Bezafibrate Infarction Prevention Research Articles

Triglycerides and coronary heart disease: implications of recent clinical trials.

This paper reviews the clinical trial data that offer insight into the question of whether, and in what groups of people, triglycerides might be an appropriate therapeutic target for the primary or secondary prevention of atherosclerotic cardiovascular disease. Two angiographic trials (the Lopid Coronary Angiography Trial and the Bezafibrate Coronary Atherosclerosis Intervention Trial) and three clinical endpoint trials (the Helsinki Heart Study, the Bezafibrate Infarction Prevention Study, and the VA HDL Intervention Trial) are reviewed. Hypertriglyceridemia per se is probably not an appropriate therapeutic target for the prevention of atherosclerotic cardiovascular disease because it is a poor marker of atherogenic risk and because there have been no clinical trials that have directly addressed the question of whether lowering the triglyceride level reduces the number of clinical events. The studies reviewed here, however, suggest that patients with established coronary heart disease and a high triglyceride level, in association with either a low high-density lipoprotein-cholesterol level or perhaps other features of the metabolic syndrome, such as obesity, diabetes, or hypertension, may benefit from fibrate therapy. For patients without established coronary heart disease, it is reasonable to consider hypertriglyceridemia as a risk marker prompting the aggressive treatment of other risk factors such as hypertension, diabetes, high low-density lipoprotein-cholesterol, and obesity.

Treatment of Dyslipidaemias in Patients with Established Vascular Disease: A Revival of the Fibrates

SummaryThe key ‘statin trials’ focussed on the beneficial effect of lowering the circulating concentrations of low-density lipoprotein cholesterol (LDL). However, epidemiological surveys, mainly based on healthy populations, indicate that other lipid-related variables, such as high-density cholesterol (HDL), triglycerides (TG), dense LDL subfraction distribution, and possibly lipoprotein (a) (Lp(a)), are also predictors of vascular events. Furthermore, TG and HDL levels influenced outcome within some of the statin trials. Plasma fibrinogen levels have also been shown to be powerful predictors of vascular risk in healthy subjects and patients with established ischaemic heart disease. The fibrates exert beneficial effects on all these variables that predict vascular events.The results from recent trials, the Bezafibrate Infarction Prevention (BIP) study and the Veterans Administration HDL Intervention Trial (VA-HIT) have revived our interest in fibrates. These trials involved bezafibrate and gemfibrozil that have a relatively poor LDL-lowering capacity. Therefore, the benefits reported in BIP and VA-HIT must be attributed to actions on variables other than a reduction in LDL quantity.Ciprofibrate and fenofibrate have significantly greater LDL-lowering capacity than bezafibrate or gemfibrozil. This advantage may render them more effective, especially since they retain the additional beneficial actions associated with this class of lipidlowering drugs.

Clinical Characteristics of Coronary Heart Disease as Predictors of Ischemic Stroke: A Long-term Prospective Follow-up in the BIP Study.

P126 Objective: To assess characteristics and severity of coronary heart disease (CHD) predisposing to ischemic stroke, beyond conventional vascular risk factors. Methods: We prospectively followed up 3,122 patients with documented CHD included in a secondary prevention trial of lipid modification, the Bezafibrate Infarction Prevention trial. Patients had CHD documented by a history of myocardial infarction ≥6 months and Results: During a mean follow-up period of 8.2 years, 186 patients developed an ischemic stroke. The rate of ischemic stroke was 8.8% among patients with an active anginal syndrome[class ≥2 according to the Canadian Cardiovascular Society angina Classification, (CCSC)]vs. 5.1% in patients with a CCSC class of 1 (p Conclusion: Active angina (CCSC class ≥2)and hospitalization for unstable angina during follow-up among CHD patients,confer an independent increased risk of ischemic stroke, beyond conventional vascular risk factors.

High-density lipoprotein and coronary heart disease: lessons from recent intervention trials.

Epidemiologic studies have consistently implicated low plasma high-density lipoprotein cholesterol as an important, independent risk factor for the development of coronary heart disease. However, clinical trials specifically designed to evaluate the role of lipid therapy in patients with low high-density lipoprotein cholesterol have only been recently reported. They include two trials with angiographic end points, the Lopid Coronary Angiography Trial and the Bezafibrate Coronary Atherosclerosis Intervention Trial, and three clinical end points trials, the Air Force/Texas Coronary Atherosclerosis Prevention study, the Department of Veterans Affairs High-Density Lipoprotein Intervention Trial, and the Bezafibrate Infarction Prevention study. These and other trials clearly indicate that persons with coronary heart disease and high low-density lipoprotein cholesterol (>130 mg/dL [3.36 mmol/L]), with or without low high-density lipoprotein cholesterol, benefit from statin therapy. The Air Force/Texas Coronary Atherosclerosis Prevention study showed that persons at high risk of coronary heart disease but without known disease, who have moderate levels of low-density lipoprotein cholesterol as well as low levels of high-density lipoprotein cholesterol, also appear to benefit from statin therapy although the cost effectiveness of this approach is unclear. The results from the Department of Veterans Affairs High Density Lipoprotein Intervention Trial provide convincing evidence that patients without high low-density lipoprotein cholesterol and with established coronary heart disease and low high-density lipoprotein cholesterol benefit from gemfibrozil. This drug may be particularly beneficial for patients who, in addition to low high-density lipoprotein cholesterol, present with other features of the metabolic syndrome, such as obesity, glucose intolerance, and high triglycerides. Whether other fibrates, niacin, or statins lower coronary heart disease risk in persons with low high-density lipoprotein cholesterol in the absence of high or moderately high low-density lipoprotein cholesterol is unknown. (c)2000 by CHF, Inc.

Fibrates, dyslipoproteinaemia and cardiovascular disease.

Recent epidemiological data have reaffirmed that elevated plasma triglyceride and low HDL-cholesterol levels are important risk factors for atherosclerotic vascular disease. The rationale for the clinical use of fibric acid derivatives, which are designed to correct this metabolic nexus, is now on firmer ground. The mechanism of action of fibrates on lipoprotein metabolism has recently been elucidated at the molecular level and involves the activation of peroxisome proliferator-activated receptor-alpha 1 in the liver, with the net effect of improving the plasma transport rates of several lipoproteins. Other potential anti-atherothrombotic effects include the inhibition of coagulation and enhancement of fibrinolysis, as well as the inhibition of inflammatory mediators involved in atherogenesis. These consequences probably underpin the favourable effects of fibrates seen in recent angiographic and clinical trials. Two important clinical trials on the effect of gemfibrozil (Veterans Administration-HDL-Cholesterol Intervention Trial) and bezafibrate (Bezafibrate Infarction Prevention Study) have recently been completed in subjects with elevated triglyceride, low HDL and normal or near-normal LDL-cholesterol levels. The results testify to the efficacy of these agents in decreasing the incidence of cardiovascular events, particularly in patients with multiple risk factors and plasma triglyceride levels of over 2.2 mmol/l. The findings of these trials are compared with the statin-based Air Force/Texas Coronary Atherosclerosis Prevention Study, with a recommendation that future studies in appropriately selected patients should examine the synergistic effect of the fibrate/statin combination. The absolute risk reduction in the incidence of coronary events in the Veterans Administration-HDL-Cholesterol Intervention Trial compares favourably with the statin trials. The therapeutic aspects of the efficacy and safety of fibrates are reviewed. Besides primary mixed hyperlipidaemias, particular indications for the clinical use of fibrates include type 2 diabetes, the metabolic syndrome and renal insufficiency. The St Mary's, Ealing, Northwick Park Diabetes Cardiovascular Disease Prevention Study has suggested that fibrates may decrease the incidence of coronary events in type 2 diabetes, but this hypothesis will be more extensively tested in the Diabetes Atherosclerosis Intervention Study, Fenofibrate in Event Lowering in Diabetes Study and Lipids in Diabetes Study projects. Although significant new knowledge has accrued over the past few years concerning the fundamental and clinical aspects of fibrates, the success of these agents in clinical practice depends on the availability of methods for assessing cardiovascular risk as well as on treatment guidelines, which as presently designed and recommended may be inaccurate and suboptimal.

Antihyperglycemic Treatment in Diabetics with Coronary Disease: Increased Metformin-Associated Mortality over a 5-Year Follow-Up

Mortality rates are considerably higher in chronic ischemic heart disease (IHD) patients with non-insulin-dependent diabetes mellitus (NIDDM) than in those who are nondiabetics. The relationship between different types of antihyperglycemic pharmacological therapy and mortality rate in this NIDDM population is uncertain. We aimed to examine the survival in NIDDM patients with IHD using various types of oral antidiabetic treatments over a 5-year follow-up period. The study sample comprised 11,440 patients with a previous myocardial infarction and/or stable anginal syndrome, aged 45–74 years, who were screened, but not included in the Bezafibrate Infarction Prevention study. Among them, 9,045 were nondiabetics and 2,395 diabetics. The diabetic patients were divided into four groups on the basis of their therapeutic regimen at screening: diet alone (n = 990), sulfonylureas (n = 1,041), metformin (n = 78) and a combination of a sulfonylurea and metformin (n = 266). All NIDDM groups were similar with regard to age, gender, hypertension, smoking, heart failure, angina and prior myocardial infarction. Crude mortality rate was lower in the nondiabetic group (11.21 vs. 21.8%; p < 0.001). In the diabetic group, mortality was 18.5% for patients on diet alone, 22.5% for those on sulfonylureas, 25.6% for patients on metformin, and 31.6% for the combined sulfonylurea/metformin group (p < 0.01). When analyzing age-adjusted mortality rate and actuarial survival curves, the lowest mortality was found in patients on diet alone and the highest in patients on metformin (alone or in combination with sulfonylureas). After adjustment for variables connected with long-term prognosis, the use of metformin was associated with increased relative risk (RR) for all-cause mortality of 1.42 (95% CI 1.10–1.85), whereas the use of sulfonylureas alone was not [RR 1.11 (95% CI 0.90–1.36)]. NIDDM patients with IHD using metformin, alone or in combination with sulfonylureas, exhibited a significantly increased mortality. Until the results of problem-oriented prospective studies on oral control of NIDDM will be available, alternative therapeutic approaches should be investigated in these patients.

Elevated Serum Triglyceride Levels and Long-Term Mortality in Patients With Coronary Heart Disease

The association between elevated blood triglyceride levels and subsequent mortality risk in patients with established coronary heart disease (CHD) has been investigated rarely. The aim of the present study was to investigate this association. We evaluated mortality over a mean follow-up time of 5. 1 years among 9033 male and 2499 female CHD patients who were screened for participation in the Bezafibrate Infarction Prevention (BIP) Study. A stepwise increase in mortality with increasing serum triglyceride levels was observed in patients with desirable or elevated serum total cholesterol levels and in patients with either desirable or abnormally low HDL cholesterol levels. Multivariate adjustment for factors other than HDL cholesterol yielded a slightly increased adjusted mortality risk with a 1-natural-log-unit elevation of triglyceride levels in men (hazard ratio [HR] 1.14, 95% CI 1.00 to 1.30) and women (HR 1.37, 95% CI 1.04 to 1.88). Excess covariate-adjusted risk was noted among patients with elevated total and LDL cholesterol and in women with HDL cholesterol levels >45 mg/dL. After additional adjustment for HDL cholesterol, the risk of mortality with a 1-natural-log-unit elevation of triglycerides declined in men (HR 1.09, 95% CI 0.94 to 1.26) and in women (HR 1.10, 95% CI 0.80 to 1.50). A trend for increased mortality risk remained in patients with elevated total and LDL cholesterol and in women with HDL cholesterol >45 mg/dL. Elevated triglyceride levels were associated with a small, independent increased mortality risk in CHD patients. This risk may be increased among subgroups of patients with elevated total cholesterol and LDL cholesterol levels.

Prevalence and prognostic significance of unrecognized systemic hypertension in patients with diabetes mellitus and healed myocardial infarction and/or stable angina pectoris

Few data are available regarding the prevalence and prognostic significance of the triple coexistence of undiagnosed systemic hypertension, diabetes mellitus, and coronary heart disease. This study aimed to evaluate the prevalence and prognostic significance of unrecognized hypertension in cardiac diabetic patients previously defined as “normotensives” over a 5-year follow-up period. The study sample comprised 11,515 patients aged 45 to 74 years with a previous myocardial infarction and/or anginal syndrome who were screened but not included in the Bezafibrate Infarction Prevention study. Among them, 9,033 were nondiabetics and 2,482, diabetics. The diabetics were divided into 3 groups: (1) 1,272 normotensives, (2) 152 patients without history of hypertension but with elevated blood pressure (“unrecognized hypertensives”), and (3) 1,058 hypertensives with established diagnosis. The prevalence of both diagnosed and unrecognized hypertension in diabetics pooled together increased from 49% to 69% when World Health Organization and new Joint National Committee-VI criteria were compared. Crude all-cause mortality was lower in nondiabetics than in diabetics (11.2% vs 22.0%; p <0.001). Among diabetics the lowest all-cause mortality was documented for normotensives (19.3%), whereas the highest mortality was observed in unrecognized hypertensives (26.3%, p = 0.003). Both unrecognized and established hypertensives demonstrated a significant stroke-related mortality excess: about four- and threefold increases in cerebrovascular accident–related death, respectively, were observed (p = 0.002). On multivariate analysis, both unrecognized and diagnosed hypertension were consistent predictors of increased all-cause mortality, with a hazard ratio of 1.28 (95% confidence interval 0.90 to 1.82) and 1.24 (95% confidence interval 1.03 to 1.49), respectively. Our findings demonstrate widespread undiagnosed hypertension in diabetic coronary patients; their 5-year mortality was significantly increased compared with normotensives, and tended to be even higher than in diabetics previously identified as hypertensives.

Recent developments in the treatment of hypertriglyceridemia.

Hypertriglyceridemia is now recognized as an independent risk factor of coronary artery disease (CAD). A recent secondary prevention study of CAD with a statin suggested that it may be prudent to target fasting triglycerides to less than 150 mg/dL. Secondary prevention trials of CAD with drugs acting primarily on triglycerides (fibrates) have shown that reducing triglycerides and increasing high-density lipoprotein (HDL) cholesterol, without significantly affecting low-density lipoprotein cholesterol slows down coronary artery luminal narrowing (Lopid Coronary Angiography Trial [LOCAT], Bezafibrate Coronary Atherosclerosis Intervention Trial [BECAIT], Bezafibrate Infarction Prevention [BIP]). Furthermore, Veterans Administration-HDL Intervention Trial (VA-HIT) and Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto-1 (GISSI) studies recently showed that gemfibrozil and fish oils, respectively, decreased CAD mortality in secondary prevention trials. Statins are also capable of significantly reducing high triglyceride levels. Further clinical studies are necessary to confirm in terms of mortality the beneficial effect of reducing triglycerides and increasing high-density lipoprotein cholesterol in secondary CAD prevention; whereas, in primary prevention the beneficial effect of drastically reducing triglycerides by the way of pharmacology needs to be proved.

Aspirin and mortality in patients treated with angiotensin-converting enzyme inhibitors: A cohort study of 11,575 patients with coronary artery disease

OBJECTIVESThe purpose of this study was to investigate the significance of the possible negative interaction between aspirin and angiotensin-converting enzyme (ACE) inhibitors.BACKGROUNDSeveral provocative reports have recently suggested that aspirin is unsafe in patients with heart failure and has negative interaction with ACE inhibitors that might attenuate their beneficial effects upon survival.METHODSWe analyzed mortality data of 11,575 patients with coronary artery disease screened for the Bezafibrate Infarction Prevention trial. A total of 1,247 patients (11%) were treated with ACE inhibitors. Of them, 618 patients (50%) used aspirin.RESULTSFive-year mortality was lower among patients on ACE inhibitors and aspirin than patients on ACE inhibitors without aspirin (19% vs. 27%; p < 0.001). After adjusting for confounders, treatment with aspirin and ACE inhibitors remained associated with lower mortality risk than using ACE inhibitors only (relative risk [RR] = 0.71; 95% confidence interval [CI] = 0.56 to 0.91). Subgroup analysis of 464 patients with congestive heart failure treated with ACE inhibitors revealed 221 patients (48%) on aspirin and 243 patients not on aspirin. Although clinical characteristics and therapy were similar, patients taking aspirin experienced lower mortality than patients who did not (24% vs. 34%; p = 0.001). After adjustment, treatment with aspirin was still associated with lower mortality (RR = 0.70; 95% CI = 0.49 to 0.99).CONCLUSIONSAmong coronary artery disease patients with and without heart failure who are treated with ACE inhibitors, the use of aspirin was associated with lower mortality than treatment without aspirin. Our findings contradict the claim that aspirin attenuates the beneficial effect of ACE inhibitors and supports its use in patients with coronary artery disease treated with ACE inhibitors.

The bezafibrate infarction prevention study (BIP): Seasonal variations in plasma lipids during 6.5 years in 3123 CHD patients in Israel

The bezafibrate infarction prevention study (BIP): Seasonal variations in plasma lipids during 6.5 years in 3123 CHD patients in Israel

Hypertension in diet versus pharmacologically treated diabetics: mortality over a 5-year follow-up.

The natural history of non-insulin-dependent diabetes mellitus (NIDDM) differs markedly between patients with diet treated and pharmacologically treated disease. However, the interrelationship between hypertension and these common diabetes types has not been specifically addressed in previous studies. This study was designed to evaluate the prognostic significance and prevalence of hypertension in coronary patients with diet versus pharmacologically treated NIDDM over a 5-year follow-up period. The study sample comprised 11 515 patients aged 45 to 74 years with a previous myocardial infarction and/or anginal syndrome who had been screened but were not included in the Bezafibrate Infarction Prevention study. Among them, 9033 were nondiabetics and 2482, diabetics (987 diet treated and 1495 pharmacologically treated). The prevalence of hypertension among nondiabetics, diet-treated diabetics, and pharmacologically treated diabetics was 31%, 42%, and 43%, respectively. Crude all-cause mortality (CM) was lower in the nondiabetic patients (11.2% versus 22.0%; P<0.001). Among diabetics, 548 patients died: 81 diet treated normotensives (CM 14%); 100 diet-treated hypertensives (CM 24.4%); 205 pharmacologically treated normotensives (CM 24.2%); and 162 pharmacologically treated hypertensive patients (CM 25.0%). Age-adjusted mortality was lowest for the normotensive patients in the diet-treated group and highest for the hypertensive pharmacologically treated patients. Multivariate analysis shows that hypertension is a strong and independent predictor of increased CM in diet-treated but not in pharmacologically treated NIDDM: hazard ratio (HR) was 1.68 (95% confidence interval [CI] 1.24 to 2.29) for the diet-treated versus 1. 01 (95% CI 0.82 to 1.26) for the pharmacologically treated diabetics. The contribution of hypertension to stroke mortality was substantial for both diet treated and pharmacologically treated NIDDM: hazard ratios were 3.17 (95% CI 1.12 to 8.98) and 2.21 (95% CI 0.72 to 6.77), respectively. The increased risk of mortality associated with hypertension in relatively mild diet-treated NIDDM strongly supports the clinical benefit of early blood pressure control among diabetic patients with ischemic heart disease.

Effects of aspirin treatment on survival in non-insulin-dependent diabetic patients with coronary artery disease

PURPOSE: The benefit of aspirin treatment among diabetic patients with chronic coronary artery disease is not well established. The purpose of this study was to assess the effect of aspirin on cardiac and total mortality in a large cohort of diabetic patients with established coronary artery disease and to compare it with the effect of aspirin in nondiabetic counterparts. PATIENTS AND METHODS: In this observational study among patients screened for participation in the Bezafibrate Infarction Prevention Study, the effects of aspirin treatment in 2,368 non-insulin-dependent diabetic patients with coronary artery disease were compared to those in 8,586 nondiabetic patients. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated with proportional hazards models. RESULTS: Fifty-two percent of diabetic patients and 56% of nondiabetic patients reported aspirin therapy. After 5.1 ± 1.3 (mean ± SD) years of follow-up, the absolute benefit per 100 patients treated with aspirin was greater in diabetic patients than in nondiabetic patients (cardiac mortality benefit: 5.0 versus 2.1, and all-cause mortality benefit: 7.8 versus 4.1). Overall cardiac mortality among diabetic patients treated with aspirin was 10.9% versus 15.9% in the nonaspirin group ( P <0.001), and all-cause mortality was 18.4% and 26.2% ( P <0.001). After adjustment for possible confounders, treatment with aspirin was an independent predictor of reduced overall cardiac (HR = 0.8; 95% CI: 0.6–1.0) and all-cause mortality (HR = 0.8; 95% CI: 0.7–0.9) among diabetic patients, similar to those in nondiabetic patients. CONCLUSION: Treatment with aspirin was associated with a significant reduction in cardiac and total mortality among non-insulin-dependent diabetic patients with coronary artery disease. The absolute benefit of aspirin was greater in diabetic patients than in those without diabetes.

Sun education in Africa: Nigeria and West African subregion

The benefit of β-blocker therapy in patients after myocardial infarction is well established. The use of β blockers in the high-risk subgroup of patients with combined diabetes mellitus (DM) and coronary artery disease (CAD) remains controversial. From a database of 14,417 patients with chronic CAD who had been screened for participation in the Bezafibrate Infarction Prevention (BIP) study, 2,723 (19%) had non-insulin-dependent DM. Baseline characteristics and 3-year mortality were analyzed in patients with DM receiving (n = 911; 33%) and not receiving (n = 1,812; 67%) β blockers. Total mortality during a 3-year follow-up was 7.8% in those receiving β blockers compared with 14.0% in those who were not (a 44% reduction). A reduction in cardiac mortality of 42% between the 2 groups was also noted. Three-year survival curves showed significant differences in mortality with increasing divergence (p = 0.0001). After multiple adjustment, multivariate analysis identified β-blocker therapy as a significant independent contributor to improved survival (relative risk = 0.58; 90% confidence interval 0.46 to 0.74). Within the diabetic population, the main benefit associated with β-blocker therapy was observed in older patients, in those with a history of myocardial infarction, those with limited functional capacity, and those at lower risk. Thus, therapy with β blockers appears to be associated with improved long-term survival in the high-risk subpopulation of patients with DM and CAD.

Effect of Beta-Blocker Therapy in Patients With Coronary Artery Disease in New York Heart Association Classes II and III

The aim of the study was to investigate the effect of β-blocker treatment on a large cohort of patients with coronary artery disease in functional classes II and III according to the New York Heart Association (NYHA) classification. Among 11,575 patients with coronary artery disease screened for participation, but not included in the Bezafibrate Infarction Prevention (BIP) study, 3,225 (28%) were in NYHA classes II and III. In the latter group of patients we compared the prognosis of 1,109 (34%) treated with β blockers with 2,116 counterparts not receiving β-blocker therapy. After a mean follow-up of 4 years, all-cause and cardiac mortality rates were significantly lower among β-blocker users, 9% and 5%, respectively, than among β-blocker nonusers, 17% and 11%, respectively (p <0.01 for both). After multivariate adjustment, treatment with β blockers was associated with a lower all-cause mortality risk (hazards ratio [HR] 0.62, 95% confidence interval [CI] 0.49 to 0.78), and a lower cardiac mortality risk (HR = 0.61, 95% CI 0.45 to 0.83) than was no treatment with a β blocker. Lower total mortality risk was noted among patients in NYHA class II (HR 0.63, 95% CI 0.48 to 0.82) and in NYHA class III (HR 0.57, 95% CI 0.37 to 0.87) as well as in patients with (HR 0.62, 95% CI 0.48 to 0.81) or without (HR 0.70, 95% CI 0.45 to 1.09) a previous myocardial infarction. We conclude that β-blocker therapy in coronary patients in NYHA classes II or III is safe and associated with a lower risk for all-cause and cardiac mortality.

Calcium Channel Blocking Agents and Risk of Cancer in Patients With Coronary Heart Disease

Objectives. This analysis sought to estimate the risk ratio for cancer incidence and cancer-related mortality associated with the use of calcium channel blocking agents (CCBs) in a large group of patients with chronic coronary heart disease (CHD).Background. Recent publications contend that the use of short-acting CCBs may double the risk of cancer incidence and possibly increase mortality in hypertensive patients.Methods. Cancer incidence data were obtained for 11,575 patients screened for the Bezafibrate Infarction Prevention (BIP) study, one-half of whom were treated at the time of screening with CCBs, over a mean follow-up period of 2.8 years. Cause-specific mortality was available through September 1996 (mean follow-up 5.2 years). The statistical power of detecting an odds ratio ≥1.5 (given the cancer incidence rate of 2.1 in the nonusers of CCBs) was 0.91. The power declined to 0.77, 0.54 and 0.41, with declining odds ratios of 1.4, 1.3 and 1.25, respectively.Results. Of 246 incident cancer cases, 129 occurred among the users (2.3%) and 117 among nonusers of CCBs (2.1%). After adjustment for age, gender and smoking, the odds ratio estimates for all cancers combined was 1.07 (95% confidence interval [CI] 0.83 to 1.37) for CCB users relative to nonusers. The adjusted risk ratio for all-cause mortality for age, gender and smoking and pertinent prognostic clinical characteristics was estimated at 0.94 (95% CI 0.85 to 1.04). The adjusted risk ratio for cancer-related mortality was 1.03 (95% CI 0.75 to 1.41).Conclusions. Patients with CHD treated with CCBs exhibited a similar risk of cancer incidence and total and cancer-related mortality compared with nonusers of CCBs. This analysis provides a certain assurance that CCB use in middle-aged and elderly patients with CHD is not associated with a meaningful difference in cancer incidence and related mortality.

Effect of aspirin on mortality in women with symptomatic or silent myocardial ischemia

The benefit of aspirin therapy among women with coronary artery disease (CAD) is not well established. Previous studies have shown conflicting results among women. Data from 2,418 women with CAD screened for participation in the ongoing Bezafibrate Infarction Prevention (BIP) study were analyzed: 45% reported aspirin therapy. Baseline characteristics were similar in both groups. Cardiovascular mortality at 3.1 ± 0.9 years of follow-up was 2.7% in the aspirin treated group versus 5.1% in the non-aspirin-treated women (p = 0.002). All cause mortality was 5.1% and 9.1%, respectively (p = 0.0001). Treatment with aspirin emerged as an independent predictor of reduced cardiovascular (RR = 0.61, 95% confidence interval [CI] 0.38 to 0.97) and all cause (RR = 0.66, 95% CI 0.47 to 0.93) mortality after multiple adjustment for possible confounders such as age, history of myocardial infarction, systemic hypertension, diabetes mellitus, peripheral vascular disease, current smoking, New York Heart Association classification, and concomitant treatment with digitalis. Women who benefited the most from aspirin therapy were older, diabetic, symptomatic, or had a previous myocardial infarction. Thus, treatment with aspirin was associated with reduced mortality among women with CAD. This study suggests that women with CAD should be treated with aspirin, unless specific contraindications exist.

Bezafibrate. An update of its pharmacology and use in the management of dyslipidaemia.

The lipid-modifying profile of bezafibrate is characterised by marked decreases in elevated triglyceride levels, increases in high density lipoprotein (HDL) cholesterol levels and decreases in total and low density lipoprotein (LDL) cholesterol levels. Bezafibrate also reduces elevated levels of lipoprotein(a) [Lp(a)] and fibrinogen, which are independent cardiovascular risk factors. Bezafibrate is effective in most types of primary and secondary dyslipidaemia. It is of greatest benefit in conditions featuring hypertriglyceridaemia and/or HDL cholesterol deficiency. This is particularly true for patients with diabetes mellitus, notably those with non-insulin-dependent diabetes mellitus (NIDDM) who are also likely to have increased fibrinogen levels. In the limited comparisons available, there appear to be few consistent differences in lipid-modifying effects between bezafibrate and other fibrates. Compared with HMG-CoA reductase inhibitors, bezafibrate causes larger changes in triglyceride and, in general, HDL cholesterol levels, and has a lesser influence on LDL and total cholesterol levels. These differences are advantageous when bezafibrate and HMG-CoA reductase inhibitors are used as combined therapy in patients with severe dyslipidaemia unresponsive to either modality alone. The combination of bezafibrate plus an HMG-CoA reductase inhibitor in clinical trials has not led to the predicted increase in myalgia. Indeed, bezafibrate is generally free of serious unwanted effects: rhabdomyolysis is rare and has occurred mainly in patients with renal dysfunction given excessive dosages. Other patient groups in whom bezafibrate has improved serum lipid profiles are those with isolated HDL cholesterol deficiency, dyslipidaemia secondary to renal insufficiency, and following cardiac surgery or other procedures. However, data for these indications are not extensive. Evidence is now available to show a beneficial effect of bezafibrate on retarding atherosclerotic processes and in reducing risk of coronary heart disease. The 5-year Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) in young male survivors of myocardial infarction demonstrated a smaller decrease in luminal diameter and a reduction in coronary events with bezafibrate compared with placebo. The Bezafibrate Infarction Prevention (BIP) study is expected to provide mortality data which is currently lacking for bezafibrate. In conclusion, bezafibrate is a useful and well-tolerated lipid-modifying agent in the management of primary and secondary dyslipidaemia. It has particularly beneficial effects in patients with hypertriglyceridaemia and/or low HDL cholesterol levels, and reduces fibrinogen levels. Together with its ability to sustain or improve glycaemic control, these properties make it a logical choice for treating patients with diabetes mellitus and dyslipidaemia. Additionally, the drug may be of value as combination therapy in patients with severe dyslipidaemia. Importantly, there is evidence that the drug can slow the atherosclerotic process and reduce cardiovascular morbidity. The ongoing BIP secondary intervention study and other investigations will help clarify the effects of bezafibrate on cardiovascular mortality and morbidity.

Calcium antagonists and mortality in patients with coronary artery disease: A Cohort study of 11,575 patients

Objectives. This study sought to establish the risk ratio for mortality associated with calcium antagonists in a large population of patients with chronic coronary artery disease.Background. Recent reports have suggested that the use of short-acting nifedipine may cause an increase in overall mortality in patients with coronary artery disease and that a similar effect may be produced by other calcium antagonists, in particular those of the dihydropyridine type.Methods. Mortality data were obtained for 11,575 patients screened for the Bezafibrate Infarction Prevention study (5,843 with and 5,732 without calcium antagonists) after a mean follow-up period of 3.2 years.Results. There were 495 deaths (8.5%) in the calcium antagonist group compared with 410 in the control group (7.2%). The age-adjusted risk ratio for mortality was 1.08 (95% confidence interval [CI] 0.95 to 1.24). After adjustment for the differences between the groups in age and gender and the prevalence of previous myocardial infarction, angina pectoris, hypertension, New York Heart Association functional class, peripheral vascular disease, chronic obstructive pulmonary disease, diabetes and current smoking, the adjusted risk ratio declined to 0.97 (95% CI 0.84 to 1.11). After further adjustment for concomintant medication, the risk ratio was estimated at 0.94 (95% CI 0.82 to 1.08).Conclusions. The current analysis does not support the claim that calcium antagonist therapy in patients with chronic coronary artery disease, whether myocardial infarction survivors or others, harbors an increased risk of mortality.

Usefulness of beta-blocker therapy in patients with non-insulin-dependent diabetes mellitus and coronary artery disease

The benefit of β-blocker therapy in patients after myocardial infarction is well established. The use of β blockers in the high-risk subgroup of patients with combined diabetes mellitus (DM) and coronary artery disease (CAD) remains controversial. From a database of 14,417 patients with chronic CAD who had been screened for participation in the Bezafibrate Infarction Prevention (BIP) study, 2,723 (19%) had non-insulin-dependent DM. Baseline characteristics and 3-year mortality were analyzed in patients with DM receiving (n = 911; 33%) and not receiving (n = 1,812; 67%) β blockers. Total mortality during a 3-year follow-up was 7.8% in those receiving β blockers compared with 14.0% in those who were not (a 44% reduction). A reduction in cardiac mortality of 42% between the 2 groups was also noted. Three-year survival curves showed significant differences in mortality with increasing divergence (p = 0.0001). After multiple adjustment, multivariate analysis identified β-blocker therapy as a significant independent contributor to improved survival (relative risk = 0.58; 90% confidence interval 0.46 to 0.74). Within the diabetic population, the main benefit associated with β-blocker therapy was observed in older patients, in those with a history of myocardial infarction, those with limited functional capacity, and those at lower risk. Thus, therapy with β blockers appears to be associated with improved long-term survival in the high-risk subpopulation of patients with DM and CAD.