Doses Of Bisoprolol Research Articles

P197 TAKO TSUBO SYNDROME IN MAN FOR ‘SMART WORKING’ COMPLICATED BY ACUTE HEART FAILURE AND SAM. PRESENCE OF MYOCARDIAL BRIDGE OF IVA ‘INNOCENT BYSTANDER’ OF THE CLINICAL PICTURE

Abstract Male, 59 years old with no significant pathological history or cardiovascular risk factors. Access to the ER ( 12.30 AM ) with infero–lateral STEMI (Killip I, 2 hours of symptom onset; haemodynamic and electrical stability): chest pain associated with profuse sweating and transient arterial hypotension, ST elevation in V3–V6 and inferior leads on the ECG and apical hypokinesia with slight reduction of LVEF (50%) on the Trans–Thoracic Echocardiography. Urgent coronary angiography: non–obstructive coronary arteries stenosis, short intramyocardial tract of DA with moderate systolic compression with ‘milking effect‘. Blood sampling: mild elevation of cardiac troponin hs value (479 pg / ml), mild anemia and thrombocytopenia; normal value of markes of liver and kidney function. Hospitalization in Cardiac ICU with standard antithrombotic and anti–ischemic therapy. 12 hours after admission (01.00 PM) acute low–flow heart failure with pulmonary edema treated with inotropic agent and need of endotracheal intubation and ventilatory support (ineffective attempt of NIV); ECG unchanged from the previous one and appearance of LVEF 25% for akinesia of septum, apex and lateral wall. Peak of troponin 2083 pg / ml III day: effective extubation with successive cycles of NIV and weaning from noradrenaline. Progressive recovery of LVEF with appearance of SAM with LVOT dynamic obstruction (v max> 4m / s at pulsed doppler) and moderate mitral regurgitation: stop inotropic agent and start beta–blocker therapy (atenolol) not tolerated for hypokinetic arrhythmias (also total BAV) and then successful replaced in the following days with low doses of bisoprolol. Post–Iintubation pneumonia treated with antibiotic therapy. X day: hemodynamic and electrical stability, disappearance of the SAM with complete recovery of the left ventricle contractile function, mild mitral regurgitation(minimal valve prolapse) Cardiac MRI: normal LVEF, absence of myocardial LGE with the exception of small areas of the papillary muscles due to traction of the mitral flaps. In the patient‘s medical history: stressful last months related to smart working and family problems; absence of a specific identifiable trigger. Conclusions Stress cardiomyopathy in man patient complicated by progressive acute heart failure and SAM with rapid restitutio ad integrum. Presence of DA myocardial bridge with absence of myocardial LGE on MRI.

Effectiveness and Tolerability of Trimetazidine 80Mg Once Daily in Patients with Stable Angina Uncontrolled with Bisoprolol-Based Therapy: The Modus Vivendi Observational Study.

IntroductionModus Vivendi was conducted in routine clinical practice to evaluate the effect of adding trimetazidine 80 mg once daily (TMZ 80 OD) to treat patients with persistent symptoms despite treatment with background antianginal therapies including maximally tolerated bisoprolol.MethodsThis multicenter, prospective, observational, open-label, uncontrolled study recruited adult outpatients with a confirmed diagnosis of stable angina to whom physicians had decided to prescribe TMZ 80 OD. All patients were symptomatic despite treatment, including maximally tolerated doses of bisoprolol. Data on number of angina attacks, use of short-acting nitrates, and quality of life (QoL) were collected at baseline (V1) and at 1-month (V2) and 3-month (V2) follow-up visits. Two sub-analyses assessed efficacy in patients who remained on a stable bisoprolol dose throughout the study, and in patients in whom background antianginal therapy was known.ResultsA total of 1939 patients were recruited (57.2% women). The mean age was 65.6 ± 8.8 years; 73.8% had class II and 26.2% class III angina. At V1, the mean number of angina attacks per week was 6.2 ± 6.5 despite antianginal therapy including maximally tolerated bisoprolol dosage. Following the addition of TMZ 80 OD, this decreased to 3.4 ± 4.2 attacks per week at V2, and 1.6 ± 2.6 at V3 (P < 0.05 at V2 and V3), with concomitant reductions in short-acting nitrate use (P < 0.05). Significant improvements in QoL were observed throughout the study. Subgroup analyses showed that the addition of TMZ 80 OD to guideline-recommended antianginal therapy was associated with significant reductions in the mean number of weekly angina attacks and consumption of short-acting nitrates and improvements in QoL whether patients were treated with maximally tolerated bisoprolol and TMZ 80 OD alone, or maximally tolerated bisoprolol and TMZ 80 OD on top of other antianginal therapies. Treatment was well tolerated.ConclusionThe study findings support the addition of TMZ 80 OD to bisoprolol with or without other antianginal therapies for patients with persistent angina.Trial RegistrationThis study was retrospectively registered under the number ISRCTN29992579.

Concomitant Treatment of Hypertensive Patients with Bisoprolol and Perindopril in Routine Clinical Practice: A Post Hoc Analysis of the CONFIDENCEII, PROTECTI, and PROTECTIII Observational Studies.

IntroductionThe combination of angiotensin-converting enzyme inhibitors and beta-blockers is recommended in a wide range of patients with hypertension, including those with stable coronary artery disease and/or elevated heart rate. This post hoc analysis of three observational studies provides effectiveness and safety data on treatment with perindopril on top of bisoprolol-based therapy, in routine clinical practice.MethodsData were analyzed from three open-label, prospective, multicenter, observational studies of Canadian patients with mild-to-moderate hypertension, which shared the same inclusion and exclusion criteria, treatment duration, and primary outcome. This post hoc analysis focused on the subpopulation of patients treated with perindopril on top of bisoprolol-based therapy. All patients were followed for 16 weeks and underwent baseline, week 4, and week 16 visits. Primary outcomes were mean changes in blood pressure (BP) and proportion of patients achieving BP control (< 140/90 mmHg) in the full analysis set (FAS).ResultsA total of 845 patients (mean age 68.3 ± 11.3 years, mean baseline BP 151.5/86.0 mmHg) were analyzed in the FAS. After 16 weeks, mean SBP/DBP decreased by − 20.4/− 9.8 mmHg with statistically significant reductions observed at all visits in all three studies allowing 78% of patients to achieve the BP treatment goal. No statistically significant changes in heart rate were observed and no serious adverse events reported. The most frequent doses of bisoprolol and perindopril were 5 + 4 mg (34.9%), followed by 5 + 8 mg (16.9%), and 2.5 + 4 mg (12.5%).ConclusionThe addition of perindopril on top of bisoprolol-based therapy in patients with mild-to-moderate hypertension was associated with significant reductions in BP compared with baseline and with achievement of BP targets in the majority of patients. The results suggest this strategy is safe and effective for use in routine clinical practice.

The role of SST2 in the prediction of left ventricular remodeling and the adverse cardiovascular events in patients with STEMI

Background and Aims: Contemporary studies show that sST2 may be considered as a promising predictor of LV remodeling and adverse prognosis in patients with acute myocardial infarction (AMI). The aim of the study was to investigate the effect of sST2 on the development of LV remodeling in patients with STEMI and the efficacy of different doses of bisoprolol in reducing the incidence of adverse events.

Pharmacogenetic testing by polymorphic markers G1846A (CYP2D6*4) and C100T (CYP2D6*10) of the CYP2D6 gene in coronary heart disease patients taking ββ-blockers in the Republic of Sakha (YAKUTIA).

Background The aim of this study was to determine carrier frequencies of the polymorphic markers G1846A (CYP2D6*4) and C100T (CYP2D6*10) of the CYP2D6 gene in coronary heart disease (CHD) patients in Russian and Yakut ethnic groups. The association between the administration of higher doses of bisoprolol and metoprolol and the carriage of these polymorphic markers related to the decreased function of the haplotype of CYP2D6 was also studied. Methods The study included 201 CHD patients (aged 66±8.7 years) receiving metoprolol in titrated dose (12.5-150 mg), bisoprolol (2.5-10 mg) or atenolol (50 mg). Ninety-three patients were Russian (30 men and 63 women), and 108 patients were Yakut (54 men and 54 women). Results In genotyping CHD patients in the Russian and Yakut ethnic groups, there was no significant difference in the prevalence rate of the polymorphic markers G1846A (10.8 vs. 10.2; p=0.871) and C100T (16.1 vs. 16.2; p=1). In patients carrying the polymorphic marker G1846A, the dose of bisoprolol was established to be lower than that in the control group (p=0.0289). Conclusions The carriage frequency of polymorphic markers, which theoretically should differ between Russians and Yakuts as representatives of two different races, in practice turned out to be the same.

Achievement of a target dose of bisoprolol may not be a preferred option for attenuating pressure overload-induced cardiac hypertrophy and fibrosis.

Bisoprolol is a drug that acts via the mechanism of specifically and selectively inhibiting the β1-adrenoreceptor in cardiac myocytes, and provides a pure reduction of heart rate without changing other cardiac parameters. It has long been clinically used to treat cerebrovascular and cardiovascular illnesses. However, there is little information available on whether the role of bisoprolol in the attenuation of ventricular remodeling is dependent upon the achievement of a target dose, and whether it must be used as a preferred option. The aim of the present study was to clarify the underlying benefits of bisoprolol in the attenuation of pressure overload-induced cardiac hypertrophy and fibrosis at different doses. C57BL/6J male mice, aged 6–8 weeks, were treated with saline or one of three different doses of bisoprolol (Biso: 2.5, 5 or 10 mg/kg/day) for 8 weeks from day 1 after aortic banding (AB). A number of mice underwent sham surgery and were treated with saline or bisoprolol. The mice were randomly assigned into the sham (n=24) and AB (n=62) groups. The results revealed that bisoprolol had a protective role against the cardiac hypertrophy, fibrosis and dysfunction caused by AB. This was determined on the basis of heart/body and lung/body weight ratios and heart weight/tibia length ratios, as well as echocardiographic and hemodynamic parameters, histological analysis, and the gene expression levels of hypertrophic and fibrotic markers. The present study revealed that administration of bisoprolol for a long time period may enhance its role in the prevention of cardiac hypertrophy and fibrosis induced by AB, whereas no statistically significant difference was observed between the middle- and high-doses. These observations indicated that the function of bisoprolol in protecting against cardiac hypertrophy, fibrosis and dysfunction is time-dependent. Furthermore, it is proposed that a middle dose of bisoprolol may be a better option for patients with cardiovascular illnesses, particularly those undertaking coronary artery bypass graft and cardiac pacemaker surgeries. These promising results require further clinical investigation.

The impact of an algorithm on the optimization of beta-blockers after cardiac surgery.

To evaluate the impact of a simple written algorithm of early postoperative beta-blocker administration on daily practices. A prospective, single center observational study. A 16-bed cardiac surgical intensive care unit in a university teaching hospital. One hundred twenty-five consecutive adult patients chronically treated with beta-blockers and scheduled for conventional cardiac surgery. Two successive 4-month phases: Phase 1 = uncontrolled early postoperative beta-blocker administration (n = 73) and phase 2 = beta-blocker administration by an institutional written algorithm using incremental doses of bisoprolol and/or esmolol (n = 52). The main endpoint was the number of patients receiving beta-blockers on the morning of postoperative day 1. Secondary endpoints were the number of patients receiving beta-blockers on the morning of postoperative day 1 and reaching the targeted therapeutic goal and the incidence of postoperative atrial fibrillation in the intensive care unit. A 79% increase in the number of patients receiving beta-blockers on the morning of postoperative day 1 (42% v 75%, p<0.001) was observed during the second phase of the study. The number of patients receiving beta-blockers on the morning of postoperative day 1 and reaching the targeted therapeutic goal was increased significantly by 127% (33% v 75%, p<0.001). The incidence of atrial fibrillation was similar between both phases of the study: 37% versus 31%, p = 0.567. A simple written algorithm markedly improved early postoperative continuation of beta-blockers in chronically treated patients undergoing conventional cardiac surgery.

Efficacy and safety of bisoprolol fumarate compared with carvedilol in Japanese patients with chronic heart failure: results of the randomized, controlled, double-blind, Multistep Administration of bisoprolol IN Chronic Heart Failure II (MAIN-CHF II) study

Bisoprolol fumarate (bisoprolol) is a β-blocker widely used to treat chronic heart failure (CHF). However, few studies have compared its efficacy and safety with those of the widely used β-blocker carvedilol in Japanese patients with CHF. We designed a confirmatory trial of bisoprolol using carvedilol as a control drug; however, the trial was discontinued after an off-label use of bisoprolol was approved during the study. Bisoprolol and carvedilol were administered for 32 weeks in 31 and 28 patients, respectively. The mean maintenance doses of bisoprolol and carvedilol were 3.3 and 13.6 mg/day, respectively, and the mean durations of treatment were 188.2 and 172.9 days, respectively. Heart-rate changes were similar in both groups. The mean changes from baseline to Week 32 in left ventricular (LV) ejection fraction (EF) (bisoprolol vs carvedilol groups; 11.7 % ± 8.6 % vs 10.1 % ± 10.5 %), LV end-diastolic volume (-37.5 ± 48.7 vs -24.7 ± 29.4 ml), and LV end-systolic volume (-41.9 ± 43.0 vs -29.3 ± 25.9 ml) revealed a decrease in LV volume and an increase in LVEF in both groups. The cumulative event-free rate for a composite of cardiovascular death or admissions to hospital for worsening of CHF was 92.4 % and 94.7 % in the bisoprolol and carvedilol groups, respectively. Overall, 90.3 % and 85.7 % of patients were titrated up to the maintenance doses of bisoprolol and carvedilol, respectively. Bisoprolol, at half the dose used in other countries, is well tolerated and is as effective as carvedilol for treating Japanese patients with mild to moderate CHF.

Acute heart failure due to myocarditis in the first trimester of pregnancy

The incidence of cardiovascular diseases in pregnancy is estimated at about 1%. Pregnant women suffer from rheumatic diseases of the heart valves, hypertension, congenital heart deffects, inflammatory and ischemic disorders or pathologies of the electrical conduction system of the heart. Myocarditis during pregnancy occurs very seldom. Few cases of severe myocarditis during gestation have been reported in the literature. This report presents a case of a 27-year-old Asian patient, at 8 weeks of gestation, diagnosed with an acute myocarditis. The woman was admitted to the hospital, presenting with early and nonspecific symptoms, (fever up of 38.5 degrees Celsiuss, abdominal pain and nausea). After temporary improvement, the patient's condition deteriorated. On the fourth day of the hospitalization, myocarditis led to heart failure and the patient had to be transffered to the Intensive Care Unit. Wide-spectrum antibiotics, glucocorticoids, diuretics, bisoprolol, as well as fluid and electrolyte supplementation, were administered. After 22 days of treatment the patient was discharged home in good condition. Afterwards she attended follow-up visits at the Gynecology-Obstetric Outpatient Clinic. She delivered a healthy son (2340 grams, 51 centimetres, Apgar 10) at 37 weeks of gestation. At present, she remains under the care of the Cardiac Clinic and requires small doses of bisoprolol because of periodic supraventricular arrhythmias.

501 The Influence of Beta - Blocker (Bisoprolol) on Heart Rate Variability in Children with Mitral Valve Prolapse

The carried out research has included 50 children: I group (bisoprolol)-60% children and II group (placebo) - 40.0%, average age (13.5±0.60) years; doses of bisoprolol (PO): 1.25–2.5mg/kg/dose.ECG monitoring has defined...

Influence of order and type of drug (bisoprolol vs. enalapril) on outcome and adverse events in patients with chronic heart failure: apost hocanalysis of the CIBIS-III trial

Angiotensin-converting enzyme inhibitors (ACE-Is) and beta-blockers are associated with improved outcome in patients with chronic heart failure (CHF). In this post hoc analysis of the CIBIS III trial, we examined the influence of the order of drug administration on clinical events and achieved dose. We also assessed the relations between dose levels and baseline variables or adverse events. In the CIBIS III trial, 1010 patients (mean age: 72.4 years; mean ejection fraction: 28.8%; male: 68.2%) with stable CHF were randomized to up-titration of monotherapy with either bisoprolol (target dose 10 mg o.d.) or enalapril (target dose 10 mg b.i.d.) for 6 months, followed by their combination for 6-24 months. Endpoints were mortality or all-cause hospitalization, mortality alone and mortality or cardiovascular hospitalization. The study drug (ACE-I or beta-blocker) was last prescribed at ≥50% of target dose to significantly more patients for the first initiated drug in both treatment groups (both P< 0.001). Sixty per cent of endpoints were reached during the monotherapy phase and randomized treatment during monotherapy was not a predictor of the three assessed outcomes. Monotherapy phase was the strongest independent predictor of outcome (P< 0.0001 for all endpoints). Older age, NYHA class III, impaired renal function, lower body weight and blood pressure at baseline, and hypotension, bradycardia and heart failure during treatment were associated with the inability to reach high dose of both study drugs. The order of drug administration plays an important role in whether CHF patients reach target doses of bisoprolol and enalapril. For both study drugs, the dose level reached was associated with baseline characteristics and adverse events. In CHF patients not treated with an ACE-I or a beta-blocker, the duration of monotherapy with either type of drug should be shorter than 6 months.

Rationale and design of the Newer Versus Older Antihypertensive Agents in African Hypertensive Patients (NOAAH) trial

Background. Sub-Saharan Africa experiences an epidemic surge in hypertension. Studies in African Americans led to the recommendation to initiate antihypertensive treatment in Blacks with a diuretic or a low-dose fixed combination including a diuretic. We mounted the Newer versus Older Antihypertensive Agents in African Hypertensive Patients (NOAAH) trial to compare in native African patients a fixed combination of newer drugs, not involving a diuretic, with a combination of older drugs including a diuretic. Methods. Patients aged 30–69 years with uncomplicated hypertension (140–179/90–109 mmHg) and two or fewer associated risk factors are eligible. After a 4-week run-in period off treatment, 180 patients will be randomized to once daily bisoprolol/hydrochlorothiazide 5/6.25 mg or amlodipine/valsartan 5/160 mg. To attain and maintain blood pressure below 140/90 mmHg during 6 months of follow-up, the doses of bisoprolol and amlodipine in the combination tablets will be increased to 10 mg/day with the possible addition of α-methyldopa or hydralazine. NOAAH is powered to demonstrate a 5-mmHg between-group difference in sitting systolic pressure with a two-sided p-value of 0.01 and 90% power. NOAAH is investigator-led and complies with the Helsinki declaration. Results. Six centers in four sub-Saharan countries started patient recruitment on September 1, 2010. On December 1, 195 patients were screened, 171 were enrolled, and 51 were randomized and followed up. The trial will be completed in the third quarter of 2011. Conclusions. NOAAH (NCT01030458) is the first randomized multicenter trial of antihypertensive medications in hypertensive patients born and living in sub-Saharan Africa.

DRUGS AND SMOKING

Smoking is a well – known risk factor of many diseases. It influences the efficacy and safety of drug treatment by affecting the course of different physiological processes and modifying the metabolism of drugs. The number of researches showed decrease in efficacy of some cardiovascular drugs in smokers. Aim. To compare efficacy and safety of selective and non-selective beta–adrenoceptor blockers in smokers and nonsmokers with chronic ischemic disease. Material and Methods. Antianginal efficacy of drugs in patients of both groups was evaluated by burden tests on treadmill, effective doses of bisoprolol and propranolol were adjusted. Results. The result shows that smokers two times more often need prescription of double doses of drugs. Depressed antianginal activity of both beta-adrenoceptor blockers, especially of non-selective propranolol, in smokers was revealed. When evaluating the parameters of spirography, it was found that non-selective beta-adrenoceptor blocker propranol statistically significant decreases figures of bronchial passage, irrespective of the status of smoking. Moreover, with propranol treatment, bigger number of side effects is registered in both groups, demonstrating 30% more in smok???ers compared to nonsmokers. Conclusion. Smoking attenuates efficacy and safety of beta-blockers, especially these of non-selective ones.

Effects of bisoprolol in patients with stable congestive heart failure

Aim of the study. – To analyze the effect of bisoprolol in patients with stable congestive heart failure and who tolerated beta-blockers. Material and methods. – Two hundred and one patients performed before and 3 months after maximal tolerated doses of bisoprolol have been reached, a clinical evaluation, an echocardiography, a radionuclide angiography, a cardiopulmonary exercise test and hormonal determinations. Results. – Mean dose of bisoprolol was 8.8 ± 2.4 mg/d. Patients had a significant improvement in NYHA classification. Heart rate at rest decreased from 87 ± 17 to 66 ± 12 beats/min ( P < 0.0001) without any effect on electrocardiographic parameters. Left ventricular ejection fraction improved from 31 ± 11 to 41 ± 13% ( P < 0.0001), with a significant decrease in end-diastolic and end-systolic left ventricle diameters and volumes. Mitral profil improved. Peak VO 2 increased from 16.1 ± 5 to 16.8 ± 5.5 ml/min/kg ( P = 0.001) with a significant increase in O 2 pulse (from 8.52 ± 2.7 to 11.2 ± 3.5 ml/min/beats, P < 0.0001). Plasma levels of A-type and of B-type natriuretic peptides and of norepinephrine significantly decreased after bisoprolol. Conclusions. – Bisoprolol significantly improved left ventricle ejection fraction with a reverse remodeling of the left ventricle, a decrease in hormonal activation and a modest improvement in exercise capacity.

Beta-blocker efficacy according to heart rate and rhythm in patients with heart failure. Commentary on the Cardiac Insufficiency Bisoprolol Study II analysis.

Large randomized trials have demonstrated that beta-blocker treatment reduces morbidity and mortality in patients in chronic heart failure. Questions remain about the influence of individual characteristics on the magnitude of the benefit of beta-blockers in patients with heart failure including the influence of heart rate and cardiac rhythm. In the Cardiac Insufficiency Bisoprolol Study II, baseline heart rate and heart rate change over time had prognostic value but treatment with bisoprolol was associated with a benefit at all levels of baseline heart rate and additional benefit related to heart rate slowing was observed. In the subgroup of patients with atrial fibrillation, morbidity and mortality rates were similar in placebo and bisoprolol treated patients. It is possible that patients with atrial fibrillation had a higher level of sympathetic stimulation that would have required higher doses of bisoprolol to achieve a similar level of beta-blockade. Alternatively, the failure to observe improved outcome in the subgroup with atrial fibrillation may have been due to chance. However, because this finding was not observed in other large trials, and because there was no clear explanation, it should not be concluded that patients with chronic heart failure and atrial fibrillation do not benefit from beta-blockade.

Empleo de bisoprolol en la insuficiencia cardíaca. Resultados del estudio BISOCOR

The benefits of beta blockers in heart failure are highly dependent on dosage. This study aimed to analyze the degree of concordance between targeted (CIBIS II) and achieved doses of bisoprolol in a group of patients with stable heart failure on conventional treatment. We also evaluated functional parameters, adverse effects and the reasons for withdrawal or drop-out. The study group consisted of 334 patients with stable systolic heart failure who were receiving conventional treatment. Treatment with bisoprolol was initiated according to current guidelines (starting dose 1.25 mg/day, with weekly increments to 5 mg/day, and then increments every four weeks to a targeted dosis of 10 mg/day). The main endpoint was the comparison between targeted dose and dose reached at each follow-up. Secondary endpoints were quality of life assessment (Minnesota Living with Heart Failure Questionnaire), functional status (New York Heart Association), ejection fraction change, and side effects during the 9-month follow-up period. Thirty-four (10%) patients did not finish the study: 1 because of sudden death, 2 because of surgery, and 31 because of side effects. 63% of the patients attained the maximum targeted dose; the mean dose at the end of follow-up was 8.5 mg. Functional status, quality of life and ejection fraction improved significantly between the beginning and the end of the study. Only 4 patients had severe adverse effects. This is the first study in Spain to show that bisoprolol can be used effectively at the maximum recommended doses, for the outpatient treatment of heart failure.

Influences of nonselective, β 1-selective and vasodilatory β 1-selective β-blockers on arterial pulse wave velocity in normotensive subjects

β-Adrenoceptor blockers with disparate properties may have differential influences on arterial pulse wave velocity (PWV). Therefore, influences of single medium doses of bisoprolol, propranolol and celiprolol on PWV were compared in healthy subjects. Arterial PWV was obtained from the time delay between flow pulses measured from the root of the aorta and the popliteal artery. Bisoprolol and propranolol decreased arterial PWV more than placebo ( P≤.002) and celiprolol ( P<.0001). In conclusion, the acute effects of bisoprolol and propranolol on arterial PWV in normotensive subjects seem to differ from that of celiprolol.

Beta-adrenergic receptor blockade in chronic heart failure.

The medical treatment of chronic heart failure has undergone a remarkable transition in the past 10 years. The approach has changed from a short-term hemodynamic/pharmacological paradigm to a more long-term, reparative strategy that aims to favorably alter the biological properties of the failing heart.1 This is dramatically illustrated by the recent success in treating mild-to-moderate chronic heart failure with β-adrenergic blocking agents. This review describes how a treatment that began as a contraindication1 2 3 became an established treatment of chronic heart failure. The failing human heart is adrenergically activated,4 5 6 which helps to maintain cardiac performance over the short term by increasing contractility and heart rate. In contrast, in the resting state there is no adrenergic support of normally functioning human left ventricles.6 Multiple lines of evidence7 8 9 indicate that it is the increase in cardiac adrenergic drive rather than an increase in circulating norepinephrine that is both initially supportive and then ultimately damaging to the failing human heart. As shown in Table 1⇓, there are 3 adrenergic receptors (β1, β2, and α1) in human cardiac myocytes coupled to a positive inotropic response and cell growth.10 11 12 β-Adrenergic receptors are coupled via the “stimulatory” G protein Gs to the effector enzyme adenylyl cyclase, which converts the substrate MgATP to cAMP. cAMP is a positively inotropic and chronotropic second messenger and is strongly growth promoting. In nonfailing human left or right ventricles, the β1/β2 ratio is 70 to 80/30 to 20, but in failing human ventricles, 35% to 40% of the total number of β-receptors are β2 because of selective downregulation in the β1 subtype.10 11 α1 Receptors are coupled via a different G protein (G …

Effects of small doses of bisoprolol on blood pressure and lipoprotein concentrations in hypertensive patients

The effects of bisoprolol 2.5 and 5 mg per day on blood pressure, and lipoprotein and apolipoprotein concentrations were compared in 18 newly detected hypertensives in a double-blind, crossover study. All treatment results were related to the values at the end of a four-week placebo run-in period. Each of the two following treatment periods lasted for 3 months. The systolic and diastolic pressures in the supine position were reduced by 19.5/11.7 mm Hg and 14.6/10.4 mm Hg by 2.5 and 5 mg bisoprolol per day, respectively, with no significant difference in effect. Supine heart rate was reduced by 4.7 and 8.2 beats.min-1, respectively, (P = 0.0517 for different effects). The cholesterol concentration in low-density (LDL) and high-density (HDL) lipoproteins was reduced during both regimens, by about 0.3 and 0.1 mmol.l-1, respectively, difference not significant. Triglyceride concentrations were not significantly affected during either regimen. We conclude that, in this study population, treatment with bisoprolol 2.5 mg per day was equally effective as 5.0 mg per day in reducing blood pressure. The effects on lipoprotein concentrations were small and included an unexpected reduction in LDL-cholesterol concentration. A low dose of a highly selective beta-adrenoceptor blocker like bisoprolol appears to retain the blood pressure reducing capacity and has lost most of the unfavourable effects on lipoproteins characteristic of higher doses.

A dose-ranging study to evaluate the β1-adrenoceptor selectivity of bisoprolol

A dose-ranging study was performed to compare the β1-adrenoceptor selectivity of bisoprolol with that of atenolol and nadolol. Seven normal subjects (mean age 26 y) were given single oral doses of bisoprolol 5 mg (B5), 10 mg (B10), 20 mg (B20); atenolol 50 mg (A50), 100 mg (A100); nadolol 40 mg (N40); and placebo (PL), in a single blind randomised cross-over design. β2-adrenoceptor responses were assessed by attenuation of finger tremor and cardiovascular responses to graded isoprenaline infusions. Dose-response curves were constructed, and doses of isoprenaline required to increase finger tremor by 100% (IT100), heart rate by 25 beats/min (IH25), SBP by 25 mm Hg (IS25), cardiac output by 35% (IC35), and decrease DBP by 10 mm Hg (ID10), after each treatment were calculated. These indices were compared with placebo response and expressed as dose-ratios. Exercise heart rate (EHR) was used to assess β1-adrenoceptor blockade.