dyslipidemia, whereas PPAR beta/delta properties may prevent the development of overweight. Bezafibrate, as all fibrates, significantly reduced plasma triglycerides and increased HDL-C level (but considerably stronger than other major fibrates). Bezafibrate significantly decreased prevalence of small, dense low density lipoproteins particles, remnants, induced atherosclerotic plaque regression in thoracic and abdominal aorta and improved endothelial function. In addition, Bezafibrate has important fibrinogen-related properties and anti-inflammatory effects. In clinical trials Bezafibrate was highly effective for cardiovascular risk reduction in patients with metabolic syndrome and atherogenic dyslipidemia. The principal differences between Bezafibrate and other fibrates are related to effects on glucose level and insulin resistance. Bezafibrate decreases blood glucose level, HbA1C, insulin resistance and reduces the incidence of T2DM compared to placebo or other fibrates. Currently statins are the cornerstone of the treatment and prevention of cardiovascular diseases related to atherosclerosis. However, despite the increasing use of statins as monotherapy for low density lipoprotein- cholesterol (LDL-C) reduction, a significant residual cardiovascular risk is still presented in patients with atherogenic dyslipidemia and insulin resistance, which is typical for T2DM and metabolic syndrome. Recently, concerns were raised regarding the development of diabetes in statin-treated patients. Combined Bezafibrate/statin therapy is more effective in achieving a comprehensive lipid control and residual cardiovascular risk reduction. Based on the beneficial effects of pan-PPAR agonist Bezafibrate on glucose metabolism and prevention of new-onset diabetes, one could expect a neutralization of the adverse pro-diabetic effect of statins using the strategy of a combined statin/fibrate therapy.

  • Long-term effects of peroxisome proliferator-activated receptor ligand Bezafibrate on N-terminal pro-B type natriuretic peptide in patients with advanced functional capacity impairment
    Cardiovascular Diabetology, 2009
    Co-Authors: Koichi Node, Enrique Z Fisman, Teruo Inoue, Valentin Boyko, Ilan Goldberg, Yehuda Adler, Ehud Schwammenthal, Zipora Matas, Solomon Behar, Alexander Tenenbaum
    Abstract:

    Background The effects of pan-peroxisome proliferator-activated receptor (PPAR) ligand Bezafibrate on N-terminal pro-B type natriuretic peptide (ProBNP) level in patients with coronary artery disease (CAD) is unknown. The current study aimed to investigate the long-term effects of Bezafibrate on ProBNP level in patients with pre-existing CAD and advanced functional capacity impairment. Methods Metabolic and inflammatory parameters were analyzed from stored frozen serum samples obtained from 108 patients enrolled in the Bezafibrate Infarction Prevention (BIP) Study. They presented with New York Heart Association (NYHA) functional class III, comprising 58 patients in the Bezafibrate group and 50 in the placebo groups, and completed a 2-year prospective, double-blind, placebo-controlled follow-up. Results During follow-up ProBNP level did not change significantly in the placebo group, whereas it increased slightly in the Bezafibrate group, which was older and with lower baseline ProBNP values. No significant differences between the groups were found for ProBNP levels after 2 year of follow-up. Analysis-of-covariance (ANCOVA) -taking into account age and baseline ProBNP level- showed that Bezafibrate was not associated with longitudinal ProBNP changes during the follow-up period (p = 0.3). Conclusion Long-term treatment by Bezafibrate was not associated with longitudinal ProBNP changes in patients with pre-existing CAD and advanced functional capacity impairment.

  • attenuation of progression of insulin resistance in patients with coronary artery disease by Bezafibrate
    JAMA Internal Medicine, 2006
    Co-Authors: Alexander Tenenbaum, Enrique Z Fisman, Zipora Matas, Valentina Boyko, David Tanne, Michael Motro, Michal Benderly, Moti Haim, Solomon Behar
    Abstract:

    Background: Development of insulin resistance (IR) may be important in the pathogenesis of both metabolic syndrome and type 2 diabetes mellitus. Few data are available regarding the short-term efficacy of the peroxisome proliferator–activated receptor ligand Bezafibrate on IR, and its long-term effect is unknown. The present analysis aimed to investigate the effect of Bezafibrate on IR in patients with coronary artery disease enrolled in the Bezafibrate Infarction Prevention Study. Methods: Metabolic and inflammatory parameters were analyzed from stored frozen plasma samples obtained from patients who completed a 2-year, randomized, doubleblind, placebo-controlled study. The homeostatic indexes of IR (HOMA-IRs) were calculated according to the homeostasis model of assessment. Results: Both the patients taking Bezafibrate (n = 1262) and those taking placebo (n = 1242) displayed similar baseline characteristics. The HOMA-IRs significantly correlated at baseline and during follow-up with glucose (r=0.35 and 0.31, respectively) and triglycerides (r=0.16 and 0.19, respectively). In a subgroup of 351 patients with diabetes, HOMA-IR at baseline was 88% higher than in their counterparts with normal glucose levels (P.001). In the placebo group, during follow-up there was a significant 34.4% rise in HOMA-IR. In contrast, in the Bezafibrate group there was only a nonsignificant 6.6% change in HOMA-IR. The intergroup differences in percentage changes of HOMA-IR were in favor of Bezafibrate (P.001). Conclusions: In patients with coronary artery disease enrolled in our study, as represented by the placebo group, HOMA-IR increased over time. During the 2 years of the follow-up, Bezafibrate significantly attenuated this process. Arch Intern Med. 2006;166:737-741

  • effect of Bezafibrate on incidence of type 2 diabetes mellitus in obese patients
    European Heart Journal, 2005
    Co-Authors: Alexander Tenenbaum, Enrique Z Fisman, Yehuda Adler, Ehud Schwammenthal, Valentina Boyko, David Tanne, Michael Motro, Joseph Shemesh, Jonathan Leor, Solomon Behar
    Abstract:

    Aims To assess the effect of fibric acid derivative Bezafibrate on incidence of type 2 diabetes in obese patients over a median 6.3 years follow-up period. Methods and results The study sample comprised 339 non-diabetic obese patients (body mass index ≥30.0 kg/m2) aged 42–74. Patients received either Bezafibrate retard 400 mg (178 patients) or placebo (161 patients) once daily. Development of new diabetes was recorded in 98 patients: in 56 (37.0%) from the placebo group vs. 42 (27.1%) from the Bezafibrate group, ( P log-rank=0.01). The median time (interquartile range) until onset of new diabetes was significantly delayed in patients on Bezafibrate when compared with those on placebo: 4.0 (2.1–5.0) vs. 2.0 (0.5–3.5) years, P =0.002. Multivariable analysis identified Bezafibrate treatment as an independent predictor of reduced risk of new diabetes with hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.39–0.91]. Other significant variables associated with future overt type 2 diabetes in obese patients were triglycerides (50 mg/dL increment) with HR 1.15 (95% CI 1.02–1.28) and fasting glucose (10 mg/dL increment) with HR 2.27 (95% CI 1.83–2.81). Conclusion Bezafibrate, when compared with placebo, reduced the incidence and delayed the onset of type 2 diabetes in obese patients over a long-term follow-up period.

Enrique Z Fisman - One of the best experts on this subject based on the ideXlab platform.

  • Bezafibrate for the treatment of dyslipidemia in patients with coronary artery disease 20 year mortality follow up of the bip randomized control trial
    Cardiovascular Diabetology, 2016
    Co-Authors: Yaron Arbel, Robert Klempfner, Aharon Erez, Ilan Goldenberg, Sagit Benzekry, Nir Shlomo, Enrique Z Fisman, Alexander Tenenbaum
    Abstract:

    Recent data support the renewed interest in hypertriglyceridemia as a possible important therapeutic target for cardiovascular risk reduction. This study was designed to address the question of all-cause mortality during extended follow-up of the BIP trial in patients stratified by baseline triglyceride levels. In the BIP trial 3090 patients with proven coronary artery disease were randomized to Bezafibrate 400 mg/day or placebo. All-cause mortality data after 20 years of follow-up, were obtained from the National Israeli Population Registry. Patients with hypertriglyceridemia (triglycerides ≥200 mg/dL, n = 458) were equally distributed among the study groups (15 % in both placebo and Bezafibrate groups). During follow-up 1869 patients died (952 in placebo vs. 917 in Bezafibrate group). Following multivariate adjustment allocation to Bezafibrate was associated with small but significant 10 % mortality risk reduction (HR 0.90; 95 % CI 0.82–0.98, p = 0.026). Variables associated with significantly increased mortality risk were history of a past MI, NYHA class, diabetes, age, higher BMI and glucose level. In patients with hypertriglyceridemia multivariate analysis demonstrated a 25 % all-cause mortality risk reduction associated with allocation to Bezafibrate (HR 0.75, CI 95 % 0.60–0.94; p = 0.012). In patients without hypertriglyceridemia Bezafibrate had no significant effect on long-term mortality. During long-term follow-up Bezafibrate-allocated patients experienced a modest but significant 10 % reduction in the adjusted risk of mortality. This effect of Bezafibrate was more prominent among patients with baseline hypertriglyceridemia (25 % mortality risk reduction).

  • balanced pan ppar activator Bezafibrate in combination with statin comprehensive lipids control and diabetes prevention
    Cardiovascular Diabetology, 2012
    Co-Authors: Alexander Tenenbaum, Enrique Z Fisman
    Abstract:

    All fibrates are peroxisome proliferators-activated receptors (PPARs)-alpha agonists with ability to decrease triglyceride and increase high density lipoprotein- cholesterol (HDL-C). However, Bezafibrate has a unique characteristic profile of action since it activates all three PPAR subtypes (alpha, gamma and delta) at comparable doses. Therefore, Bezafibrate operates as a pan-agonist for all three PPAR isoforms. Selective PPAR gamma agonists (thiazolidinediones) are used to treat type 2 diabetes mellitus (T2DM). They improve insulin sensitivity by up-regulating adipogenesis, decreasing free fatty acid levels, and reversing insulin resistance. However, selective PPAR gamma agonists also cause water retention, weight gain, peripheral edema, and congestive heart failure. The expression of PPAR beta/ delta in essentially all cell types and tissues (ubiquitous presence) suggests its potential fundamental role in cellular biology. PPAR beta/ delta effects correlated with enhancement of fatty acid oxidation, energy consumption and adaptive thermogenesis. Together, these data implicate PPAR beta/delta in fuel combustion and suggest that pan-PPAR agonists that include a component of PPAR beta/delta activation might offset some of the weight gain issues seen with selective PPAR gamma agonists, as was demonstrated by Bezafibrate studies. Suggestively, on the whole body level all PPARs acting as one orchestra and balanced pan-PPAR activation seems as an especially attractive pharmacological goal. Conceptually, combined PPAR gamma and alpha action can target simultaneously insulin resistance and atherogenic dyslipidemia, whereas PPAR beta/delta properties may prevent the development of overweight. Bezafibrate, as all fibrates, significantly reduced plasma triglycerides and increased HDL-C level (but considerably stronger than other major fibrates). Bezafibrate significantly decreased prevalence of small, dense low density lipoproteins particles, remnants, induced atherosclerotic plaque regression in thoracic and abdominal aorta and improved endothelial function. In addition, Bezafibrate has important fibrinogen-related properties and anti-inflammatory effects. In clinical trials Bezafibrate was highly effective for cardiovascular risk reduction in patients with metabolic syndrome and atherogenic dyslipidemia. The principal differences between Bezafibrate and other fibrates are related to effects on glucose level and insulin resistance. Bezafibrate decreases blood glucose level, HbA1C, insulin resistance and reduces the incidence of T2DM compared to placebo or other fibrates. Currently statins are the cornerstone of the treatment and prevention of cardiovascular diseases related to atherosclerosis. However, despite the increasing use of statins as monotherapy for low density lipoprotein- cholesterol (LDL-C) reduction, a significant residual cardiovascular risk is still presented in patients with atherogenic dyslipidemia and insulin resistance, which is typical for T2DM and metabolic syndrome. Recently, concerns were raised regarding the development of diabetes in statin-treated patients. Combined Bezafibrate/statin therapy is more effective in achieving a comprehensive lipid control and residual cardiovascular risk reduction. Based on the beneficial effects of pan-PPAR agonist Bezafibrate on glucose metabolism and prevention of new-onset diabetes, one could expect a neutralization of the adverse pro-diabetic effect of statins using the strategy of a combined statin/fibrate therapy.

  • Long-term effects of peroxisome proliferator-activated receptor ligand Bezafibrate on N-terminal pro-B type natriuretic peptide in patients with advanced functional capacity impairment
    Cardiovascular Diabetology, 2009
    Co-Authors: Koichi Node, Enrique Z Fisman, Teruo Inoue, Valentin Boyko, Ilan Goldberg, Yehuda Adler, Ehud Schwammenthal, Zipora Matas, Solomon Behar, Alexander Tenenbaum
    Abstract:

    Background The effects of pan-peroxisome proliferator-activated receptor (PPAR) ligand Bezafibrate on N-terminal pro-B type natriuretic peptide (ProBNP) level in patients with coronary artery disease (CAD) is unknown. The current study aimed to investigate the long-term effects of Bezafibrate on ProBNP level in patients with pre-existing CAD and advanced functional capacity impairment. Methods Metabolic and inflammatory parameters were analyzed from stored frozen serum samples obtained from 108 patients enrolled in the Bezafibrate Infarction Prevention (BIP) Study. They presented with New York Heart Association (NYHA) functional class III, comprising 58 patients in the Bezafibrate group and 50 in the placebo groups, and completed a 2-year prospective, double-blind, placebo-controlled follow-up. Results During follow-up ProBNP level did not change significantly in the placebo group, whereas it increased slightly in the Bezafibrate group, which was older and with lower baseline ProBNP values. No significant differences between the groups were found for ProBNP levels after 2 year of follow-up. Analysis-of-covariance (ANCOVA) -taking into account age and baseline ProBNP level- showed that Bezafibrate was not associated with longitudinal ProBNP changes during the follow-up period (p = 0.3). Conclusion Long-term treatment by Bezafibrate was not associated with longitudinal ProBNP changes in patients with pre-existing CAD and advanced functional capacity impairment.

  • attenuation of progression of insulin resistance in patients with coronary artery disease by Bezafibrate
    JAMA Internal Medicine, 2006
    Co-Authors: Alexander Tenenbaum, Enrique Z Fisman, Zipora Matas, Valentina Boyko, David Tanne, Michael Motro, Michal Benderly, Moti Haim, Solomon Behar
    Abstract:

    Background: Development of insulin resistance (IR) may be important in the pathogenesis of both metabolic syndrome and type 2 diabetes mellitus. Few data are available regarding the short-term efficacy of the peroxisome proliferator–activated receptor ligand Bezafibrate on IR, and its long-term effect is unknown. The present analysis aimed to investigate the effect of Bezafibrate on IR in patients with coronary artery disease enrolled in the Bezafibrate Infarction Prevention Study. Methods: Metabolic and inflammatory parameters were analyzed from stored frozen plasma samples obtained from patients who completed a 2-year, randomized, doubleblind, placebo-controlled study. The homeostatic indexes of IR (HOMA-IRs) were calculated according to the homeostasis model of assessment. Results: Both the patients taking Bezafibrate (n = 1262) and those taking placebo (n = 1242) displayed similar baseline characteristics. The HOMA-IRs significantly correlated at baseline and during follow-up with glucose (r=0.35 and 0.31, respectively) and triglycerides (r=0.16 and 0.19, respectively). In a subgroup of 351 patients with diabetes, HOMA-IR at baseline was 88% higher than in their counterparts with normal glucose levels (P.001). In the placebo group, during follow-up there was a significant 34.4% rise in HOMA-IR. In contrast, in the Bezafibrate group there was only a nonsignificant 6.6% change in HOMA-IR. The intergroup differences in percentage changes of HOMA-IR were in favor of Bezafibrate (P.001). Conclusions: In patients with coronary artery disease enrolled in our study, as represented by the placebo group, HOMA-IR increased over time. During the 2 years of the follow-up, Bezafibrate significantly attenuated this process. Arch Intern Med. 2006;166:737-741

  • effect of Bezafibrate on incidence of type 2 diabetes mellitus in obese patients
    European Heart Journal, 2005
    Co-Authors: Alexander Tenenbaum, Enrique Z Fisman, Yehuda Adler, Ehud Schwammenthal, Valentina Boyko, David Tanne, Michael Motro, Joseph Shemesh, Jonathan Leor, Solomon Behar
    Abstract:

    Aims To assess the effect of fibric acid derivative Bezafibrate on incidence of type 2 diabetes in obese patients over a median 6.3 years follow-up period. Methods and results The study sample comprised 339 non-diabetic obese patients (body mass index ≥30.0 kg/m2) aged 42–74. Patients received either Bezafibrate retard 400 mg (178 patients) or placebo (161 patients) once daily. Development of new diabetes was recorded in 98 patients: in 56 (37.0%) from the placebo group vs. 42 (27.1%) from the Bezafibrate group, ( P log-rank=0.01). The median time (interquartile range) until onset of new diabetes was significantly delayed in patients on Bezafibrate when compared with those on placebo: 4.0 (2.1–5.0) vs. 2.0 (0.5–3.5) years, P =0.002. Multivariable analysis identified Bezafibrate treatment as an independent predictor of reduced risk of new diabetes with hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.39–0.91]. Other significant variables associated with future overt type 2 diabetes in obese patients were triglycerides (50 mg/dL increment) with HR 1.15 (95% CI 1.02–1.28) and fasting glucose (10 mg/dL increment) with HR 2.27 (95% CI 1.83–2.81). Conclusion Bezafibrate, when compared with placebo, reduced the incidence and delayed the onset of type 2 diabetes in obese patients over a long-term follow-up period.

David Tanne - One of the best experts on this subject based on the ideXlab platform.

  • Long-term Benefit of High-Density Lipoprotein Cholesterol–Raising Therapy With Bezafibrate: 16-Year Mortality Follow-up of the Bezafibrate Infarction Prevention Trial
    Archives of internal medicine, 2009
    Co-Authors: Ilan Goldenberg, Solomon Behar, Valentina Boyko, Alexander Tennenbaum, David Tanne, Victor Guetta
    Abstract:

    Background Major randomized trials of fibrate therapy demonstrate an inverse relationship between on-treatment high-density lipoprotein cholesterol (HDL-C) increments and clinical outcome. We hypothesized that the degree of HDL-C response to Bezafibrate is independently associated with subsequent long-term mortality. Methods The risk of death at 16 years of follow-up among 3026 patients with coronary heart disease allocated to the original Bezafibrate (n = 1509) and placebo (n = 1517) arms of the Bezafibrate Infarction Prevention (BIP) trial was related to HDL-C response to Bezafibrate therapy, categorized as upper-tertile (>8 mg/dL) or lower-tertile (≤8 mg/dL) on-treatment HDL-C change. Results Multivariate analysis demonstrated that patients allocated to Bezafibrate therapy experienced a significant 11% reduction ( P  = .06) in the risk of long-term mortality compared with placebo-allocated patients. Mortality reduction among Bezafibrate-allocated patients was related to a significant 22% ( P  = .008) reduction in the risk of death in patients with an upper-tertile HDL-C response to therapy, whereas among patients with a lower HDL-C response, the risk of death was similar to that of the placebo group (hazard ratio, 0.95; P  = .43). Accordingly, the cumulative probability of death at 16 years was significantly lower among Bezafibrate-allocated patients with an upper-tertile HDL-C response (32.1%) compared with the placebo group (37.9%; P  = .02), whereas patients with a lower HDL-C response to treatment displayed a mortality rate (36.8%) similar to the placebo group ( P  = .57). Conclusion Our findings suggest that HDL-C level–raising therapy with Bezafibrate is associated with long-term mortality reduction that may be related to the degree of HDL-C response to treatment.

  • long term benefit of high density lipoprotein cholesterol raising therapy with Bezafibrate 16 year mortality follow up of the Bezafibrate infarction prevention trial
    JAMA Internal Medicine, 2009
    Co-Authors: Ilan Goldenberg, Solomon Behar, Valentina Boyko, Alexander Tennenbaum, David Tanne, Victor Guetta
    Abstract:

    Background Major randomized trials of fibrate therapy demonstrate an inverse relationship between on-treatment high-density lipoprotein cholesterol (HDL-C) increments and clinical outcome. We hypothesized that the degree of HDL-C response to Bezafibrate is independently associated with subsequent long-term mortality. Methods The risk of death at 16 years of follow-up among 3026 patients with coronary heart disease allocated to the original Bezafibrate (n = 1509) and placebo (n = 1517) arms of the Bezafibrate Infarction Prevention (BIP) trial was related to HDL-C response to Bezafibrate therapy, categorized as upper-tertile (>8 mg/dL) or lower-tertile (≤8 mg/dL) on-treatment HDL-C change. Results Multivariate analysis demonstrated that patients allocated to Bezafibrate therapy experienced a significant 11% reduction ( P  = .06) in the risk of long-term mortality compared with placebo-allocated patients. Mortality reduction among Bezafibrate-allocated patients was related to a significant 22% ( P  = .008) reduction in the risk of death in patients with an upper-tertile HDL-C response to therapy, whereas among patients with a lower HDL-C response, the risk of death was similar to that of the placebo group (hazard ratio, 0.95; P  = .43). Accordingly, the cumulative probability of death at 16 years was significantly lower among Bezafibrate-allocated patients with an upper-tertile HDL-C response (32.1%) compared with the placebo group (37.9%; P  = .02), whereas patients with a lower HDL-C response to treatment displayed a mortality rate (36.8%) similar to the placebo group ( P  = .57). Conclusion Our findings suggest that HDL-C level–raising therapy with Bezafibrate is associated with long-term mortality reduction that may be related to the degree of HDL-C response to treatment.

  • attenuation of progression of insulin resistance in patients with coronary artery disease by Bezafibrate
    JAMA Internal Medicine, 2006
    Co-Authors: Alexander Tenenbaum, Enrique Z Fisman, Zipora Matas, Valentina Boyko, David Tanne, Michael Motro, Michal Benderly, Moti Haim, Solomon Behar
    Abstract:

    Background: Development of insulin resistance (IR) may be important in the pathogenesis of both metabolic syndrome and type 2 diabetes mellitus. Few data are available regarding the short-term efficacy of the peroxisome proliferator–activated receptor ligand Bezafibrate on IR, and its long-term effect is unknown. The present analysis aimed to investigate the effect of Bezafibrate on IR in patients with coronary artery disease enrolled in the Bezafibrate Infarction Prevention Study. Methods: Metabolic and inflammatory parameters were analyzed from stored frozen plasma samples obtained from patients who completed a 2-year, randomized, doubleblind, placebo-controlled study. The homeostatic indexes of IR (HOMA-IRs) were calculated according to the homeostasis model of assessment. Results: Both the patients taking Bezafibrate (n = 1262) and those taking placebo (n = 1242) displayed similar baseline characteristics. The HOMA-IRs significantly correlated at baseline and during follow-up with glucose (r=0.35 and 0.31, respectively) and triglycerides (r=0.16 and 0.19, respectively). In a subgroup of 351 patients with diabetes, HOMA-IR at baseline was 88% higher than in their counterparts with normal glucose levels (P.001). In the placebo group, during follow-up there was a significant 34.4% rise in HOMA-IR. In contrast, in the Bezafibrate group there was only a nonsignificant 6.6% change in HOMA-IR. The intergroup differences in percentage changes of HOMA-IR were in favor of Bezafibrate (P.001). Conclusions: In patients with coronary artery disease enrolled in our study, as represented by the placebo group, HOMA-IR increased over time. During the 2 years of the follow-up, Bezafibrate significantly attenuated this process. Arch Intern Med. 2006;166:737-741

  • effect of Bezafibrate on incidence of type 2 diabetes mellitus in obese patients
    European Heart Journal, 2005
    Co-Authors: Alexander Tenenbaum, Enrique Z Fisman, Yehuda Adler, Ehud Schwammenthal, Valentina Boyko, David Tanne, Michael Motro, Joseph Shemesh, Jonathan Leor, Solomon Behar
    Abstract:

    Aims To assess the effect of fibric acid derivative Bezafibrate on incidence of type 2 diabetes in obese patients over a median 6.3 years follow-up period. Methods and results The study sample comprised 339 non-diabetic obese patients (body mass index ≥30.0 kg/m2) aged 42–74. Patients received either Bezafibrate retard 400 mg (178 patients) or placebo (161 patients) once daily. Development of new diabetes was recorded in 98 patients: in 56 (37.0%) from the placebo group vs. 42 (27.1%) from the Bezafibrate group, ( P log-rank=0.01). The median time (interquartile range) until onset of new diabetes was significantly delayed in patients on Bezafibrate when compared with those on placebo: 4.0 (2.1–5.0) vs. 2.0 (0.5–3.5) years, P =0.002. Multivariable analysis identified Bezafibrate treatment as an independent predictor of reduced risk of new diabetes with hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.39–0.91]. Other significant variables associated with future overt type 2 diabetes in obese patients were triglycerides (50 mg/dL increment) with HR 1.15 (95% CI 1.02–1.28) and fasting glucose (10 mg/dL increment) with HR 2.27 (95% CI 1.83–2.81). Conclusion Bezafibrate, when compared with placebo, reduced the incidence and delayed the onset of type 2 diabetes in obese patients over a long-term follow-up period.

  • Bezafibrate for the secondary prevention of myocardial infarction in patients with metabolic syndrome
    JAMA Internal Medicine, 2005
    Co-Authors: Alexander Tenenbaum, Enrique Z Fisman, Valentina Boyko, David Tanne, Michael Motro, Solomon Behar
    Abstract:

    fidenceinterval[CI],0.54-0.95)and0.67(95%CI,0.490.91), respectively. The cardiac mortality risk tended to be lower in patients taking Bezafibrate (HR, 0.74; 95% CI, 0.54-1.03). In 575 patients with augmented features of MS (4-5 risk factors), the remarkable strengthening of cardiac mortality reduction when taking Bezafibrate (HR, 0.44; 95% CI, 0.25-0.80) should be noted. Conclusion: Bezafibrate reduces the incidence of MI in patients with MS during long-term follow-up. Arch Intern Med. 2005;165:1154-1160

Valentina Boyko - One of the best experts on this subject based on the ideXlab platform.

  • Long-term Benefit of High-Density Lipoprotein Cholesterol–Raising Therapy With Bezafibrate: 16-Year Mortality Follow-up of the Bezafibrate Infarction Prevention Trial
    Archives of internal medicine, 2009
    Co-Authors: Ilan Goldenberg, Solomon Behar, Valentina Boyko, Alexander Tennenbaum, David Tanne, Victor Guetta
    Abstract:

    Background Major randomized trials of fibrate therapy demonstrate an inverse relationship between on-treatment high-density lipoprotein cholesterol (HDL-C) increments and clinical outcome. We hypothesized that the degree of HDL-C response to Bezafibrate is independently associated with subsequent long-term mortality. Methods The risk of death at 16 years of follow-up among 3026 patients with coronary heart disease allocated to the original Bezafibrate (n = 1509) and placebo (n = 1517) arms of the Bezafibrate Infarction Prevention (BIP) trial was related to HDL-C response to Bezafibrate therapy, categorized as upper-tertile (>8 mg/dL) or lower-tertile (≤8 mg/dL) on-treatment HDL-C change. Results Multivariate analysis demonstrated that patients allocated to Bezafibrate therapy experienced a significant 11% reduction ( P  = .06) in the risk of long-term mortality compared with placebo-allocated patients. Mortality reduction among Bezafibrate-allocated patients was related to a significant 22% ( P  = .008) reduction in the risk of death in patients with an upper-tertile HDL-C response to therapy, whereas among patients with a lower HDL-C response, the risk of death was similar to that of the placebo group (hazard ratio, 0.95; P  = .43). Accordingly, the cumulative probability of death at 16 years was significantly lower among Bezafibrate-allocated patients with an upper-tertile HDL-C response (32.1%) compared with the placebo group (37.9%; P  = .02), whereas patients with a lower HDL-C response to treatment displayed a mortality rate (36.8%) similar to the placebo group ( P  = .57). Conclusion Our findings suggest that HDL-C level–raising therapy with Bezafibrate is associated with long-term mortality reduction that may be related to the degree of HDL-C response to treatment.

  • long term benefit of high density lipoprotein cholesterol raising therapy with Bezafibrate 16 year mortality follow up of the Bezafibrate infarction prevention trial
    JAMA Internal Medicine, 2009
    Co-Authors: Ilan Goldenberg, Solomon Behar, Valentina Boyko, Alexander Tennenbaum, David Tanne, Victor Guetta
    Abstract:

    Background Major randomized trials of fibrate therapy demonstrate an inverse relationship between on-treatment high-density lipoprotein cholesterol (HDL-C) increments and clinical outcome. We hypothesized that the degree of HDL-C response to Bezafibrate is independently associated with subsequent long-term mortality. Methods The risk of death at 16 years of follow-up among 3026 patients with coronary heart disease allocated to the original Bezafibrate (n = 1509) and placebo (n = 1517) arms of the Bezafibrate Infarction Prevention (BIP) trial was related to HDL-C response to Bezafibrate therapy, categorized as upper-tertile (>8 mg/dL) or lower-tertile (≤8 mg/dL) on-treatment HDL-C change. Results Multivariate analysis demonstrated that patients allocated to Bezafibrate therapy experienced a significant 11% reduction ( P  = .06) in the risk of long-term mortality compared with placebo-allocated patients. Mortality reduction among Bezafibrate-allocated patients was related to a significant 22% ( P  = .008) reduction in the risk of death in patients with an upper-tertile HDL-C response to therapy, whereas among patients with a lower HDL-C response, the risk of death was similar to that of the placebo group (hazard ratio, 0.95; P  = .43). Accordingly, the cumulative probability of death at 16 years was significantly lower among Bezafibrate-allocated patients with an upper-tertile HDL-C response (32.1%) compared with the placebo group (37.9%; P  = .02), whereas patients with a lower HDL-C response to treatment displayed a mortality rate (36.8%) similar to the placebo group ( P  = .57). Conclusion Our findings suggest that HDL-C level–raising therapy with Bezafibrate is associated with long-term mortality reduction that may be related to the degree of HDL-C response to treatment.

  • attenuation of progression of insulin resistance in patients with coronary artery disease by Bezafibrate
    JAMA Internal Medicine, 2006
    Co-Authors: Alexander Tenenbaum, Enrique Z Fisman, Zipora Matas, Valentina Boyko, David Tanne, Michael Motro, Michal Benderly, Moti Haim, Solomon Behar
    Abstract:

    Background: Development of insulin resistance (IR) may be important in the pathogenesis of both metabolic syndrome and type 2 diabetes mellitus. Few data are available regarding the short-term efficacy of the peroxisome proliferator–activated receptor ligand Bezafibrate on IR, and its long-term effect is unknown. The present analysis aimed to investigate the effect of Bezafibrate on IR in patients with coronary artery disease enrolled in the Bezafibrate Infarction Prevention Study. Methods: Metabolic and inflammatory parameters were analyzed from stored frozen plasma samples obtained from patients who completed a 2-year, randomized, doubleblind, placebo-controlled study. The homeostatic indexes of IR (HOMA-IRs) were calculated according to the homeostasis model of assessment. Results: Both the patients taking Bezafibrate (n = 1262) and those taking placebo (n = 1242) displayed similar baseline characteristics. The HOMA-IRs significantly correlated at baseline and during follow-up with glucose (r=0.35 and 0.31, respectively) and triglycerides (r=0.16 and 0.19, respectively). In a subgroup of 351 patients with diabetes, HOMA-IR at baseline was 88% higher than in their counterparts with normal glucose levels (P.001). In the placebo group, during follow-up there was a significant 34.4% rise in HOMA-IR. In contrast, in the Bezafibrate group there was only a nonsignificant 6.6% change in HOMA-IR. The intergroup differences in percentage changes of HOMA-IR were in favor of Bezafibrate (P.001). Conclusions: In patients with coronary artery disease enrolled in our study, as represented by the placebo group, HOMA-IR increased over time. During the 2 years of the follow-up, Bezafibrate significantly attenuated this process. Arch Intern Med. 2006;166:737-741

  • effect of Bezafibrate on incidence of type 2 diabetes mellitus in obese patients
    European Heart Journal, 2005
    Co-Authors: Alexander Tenenbaum, Enrique Z Fisman, Yehuda Adler, Ehud Schwammenthal, Valentina Boyko, David Tanne, Michael Motro, Joseph Shemesh, Jonathan Leor, Solomon Behar
    Abstract:

    Aims To assess the effect of fibric acid derivative Bezafibrate on incidence of type 2 diabetes in obese patients over a median 6.3 years follow-up period. Methods and results The study sample comprised 339 non-diabetic obese patients (body mass index ≥30.0 kg/m2) aged 42–74. Patients received either Bezafibrate retard 400 mg (178 patients) or placebo (161 patients) once daily. Development of new diabetes was recorded in 98 patients: in 56 (37.0%) from the placebo group vs. 42 (27.1%) from the Bezafibrate group, ( P log-rank=0.01). The median time (interquartile range) until onset of new diabetes was significantly delayed in patients on Bezafibrate when compared with those on placebo: 4.0 (2.1–5.0) vs. 2.0 (0.5–3.5) years, P =0.002. Multivariable analysis identified Bezafibrate treatment as an independent predictor of reduced risk of new diabetes with hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.39–0.91]. Other significant variables associated with future overt type 2 diabetes in obese patients were triglycerides (50 mg/dL increment) with HR 1.15 (95% CI 1.02–1.28) and fasting glucose (10 mg/dL increment) with HR 2.27 (95% CI 1.83–2.81). Conclusion Bezafibrate, when compared with placebo, reduced the incidence and delayed the onset of type 2 diabetes in obese patients over a long-term follow-up period.

  • Bezafibrate for the secondary prevention of myocardial infarction in patients with metabolic syndrome
    JAMA Internal Medicine, 2005
    Co-Authors: Alexander Tenenbaum, Enrique Z Fisman, Valentina Boyko, David Tanne, Michael Motro, Solomon Behar
    Abstract:

    fidenceinterval[CI],0.54-0.95)and0.67(95%CI,0.490.91), respectively. The cardiac mortality risk tended to be lower in patients taking Bezafibrate (HR, 0.74; 95% CI, 0.54-1.03). In 575 patients with augmented features of MS (4-5 risk factors), the remarkable strengthening of cardiac mortality reduction when taking Bezafibrate (HR, 0.44; 95% CI, 0.25-0.80) should be noted. Conclusion: Bezafibrate reduces the incidence of MI in patients with MS during long-term follow-up. Arch Intern Med. 2005;165:1154-1160