Beta-blockers improve in-hospital and long-term survival in patients with severe left ventricular dysfunction undergoing major vascular surgery.

OBJECTIVES: To study whether beta-blockers reduce in-hospital and long-term mortality in patients with severe left ventricular dysfunction (LVD) undergoing major vascular surgery. DESIGN: Observational cohort study. MATERIALS: Five hundred and eleven patients with severe LVD (ejection fraction<30%) undergoing major non-cardiac vascular surgery. METHODS: In all patients, cardiac risk factors, medication (including beta-blockers), and dobutamine stress echocardiography (DSE) results were noted prior to surgery. DSE was evaluated for rest and stress-induced new wall motion abnormalities. Endpoint was in-hospital and long-term mortality. Propensity scores for beta-blockers were calculated and regression models were used to analyse the relation between beta-blockers and mortality. RESULTS: Mean age was 64+/-11 years and 383 patients (75%) were male. 139 patients (27%) used beta-blockers. Stress-induced ischemia occurred in 82 patients (16%). Median follow-up was 7 years (interquartile range: 3-10). In-hospital and long-term mortality was observed in 64 (13%) and 171 (33%) patients, respectively. After adjusting for clinical variables, DSE results and propensity scores, beta-blockers were significantly associated with reduced in-hospital and long-term mortality (OR: 0.18, 95% CI: 0.04-0.74 and HR: 0.38, 95% CI: 0.22-0.65, respectively). CONCLUSION: In patients with severe LVD undergoing major vascular surgery, the use of beta-blockers is associated with a reduced incidence of in-hospital and long-term postoperative mortality.

Bisoprolol reduces cardiac death and myocardial infarction in high-risk patients as long as 2 years after successful major vascular surgery.

AIM: To assess the long-term cardioprotective effect of bisoprolol in a randomized high-risk population after successful major vascular surgery. High-risk patients were defined by the presence of one or more cardiac risk factor(s) and a dobutamine echocardiography test positive for ischaemia. METHODS: 1351 patients were screened prior to surgery, 846 patients had one or more risk factor(s), and 173 of these patients also had ischaemia during dobutamine echocardiography. One hundred and twelve patients could be randomized for additional bisoprolol therapy or standard care. Eleven patients died in the peri-operative period (up to 1 month after surgery). Randomized patients continued bisoprolol or standard care after surgery. During follow-up of 101 survivors (median 22 months, range 11-30) cardiac death or myocardial infarction was noted. No patient was lost during follow-up. Results The incidence of cardiac events during follow-up in the bisoprolol group was 12% vs 32% in the standard care group (P=0.025). Cardiac death occurred in 15 patients, nine patients in the standard care and in six in the bisoprolol group; myocardial infarction occurred in six patients, five in the standard care and one in the bisoprolol group. The odds ratio for cardiac death or myocardial infarction after surgery in high-risk patients with additional bisoprolol therapy was 0.30 (0.11-0.83). CONCLUSIONS: Bisoprolol significantly reduced long-term cardiac death and myocardial infarction in high-risk patients after successful major cardiac vascular surgery.

Predictors of cardiac events after major vascular surgery: Role of clinical characteristics, dobutamine echocardiography, and beta-blocker therapy.

CONTEXT: Patients who undergo major vascular surgery are at increased risk of perioperative cardiac complications. High-risk patients can be identified by clinical factors and noninvasive cardiac testing, such as dobutamine stress echocardiography (DSE); however, such noninvasive imaging techniques carry significant disadvantages. A recent study found that perioperative beta-blocker therapy reduces complication rates in high-risk individuals. OBJECTIVE: To examine the relationship of clinical characteristics, DSE results, beta-blocker therapy, and cardiac events in patients undergoing major vascular surgery. DESIGN AND SETTING: Cohort study conducted in 1996-1999 in the following 8 centers: Erasmus Medical Centre and Sint Clara Ziekenhuis, Rotterdam, Twee Steden Ziekenhuis, Tilburg, Academisch Ziekenhuis Utrecht, Utrecht, and Medisch Centrum Alkmaar, Alkmaar, the Netherlands; Ziekenhuis Middelheim, Antwerp, Belgium; and San Gerardo Hospital, Monza, Istituto di Ricovero e Cura a Carattere Scientifico, San Giovanni Rotondo, Italy. PATIENTS: A total of 1351 consecutive patients scheduled for major vascular surgery; DSE was performed in 1097 patients (81%), and 360 (27%) received beta-blocker therapy. MAIN OUTCOME MEASURE: Cardiac death or nonfatal myocardial infarction within 30 days after surgery, compared by clinical characteristics, DSE results, and beta-blocker use. RESULTS: Forty-five patients (3.3%) had perioperative cardiac death or nonfatal myocardial infarction. In multivariable analysis, important clinical determinants of adverse outcome were age 70 years or older; current or prior angina pectoris; and prior myocardial infarction, heart failure, or cerebrovascular accident. Eighty-three percent of patients had less than 3 clinical risk factors. Among this subgroup, patients receiving beta-blockers had a lower risk of cardiac complications (0.8% [2/263]) than those not receiving beta-blockers (2.3% [20/855]), and DSE had minimal additional prognostic value. In patients with 3 or more risk factors (17%), DSE provided additional prognostic information, for patients without stress-induced ischemia had much lower risk of events than those with stress-induced ischemia (among those receiving beta-blockers, 2.0% [1/50] vs 10.6% [5/47]). Moreover, patients with limited stress-induced ischemia (1-4 segments) experienced fewer cardiac events (2.8% [1/36]) than those with more extensive ischemia (>/=5 segments, 36% [4/11]). CONCLUSION: The additional predictive value of DSE is limited in clinically low-risk patients receiving beta-blockers. In clinical practice, DSE may be avoided in a large number of patients who can proceed safely for surgery without delay. In clinically intermediate- and high-risk patients receiving beta-blockers, DSE may help identify those in whom surgery can still be performed and those in whom cardiac revascularization should be considered.

The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group.

BACKGROUND: Cardiovascular complications are the most important causes of perioperative morbidity and mortality among patients undergoing major vascular surgery. METHODS: We performed a randomized, multicenter trial to assess the effect of perioperative blockade of beta-adrenergic receptors on the incidence of death from cardiac causes and nonfatal myocardial infarction within 30 days after major vascular surgery in patients at high risk for these events. High-risk patients were identified by the presence of both clinical risk factors and positive results on dobutamine echocardiography. Eligible patients were randomly assigned to receive standard perioperative care or standard care plus perioperative beta-blockade with bisoprolol. RESULTS: A total of 1351 patients were screened, and 846 were found to have one or more cardiac risk factors. Of these 846 patients, 173 had positive results on dobutamine echocardiography. Fifty-nine patients were randomly assigned to receive bisoprolol, and 53 to receive standard care. Fifty-three patients were excluded from randomization because they were already taking a beta-blocker, and eight were excluded because they had extensive wall-motion abnormalities either at rest or during stress testing. Two patients in the bisoprolol group died of cardiac causes (3.4 percent), as compared with nine patients in the standard-care group (17 percent, P=0.02). Nonfatal myocardial infarction occurred in nine patients given standard care only (17 percent) and in none of those given standard care plus bisoprolol (P<0.001). Thus, the primary study end point of death from cardiac causes or nonfatal myocardial infarction occurred in 2 patients in the bisoprolol group (3.4 percent) and 18 patients in the standard-care group (34 percent, P<0.001). CONCLUSIONS: Bisoprolol reduces the perioperative incidence of death from cardiac causes and nonfatal myocardial infarction in high-risk patients who are undergoing major vascular surgery.

Impact of antihypertensive treatment on quality of life: comparison between bisoprolol and bendrofluazide.

OBJECTIVES: To compare quality of life with the selective beta1-blocker bisoprolol and the thiazide diuretic bendrofluazide in patients with mild to moderate hypertension. DESIGN AND SETTING: Multi centric, randomised, double-blind, two-way crossover study carried out at six general practice centres. SUBJECTS: Eighty-one patients with newly diagnosed or previously treated hypertension, who had a mean diastolic blood pressure (BP) of 95-120 mm Hg after receiving placebo for 4-6 weeks. INTERVENTIONS: In random order, patients received bisoprolol (5 mg once daily) or bendrofluazide (2. 5 mg once daily) for 8 weeks. MAIN OUTCOME MEASURES: Quality of life and antihypertensive effect. RESULTS: Decrease in systolic/diastolic BP did not differ between bisoprolol (10 +/- 2/13 +/- 1 mm Hg) and bendrofluazide (9 +/- 2/11 +/- 1 mm Hg). Between bisoprolol and bendrofluazide neither in the intention-to-treat nor in the efficacy analysis any difference was found in quality of life variables, such as Health Status Index, somatic symptoms, anxiety, depression, total psychiatric morbidity, cognitive symptoms and hostility score. Compared to baseline the Health Status Index improved (P < 0.05) during bisoprolol. None of the other investigated quality of life variables changed compared to baseline. No patients dropped out during bisoprolol or bendrofluazide treatment. Although, the total number of reported adverse events appeared lower during bendrofluazide than during bisoprolol treatment, it is unclear whether drug related adverse events also differ between the two drugs. CONCLUSIONS: At equipotent antihypertensive dosages, the effect of an 8-week treatment on quality of life does not differ between the selective beta1-blocker bisoprolol and the thiazide diuretic bendrofluazide.

Prophylactic treatment of migraine with bisoprolol: a placebo-controlled study.

The objective of the present study was to assess the efficacy of bisoprolol in migraine prophylaxis. A double-blind placebo-controlled study was conducted in 226 patients with migraine with or without aura, a migraine history of at least 2 years at least 3 documented attacks during the 28 days run-in period. The duration of treatment was 12 weeks following an initial 28 days' run-in period. Patients reported the number of attacks and their severity in a diary. Treatment with bisoprolol 5 mg resulted in a significant reduction in the frequency of migraine attacks (39% vs 22%) compared to placebo treatment (p < 0.05). Treatment had no effect on the duration and severity of the attacks. Bisoprolol was well tolerated.

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.

Effects of beta-blockade on atrial and atrioventricular nodal refractoriness, and atrial fibrillatory rate during atrial fibrillation in pigs.

Despite their widespread use in atrial fibrillation, the effects of beta-adrenoceptor blockers on atrial and atrioventricular (AV) nodal refractoriness, and atrial fibrillatory rate during atrial fibrillation have been incompletely characterised. In particular, it is unknown whether additional sodium channel (class I) blocking effects play a role. Effects of bisoprolol (no class I effect) and metoprolol (mild class I effect) were therefore compared in 12 open-chest pigs. Atrial and AV-nodal effective refractory periods were determined at pacing cycle length 500 ms and 300 ms. Atrial fibrillation was then induced by premature stimulation and topical application of metacholine, and atrial fibrillatory intervals and ventricular intervals were recorded. After resumption of sinus rhythm, bisoprolol 0.1 mg/kg or metoprolol 0.3 mg/kg was administered, and measurements were repeated. Also, effects on plasma catecholamines and signal-averaged QRS duration were determined. Both bisoprolol and metoprolol prolonged atrial and AV-nodal effective refractory periods at both pacing cycle lengths, however, no differences were noted between the two drugs. No significant effects were observed on atrial and ventricular intervals during atrial fibrillation. Plasma catecholamines were low and unaffected by either drug, as was the QRS duration. It is concluded that the mild class I effect of metoprolol does not play a role in atrial fibrillation. Also, the results confirm the clinical notion that beta-blockers exert insignificant effects during atrial fibrillation in the setting of low sympathetic tone.

Treatment of the hyperventilation syndrome with bisoprolol: a placebo-controlled clinical trial.

The hyperventilation syndrome (HVS) can be regarded as a form of panic disorder associated with a relative increase in sympathomimetic tone, the effects of which can be counterbalanced by beta-adrenoceptor blockade. The efficacy of the beta-blocker bisoprolol was investigated in a double-blind placebo-controlled randomised crossover trial involving 60 patients from 17 general practices. Following a single-blind placebo prephase, patients who met the inclusion criteria were randomised to treatment with either 5 mg bisoprolol or an identical-looking placebo tablet once daily for three weeks. They were then crossed over to the other treatment arm. At the end of each treatment phase the number of hyperventilation attacks and the severity of symptoms were assessed and side effects recorded. The number of attacks decreased from 4.04 per week at baseline to 3.52 with placebo and to 1.26 with bisoprolol. The decrease of attacks with bisoprolol was significant (p < 0.05) compared to baseline and placebo. The severity of the complaints improved from 29 (scale 0 to 64) at baseline not significantly to 26 with placebo and significantly (p < 0.05) to 15 with bisoprolol. No serious side effects were reported. Five milligrams of bisoprolol once daily is effective and safe in the maintenance of symptom reduction in patients with the hyperventilation syndrome.

Which drug to choose for stable angina pectoris: a comparative study between bisoprolol and nitrates.

The choice between beta-blockade or nitrates as first line treatment for stable angina pectoris is based upon the different mechanisms of action and patient characteristics. We performed a clinical trial comparing the efficacy of the longacting beta-blocker bisoprolol once daily and the short acting nitrate, isosorbide dinitrate, three times daily in the reduction of anginal complaints in daily life and under stress. Thirty patients were enrolled in a double-blind randomised cross-over study. Both bisoprolol and isosorbide dinitrate were effective in reducing anginal attacks and nitroglycerin consumption significantly, but bisoprolol was significantly more effective than isosorbide dinitrate. Bisoprolol improved the workload during bicycle exercise testing significantly, but the improvement with isosorbide dinitrate was not significant. Despite the reduction in maximal rate pressure product, bisoprolol was significantly (P < 0.05) more effective at improving total workload and reducing the time to onset of angina than isosorbide dinitrate. The rate pressure product did not change significantly with isosorbide dinitrate. In this study, bisoprolol 10 mg once daily was more effective and caused less side effects than isosorbide dinitrate 20 mg three times a day. It seems questionable if monotherapy of isosorbide dinitrate 20 mg t.i.d is an adequate drug regime for stable angina pectoris.

The influence of chronic treatment with betablockade and angiotensin converting enzyme inhibition on the peripheral blood flow in hypertensive patients with and without concomitant intermittent claudication. A comparative cross-over trial.

In a comparative cross-over trial we examined the influence of the betablocker bisoprolol and the ACE-inhibitor lisinopril on the peripheral blood flow of 2 groups of hypertensive patients with and without concomitant intermittent claudication. In 11 patients with hypertension without peripheral arterial obstructive disease and 11 patients with hypertension and claudication we assessed the blood pressure, leg blood flow, vascular resistance, walking distance, transcutaneous oxygen consumption and Laser-Doppler flow after treatment of one month with 10 mg bisoprolol once daily or 20 mg lisinopril once daily. The walking distance of patients with claudication improved in all patients while participating in an exercise program. For both treatment groups this improvement was significant (p < 0.05) compared to baseline, from 264 m at baseline to 313 m with bisoprolol and to 400 m with lisinopril. The difference was not significant between the both drugs. In patients without peripheral vascular obstructive disease we found a significant (p < 0.05) reduction in blood flow for both drugs. The peripheral blood flow parameters of 38 legs showed no statistical significant effect of bisoprolol nor lisinopril on the local vascular resistance at rest, after occlusion or after exercise.

Comparison of the safety and efficacy of bisoprolol versus atenolol in stable exercise-induced angina pectoris: a Multicenter International Randomized Study of Angina Pectoris (MIRSA).

Bisoprolol 10 mg and atenolol 100 mg once daily were compared regarding efficacy and safety in stable effort angina in a 12-week, multicenter, double-blind, randomized, parallel-group study. Efficacy was evaluated with angina pectoris diaries and bicycle exercise tests. Spontaneously mentioned complaints and side effects were recorded at each visit. In 11 centers, 147 patients completed the study; 76 received bisoprolol 10 mg, and 71 received atenolol 100 mg. After 12 weeks, weekly anginal attack rate was reduced significantly (p less than 0.05) with bisoprolol (5 +/- 0.5 to 2 +/- 0.6) and with atenolol (4 +/- 0.4 to 1 +/- 0.2). Peak exercise capacity (in W x min) increased significantly (p less than 0.05) with bisoprolol (772 +/- 47 to 878 +/- 52) and with atenolol (891 +/- 46 to 986 +/- 53). Rate pressure product (RPP) at peak exercise (in beats/min x mm Hg) decreased significantly (p less than 0.05) with both bisoprolol (25,003 +/- 692 to 20,116 +/- 637) and atenolol (26,544 +/- 557 to 21,603 +/- 576) (all values are mean +/- SE). The differences between the groups were not statistically significant. There were no significant differences regarding nature and incidence of adverse events between the groups. Thus, bisoprolol 10 mg once daily and atenolol 100 mg once daily are equipotent in their effects on stable effort angina. Both regimens were comparable with respect to incidence and nature of side effects.

Bisoprolol and hypertension: effects on sexual functioning in men.

OBJECTIVES: To investigate prospectively the effects of the selective beta 1 adrenoceptor blocker bisoprolol on sexuality of men with hypertension. DESIGN: In newly diagnosed patients (group I): double-blind, crossover, placebo controlled. In men with hypertension on antihypertensive treatment (group II): crossover design. SETTING: Large area in and around Rotterdam, The Netherlands. PATIENTS: Twenty-six men (criteria: between 25 and 70; no disease etc. known to affect sexual functioning) were recruited through their general practitioners. Group I (n = 13) fulfilled the selection criteria, sitting blood pressure systolic > or = 160 mm Hg and/or diastolic > or = 95 mm Hg, measured on 3 different days. Group II (n = 13) patients already on antihypertensive treatment. MAIN OUTCOME MEASURES: Data on blood pressure. Qualitative and quantitative data on sexuality through questionnaires, including personal and sexual history, sexual functioning, sexual satisfaction and erectile difficulties. RESULTS: Bisoprolol is an effective antihypertensive drug with no detrimental effects on sexuality in newly diagnosed men with hypertension. In men already on antihypertensive medication bisoprolol improved sexuality in some parameters, i.e. firmness of erection during coitus, contentedness with sexual functioning and satisfaction with own sexuality. CONCLUSION: Bisoprolol is an effective antihypertensive agent with no sexual side effects.