ß-Blocker Use and Risk of Mortality in Heart Failure Patients Initiating Maintenance Dialysis.

RATIONAL & OBJECTIVE: Beta-blockers are recommended for patients with heart failure (HF) but their benefit in the dialysis population is uncertain. Beta-blockers are heterogeneous, including with respect to their removal by hemodialysis. We sought to evaluate whether ß-blocker use and their dialyzability characteristics were associated with early mortality among patients with chronic kidney disease with HF who transitioned to dialysis. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults patients with chronic kidney disease (aged≥18 years) and HF who initiated either hemodialysis or peritoneal dialysis during January 1, 2007, to June 30, 2016, within an integrated health system were included. EXPOSURES: Patients were considered treated with ß-blockers if they had a quantity of drug dispensed covering the dialysis transition date. OUTCOMES: All-cause mortality within 6 months and 1 year or hospitalization within 6 months after transition to maintenance dialysis. ANALYTICAL APPROACH: Inverse probability of treatment weights using propensity scores was used to balance covariates between treatment groups. Cox proportional hazard analysis and logistic regression were used to investigate the association between ß-blocker use and study outcomes. RESULTS: 3,503 patients were included in the study. There were 2,115 (60.4%) patients using ß-blockers at transition. Compared with nonusers, the HR for all-cause mortality within 6 months was 0.79 (95% CI, 0.65-0.94) among users of any ß-blocker and 0.68 (95% CI, 0.53-0.88) among users of metoprolol at transition. There were no observed differences in all-cause or cardiovascular-related hospitalization. LIMITATIONS: The observational nature of our study could not fully account for residual confounding. CONCLUSIONS: Beta-blockers were associated with a lower rate of mortality among incident hemodialysis patients with HF. Similar associations were not observed for hospitalizations within the first 6 months following transition to dialysis.

Left ventricular hypertrophy diagnosed after a stroke: a case report.

BACKGROUND: Stroke is a recognized clinical course of hypertrophic cardiomyopathy. This interesting case showed notable difference on the electrocardiogram of a patient 4 months prior to suffering a stroke and 10 days after suffering a stroke. The pre-stroke electrocardiogram showed atrial fibrillation with a narrow QRS complex, while the post-stroke electrocardiogram showed marked left ventricular hypertrophy. Left ventricular hypertrophy was diagnosed using the Sokolow-Lyon indices. The development of left ventricular hypertrophy a few days after suffering a stroke has not previously been reported. CASE PRESENTATION: An 83-year-old white British woman with a background history of permanent atrial fibrillation, hypertension, and previous stroke attended the emergency department with a 2-day history of exertional dyspnea, and chest tightness. On examination, she had bibasal crepitations with a systolic murmur loudest at the apex. In-patient investigations include an electrocardiogram, blood tests, chest X-ray, contrast echocardiogram, coronary angiogram, and cardiovascular magnetic resonance imaging. An electrocardiogram showed atrial fibrillation, with inferolateral T wave inversion, and left ventricular hypertrophy. A chest X-ray showed features consistent with pulmonary edema. A contrast echocardiogram showed marked hypertrophy of the mid to apical left ventricle, appearance consistent with apical hypertrophic cardiomyopathy. Coronary angiography showed eccentric shelf-type plaque with non-flow-limiting stenosis in the left coronary artery main stem. Cardiovascular magnetic resonance imaging reported findings highly suggestive of apical hypertrophic cardiomyopathy. Our patient was treated and discharged on rivaroxaban, bisoprolol, and atorvastatin with a follow-up in the cardiomyopathy outpatient clinic. CONCLUSIONS: Electrocardiogram diagnosis of left ventricular hypertrophy led to the diagnosis of apical hypertrophic cardiomyopathy in this patient. Left ventricular hypertrophy was only evident a few days after our patient suffered a stroke. The underlying mechanisms responsible for this remain unclear. Furthermore, differential diagnosis of hypertrophic cardiomyopathy should be considered in people with electrocardiogram criteria for left ventricular hypertrophy. Cardiovascular magnetic resonance imaging is an important diagnostic tool in identifying causes of left ventricular hypertrophy. Family screening should be recommended in patients with new diagnosis of hypertrophic cardiomyopathy.

Gestante a término con miocardiopatía no compactada / A full-term pregnant woman with non-compaction cardiomyopathy

La miocardiopatía no compactada es una miocardiopatía primaria de origen genético. Las pacientes embarazas con miocardiopatía no compactada son más susceptibles a presentar complicaciones, como insuficiencia cardíaca, arritmias y fenómenos embólicos. Presentamos el caso de una embarazada a término con miocardiopatía no compactada asintomática y en tratamiento con bisoprolol a la que se le realizó analgesia epidural para el parto evolucionando de manera favorable. Se describe el curso clínico y se realiza una somera revisión (AU)

Non-compaction cardiomyopathy, a genetic primary cardiomyopathy, is being increasingly diagnosed. Pregnant women with non-compaction cardiomyopathy are more susceptible to complications, such as heart failure, arrhythmias and embolic events. This paper reports the case of a pregnant woman with non-compaction cardiomyopathy under treatment and asymptomatic, who received epidural analgesia during labor and delivery. The clinical course is described and a brief review is presented (AU)

[Broadened indications for the use of selective ß-adrenoblockers].

Broadened Indications to the prescription of selective -adrenoblockers in international and European recommendations are considered in this review. Selective ß-adrenoblockers have been shown to possess both good antihypertensive and neutral metabolic actions. Bisoprolol does not worsen lipid, carbohydrate metabolisms, and sexual function in men. Antiischemic activity of bisoprolol exceeds that of calcium channel blocker nifedipine. Generic preparation of bisoprolol according to a series of clinical studies can be successfully used both in patients with arterial hypertension and concomitant diseases and in patients with ischemic heart disease.

The effect of beta-blockers on the adaptive immune system in chronic heart failure.

It remains possible that the benefit from beta-blockers (BBs) in chronic heart failure (CHF) may not entirely be derived from a class-specific effect. Several experimental reports have alluded to the capability of immunomodulation by individual BBs. Given the increasingly recognized importance of the immune system in the pathogenesis of CHF, we studied the effects of BBs on the circulating immune system of these patients. Blood samples from CHF outpatients were prospectively analyzed using flow cytometry and gating software. Results were analyzed against comprehensive clinical details that were recorded during sample donation, including the type of BB administered. 273 blood samples were analyzed from 141 CHF patients, with an average ejection fraction of 31.9% and a mean age of 69.1 years. Patients taking carvedilol had a significantly lower expression of CD107a on cytotoxic T cells compared to bisoprolol (P= 0.001) and nebivolol (P= 0.008). They also had a significantly lower expression of HLA-DR on lymphocytes (P < 0.001 and P= 0.009 for bisoprolol and nebivolol, respectively). Cytotoxic T cells and lymphocytes expressing HLA-DR have been implicated in the pathogenesis of CHF. The fact that carvedilol, but not other commonly used beta-blockers, appears to modulate these important parameters, supports the concept that important differences exist between these agents, which may affect outcomes in CHF.

[Spasmodic laughter syncope. An unusual complication of pseudobulbar palsy]. / Syncope du rire spasmodique. Une complication inhabituelle du syndrome pseudobulbaire.

INTRODUCTION: Spasmodic laughter is a classical sign of pseudobulbar palsy, but it has never been reported, to our knowledge, to provoke syncope. CASE REPORT: A 63-year-old hypertensive and diabetic man with peripheral neuropathy and lacunar pseudobulbar palsy presented with three episodes of spasmodic laughter which had induced syncope. No new episode was observed after the beginning of low dose bisoprolol. DISCUSSION: Sustained or spasmodic laughter is accompanied by repetitive bursts of forced expiration, corresponding to short repetitive Valsalva maneuvers. Laughter-induced syncope is considered as one of the many Valsalva-type/vagally mediated syncopal attacks leading to rapid fall in blood pressure without compensatory tachycardia. The presence of autonomic diabetic neuropathy may also contribute to these attacks.

[Clinical efficacy of antihypertensive therapy of pregnant women with arterial hypertension with long acting nifedipine and bisoprolol].

Study aim was assessment of clinical efficacy of mono therapy with nifedipine SR/GITS and combination of nifedipine SR/GITS and bisoprolol as well as investigation of functional state of sympathoadrenal system (SAS) in pregnant women with arterial hypertension. Examination and treatment with nifedipine SR/GITS 30 mg/day and bisoprolol 2,5 - 5 mg/day was carried out in 21 patients with stage II hypertensive disease (HD) during trimester II of pregnancy. Initially all women including 20 practically healthy pregnant women (control group) had elevation of functional activity of SAS what was determined by high values of b-adrenoception of membranes of erythrocytes. In patients with stage II HD this parameter significantly exceeded that of control group. Administration of antihypertensive drugs for 3 weeks promoted significant lowering of all parameters of 24 hour blood pressure monitoring down to optimal level, lessening of pathological types of 24 hour blood pressure profile and lowering of functional activity of SAS.

Circadian blood pressure variation and antihypertensive medication adjustment in normoalbuminuric type 2 diabetes patients.

BACKGROUND/AIMS: The aim of the study was to assess the effect of an antihypertensive treatment adjustment on 24-hour blood pressure variation in type 2 diabetes patients. METHODS: The study group included 59 hypertensive type 2 diabetes patients subjected to a single one-step antihypertensive agent dose adjustment (increase or decrease). Ambulatory blood pressure monitoring was performed at baseline and 4-6 weeks after the treatment modification. Controls were 41 matched patients, in whom antihypertensive treatment remained unchanged. RESULTS: At baseline, 45 (76%) study group patients and 29 (71%) controls were 'non-dippers'; a similar number of patients in both groups converted to 'dipping' or vice versa: 11 (19%) from the study group and 7 (17%) controls. 'Converters' from the study group were significantly younger (47.5 +/- 3.9 vs. 56.4 +/- 12.2 years; p < 0.05) and had lower 24-hour systolic blood pressure than 'non-converters': 113.7 +/- 7.2 vs. 127.7 +/- 20.3 mm Hg (p < 0.01). CONCLUSION: A single one-step antihypertensive medication adjustment does not affect 'dipping' status in type 2 diabetes patients. However, the assessment of blood pressure variation should be made with greater caution in younger type 2 diabetes subjects with low systolic blood pressure.

[Graves' disease and papillary thyroid cancer--coincidence or association?]. / Basedow-Struma mit papillärem Schilddrüsenkarzinom--Zufall oder Zusammenhang?

HISTORY AND ADMISSION FINDINGS: A 41-year-old woman presented with hyperhydrosis, tremor, restlessness, sleeplessness and diarrhea. She had a tachycardia and later she developed soreness of her conjunctives. A tender goitre could be palpated. INVESTIGATIONS: Laboratory results showed thryeotoxicosis and later elevated TRAK. Ultrasound revealed a thyroid nodule. Scintigraphic uptake was generally elevated. Graves disease was diagnosed. TREATMENT AND COURSE: After 12 months of thyreostatic medication recurrence occurred and a thyroidectomy was performed. Histologically a papillary cancer was found and postoperative radioiodinetherapy was added. CONCLUSION: Due to leading symptoms of thyreotoxicosis the thyroid nodule has preoperatively not been paid enough attention to. A pathophysiologic association of Graves disease and differentiated thyroid cancer is controversely discussed but seems possible considering present literature data. Scintigraphically "cold" nodules in graves disease, as in simple nodular goitre, have a higher probability of malignancy.

Practical recommendations for the use of ACE inhibitors, beta-blockers, aldosterone antagonists and angiotensin receptor blockers in heart failure: putting guidelines into practice.

Surveys of prescribing patterns in both hospitals and primary care have usually shown delays in translating the evidence from clinical trials of pharmacological agents into clinical practice, thereby denying patients with heart failure (HF) the benefits of drug treatments proven to improve well-being and prolong life. This may be due to unfamiliarity with the evidence-base for these therapies, the clinical guidelines recommending the use of these treatments or both, as well as concerns regarding adverse events. ACE inhibitors have long been the cornerstone of therapy for systolic HF irrespective of aetiology. Recent trials have now shown that treatment with beta-blockers, aldosterone antagonists and angiotensin receptor blockers also leads to substantial improvements in outcome. In order to accelerate the safe uptake of these treatments and to ensure that all eligible patients receive the most appropriate medications, a clear and concise set of clinical recommendations has been prepared by a group of clinicians with practical expertise in the management of HF. The objective of these recommendations is to provide practical guidance for non-specialists, in order to increase the use of evidenced based therapy for HF. These practical recommendations are meant to serve as a supplement to, rather than replacement of, existing HF guidelines.

Factors related to the occurrence of microalbuminuria during antihypertensive treatment in essential hypertension.

The objective of the study was to assess the factors related to the occurrence of microalbuminuria during the follow-up of a young adult group with essential hypertension that had not been previously treated. Normo-albuminuric essential hypertensives, <50 years old, who had not been previously treated with antihypertensive drugs and who did not have diabetes mellitus were included. After the initial evaluation, patients were treated using only nonpharmacological measures (n=62), beta-blockers (n=38), ACE inhibitors (n=64), calcium channel blockers (n=8), and several classes (n=15). Measurements were taken for office blood pressure, biochemical profile, and 24-hour urinary albumin excretion at the beginning of the study and were measured yearly during an average of 2.7+/-1.2 years of follow-up. Among the 187 patients included, 22 (11,7%) developed microalbuminuria (progressors, 4.4/100 patients/y). No differences were present between progressors and those who remained normo-albuminuric (nonprogressors) in terms of age, gender, body mass index, disease duration, blood pressure values, biochemical profile, familial history of diabetes or hypertension, smoking habits, or the presence of EKG left ventricular hypertrophy. The group with the lowest progression rate was the patients treated with ACE inhibitors (n=5; 2.9/100 patients/y), followed by the diet group (n=5; 3.3/100 patients/y) and the beta-blockers group (n=5; 4.1/100 patients/y). When we excluded patients treated with calcium channel blockers or those who changed over time between different classes of treatment, no significant differences in the incidence of microalbuminuria were observed among the groups. Progressors showed higher slopes of fasting glucose (4.78+/-11.4 versus 0.50+/-6.8 mg/y, P<0.02) and uric acid (0.58+/-0.93 versus 0.05+/-1.10 mg/y, P<0.03) compared with the slopes of nonprogressors. Both the slopes for glucose and systolic blood pressure over time were associated independently with the slope of the logarithm of urinary albumin excretion when adjusted for age, gender, and treatment groups. Cox proportional hazard model for progression of microalbuminuria showed that baseline urinary albumin excretion (risk ratio [RR]=1.06; confidence interval [CI] 95%, 1.01 to 1.11), slope for systolic blood pressure (RR=1.11; CI 95%, 1.03 to 1.20), and slope for glucose (RR=1.08; CI 95%, 1.03 to 1.14) were independently associated to the development of microalbuminuria. In conclusion, in a group of young adults with essential hypertension that had not been previously treated, the main factors influencing the occurrence of microalbuminuria during antihypertensive treatment were the values of microalbuminuria at baseline and the slopes for systolic blood pressure and fasting glucose.

Efficacy, safety, and effects on quality of life of bisoprolol/hydrochlorothiazide versus amlodipine in elderly patients with systolic hypertension.

BACKGROUND: Several studies have shown the benefits of antihypertensive treatment in elderly patients in terms of cardiovascular morbidity and mortality rate reduction. Low-dose drug combinations may be of interest in treating older subjects. A randomized, multicenter, double-blind, parallel group study was conducted to compare the efficacy and safety of bisoprolol 2.5 mg/hydrochlorothiazide 6.25 mg (n = 84) to amlodipine 5 mg (n = 80) in isolated systolic hypertension in patients older than 60 years. METHODS: After a 2- to 4-week placebo washout period, both drugs were administered once daily and taken for 12 weeks. Blood pressure was measured 24 hours after treatment administration. RESULTS: Systolic and diastolic blood pressure changes from baseline to week 12 were similar for both the bisoprolol and amlodipine groups (-20. 0/-4.5 mm Hg and -19.6/-2.4 mm Hg, respectively). Overall adverse events for bisoprolol and amlodipine were 39% and 40%, respectively. Changes in quality of life scores were +2.5 for bisoprolol and +3.2 for amlodipine, with a positive change indicating improvement. CONCLUSIONS: This study demonstrates comparable efficacy and tolerability of bisoprolol 2.5 mg/hydrochlorothiazide 6.25 mg and amlodipine 5 mg. The low-dose combination of bisoprolol and hydrochlorothiazide may be an appropriate alternative for elderly patients with systolic hypertension.

Bisoprolol and nifedipine retard in elderly hypertensive patients: effect on quality of life.

Subjects over the age 60 with sustained sitting diastolic pressures of 95-115 mm Hg were randomised to a regime based on bisoprolol (n = 368) or nifedipine retard (n = 379) for 24 weeks. The goal diastolic pressure was < or =90 mm Hg and to achieve this, double-blind medication could be doubled (5/10 mg bisoprolol, 40/80 mg nifedipine retard) or hydrochlorothiazide 25 mg (unblinded) could be added to the higher dose. In an intention-to-treat analysis, 309 subjects in both the bisoprolol and nifedipine retard treated group provided at least a baseline and a second quality of life assessment (82%). An excess of symptoms was observed in the nifedipine group for oedema of the legs, nocturia, constipation, racing heart and heart thumping. Fewer patients reported wheeze in the nifedipine group. For quality of life, there were no statistically significant differences between the two groups after 8 weeks. However, when analysing the results of the last available assessment (usually at 24 weeks) there were significant (P < 0.05) improvements in tension/anxiety, anger/ hostility, vigour/activity, and confusion/bewilderment, assessed by the Profile of Mood States (POMS) in patients receiving bisoprolol in comparison to those receiving nifedipine retard. The Sickness Impact Profile and objective tests of cognitive function did not differ statistically between the two groups. Quality of life was maintained at a good level on both treatments with advantages for bisoprolol in certain areas. Journal of Human Hypertension (2000) 14, 205-212.

Comparative effects of bisoprolol and nitrendipine on exercise capacity in hypertensive patients with regular physical activity.

The aim of this study was to evaluate the long-term effects of administering bisoprolol compared with nitrendipine on the duration of the exercise tolerated by male and female patients, aged 18-65 years, having mild to moderate hypertension and taking regular exercise. In this double-blind, randomized prospective study, 96 patients (85 men and 11 women, 48+/-10 years) formed two groups: 49 in the bisoprolol group, and 47 in the nitrendipine group. After a washout period of 14 days, either 10 mg of bisoprolol or 20 mg of nitrendipine was given daily over a treatment period of 12 weeks. During the treatment period, the stability of the physical training was monitored weekly by using a questionnaire. The results of two maximal triangular exercise tolerance tests (ETTs) on an ergometric bicycle performed at D0 under placebo and at D84 under active treatment were compared. No statistical difference was observed between both groups, concerning age, gender, morphologic characteristics, resting cardiovascular parameters, or physical training. Both groups maintained the same training level throughout the study. No significant differences between the groups were noted for duration of ETT [D0 892+/-284 s, D84, 919+/-267 s (NS) vs. D0 929+/-290 s, D84 904+/-324 s (NS)], or maximal work load [D0 190+/-49 W, D84 197+/-48 W (NS) vs. D0 198+/-49 W, D84 196+/-55 W (NS)]. On the other hand, both groups differed in maximal systolic blood pressure [D0 239+/-24 mm Hg, D84 215+/-22 mm Hg (p<0.001) vs. D0 237+/-24 mm Hg, D84 222+/-27 mm Hg (p<0.05)] (p = 0.05), and maximal pulse rate during exercise [141+/-18 vs. 163+/-17] (p<0.001), albeit not in maximal diastolic blood pressure [D0 113+/-13 mm Hg, D84 106+/-17 mm Hg (p<0.05) vs. D0 112+/-13 mm Hg, D84 104+/-15 mm Hg (p<0.05)]. The patient's own perception of the maximal effort (Borg scale) was not significantly different in either of the groups (placebo vs. treatment). Overall, in a population of hypertensive patients taking regular exercise, long-term treatment with bisoprolol produced no significant changes in the duration of peak effort, maximal workload, or the effort perceived by the patients themselves. The effects of regular exercise were comparable in both groups (bisoprolol or nitrendipine). Because previous studies have shown that dihydropyridines do not modify exercise performance in hypertensive patients, it may be concluded that the antihypertensive therapy with bisoprolol is well tolerated in a population of active hypertensive patients during dynamic exercise.

Heart rate variability and ischaemia in patients with coronary heart disease and stable angina pectoris; influence of drug therapy and prognostic value. TIBBS Investigators Group. Total Ischemic Burden Bisoprolol Study.

AIMS: Determination of the influence of therapy with bisoprolol and nifedipine on the heart rate variability of patients from the Total Ischemic Burden Bisoprolol Study and examination of the prognostic value. METHODS AND RESULTS: Four hundred and twenty-two patients with stable angina were included. The heart rate variability was determined over a period of 24 h. Parameters determined: standard deviation of the mean of all corrected RR intervals, standard deviation of all 5 min mean cycle lengths, square root of the mean of the squared differences of successive corrected RR intervals. Nifedipine reduced the mean values of all heart rate variability parameters tested. Square root of the mean of the square differences of successive corrected RR intervals increased under bisoprolol. Standard deviation of the mean of all corrected RR intervals and standard deviation of all 5 min mean cycle lengths increased from low baseline values and declined from higher baseline values. The increase in heart rate variability under therapy was accompanied by a tendency towards a better prognosis. Patients with an increase in heart rate variability and simultaneous complete suppression of ischaemia under therapy displayed no serious events in the course of one year. CONCLUSIONS: The increase in the heart rate variability, which can be regarded as prognostically favourable, was predominantly observed under bisoprolol. The parameter constellation of an increase in heart rate variability and complete ischaemia suppression on the 48-h Holter ECG was associated with the greatest benefit.

Differential effects of antihypertensive drugs with differing pharmacological properties on the basal ambulatory blood pressure. Japanese Ambulatory Pressure-ANtihypertensive Effects SEarching study group.

To investigate how antihypertensive drugs with different pharmacological properties affect ambulatory blood pressure (BP) the JAPANESE Study Group developed a database of clinic and ambulatory BPs before and after antihypertensive treatment of patients throughout Japan. Drugs evaluated were nilvadipine (n = 195; b.i.d, 4-8 mg/day), amlodipine (n = 75; q.d., 2.5-10 mg/day), lisinopril (n = 80; q.d., 10-20 mg/day) and bisoprolol (n = 49; q.d., 5-10 mg/day). The relationship between basal ambulatory BP and the hypotensive effect on ambulatory BP during treatment was examined. All antihypertensive drugs significantly decreased both clinic BP and ambulatory BP. The hypotensive effect determined by measurement of clinic BP was significantly greater than that determined by ambulatory BP. The hypotensive effect was positively correlated with basal ambulatory BP. However, there was a quantitative difference in this characteristic among the drugs. The critical daytime systolic ambulatory BP below which a hypotensive effect was not observed was extrapolated to 128, 127 and 124 mm Hg with nilvadipine, amlodipine and bisoprolol, respectively, while that with lisinopril was 97 mm Hg. The slope of the correlation coefficient between basal daytime ambulatory systolic BP and hypotensive effect with lisinopril was significantly smaller than those with the other drugs (P < 0.0001). The slope for the relationship between night-time ambulatory systolic BP and the hypotensive effect with bisoprolol was the steepest (P < 0.0001). Antihypertensive drugs with different pharmacological properties exhibited differing hypotensive effects on the basal ambulatory BP. Such differences in efficacy of the drugs on the basal ambulatory BP may reflect adverse effects of the drugs and the prognosis of hypertension.

Quality of life comparison between bisoprolol and nifedipine retard in hypertension.

Quality of life with the selective beta1-blocker bisoprolol and the calcium channel blocker nifedipine as a retard formulation was compared in patients with essential hypertension. A multicenter randomized, double-blind, two-way, crossover study design was used. After a placebo run-in period (4-6 weeks), during which all antihypertensive therapy was withdrawn, 82 patients were randomized. During the active treatment periods (8 weeks each), patients received either bisoprolol once daily or nifedipine retard twice daily, using the double-dummy technique. A washout period (4-6 weeks) separated the treatment periods. Data at baseline (at randomization) and at the end of each treatment period were compared. Seventy-five patients completed the study. Blood pressure (168 +/- 2/103 +/- 1 mmHg) decreased (p < 0.001) similarly with bisoprolol (153 +/- 2/90 +/- 1 mmHg) and nifedipine (154 +/- 2/90 +/- 1 mmHg). Compared with baseline values, none of the quality of life variables investigated changed during bisoprolol or nifedipine retard use. Neither in the intention-to-treat nor the efficacy analysis were differences between bisoprolol and nifedipine found in quality of life variables, such as the Health Status Index, somatic symptoms, anxiety, depression, total psychiatric morbidity, cognitive symptoms, and hostility score. Only in the efficacy analysis did Health Status Index tend to be better (p = 0.055) during nifedipine intake when compared with bisoprolol. This trend was not present in the intention-to-treat analysis. The number of dropouts during bisoprolol (n = 2) and nifedipine (n = 3) treatment, and the number of patients reporting side effects (21% and 16%, respectively) did not differ (p = 0.64) between both treatments. It can be concluded that at equipotent antihypertensive dosages, an 8-week treatment period with the selective beta1-blocker bisoprolol or the calcium antagonist nifedipine as a retard formulation does not result in any difference in quality of life variables. It is not clear whether the trend of Health Status Index to become better during nifedipine intake, which was only found in the efficacy analysis and not in the intention-to-treat analysis, is of clinical relevance.

[Effectiveness and tolerability of bisoprolol vs. nifedipine in uremic patients with ischemic cardiopathy in dialysis treatment]. / Efficacia e tollerabilità di bisoprololo e nifedipina in pazienti uremici con cardiopatia ischemica in trattamento dialitico.

The effects of bisoprolol on transient myocardial ischemia have been compared with those of nifedipine in patients with coronary artery disease in end-stage renal failure maintained on haemodialysis. We also evaluated the tolerability of both drugs. Sixty patients (42 males, 18 females, mean age 52 +/- 4 years) in renal failure maintained on haemodialysis, with coronary artery disease and more than four significant episodes of transient myocardial ischemia (> or = 1 min) during 48-hour Holter monitoring, were included in the study. All cardiovascular drugs were discontinued > or = 6 days before this 48-hour ambulatory ECG monitoring, with the exception of sublingual nitrates allowed for relief of anginal attacks. Patients were then randomized to receive either bisoprolol or nifedipine for 2 weeks. After a 15-day wash-out period, they were crossed over to receive either bisoprolol or nifedipine for other 2 weeks. Statistical analysis was carried out using the Student's t test. A p value < 0.01 was considered significant. Both bisoprolol and nifedipine reduced number and duration of transient ischemic episodes as well as the total ischemic burden. Reductions were statistically significant for both antianginal drugs. Only bisoprolol was effective in silent ischemia (p < 0.001). It also reduced heart rate (p < 0.001), while nifedipine raised it (p < 0.001). Both drugs reduced systolic and diastolic blood pressure. The circadian variations of transient ischemic episodes showed two peaks in the 24 hours. Both peaks were reduced with bisoprolol. Nifedipine brought a clear overall reduction in the number of episodes but the circadian pattern was unchanged. During the study, 10 patients taking bisoprolol and 12 patients taking nifedipine had drug adverse effects. No one of them had to be withdrawn from treatment. In conclusion, bisoprolol seems to be more useful than nifedipine because its effects, in transient ischemic episodes, are greatly superior to those of nifedipine, and because it is effective also in silent ischemia. Both drugs showed a good tolerability in these patients. Bisoprolol, reducing the two daily peaks of ischemic episodes frequency, has a protective role towards mortality due to coronary artery disease.

Prognostic significance of transient ischemic episodes: response to treatment shows improved prognosis. Results of the Total Ischemic Burden Bisoprolol Study (TIBBs) follow-up.

OBJECTIVES: The Total Ischemic Burden Bisoprolol Study (TIBBS) follow-up examined cardiac event rates in relation to transient ischemia and its treatment. BACKGROUND: It is unclear whether transient ischemia on the ambulatory electrocardiogram has prognostic implications in stable angina and whether medical treatment can improve the prognosis. METHODS: The TIBBS trial was an 8-week, randomized, controlled comparison of the effects of bisoprolol and nifedipine on transient ischemic episodes in patients with stable angina pectoris. Of the 545 patients screened, 520 (95.4%) could be followed up. Rates of cardiac and noncardiac death, nonfatal acute myocardial infarction, hospital admission for unstable angina and need for coronary artery bypass graft surgery or percutaneous transluminal coronary angioplasty were recorded. RESULTS: A total of 145 events occurred in 120 (23.1%) of 520 patients. Patients with more than six episodes had an event rate of 32.5% compared with 25.0% for patients with two to six episodes and 13.2% for patients with less than two episodes (p < 0.001). Hard events (death, acute myocardial infarction, hospital admission for unstable angina pectoris) were more frequent in patients with two or more ischemic episodes (12.2% vs. 4.7%, p = 0.0049). Patients with a 100% response rate of transient ischemic episodes during the TIBBS trial had a 17.5% event rate at 1 year compared with 32.3% for non-100% responders (p = 0.008). Patients receiving bisoprolol during the TIBBS tria had a lower event rate (22.1%) at 1 year than patients randomized to nifedipine (33.1%, p = 0.033). CONCLUSIONS: In patients with stable angina pectoris, frequent episodes of transient ischemia are a marker for an increased event rate. A 100% response to medical treatment reduces the event rate. The greater reduction of ischemia with bisoprolol than nifedipine during the TIBBS trial translated into an improved outcome at 1 year.