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Biomedical subjects

Alexander Tenenbaum

Publications and source records attributed to Alexander Tenenbaum.

At least 19 recordsLinked to original sources
PubMed2006

Effects of peroxisome proliferator-activated receptor ligands, bezafibrate and fenofibrate, on adiponectin level.

OBJECTIVE: Adiponectin is adipose-specific secretory protein and acts as anti-diabetic and anti-atherosclerotic molecule. We previously found peroxisome proliferators response element in adiponectin promoter region, suggesting that peroxisome proliferator-activated receptor (PPAR) ligands elevate adiponectin. Fibrates are known to be PPARalpha ligands and were shown to reduce risks of diabetes and cardiovascular disease. Effect of fibrates on adiponectin has not been clarified, whereas thiazolidinediones enhance adiponectin. Thus, we explored the possibility and mechanism that fibrates enhance adiponectin in humans, mice, and cells. METHODS AND RESULTS: Significant increase of serum adiponectin was observed in bezafibrate-treated subjects compared with placebo group in patients enrolled in The Bezafibrate Infarction Prevention study. Higher baseline adiponectin levels were strongly associated with reduced risk of new diabetes. Fibrates, bezafibrate and fenofibrate, significantly elevated adiponectin levels in wild-type mice and 3T3-L1 adipocytes. Such an effect was not observed in PPARalpha-deficient mice and adipocytes. Fibrates activated adiponectin promoter but failed to enhance its activity when the point mutation occurred in peroxisome proliferators response element site and the endogenous PPARalpha was knocked down by PPARalpha-RNAi. CONCLUSIONS: Our results suggest that fibrates enhance adiponectin partly through adipose PPARalpha and measurement of adiponectin might be a useful tool for searching subjects at high risk for diabetes.

Adipocytes↗
PubMed2006

Calcification of the thoracic aorta by spiral computed tomography among hypertensive patients: associations and risk of ischemic cerebrovascular events.

BACKGROUND: Calcium is often deposited in the aorta, but the associations and clinical implications of calcification of the aorta have not yet been elucidated. METHODS: In a prospective cohort of 455 hypertensive patients with at least 1 additional risk factor for atherosclerosis that underwent dual slice spiral computed tomography of the chest for assessment of arterial calcification (mean age 65.7+/-5.8, range 52-80 years, 48% female), we assessed for calcifications of the ascending and descending aorta and their association with the risk of subsequent ischemic cerebrovascular events during 3-year follow-up. RESULTS: Calcification of the ascending or descending aorta was present in 342 (75%) patients (60% calcification of the ascending aorta and 56% of the descending aorta). The main associations of calcification of the thoracic aorta were increasing age and the presence of coronary calcification, mitral annulus calcification, and aortic valve calcification. In a logistic regression model the main predictors of ischemic cerebrovascular events (n=27) during follow-up were the presence of severe calcification (thickness of > or = 5 mm) of the descending aorta (OR 4.9, 95%CI 1.8 to 13.5) and cigarette smoking (OR 2.8, 95%CI 1.1 to 6.7). CONCLUSIONS: Calcification of the thoracic aorta is highly prevalent among women and men with hypertension, is age-related, and correlates with calcification of the coronary arteries and heart valves. Only severe calcification of the descending aorta is associated with subsequent ischemic cerebrovascular events, suggesting that calcification of the thoracic aorta is a marker of the burden of vascular disease.

Aged↗
PubMed2006

Underuse of standard care and outcome of patients with acute myocardial infarction and chronic renal insufficiency.

OBJECTIVES: To investigate characteristics, management and outcome of patients with acute myocardial infarction (AMI) and chronic renal insufficiency (CRI). BACKGROUND: Patients with AMI and CRI are considered to be at high risk of complications and death. Physicians may be reluctant to prescribe life-saving medications to patients with concomitant CRI. METHODS: We compared clinical characteristics, management and outcome of 1,683 consecutive AMI patients in three categories of renal function: (1) normal renal function (<1.5 mg/dl) (n = 1,559), (2) mild to moderate CRI (1.5-3.5 mg/dl) (n = 77), and (3) severe CRI (>3.5 mg/dl) (n = 47). RESULTS: CRI patients were older and were more likely to have other co-morbidities such as hypertension, diabetes mellitus, prior AMI, stroke, angina and heart failure. Compared with patients with normal renal function, standard therapy for AMI including thrombolysis, aspirin, angiotensin-converting-enzyme inhibitors, beta-blockers and lipid lowering agents was underutilized in CRI patients and these patients were more likely to have in-hospital complications such as heart failure, atrial or ventricular fibrillation, cardiogenic shock, sepsis, worsening of renal function and death within 30 days [odds ratio (OR) = 3.3; 95% confidence interval (CI) = 2.0-4.8]. After adjustment for age and co-morbidities, the association between mild to moderate CRI and 30-days mortality declined, whereas severe CRI remained an independent determinant of mortality (OR = 4.8; 95% CI = 2.0-11.4). Adjustment for aspirin, angiotensin-converting-enzyme inhibitors and beta-blocker therapy weakened the association between CRI and death within 30 days after AMI. CONCLUSIONS: CRI patients are more likely to experience serious complications and death early after AMI. Underutilization of standard care, particularly beta-blocker therapy, contributes to increased mortality risk in these patients.

Adrenergic beta-Antagonists↗
PubMed2006

Atherogenic dyslipidemia in metabolic syndrome and type 2 diabetes: therapeutic options beyond statins.

Lowering of low-density lipoprotein cholesterol with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) is clearly efficacious in the treatment and prevention of coronary artery disease. However, despite increasing use of statins, a significant number of coronary events still occur and many of such events take place in patients presenting with type 2 diabetes and metabolic syndrome. More and more attention is being paid now to combined atherogenic dyslipidemia which typically presents in patients with type 2 diabetes and metabolic syndrome. This mixed dyslipidemia (or "lipid quartet"): hypertriglyceridemia, low high-density lipoprotein cholesterol levels, a preponderance of small, dense low-density lipoprotein particles and an accumulation of cholesterol-rich remnant particles (e.g. high levels of apolipoprotein B)--emerged as the greatest "competitor" of low-density lipoprotein-cholesterol among lipid risk factors for cardiovascular disease. Most recent extensions of the fibrates trials (BIP - Bezafibrate Infarction Prevention study, HHS - Helsinki Heart Study, VAHIT--Veterans Affairs High-density lipoprotein cholesterol Intervention Trial and FIELD--Fenofibrate Intervention and Event Lowering in Diabetes) give further support to the hypothesis that patients with insulin-resistant syndromes such as diabetes and/or metabolic syndrome might be the ones to derive the most benefit from therapy with fibrates. However, different fibrates may have a somewhat different spectrum of effects. Other lipid-modifying strategies included using of niacin, ezetimibe, bile acid sequestrants and cholesteryl ester transfer protein inhibition. In addition, bezafibrate as pan-peroxisome proliferator activated receptor activator has clearly demonstrated beneficial pleiotropic effects related to glucose metabolism and insulin sensitivity. Because fibrates, niacin, ezetimibe and statins each regulate serum lipids by different mechanisms, combination therapy--selected on the basis of their safety and effectiveness - may offer particularly desirable benefits in patients with combined hyperlipidemia as compared with statins monotherapy.

Clofibric Acid↗
PubMed2006

Long-term effect of bezafibrate on pancreatic beta-cell function and insulin resistance in patients with diabetes.

OBJECTIVE: Development of insulin resistance (IR) and the progressive failure of the pancreatic beta-cell function (BCF) may be important in the pathogenesis of type 2 diabetes. Influence of peroxisome proliferator-activated receptors ligand bezafibrate on BCF and IR in patients with diabetes is unknown. The present study was aimed to investigate the long-term effect of bezafibrate on these parameters in diabetic patients enrolled in the Bezafibrate Infarction Prevention (BIP) Study. METHODS: Metabolic and inflammatory parameters were analyzed from stored frozen plasma samples obtained from 351 diabetic patients (168 treated by bezafibrate and 183 by placebo) who completed a 2-year of randomized, double-blind, placebo-controlled study period. The homeostatic indexes of BCF (HOMA-BCF) and IR (HOMA-IR) were calculated according to the homeostasis model of assessment. RESULTS: Both groups displayed similar baseline characteristics. During follow-up, in the placebo group there was 28% rise of HOMA-IR (p<0.001). In contrast, HOMA-IR in patients in the bezafibrate group did not change (p=0.99). The intergroup differences in HOMA-IR percentage changes were in favor of bezafibrate (p=0.01). HOMA-BCF values have significantly decreased by 13.9% (p=0.04) in patients of placebo group, whereas in patients of bezafibrate group HOMA-BCF was stable during follow-up and its alterations (-2.9%) were non-significant (p=0.59). CONCLUSIONS: Diabetic patients from the placebo group demonstrated a progressive declining of BCF and an increasing of IR over 2 years of follow-up. These longitudinal changes were attenuated when patients used bezafibrate.

Aged↗
PubMed2006

C-reactive protein as a predictor of incident ischemic stroke among patients with preexisting cardiovascular disease.

BACKGROUND AND PURPOSE: C-reactive protein (CRP) has emerged as an important predictor of cardiovascular disease, but there are few prospective data on its association with risk of ischemic stroke in patients at high risk. METHODS: We examined the association between CRP levels and subsequent risk of incident ischemic stroke among 2979 patients with stable coronary heart disease included in a controlled clinical trial (Bezafibrate Infarction Prevention) that assessed the efficacy of bezafibrate, a fibric acid derivative, versus placebo for secondary prevention. CRP was measured by a high-sensitivity assay in plasma samples collected before randomization and again at the second follow-up year of an overall mean follow-up of 6.2 years. RESULTS: Risk of ischemic stroke per 1000 person-years increased from 4.1% for baseline CRP in the lowest tertile (<2.3 mg/L; n=982) to 5.9% for levels at the middle tertile (2.3 to 5.4 mg/L; n=1013) and 10.5% for CRP levels at the upper tertile (>5.4 mg/L; n=984; P<0.001). With adjustment for potential confounders, baseline CRP levels in the top versus bottom tertile were associated with a 2.16-fold increased hazard (95% CI, 1.32 to 3.53) for ischemic stroke, and CRP levels measured after 2 years were associated with a hazard ratio of 2.43 (95% CI, 1.30 to 4.57). The risk of an incident ischemic stroke did not differ between the bezafibrate group compared with the placebo group regardless of baseline CRP levels. CONCLUSIONS: These findings, based on a large prospective study, demonstrate the risk prediction for incident ischemic stroke conferred by CRP levels in patients at high risk.

Aged↗
PubMed2006

Long-term versus intermediate-term supervised exercise training in advanced heart failure: effects on exercise tolerance and mortality.

AIM: To date there have been no studies exploring the effects of long-term versus intermediate-term and short-term supervised exercise training program in patients with severe chronic heart failure (CHF) on optimal medical therapy. We assessed exercise tolerance and mortality in CHF patients undergoing long- versus intermediate-term exercise training (ET). METHODS: Forty-two consecutive severe CHF patients (New York Heart Association functional class III) were referred for a supervised exercise and cardiac rehabilitation program and were followed-up for 3 years: 20/42 (48%) patients discontinued ET after intermediate-term period of 1.6+/-0.8 years (Group A, intermediate-term ET), and 22/42 (52%) remained on the ET program for 3.0+/-0.3 years (Group B, long-term ET). Exercise duration, 6-min walked distance and metabolic equivalents (METs) assessed by modified Bruce protocol were recorded before, 4.5 months after, and 3 years after initiation of ET. RESULTS: Both groups were comparable regarding age, gender, prevalence of ischemic etiology, mean ejection fraction and medications. Risk factors for ischemic heart disease were similar, except for the prevalence of diabetes, which was higher in Group A compared to Group B (11/20 versus 5/22, p=0.03). Significantly more Group A patients died after ET discontinuation (4/20 versus 0/22, p=0.01). At the end of follow-up a significant improvement could be seen in Group B patients compared to A in exercise duration, 6-min walked distance and metabolic equivalents (p<0.01 for all). CONCLUSIONS: Higher survival rate was observed in severe CHF patients undergoing long-term versus intermediate-term exercise training. Long-term supervised exercise training is safe and improves exercise tolerance in these patients.

Exercise Therapy↗
PubMed2006

Interleukin-6 and the risk of future cardiovascular events in patients with angina pectoris and/or healed myocardial infarction.

The aim of this study was to evaluate the prognostic value of interleukin-6 (IL-6) for myocardial infarction (MI) and mortality in a population with stable coronary artery disease (CAD) during a mean period of 6.3 years. IL-6 is a major proinflammatory cytokine of acute phase response; elevated levels are associated with worse prognosis in unstable angina and after acute MI. However, data regarding its long-term prognostic value in stable CAD are limited and controversial. A nested case-control study design was used. Of 3,090 patients with stable CAD, 129 with an adequate blood sample for IL-6 and who reached the end points (MI or sudden death) were randomly selected. Each case was 1:1 matched with 129 controls (alive at the end of the study and free of cardiovascular events) according to age, gender, and treatment. Of the 129 cases, 113 had a MI as the initial event, and for the other 16 the initial event was sudden death. There were 8 patients who first had a MI and later died suddenly. IL-6 was significantly higher in cases (2.34 pg/ml) than in controls (1.65 pg/ml) (p = 0.0004). IL-6 was significantly correlated with C-reactive protein (r = 0.2, p = 0.002); a borderline significance was also found for fibrinogen (r = 0.11, p = 0.07). Each increase of 1 pg/ml in IL-6 was associated with a 1.70 (range 1.23 to 2.45) increased relative odds of subsequent MI or sudden death. Events rate per 1,000 patients-years for the 5 quintiles of IL-6 were 72.26, 89.61, 79.76, 142.53, and 181.08, respectively (p <0.0001). A significantly higher risk in the upper quintile was found (odds ratio, 3.44; 95% confidence interval 1.57 to 8.13). In conclusion, elevated IL-6 levels are strongly associated with future cardiac events and mortality in a population with stable CAD during a long-term follow-up.

Aged↗
PubMed2006

Attenuation of progression of insulin resistance in patients with coronary artery disease by bezafibrate.

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, double-blind, 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.

Aged↗
PubMed2006

Pregnancy outcome following infections by coxsackie, echo, measles, mumps, hepatitis, polio and encephalitis viruses.

Women may be infected during pregnancy with infectious agents that are often passed unnoticed; however, the causative agent may still traverse the placenta and infect the developing embryo and fetus. Several of these agents (i.e. rubella, cytomegalovirus or Toxoplasma Gondii) may cause severe fetal damage, but most other infections in pregnancy seem to be much less dangerous to the fetus. In this review we discuss the effects of several viral infections during pregnancy where the effects on the developing embryo and fetus are infrequent, but they may sometimes cause severe neonatal disease. The following viruses are discussed: coxsackie and echoviruses, measles and mumps, polioviruses, Japanese and Venezuelan equine encephalitis viruses, West Nile virus and hepatitis viruses A, B, C, D and E. Coxsackie B virus may cause an increase in early spontaneous abortions and rarely, fetal myocarditis; echoviruses do not seem to damage the fetus; measles and mumps may cause increased early and late fetal death and neonatal measles or mumps. The viruses affecting the nervous system may increase early and late spontaneous abortions and, rarely, cause severe damage to the fetal brain. Hepatitis B virus has a high rate of vertical transmission causing fetal and neonatal hepatitis. Hepatitis A, C and E are rarely transmitted trans-placentally; if transmitted, they may cause hepatitis. There is no evidence that immunization in pregnancy against these diseases (with attenuated viruses) may adversely affect pregnancy outcome.

Adult↗
PubMed2006

[Type 2 diabetes mellitus and cardiovascular diseases: evaluation, treatment and prevention strategies].

Patients with type 2 diabetes mellitus are at high risk for cardiovascular events and heart failure. The major serious complication of this disorder is large vessel atherosclerosis leading to myocardial infarction and stroke. Aggressive target setting for modifiable cardiovascular risk factors such as dyslipidemia, hypertension, and a procoagulant state, and judicious choice of efficacious therapies have been shown to produce significant reductions in cardiovascular events. The effectiveness of percutaneous coronary intervention (PCI) in diabetes is discussed, and the factors that may influence outcomes are explored. A major unresolved question is the potential role of tight glucose control for reducing macrovascular complications in patients with diabetes. With the increased attention being given to cardiovascular risk factor reduction, the opportunity exists to substantially decrease the largest causes of mortality in diabetic patients. This article reviews the current and emerging therapeutic strategies for these purposes from the cardiologists' point of view.

Cardiovascular Diseases↗
PubMed2005

Smoking and development of type 2 diabetes in patients with decreased functional capacity.

OBJECTIVE: Data regarding the possible contribution of cigarette smoking to development of type 2 diabetes are scarce and inconclusive. Patients with impaired functional capacity and diminished physical activity are prone to develop new diabetes. However, the role of smoking on diabetes incidence among these patients has not been specifically investigated. The present study was aimed to evaluate the association between cigarette smoking and development of type 2 diabetes in patients with coronary artery disease and decreased functional capacity over a 6.2-year follow-up period. METHODS: The study sample comprised 630 nondiabetic patients aged 45-74 years, with a fasting blood glucose of <126 mg/dl and with impaired functional capacity (New York Heart Association functional class II and III). The sample was classified into two groups: 1) non smokers (never and past smokers pooled together)--552 patients and 2) current smokers--78 patients. RESULTS: Smokers were younger but they had a relatively unfavorable lipid profile (with respect to apolipoproteins A, triglyceride and HDL-cholesterol levels). No significant differences between the groups were found for weight, body mass index, total cholesterol and blood pressure. During the follow-up, development of new diabetes was recorded in 98 patients: in 80 (14.5%) non smokers and in 18 (23.1%) smokers, p=0.05. Among the non smokers, there were no significant differences in diabetes incidence between 357 past smokers and 195 never smokers: respectively, 48 (13.4%) and 32 (16.4%), p=0.34. In addition, all-cause mortality among the smokers (23.1%) was significantly higher than in non smokers (12.7%), p=0.01. Multivariate analysis identified current smoking as an independent predictor of increased risk of new diabetes development with a hazard ratio of 1.94 (95% confidence interval 1.16-3.25). CONCLUSIONS: Current smoking was associated with an independent two-fold increased risk for development of type 2 diabetes in patients with impaired functional capacity.

Aged↗
PubMed2005

Dual and pan-peroxisome proliferator-activated receptors (PPAR) co-agonism: the bezafibrate lessons.

There are three peroxisome proliferator-activated receptors (PPARs) subtypes which are commonly designated PPAR alpha, PPAR gamma and PPAR beta/delta. PPAR alpha activation increases high density lipoprotein (HDL) cholesterol synthesis, stimulates "reverse" cholesterol transport and reduces triglycerides. PPAR gamma activation results in insulin sensitization and antidiabetic action. Until recently, the biological role of PPAR beta/delta remained unclear. However, treatment of obese animals by specific PPAR delta agonists results in normalization of metabolic parameters and reduction of adiposity. Combined treatments with PPAR gamma and alpha agonists may potentially improve insulin resistance and alleviate atherogenic dyslipidemia, whereas PPAR delta properties may prevent the development of overweight which typically accompanies "pure" PPAR gamma ligands. The new generation of dual-action PPARs--the glitazars, which target PPAR-gamma and PPAR-alpha (like muraglitazar and tesaglitazar) are on deck in late-stage clinical trials and may be effective in reducing cardiovascular risk, but their long-term clinical effects are still unknown. A number of glitazars have presented problems at a late stage of clinical trials because of serious side-effects (including ragaglitazar and farglitazar). The old and well known lipid-lowering fibric acid derivative bezafibrate is the first clinically tested pan--(alpha, beta/delta, gamma) PPAR activator. It is the only pan-PPAR activator with more than a quarter of a century of therapeutic experience with a good safety profile. Therefore, bezafibrate could be considered (indeed, as a "post hoc" understanding) as an "archetype" of a clinically tested pan-PPAR ligand. Bezafibrate leads to considerable raising of HDL cholesterol and reduces triglycerides, improves insulin sensitivity and reduces blood glucose level, significantly lowering the incidence of cardiovascular events and new diabetes in patients with features of metabolic syndrome. Clinical evidences obtained from bezafibrate-based studies strongly support the concept of pan-PPAR therapeutic approach to conditions which comprise the metabolic syndrome. However, from a biochemical point of view, bezafibrate is a PPAR ligand with a relatively low potency. More powerful new compounds with pan-PPAR activity and proven long-term safety should be highly effective in a clinical setting of patients with coexisting relevant lipid and glucose metabolism disorders.

Bezafibrate↗
PubMed2005

Usefulness of helical computed tomography in detection of mitral annular calcification as a marker of coronary artery disease.

BACKGROUND: Mitral annulus calcification (MAC) may be a form of atherosclerosis. The goal of the present work was to investigate whether helical CT can determine the presence of MAC and to clarify its possible association with coronary artery disease (CAD) in elderly patients. DESIGN AND METHODS: Three hundred and twenty-nine consecutive elderly patients (165 men and 164 women, age range 60-79 years) underwent double helical CT of the heart to determine MAC and coronary calcifications (CC) according to a previously described protocol. RESULTS: MAC was documented in 60 patients (25 men, 35 women; mean age 69 +/- 4.5 years, range 60-78 years). The non-MAC group (control) included 269 patients (140 men, 129 women; mean age 67 +/- 4.6 years, range 60-79 years). Age was the only risk factor which had significant association with MAC (p = 0.01). A significant difference was found between MAC and control group for mean total CC score and advanced CC (total CC > 300) (323 +/- 565 vs. 184 +/- 429, p = 0.033 and 30% vs. 16%, p = 0.017, respectively). A significant difference was also found between groups for the prevalent proven CAD (30% vs. 16%, p = 0.008). Stepwise logistic regression analysis identified age [odds ratio (OR) 3.3, 95% confidence interval (CI) 1.7-6.4, p < 0.001)], gender (male) (OR 3.1, 95% CI 1.6-6.0, p = 0.001), and MAC (OR 2.4, 95% CI 1.2-5.0, p = 0.016) as the independent variables significantly associated with CAD. The independent variables significantly associated with advanced CC (TCS > 300) were MAC (OR 2.6, 95% CI 1.3-5.2, p = 0.005), gender (male) (OR 2.3, 95% CI 1.2-4.2, p = 0.012) and age (OR 1.9, 95% CI 1.0-3.7, p = 0.052). CONCLUSIONS: Our study demonstrated the usefulness of helical computed tomography in the detection of mitral annular calcification as an additional marker of prevalent CAD. However, the diagnostic significance of the MAC detection is relatively minor and should not be considered as a direct proof for coronary atherosclerosis.

Aged↗
PubMed2005

Statins research unfinished saga: desirability versus feasibility.

Drugs in the same class are generally thought to be therapeutically equivalent because of similar mechanisms of action (the so-called "class effect"). However, statins differ in multiple characteristics, including liver and renal metabolism, half-life, effects on several serum lipid components, bioavailability and potency. Some are fungal derivatives, and others are synthetic compounds. The percentage absorption of an oral dose, amount of protein binding, degree of renal excretion, hydrophilicity, and potency on a weight basis is variable. These differences may be even greater in diabetic patients, who may present diabetes-induced abnormalities in P450 isoforms and altered hepatic metabolic pathways. Thus, it is obvious that head-to-head comparisons between different statins are preferable than trial-to-trial comparisons. Such assessments are of utmost importance, especially in cases in which specific populations with a distinct lipid profile and altered metabolic pathways, like diabetics, are studied. It should be specially pinpointed that patients with metabolic syndrome and diabetes constitute also a special population regarding their atherogenic dyslipidemia, which is usually associated with low HDL-cholesterol, hypertriglyceridemia and predominance of small dense LDL-cholesterol. Therefore, these patients may benefit from fibrates or combined statin/fibrate treatment. This policy is not accomplished since in the real world things are more complex. Trials would require very large sample sizes and long-term follow-up to detect significant differences in myocardial infarction or death between two different statins. Moreover, the fact that new compounds are under several phases of research and development represents an additional drawback for performing the trials. Ideally, head-to-head trials regarding clinically important outcomes should be conducted for all drugs. Nonetheless, the desirability of performing such trials, which epitomize modern evidence-based medicine, is frequently superseded by the feasibility dictated by pragmatic and economic circumstances. In the latter case, in absence of solid systematic documentation of comparable health benefits and long-term safety, both researchers and practicing physicians should allude to the weight of scientific endorsement behind the arguments and seek for the possible strengths and weaknesses intrinsic to each specific study. In any case, conclusions based on surrogate endpoints cannot completely substitute head-to-head comparisons regarding patients' outcome.

Clinical Trials as Topic↗
PubMed2005

Bezafibrate for the secondary prevention of myocardial infarction in patients with metabolic syndrome.

BACKGROUND: A consistent relationship between metabolic syndrome (MS) and myocardial infarction (MI) has been demonstrated. We evaluated the effect of bezafibrate retard, a fibric acid derivative, on the incidence of MI in patients with MS enrolled in the Bezafibrate Infarction Prevention (BIP) study. METHODS: Patients who displayed at least 3 of the following 5 risk factors were considered to have MS: (1) a fasting glucose level of 110 mg/dL (6.11 mmol/L); (2) a triglyceride level of 150 mg/dL (1.70 mmol/L); (3) a high-density lipoprotein cholesterol level less than 40 mg/dL (<1.04 mmol/L) in men or less than 50 mg/dL (<1.30 mmol/L) in women; (4) a systolic blood pressure of 130 mm Hg or diastolic blood pressure of 85 mm Hg; and (5) a body mass index of 28.0 kg/m(2). The study sample for this post hoc subgroup analyses comprised 1470 patients aged 42 to 74 years. The patients received either 400 mg of bezafibrate retard (740 patients) or placebo (730 patients) once a day. The mean follow-up period was 6.2 years for events and 8.1 years for mortality data. RESULTS: New MI was recorded in 193 patients: 82 (11.1%) of the 740 patients in the bezafibrate group vs 111 (15.2%) of the 730 patients in the placebo group (P = .02). Bezafibrate was associated with a reduced risk of any MI and nonfatal MI with hazard ratios (HRs) of 0.71 (95% confidence interval [CI], 0.54-0.95) and 0.67 (95% CI, 0.49-0.91), 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.

Adult↗
PubMed2005

Effect of bezafibrate on incidence of type 2 diabetes mellitus in obese patients.

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 > or = 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.

Adult↗