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Pharmacology Research & Perspectives Aug 2019The aim of this study was to evaluate the pharmacokinetic variability of beta-adrenergic blocking agents used in cardiology by reviewing single-dose and steady-state... (Review)
Review
The aim of this study was to evaluate the pharmacokinetic variability of beta-adrenergic blocking agents used in cardiology by reviewing single-dose and steady-state pharmacokinetic studies from the literature. PubMed was searched for pharmacokinetic studies of beta-adrenergic blocking agents, both single-dose and steady-state studies. The studies included reported maximum plasma concentration (C) and/or area under the concentration curve (AUC). The coefficient of variation (CV%) was calculated for all studies, and a CV% <40% was considered low or moderate variability, and a CV% >40% was considered high variability. The C and AUC were reported a total of 672 times in 192 papers. Based on AUC, metoprolol, propranolol, carvedilol, and nebivolol showed high pharmacokinetic variability (highest first), whereas bisoprolol, atenolol, sotalol, labetalol, nadolol, and pindolol showed low to moderate variability (lowest first). We have shown a high interindividual pharmacokinetic variability that varies markedly in different beta-adrenergic blocking agents; the extreme being steady state ratios as high as 30 in metoprolol. A more personalized approach to the medical treatment of patients may be obtained by combining known pharmacokinetic information about variability, pharmaco-genetics and -dynamics, and patient characteristics, to avoid adverse events or lack of treatment effect.
Topics: Adrenergic beta-Antagonists; Area Under Curve; Biological Availability; Carvedilol; Healthy Volunteers; Humans; Male; Metoprolol; Propranolol
PubMed: 31338197
DOI: 10.1002/prp2.496 -
Clinical Hypertension Mar 2021BENEFIT-KOREA (BEnefits after 24 weeks of NEbivolol administration For essential hypertensIon patients wiTh various comorbidities and treatment environments in Korea)...
BACKGROUND
BENEFIT-KOREA (BEnefits after 24 weeks of NEbivolol administration For essential hypertensIon patients wiTh various comorbidities and treatment environments in Korea) study, an observational study in South Korea, demonstrated the efficacy and safety of nebivolol in Asian patients with essential hypertension with and without comorbidities in real-world settings. We present a subanalysis of the efficacy and safety of nebivolol across age and sex in the BENEFIT-KOREA cohort.
METHODS
Adult South Korean patients with essential hypertension participated in the prospective, single-arm, open, observational BENEFIT-KOREA study; 3011 patients received nebivolol as monotherapy or add-on therapy. Changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP), and pulse rate at 12 and 24 weeks were evaluated. Participants were divided into three age groups-young males and females: < 50 years; middle-aged males and females: ≥50 years to < 70 years; and older males and females: ≥70 years.
RESULTS
The mean age of study participants was 63.5 ± 12.9 years; majority were between 50 and 69 years of age and 40.4% were females. A significant decrease was observed in mean SBP, DBP, and pulse rate from baseline at 12 and 24 weeks in males and females across all age groups analyzed (all P < 0.001 vs. baseline), with no significant difference in mean reduction in SBP and DBP from baseline between sex within the age groups. Majority of reported adverse events were mild. The incidence of adverse events was lower in young participants versus middle-aged and older participants.
CONCLUSIONS
Our subanalysis from the real-world BENEFIT-KOREA study in Asian patients with essential hypertension demonstrated the efficacy and safety of once-daily nebivolol across age groups with no between-sex differences.
TRIAL REGISTRATION
Name of the registry: clinicaltrials.gov.
TRIAL REGISTRATION NUMBER
NCT03847350 . Date of registration: February 20, 2019 retrospectively registered.
PubMed: 33722290
DOI: 10.1186/s40885-021-00165-3 -
BMJ Clinical Evidence Nov 2014Acute atrial fibrillation is rapid, irregular, and chaotic atrial activity of recent onset. Various definitions of acute atrial fibrillation have been used in the... (Review)
Review
INTRODUCTION
Acute atrial fibrillation is rapid, irregular, and chaotic atrial activity of recent onset. Various definitions of acute atrial fibrillation have been used in the literature, but for the purposes of this review we have included studies where atrial fibrillation may have occurred up to 7 days previously. Risk factors for acute atrial fibrillation include increasing age, cardiovascular disease, alcohol, diabetes, and lung disease. Acute atrial fibrillation increases the risk of stroke and heart failure. The condition resolves spontaneously within 24 to 48 hours in more than 50% of people; however, many people will require interventions to control heart rate or restore sinus rhythm.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent embolism, for conversion to sinus rhythm, and to control heart rate in people with recent-onset atrial fibrillation (within 7 days) who are haemodynamically stable? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 26 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: amiodarone, antithrombotic treatment before cardioversion, atenolol, bisoprolol, carvedilol, digoxin, diltiazem, direct current cardioversion, flecainide, metoprolol, nebivolol, propafenone, sotalol, timolol, and verapamil.
Topics: Acute Disease; Anti-Arrhythmia Agents; Atrial Fibrillation; Electric Countershock; Humans; Safety
PubMed: 25430048
DOI: No ID Found -
International Journal of Cardiology.... Sep 2023Although many studies have compared carvedilol and nebivolol in heart failure (HF) patients with reduced left ventricular ejection fraction (LVEF), such comparative...
BACKGROUND
Although many studies have compared carvedilol and nebivolol in heart failure (HF) patients with reduced left ventricular ejection fraction (LVEF), such comparative studies for the elderly have not been reported yet. Nebivolol is known to be effective for improving diastolic function of elderly patients with HF. Thus, this study aimed to determine whether nebivolol could improve LV diastolic function to a greater extent than carvedilol in older patients aged over 70 years.
METHODS
This trial was a prospective, randomized, open-label, single-center, active-controlled study that enrolled 62 patients with class II or III HF over 70 years of age with an LVEF ≥40%. Patients were randomized into a carvedilol group or a nebivolol group. Transthoracic echocardiography was performed at baseline and 12 months by the same investigator who was blinded to clinical data. The primary endpoint was E/e' measured by echocardiographic evaluation 12 months after treatment.
RESULTS
The median duration of follow-up was 24 months. Baseline clinical characteristics and echocardiographic parameters, such as LV diastolic function indices, did not differ significantly between carvedilol and nebivolol groups. Twelve-month follow-up echocardiography data showed no significant difference in E/e' or other LV diastolic function indices between the two groups. There were no significant changes in echocardiographic parameters over 12 months in either group.
CONCLUSIONS
There was no difference between carvedilol and nebivolol for improving diastolic function of elderly HF patients with LVEF ≥40%. This study showed no superiority of nebivolol over carvedilol in elderly patients with HF.
PubMed: 37575339
DOI: 10.1016/j.ijcrp.2023.200201 -
Frontiers in Medicine 2022Tenofovir disoproxil fumarate (TDF), a widely prescribed component in antiretroviral regimens, has been associated with nephrotoxicity. Nebivolol is a third generation...
BACKGROUND
Tenofovir disoproxil fumarate (TDF), a widely prescribed component in antiretroviral regimens, has been associated with nephrotoxicity. Nebivolol is a third generation selective β-1 adrenergic receptor blocker and may protect renal structure and function through the suppression of oxidative stress and enhancement of nitric oxide (NO) synthesis. We aimed to investigate whether nebivolol could be an effective therapeutic strategy to mitigate tenofovir-induced nephrotoxicity.
METHODS
We allocated Wistar rats to four groups: control (C), received a standard diet for 30 days; NBV, received a standard diet for 30 days added with nebivolol (100 mg/kg food) in the last 15 days; TDF, received a standard diet added with tenofovir (300 mg/kg food) for 30 days; and TDF+NBV, received a standard diet added with tenofovir for 30 days and nebivolol in the last 15 days.
RESULTS
Long-term exposure to tenofovir led to impaired renal function, induced hypertension, endothelial dysfunction and oxidative stress. Nebivolol treatment partially recovered glomerular filtration rate, improved renal injury, normalized blood pressure and attenuated renal vasoconstriction. Administration of nebivolol contributed to reductions in asymmetric dimethylarginine (ADMA) levels as well as increases in endothelial nitric oxide sintase (eNOS) accompanied by renin-angiotensin-aldosterone system downregulation and decreases in macrophage and T-cells infiltrate. Furthermore, nebivolol was responsible for the maintenance of the adequate balance of thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) levels and it was associated with reductions in NADPH oxidase (NOX) subunits.
CONCLUSION
Nebivolol holds multifaceted actions that promote an advantageous option to slow the progression of kidney injury in tenofovir-induced nephrotoxicity.
PubMed: 35991671
DOI: 10.3389/fmed.2022.953749 -
The Journal of International Medical... Oct 2020Our meta-analysis was undertaken to evaluate the efficacy and safety of nebivolol compared with other second-generation β blockers for hypertensive patients. (Meta-Analysis)
Meta-Analysis
PURPOSE
Our meta-analysis was undertaken to evaluate the efficacy and safety of nebivolol compared with other second-generation β blockers for hypertensive patients.
METHODS
We searched PubMed, the Cochrane Library, EMBASE, and Clinical Trials.gov databases for randomized controlled trials (RCTs). The efficacy endpoints included systolic blood pressure (SBP), diastolic blood pressure (DBP), reduction of SBP and DBP, heart rate (HR), and adverse events (AEs).
FINDINGS
Eight RCTs with 1514 patients met the inclusion criteria. HR was significantly lower in patients receiving other second-generation β blockers compared with patients receiving nebivolol. There was no difference the reduction of blood pressure (SBP and DBP) or the reduction of SBP or DBP between the groups. The incidence of AEs was lower in patients taking nebivolol compared with patients taking other second-generation β blockers.
CONCLUSIONS
No significant difference was demonstrated between nebivolol and other second-generation β blockers in the reduction of blood pressure, SBP, and DBP. The tolerability of nebivolol was significantly better compared with other second-generation β blockers, and nebivolol was also associated with a stable HR and a lower risk of AEs compared with other second-generation β blockers.
Topics: Antihypertensive Agents; Blood Pressure; Humans; Hypertension; Nebivolol; Randomized Controlled Trials as Topic
PubMed: 33081551
DOI: 10.1177/0300060520931625 -
Journal of Clinical Hypertension... Jul 2009Beta-blockers are prescribed for a variety of cardiovascular conditions including hypertension, heart failure, primary treatment of myocardial infarction (MI), and... (Review)
Review
Beta-blockers are prescribed for a variety of cardiovascular conditions including hypertension, heart failure, primary treatment of myocardial infarction (MI), and secondary prevention of ischemic cardiac events. Yet they remain underprescribed in populations at increased risk for cardiovascular disease because of tolerability and safety concerns. Beta-blockers are heterogeneous with respect to pharmacokinetic and pharmacodynamic effects. "Original" agents were nonselective, blocking both beta1-adrenoceptors and beta2-adrenoceptors. Later, new agents were developed with selectivity for beta1-adrenoceptors, and were subsequently followed by beta-blockers, which exhibit additional effects, such as vasodilation. Among newer agents, labetalol, carvedilol, and nebivolol have been approved for use in the United States. Nebivolol possesses both beta1-selectivity and nitric oxide-mediated vasodilatory effects, while carvedilol has attractive effects on insulin resistance and exhibits antioxidant effects. Newer beta-blockers may overcome concerns about efficacy, adverse effects, and tolerability, while delivering cardiovascular protection.
Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Benzopyrans; Carbazoles; Carvedilol; Ethanolamines; Heart Failure; Humans; Hypertension; Labetalol; Nebivolol; Propanolamines; Treatment Outcome
PubMed: 19583633
DOI: 10.1111/j.1751-7176.2009.00140.x -
European Review For Medical and... Mar 2022In this study, the protective effect of sodium copper chlorophyllin and nebivolol was evaluated in a mice model of CCL4 induced hepatotoxicity. Silymarin was used as a...
OBJECTIVE
In this study, the protective effect of sodium copper chlorophyllin and nebivolol was evaluated in a mice model of CCL4 induced hepatotoxicity. Silymarin was used as a traditional hepatoprotective drug.
MATERIALS AND METHODS
Thirty (30) mice were used as they were divided into five groups: the first group was the control group which received distilled water + olive oil, the second group which received 1.5 ml/kg of CCl4 diluted in olive oil three times a week, the third group which received CCl4 + Silymarin 50 mg/kg/day, the fourth group which received CCl4 + nebivolol 4 mg/kg/day, and the fifth group which received 1.5 ml/kg of CCl4+ Cu-chlorophyllin 50 mg/kg/day. The drugs were given by intraperitoneal route for 5 weeks. The detection, quantification of CCl4 induced hepatotoxicity and possible protective effect of either silymarin, nebivolol, or sodium copper chlorophyllin were assessed using biochemical analysis of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein, lipid profile, an assay of oxidants and antioxidants, assay of interleukin 6 (IL6) and tumor necrosis factor-alpha (TNF-α), and histopathological examination.
RESULTS
The administration of carbon tetrachloride (CCl4) produced pronounced liver impairment. It significantly increased ALT, AST, ALP, malondialdehyde, and serum nitric oxide levels compared to normal control group besides a decrease in total protein, serum catalase, tissue SOD, and GSH levels. IL-6 and TNF-α levels were significantly higher while total cholesterol was significantly lower in mice receiving CCL4 compared to the normal control group. CCL4 induced severe hyperemia and congestion inside the portal area with leukocytic infiltration, hepatic degeneration, and bridge fibrosis.
CONCLUSIONS
Co-administration of either silymarin, nebivolol, or sodium copper chlorophyllin with CCl4 was able to ameliorate up to almost contradict CCl4 induced hepatic injury through their anti-inflammatory and antioxidant activities.
Topics: Alanine Transaminase; Animals; Antioxidants; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Chlorophyllides; Liver; Mice; Nebivolol; Olive Oil; Plant Extracts; Silymarin; Tumor Necrosis Factor-alpha
PubMed: 35302221
DOI: 10.26355/eurrev_202203_28241 -
Turk Kardiyoloji Dernegi Arsivi : Turk... Sep 2023Resistant hypertension is associated with increased mortality and morbidity. The optimal medical therapy is not fully elucidated in resistant hypertension. There are...
OBJECTIVE
Resistant hypertension is associated with increased mortality and morbidity. The optimal medical therapy is not fully elucidated in resistant hypertension. There are relatively few studies in the literature on the treatment of resistant hypertension. In this study, we compared the effectiveness of nebivolol 5 mg, a third generation beta-blocker, with spironolactone 25 mg in patients with resistant hypertension.
METHODS
A total of 81 patients with resistant hypertension were included in the study. The spironolactone group was composed of 38 patients while the nebivolol group was composed of 43 patients. Resistant hypertension was defined as having office blood pressure ≥ 140/90 mmHg while the patients were under 3 or more antihypertensive agents treatment which included diuretic agents. Office and ambulatory blood pressure at basal and after 8 weeks of treatment were recorded.
RESULTS
Office systolic blood pressure and diastolic blood pressure in 24-hour ambulatory blood pressure monitoring were significantly lower when compared to basal values in both nebivolol and spironolactone groups. The decrease in 24-hour mean systolic and diastolic blood pressure in nebivolol group was 14.9 ± 19.8 mmHg and 9.3 ± 12.7 mmHg compared to 19.5 ± 16.4 mmHg and 13.7 ± 10.8 mmHg in the spironolactone group, respectively. The decrease in 24-hour mean systolic and diastolic blood pressure was not significantly different between the nebivolol and spironolactone groups (P = 0.338 and P = 0.153).
CONCLUSION
Nebivolol is an effective treatment option for resistant hypertension and the antihypertensive effect of nebivolol is similar to low-dose spironolactone.
Topics: Humans; Antihypertensive Agents; Spironolactone; Nebivolol; Blood Pressure Monitoring, Ambulatory; Hypertension
PubMed: 37671517
DOI: 10.5543/tkda.2023.60464 -
Journal of Hypertension Sep 2017: To treat hypertension, combining two or more antihypertensive drugs from different classes is often necessary. β-Blockers and renin-angiotensin-aldosterone system... (Review)
Review
: To treat hypertension, combining two or more antihypertensive drugs from different classes is often necessary. β-Blockers and renin-angiotensin-aldosterone system inhibitors, when combined, have been deemed 'less effective' based on partially overlapping mechanisms of action and limited evidence. Recently, the single-pill combination (SPC) of nebivolol (Neb) 5 mg - a vasodilatory β1-selective antagonist/β3 agonist - and valsartan 80 mg, an angiotensin II receptor blocker, was US Food and Drug Administration-approved for hypertension. Pharmacological profiles of Neb and valsartan, alone and combined, are well characterized. In addition, a large 8-week randomized trial in stages I-II hypertensive patients (N = 4161) demonstrated greater blood pressure-reducing efficacy for Neb/valsartan SPCs than component monotherapies with comparable tolerability. In a biomarkers substudy (N = 805), Neb/valsartan SPCs prevented valsartan-induced increases in plasma renin, and a greater reduction in plasma aldosterone was observed with the highest SPC dose vs. valsartan 320 mg/day. This review summarizes preclinical and clinical evidence supporting Neb/valsartan as an efficacious and well tolerated combination treatment for hypertension.
Topics: Antihypertensive Agents; Drug Therapy, Combination; Humans; Hypertension; Nebivolol; Randomized Controlled Trials as Topic; Valsartan
PubMed: 28509722
DOI: 10.1097/HJH.0000000000001412