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Annales Pharmaceutiques Francaises Sep 2022Beta-blockers have long been successfully used for the treatment of both supraventricular and ventricular arrhythmias. However, differences exist between their chemical... (Review)
Review
OBJECTIVES
Beta-blockers have long been successfully used for the treatment of both supraventricular and ventricular arrhythmias. However, differences exist between their chemical structure, pharmacokinetic and pharmacodynamic properties (absorption, bioavailability, metabolism, hydrophilic or lipophilic character, selective or non-selective nature, the presence or absence of intrinsic sympathomimetic activity), which may confer different antiarrhythmic properties to different beta-blockers. The aim of this study was to analyze the current existing evidence for bisoprolol for the treatment of both supraventricular and ventricular arrhythmias.
MATERIAL AND METHODS
Using the keywords "bisoprolol" and "arrhythmias" or "atrial fibrillation" or "ventricular tachycardia" or "premature ventricular complexes" or "ventricular fibrillation", the Medline database was searched for articles in English or French until April 2020 assessing the role of bisoprolol in the treatment of arrhythmias. Data was then analyzed according to the type of arrhythmia treated and the quality of evidence using the GRADE approach.
RESULTS
A total of 325 studies were identified, of which 28 were considered relevant to the current topic. Among these studies, 19 assessed the role of bisoprolol for the treatment of supraventricular arrhythmias, 8 its role in treating ventricular arrhythmias and 1 its role in supraventricular and ventricular arrhythmias. The quality of evidence varied from low (7 studies) to high (5 studies).
CONCLUSION
Current evidence exists supporting the use of bisoprolol for the treatment of supraventricular arrhythmias, especially for rate control during atrial fibrillation. Evidence also exists for its efficacy in the treatment of ventricular arrhythmias, both in primary and in secondary prevention.
Topics: Adrenergic beta-Antagonists; Atrial Fibrillation; Bisoprolol; Humans
PubMed: 35093388
DOI: 10.1016/j.pharma.2022.01.007 -
JAMA Dec 2020There is little evidence to support selection of heart rate control therapy in patients with permanent atrial fibrillation, in particular those with coexisting heart... (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
There is little evidence to support selection of heart rate control therapy in patients with permanent atrial fibrillation, in particular those with coexisting heart failure.
OBJECTIVE
To compare low-dose digoxin with bisoprolol (a β-blocker).
DESIGN, SETTING, AND PARTICIPANTS
Randomized, open-label, blinded end-point clinical trial including 160 patients aged 60 years or older with permanent atrial fibrillation (defined as no plan to restore sinus rhythm) and dyspnea classified as New York Heart Association class II or higher. Patients were recruited from 3 hospitals and primary care practices in England from 2016 through 2018; last follow-up occurred in October 2019.
INTERVENTIONS
Digoxin (n = 80; dose range, 62.5-250 μg/d; mean dose, 161 μg/d) or bisoprolol (n = 80; dose range, 1.25-15 mg/d; mean dose, 3.2 mg/d).
MAIN OUTCOMES AND MEASURES
The primary end point was patient-reported quality of life using the 36-Item Short Form Health Survey physical component summary score (SF-36 PCS) at 6 months (higher scores are better; range, 0-100), with a minimal clinically important difference of 0.5 SD. There were 17 secondary end points (including resting heart rate, modified European Heart Rhythm Association [EHRA] symptom classification, and N-terminal pro-brain natriuretic peptide [NT-proBNP] level) at 6 months, 20 end points at 12 months, and adverse event (AE) reporting.
RESULTS
Among 160 patients (mean age, 76 [SD, 8] years; 74 [46%] women; mean baseline heart rate, 100/min [SD, 18/min]), 145 (91%) completed the trial and 150 (94%) were included in the analysis for the primary outcome. There was no significant difference in the primary outcome of normalized SF-36 PCS at 6 months (mean, 31.9 [SD, 11.7] for digoxin vs 29.7 [11.4] for bisoprolol; adjusted mean difference, 1.4 [95% CI, -1.1 to 3.8]; P = .28). Of the 17 secondary outcomes at 6 months, there were no significant between-group differences for 16 outcomes, including resting heart rate (a mean of 76.9/min [SD, 12.1/min] with digoxin vs a mean of 74.8/min [SD, 11.6/min] with bisoprolol; difference, 1.5/min [95% CI, -2.0 to 5.1/min]; P = .40). The modified EHRA class was significantly different between groups at 6 months; 53% of patients in the digoxin group reported a 2-class improvement vs 9% of patients in the bisoprolol group (adjusted odds ratio, 10.3 [95% CI, 4.0 to 26.6]; P < .001). At 12 months, 8 of 20 outcomes were significantly different (all favoring digoxin), with a median NT-proBNP level of 960 pg/mL (interquartile range, 626 to 1531 pg/mL) in the digoxin group vs 1250 pg/mL (interquartile range, 847 to 1890 pg/mL) in the bisoprolol group (ratio of geometric means, 0.77 [95% CI, 0.64 to 0.92]; P = .005). Adverse events were less common with digoxin; 20 patients (25%) in the digoxin group had at least 1 AE vs 51 patients (64%) in the bisoprolol group (P < .001). There were 29 treatment-related AEs and 16 serious AEs in the digoxin group vs 142 and 37, respectively, in the bisoprolol group.
CONCLUSIONS AND RELEVANCE
Among patients with permanent atrial fibrillation and symptoms of heart failure treated with low-dose digoxin or bisoprolol, there was no statistically significant difference in quality of life at 6 months. These findings support potentially basing decisions about treatment on other end points.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02391337 and clinicaltrialsregister.eu Identifier: 2015-005043-13.
Topics: Adrenergic beta-1 Receptor Antagonists; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Bisoprolol; Digoxin; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Quality of Life; Single-Blind Method; Stroke Volume
PubMed: 33351042
DOI: 10.1001/jama.2020.23138 -
Cardiovascular Drugs and Therapy Oct 2022Bisoprolol and nebivolol are highly selective β-adrenoceptor antagonists, with clinical indications in many countries within the management of heart failure with... (Review)
Review
Therapeutic Properties of Highly Selective β-blockers With or Without Additional Vasodilator Properties: Focus on Bisoprolol and Nebivolol in Patients With Cardiovascular Disease.
Bisoprolol and nebivolol are highly selective β-adrenoceptor antagonists, with clinical indications in many countries within the management of heart failure with reduced left ventricular ejection fraction (HFrEF), ischaemic heart disease (IHD), and hypertension. Nebivolol has additional vasodilator actions, related to enhanced release of NO in the vascular wall. In principle, this additional mechanism compared with bisoprolol might lead to more potent vasodilatation, which in turn might influence the effectiveness of nebivolol in the management of HFrEF, IHD and hypertension. In this article, we review the therapeutic properties of bisoprolol and nebivolol, as representatives of "second generation" and "third generation" β-blockers, respectively. Although head-to-head trials are largely lacking, there is no clear indication from published studies of an additional effect of nebivolol on clinical outcomes in patients with HFrEF or the magnitude of reductions of BP in patients with hypertension.
Topics: Adrenergic beta-Antagonists; Benzopyrans; Bisoprolol; Cardiovascular Diseases; Ethanolamines; Heart Failure; Humans; Hypertension; Myocardial Ischemia; Nebivolol; Stroke Volume; Vasodilator Agents; Ventricular Function, Left
PubMed: 34106365
DOI: 10.1007/s10557-021-07205-y -
Trials Apr 2022Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity, mortality and healthcare costs. Beta blockers are well-established drugs widely... (Randomized Controlled Trial)
Randomized Controlled Trial
Use of the oral beta blocker bisoprolol to reduce the rate of exacerbation in people with chronic obstructive pulmonary disease (COPD): a randomised controlled trial (BICS).
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity, mortality and healthcare costs. Beta blockers are well-established drugs widely used to treat cardiovascular conditions. Observational studies consistently report that beta blocker use in people with COPD is associated with a reduced risk of COPD exacerbations. The bisoprolol in COPD study (BICS) investigates whether adding bisoprolol to routine COPD treatment has clinical and cost-effective benefits. A sub-study will risk stratify participants for heart failure to investigate whether any beneficial effect of bisoprolol is restricted to those with unrecognised heart disease.
METHODS
BICS is a pragmatic randomised parallel group double-blind placebo-controlled trial conducted in UK primary and secondary care sites. The major inclusion criteria are an established predominant respiratory diagnosis of COPD (post-bronchodilator FEV < 80% predicted, FEV/FVC < 0.7), a self-reported history of ≥ 2 exacerbations requiring treatment with antibiotics and/or oral corticosteroids in a 12-month period since March 2019, age ≥ 40 years and a smoking history ≥ 10 pack years. A computerised randomisation system will allocate 1574 participants with equal probability to intervention or control groups, stratified by centre and recruitment in primary/secondary care. The intervention is bisoprolol (1.25 mg tablets) or identical placebo. The dose of bisoprolol/placebo is titrated up to a maximum of 4 tablets a day (5 mg bisoprolol) over 4-7 weeks depending on tolerance to up-dosing of bisoprolol/placebo-these titration assessments are completed by telephone or video call. Participants complete the remainder of the 52-week treatment period on the final titrated dose (1, 2, 3, 4 tablets) and during that time are followed up at 26 and 52 weeks by telephone or video call. The primary outcome is the total number of participant reported COPD exacerbations requiring oral corticosteroids and/or antibiotics during the 52-week treatment period. A sub-study will risk stratify participants for heart failure by echocardiography and measurement of blood biomarkers.
DISCUSSION
The demonstration that bisoprolol reduces the incidence of exacerbations would be relevant not only to patients and clinicians but also to healthcare providers, in the UK and globally.
TRIAL REGISTRATION
Current controlled trials ISRCTN10497306 . Registered on 16 August 2018.
Topics: Adrenal Cortex Hormones; Adrenergic beta-Antagonists; Adult; Anti-Bacterial Agents; Bisoprolol; Disease Progression; Heart Failure; Humans; Pulmonary Disease, Chronic Obstructive
PubMed: 35422024
DOI: 10.1186/s13063-022-06226-8 -
Profiles of Drug Substances,... 2021The present study describes a comprehensive profile of Bisoprolol including detailed nomenclature; formulae, elemental analysis, appearance, its uses, applications, and...
The present study describes a comprehensive profile of Bisoprolol including detailed nomenclature; formulae, elemental analysis, appearance, its uses, applications, and methods for the preparation are outlined. The profile contains physicochemical properties of Bisoprolol including pKa value, solubility, X-ray powder diffraction, and methods of analysis (including compendial, electrochemical, spectroscopic, chromatographic and capillary electrophoresis). The study also covers thermal analysis such as differential scanning calorimetry and thermogravimetry of Bisoprolol. Which gives a brief idea of melting point, glass transition as well as differentiation between anhydrous and hydrated forms. In addition to these functional groups and structural confirmation of bisoprolol also presented with the help of Fourier transform infrared spectrometry and nuclear magnetic resonance spectroscopy, respectively. The mass fragmentation pattern of bisoprolol fumarate was reported using the electrospray ionization technique. Some recently reported methods for pharmacokinetic analysis of bisoprolol using high-performance liquid chromatography as well as liquid chromatography-mass spectrometry were also included in the study.
Topics: Bisoprolol; Chromatography, High Pressure Liquid; Drug Stability; Mass Spectrometry; Nuclear Magnetic Resonance, Biomolecular; Solubility; Spectroscopy, Fourier Transform Infrared
PubMed: 33461700
DOI: 10.1016/bs.podrm.2020.07.006 -
The Annals of Pharmacotherapy Apr 1995To review the pharmacology, pharmacokinetics, and clinical experience with bisoprolol and make recommendations regarding its potential clinical usefulness, as well as... (Comparative Study)
Comparative Study Review
OBJECTIVE
To review the pharmacology, pharmacokinetics, and clinical experience with bisoprolol and make recommendations regarding its potential clinical usefulness, as well as considerations for formulary inclusion.
DATA SOURCES
Reference citations were sought from Index Medicus and Science Citation Index. Data were collected from abstracts and articles describing experimental studies or blind clinical trials.
STUDY SELECTION
Studies designed in a randomized, blind, and placebo-controlled manner were emphasized. Studies also were included if bisoprolol was evaluated comparatively with other agents in a randomized, blind fashion.
DATA EXTRACTION
Data from human studies published in English were evaluated. Studies were assessed by sample size and the clarity of descriptions of methods and results.
DATA SYNTHESIS
Bisoprolol reduces systolic and diastolic blood pressures in patients with hypertension for a 24-hour dosing interval and is associated with beneficial hemodynamic effects in patients with myocardial ischemia. It is devoid of intrinsic sympathomimetic activity and membrane-stabilizing effects at therapeutic dosages. In patients with hypertension, bisoprolol diminishes plasma renin activity, platelet aggregation, effective renal plasma flow, and creatinine clearance. Bisoprolol has minimal effects on glucose tolerance and plasma lipid profiles. Monotherapy with bisoprolol is as effective as with atenolol, nitrendipine, or nifedipine. Low-dose combination therapy with hydrochlorothiazide is at least as effective as either bisoprolol or hydrochlorothiazide alone. Preliminary experience in the management of angina pectoris suggests that bisoprolol is at least as efficacious as atenolol or verapamil. Thus far, reported adverse effects are similar to those of other beta-blockers. No clinically important drug interactions have been reported at this time.
Topics: Angina Pectoris; Bisoprolol; Clinical Trials as Topic; Drug Interactions; Electrophysiology; Hemodynamics; Humans; Hypertension; Lipids
PubMed: 7633020
DOI: 10.1177/106002809502900412 -
American Journal of Therapeutics 2020Many patients receiving dabigatran treatment might also require bisoprolol therapy. However, there is a possibility that bisoprolol as significant P-glycoprotein...
BACKGROUND
Many patients receiving dabigatran treatment might also require bisoprolol therapy. However, there is a possibility that bisoprolol as significant P-glycoprotein inhibitor might interact with dabigatran.
STUDY QUESTION
To investigate the impact of concomitant bisoprolol therapy on dabigatran plasma level in patients with nonvalvular atrial fibrillation.
STUDY DESIGN
A pilot drug interaction study in 29 patients with nonvalvular atrial fibrillation on dabigatran therapy. Bisoprolol was administrated in 18 patients. Blood samples were collected at baseline (in the morning, before any medication was administered) and at hour 2 (2 hours after administration of dabigatran and bisoprolol).
RESULTS
The dabigatran plasma level was significantly higher at baseline and at hour 2 in patients treated with bisoprolol compared with patients without bisoprolol therapy. In addition, we have shown that this increase is affected by dabigatran dosage and concomitant treatment with proton-pump inhibitor and digoxin. The impact of bisoprolol on dabigatran concentration was still significant despite these confounders.
CONCLUSIONS
This study demonstrated the interaction between dabigatran and bisoprolol, which is modulated with dabigatran dosage and concomitant treatment with proton-pump inhibitor and digoxin.
Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Bisoprolol; Cardiotonic Agents; Dabigatran; Digoxin; Drug Interactions; Female; Humans; Male; Middle Aged; Pilot Projects; Proton Pump Inhibitors
PubMed: 30074534
DOI: 10.1097/MJT.0000000000000786 -
Vascular Health and Risk Management 2007Bisoprolol fumarate is a highly selective beta-1 receptor blocker. Bisoprolol has been extensively studied in three large mortality trials in stable chronic heart... (Review)
Review
Bisoprolol fumarate is a highly selective beta-1 receptor blocker. Bisoprolol has been extensively studied in three large mortality trials in stable chronic heart failure (CHF) patients. The CIBIS trial enrolled 641 patients and demonstrated the good tolerability of bisoprolol in a large CHF population, without evidence for any harmful effect. The CIBIS-II study was the first large randomized, double-blind, placebo-controlled study demonstrating in 2647 patients a dramatic reduction in mortality with a beta-blocking agent in CHF patients. CIBIS-III demonstrated in 1010 patients the equivalence of 2 different therapeutic strategies in de novo CHF patients. There was no difference in morbidity and mortality between sub-groups of patients receiving first bisoprolol or enalapril. These three trials also demonstrated the good tolerability of bisoprolol fumarate. Other studies were either limited in number of patients or not randomized. However, these studies confirmed the good tolerability of bisoprolol in CHF patients, even in elderly population. Bisoprolol fumarate is a selective beta-1 receptor blocker that significantly reduced morbidity and mortality in stable CHF patients. Bisoprolol is well tolerated with few significant side effects in different large trials.
Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Bisoprolol; Chronic Disease; Drug Administration Schedule; Drug Tolerance; Enalapril; Female; Heart Failure; Humans; Male; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 17969374
DOI: No ID Found -
Drugs 2002Bisoprolol is a highly selective beta(1)-adrenoceptor antagonist. Administration of bisoprolol to patients with chronic heart failure is associated with increases in... (Review)
Review
Bisoprolol is a highly selective beta(1)-adrenoceptor antagonist. Administration of bisoprolol to patients with chronic heart failure is associated with increases in left ventricular function and reductions in heart rate; increases in heart rate variability are also seen. Two major randomised, double-blind, placebo-controlled, multicentre trials have examined the clinical efficacy of bisoprolol in combination with ACE inhibitors and diuretics in patients with stable chronic heart failure (New York Heart Association class III or IV): the Cardiac Insufficiency Bisoprolol Study (CIBIS; n = 641) and CIBIS II (n = 2 647). All-cause mortality (primary endpoint) was significantly lower in bisoprolol than in placebo recipients in CIBIS II (11.8 vs 17.3%) and was reduced by bisoprolol regardless of dosage. All-cause mortality was also lower in CIBIS (16.6 vs 20.9%) although the difference did not achieve statistical significance. In a meta-analysis of CIBIS and CIBIS II (n = 3 288), a relative reduction of 29% in the incidence of all-cause mortality was seen in bisoprolol versus placebo recipients; this analysis also demonstrated that bisoprolol reduces mortality in patients with chronic heart failure regardless of aetiology or severity. In CIBIS II, there were significantly fewer cardiovascular deaths, admissions to hospital for any reason, or cardiovascular deaths or cardiovascular hospitalisations (combined endpoint) in bisoprolol, compared with placebo, recipients (secondary endpoints). Compared with standard treatment alone, the addition of bisoprolol was a cost-effective option in chronic heart failure in UK, French, German and Swedish pharmacoeconomic studies. Bisoprolol is generally well tolerated in patients with chronic heart failure. In CIBIS II, adverse events occurring more commonly in bisoprolol than placebo recipients, regardless of causal relationship with the study medication, included dizziness, bradycardia, hypotension and fatigue. Bisoprolol recipients were less likely than placebo recipients to experience worsening of heart failure, dyspnoea or tachycardia. In both CIBIS and CIBIS II there was no significant difference between bisoprolol and placebo recipients in the incidence of permanent treatment withdrawal. In conclusion, adding the highly selective beta(1)-blocker bisoprolol to a treatment regimen comprising an ACE inhibitor and a diuretic significantly improves survival in patients with stable chronic heart failure and reduces the need for hospitalisation. The use of bisoprolol in this disorder is generally well tolerated and is cost effective. Thus, bisoprolol should be considered a standard treatment option when selecting a beta-blocker for use in combination with ACE inhibitors and diuretics in patients with stable, moderate to severe chronic heart failure.
Topics: Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-Antagonists; Bisoprolol; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Drug Administration Schedule; Heart Failure; Humans; Randomized Controlled Trials as Topic
PubMed: 12466013
DOI: 10.2165/00003495-200262180-00017 -
Expert Opinion on Pharmacotherapy Feb 2008beta-Blockers are a cornerstone in the treatment of systolic heart failure treatment, but not all beta-blockers are effective or in this setting. (Review)
Review
BACKGROUND
beta-Blockers are a cornerstone in the treatment of systolic heart failure treatment, but not all beta-blockers are effective or in this setting.
OBJECTIVE
To define the role of bisoprolol, a highly selective beta(1)-antagonist in congestive heart failure due to systolic dysfunction.
METHODS
Using the keywords 'bisoprolol' and 'heart failure' PubMed and BIOSIS databases were searched for information regarding pharmacology and relevant randomised clinical trials. Supplementary publications were acquired by scrutinising reference lists of relevant papers. Additional information was obtained from the FDA website.
CONCLUSION
Bisoprolol is an effective and well-tolerated first-line beta-blocker for patients with systolic heart failure. The knowledge is primarily based on study patients with moderate-to-severe heart failure from the three CIBIS trials.
Topics: Animals; Bisoprolol; Heart Failure; Humans; Randomized Controlled Trials as Topic
PubMed: 18201151
DOI: 10.1517/14656566.9.2.293