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BMJ Open Dec 2019Metoprolol is the most frequently used β-receptor blockers; however, the prescribed dose in China is far less than the recommended doses in the guidelines. Based on the...
INTRODUCTION
Metoprolol is the most frequently used β-receptor blockers; however, the prescribed dose in China is far less than the recommended doses in the guidelines. Based on the Chinese and International guidelines and the Chinese clinical practice, we are conducting this study (NCT03413410) to test the feasibility and tolerability of the metoprolol optimal dosing pathway by observing the percentage of patients achieving target dose in Chinese acute coronary syndrome (ACS) patients during hospitalisation.
METHODS AND ANALYSIS
A total of about 1000 patients aged ≥18 years, hospitalised for ACS will be enrolled from ~15 hospital sites in China between February 2018 and April 2019. The percentage of patients achieving the target metoprolol dosage at discharge is the primary endpoint. The secondary endpoints included the following: mean heart rate (HR) and blood pressure (BP) of the patients who have achieved target dose at discharge and during the follow-up period, percentage of patients experiencing bradycardia (HR <50 beats/min), hypotension (BP <90/60 mm Hg) and drug-related temporary heart failure worsening during hospitalisation and 1 month after discharge, respectively. We will also assess the proportion of patients reporting metoprolol-related adverse events and the leading causes for metoprolol discontinuation.
ETHICS AND DISSEMINATION
The study protocol has been approved by the Ethics committee of the Chinese PLA General Hospital (number: S2017-112-01). Study findings will be disseminated through presentations at national and international conferences and submitted for publications in peer-reviewed journals.
TRIAL REGISTRATION NUMBER
ClinicalTrials.gov registry (NCT03413410).
Topics: Acute Coronary Syndrome; Adrenergic beta-1 Receptor Antagonists; Blood Pressure; China; Dose-Response Relationship, Drug; Heart Failure; Heart Rate; Hospitalization; Humans; Hypotension; Metoprolol; Multicenter Studies as Topic; Prospective Studies
PubMed: 31806613
DOI: 10.1136/bmjopen-2019-031972 -
Annals of Emergency Medicine Mar 2015We seek to examine the efficacy and safety of prereperfusion emergency medical services (EMS)-administered intravenous metoprolol in anterior ST-segment elevation... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of out-of-hospital intravenous metoprolol administration in anterior ST-segment elevation acute myocardial infarction: insights from the METOCARD-CNIC trial.
STUDY OBJECTIVE
We seek to examine the efficacy and safety of prereperfusion emergency medical services (EMS)-administered intravenous metoprolol in anterior ST-segment elevation myocardial infarction patients undergoing eventual primary angioplasty.
METHODS
This is a prespecified subgroup analysis of the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction trial population, who all eventually received oral metoprolol within 12 to 24 hours. We studied patients receiving intravenous metoprolol by EMS and compared them with others treated by EMS but not receiving intravenous metoprolol. Outcomes included infarct size and left ventricular ejection fraction on cardiac magnetic resonance imaging at 1 week, and safety by measuring the incidence of the predefined combined endpoint (composite of death, malignant ventricular arrhythmias, advanced atrioventricular block, cardiogenic shock, or reinfarction) within the first 24 hours.
RESULTS
From the total population of the trial (N=270), 147 patients (54%) were recruited during out-of-hospital assistance and transferred to the primary angioplasty center (74 intravenous metoprolol and 73 controls). Infarct size was smaller in patients receiving intravenous metoprolol compared with controls (23.4 [SD 15.0] versus 34.0 [SD 23.7] g; adjusted difference -11.4; 95% confidence interval [CI] -18.6 to -4.3). Left ventricular ejection fraction was higher in the intravenous metoprolol group (48.1% [SD 8.4%] versus 43.1% [SD 10.2%]; adjusted difference 5.0; 95% CI 1.6 to 8.4). Metoprolol administration did not increase the incidence of the prespecified safety combined endpoint: 6.8% versus 17.8% in controls (risk difference -11.1; 95% CI -21.5 to -0.6).
CONCLUSION
Out-of-hospital administration of intravenous metoprolol by EMS within 4.5 hours of symptom onset in our subjects reduced infarct size and improved left ventricular ejection fraction with no excess of adverse events during the first 24 hours.
Topics: Adrenergic beta-1 Receptor Antagonists; Emergency Medical Services; Female; Humans; Injections, Intravenous; Male; Metoprolol; Middle Aged; Myocardial Infarction; Stroke Volume; Treatment Outcome
PubMed: 25129820
DOI: 10.1016/j.annemergmed.2014.07.010 -
Annals of the American Thoracic Society Oct 2022The BLOCK COPD (β-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease) study found that metoprolol was associated with a higher... (Randomized Controlled Trial)
Randomized Controlled Trial
The BLOCK COPD (β-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease) study found that metoprolol was associated with a higher risk of severe exacerbation. To determine the mechanism underlying these results, we compared changes in lung function over the course of the study between treatment groups and evaluated whether baseline bronchodilator response or early reduction in forced expiratory volume in 1 second (FEV) or forced vital capacity (FVC) was associated with exacerbation risk. We compared changes in lung function (FEV and FVC) over the treatment period between treatment groups using linear mixed-effect models. Cox proportional hazards models were used to evaluate the association between baseline bronchodilator responsiveness (FEV, FVC, and combined FEV and FVC), early post-randomization (14 d) change in lung function, and the interaction between treatment assignment and these measures with risk of any or severe or very severe exacerbations. Negative binomial models were used to evaluate the relationship between bronchodilator responsiveness, the interaction between bronchodilator responsiveness and treatment assignment, and exacerbation rate. Over the 336-day treatment period, individuals in the metoprolol group had a significantly greater decrease in logarithmic FEV from baseline to visit on Day 28 than individuals in the placebo group. Individuals in the metoprolol group had a significantly greater decrease in FVC from baseline to visits on Days 14 and 28, and also a significantly greater decrease in logarithmic FVC from baseline to visits on Days 42 and 112 than individuals in the placebo group. There were no associations between early lung function reduction or interactions between lung function reduction and treatment assignment and time to any or severe or very severe exacerbations. There were no interactions between treatment arm and baseline bronchodilator responsiveness measures on risk or rate of exacerbations. However, those with baseline FVC bronchodilator responsiveness had a higher rate of severe or very severe exacerbations (adjusted rate ratio, 1.62; 95% confidence interval, 1.04-2.48). Metoprolol was associated with reduced lung function during the early part of the treatment period, but these effects were modest and did not persist. Early lung function reduction and baseline bronchodilator responsiveness did not interact with the treatment arm to predict exacerbations; however, baseline FVC bronchodilator responsiveness was associated with a 60% higher rate of severe or very severe exacerbations. Clinical trial registered with www.clinicaltrials.gov (NCT02587351).
Topics: Bronchodilator Agents; Forced Expiratory Volume; Humans; Lung; Metoprolol; Pulmonary Disease, Chronic Obstructive; Vital Capacity
PubMed: 35363600
DOI: 10.1513/AnnalsATS.202109-1042OC -
Chinese Medical Journal Aug 2021Postural tachycardia syndrome (POTS) is a common childhood disease that seriously affects the patient's physical and mental health. This study aimed to investigate...
Baseline left ventricular ejection fraction associated with symptom improvements in both children and adolescents with postural tachycardia syndrome under metoprolol therapy.
BACKGROUND
Postural tachycardia syndrome (POTS) is a common childhood disease that seriously affects the patient's physical and mental health. This study aimed to investigate whether pre-treatment baseline left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) values were associated with symptom improvement after metoprolol therapy for children and adolescents with POTS.
METHODS
This retrospective study evaluated 51 children and adolescents with POTS who received metoprolol therapy at the Peking University First Hospital between November 2010 and July 2019. All patients had completed a standing test or basic head-up tilt test and cardiac echocardiography before treatment. Treatment response was evaluated 3 months after starting metoprolol therapy. The pre-treatment baseline LVEF and LVFS values were evaluated for correlations with decreases in the symptom score after treatment (ΔSS). Multivariable analysis was performed using factors with a P value of <0.100 in the univariate analyses and the demographic characteristics.
RESULTS
A comparison of responders and non-responders revealed no significant differences in demographic, hemodynamic characteristics, and urine specific gravity (all P > 0.050). However, responders had significantly higher baseline LVEF (71.09% ± 4.44% vs. 67.17% ± 4.88%, t = -2.789, P = 0.008) and LVFS values (40.00 [38.00, 42.00]% vs. 36.79% ± 4.11%, Z = -2.542, P = 0.010) than the non-responders. The baseline LVEF and LVFS were positively correlated with ΔSS (r = 0.378, P = 0.006; r = 0.363, P = 0.009), respectively. Logistic regression analysis revealed that LVEF was independently associated with the response to metoprolol therapy in children and adolescents with POTS (odds ratio: 1.201, 95% confidence interval: 1.039-1.387, P = 0.013).
CONCLUSIONS
Pre-treatment baseline LVEF was associated with symptom improvement after metoprolol treatment for children and adolescents with POTS.
Topics: Adolescent; Child; Humans; Metoprolol; Postural Orthostatic Tachycardia Syndrome; Retrospective Studies; Stroke Volume; Ventricular Function, Left
PubMed: 34387611
DOI: 10.1097/CM9.0000000000001698 -
European Heart Journal Dec 2020Clinical guidelines recommend early intravenous β-blockers during ongoing myocardial infarction; however, it is unknown whether all β-blockers exert a similar...
AIMS
Clinical guidelines recommend early intravenous β-blockers during ongoing myocardial infarction; however, it is unknown whether all β-blockers exert a similar cardioprotective effect. We experimentally compared three clinically approved intravenous β-blockers.
METHODS AND RESULTS
Mice undergoing 45 min/24 h ischaemia-reperfusion (I/R) received vehicle, metoprolol, atenolol, or propranolol at min 35. The effect on neutrophil infiltration was tested in three models of exacerbated inflammation. Neutrophil migration was evaluated in vitro and in vivo by intravital microscopy. The effect of β-blockers on the conformation of the β1 adrenergic receptor was studied in silico. Of the tested β-blockers, only metoprolol ameliorated I/R injury [infarct size (IS) = 18.0% ± 0.03% for metoprolol vs. 35.9% ± 0.03% for vehicle; P < 0.01]. Atenolol and propranolol had no effect on IS. In the three exacerbated inflammation models, neutrophil infiltration was significantly attenuated only in the presence of metoprolol (60%, 50%, and 70% reductions vs. vehicle in myocardial I/R injury, thioglycolate-induced peritonitis, and lipopolysaccharide-induced acute lung injury, respectively). Migration studies confirmed the particular ability of metoprolol to disrupt neutrophil dynamics. In silico analysis indicated different intracellular β1 adrenergic receptor conformational changes when bound to metoprolol than to the other two β-blockers.
CONCLUSIONS
Metoprolol exerts a disruptive action on neutrophil dynamics during exacerbated inflammation, resulting in an infarct-limiting effect not observed with atenolol or propranolol. The differential effect of β-blockers may be related to distinct conformational changes in the β1 adrenergic receptor upon metoprolol binding. If these data are confirmed in a clinical trial, metoprolol should become the intravenous β-blocker of choice for patients with ongoing infarction.
Topics: Adrenergic beta-Antagonists; Animals; Atenolol; Humans; Inflammation; Metoprolol; Mice; Myocardial Infarction
PubMed: 33026079
DOI: 10.1093/eurheartj/ehaa733 -
British Journal of Clinical Pharmacology 1984The influence of chronic therapy with nifedipine on the pharmacokinetics of propranolol 80 mg twice daily, metoprolol 100 mg twice daily and atenolol 100 mg once daily...
The influence of chronic therapy with nifedipine on the pharmacokinetics of propranolol 80 mg twice daily, metoprolol 100 mg twice daily and atenolol 100 mg once daily was investigated in eight healthy volunteers. Nifedipine 10 mg three times daily did not affect the pharmacokinetics of metoprolol and atenolol whereas nifedipine shortened the time to peak plasma concentration for propranolol by about 1 h. Propranolol, metoprolol and atenolol provoked comparable decreases in heart rate measured at rest and during exercise. The beta-adrenoceptor blocking properties of propranolol, metoprolol and atenolol were not affected by concomitant therapy with nifedipine. The present study did not show significant pharmacokinetic and pharmacodynamic interactions between nifedipine and lipophilic beta-adrenoceptor blockers.
Topics: Adrenergic beta-Antagonists; Adult; Atenolol; Drug Interactions; Humans; Kinetics; Male; Metoprolol; Nifedipine; Propranolol
PubMed: 6146337
DOI: 10.1111/j.1365-2125.1984.tb02425.x -
Lipids in Health and Disease Apr 2011A system that can deliver multi-drug at a prolonged rate is very important for the treatment of various chronic diseases such as diabetes, asthma and heart disease....
BACKGROUND
A system that can deliver multi-drug at a prolonged rate is very important for the treatment of various chronic diseases such as diabetes, asthma and heart disease. Controlled porosity osmotic pump tablet (CPOP) system was designed to deliver Nifedipine (NP) and Metoprolol (MP) in a controlled manner up to 12 h. It was prepared by incorporating drugs in the core and coated with various types (PVP, PEG-400 and HPMC) and levels (30, 40 and 50% w/w of polymer) of pore former at a weight gain of 8, 12 & 15%.
RESULTS
Formulation variables like type and level of pore former and percent weight gain of membrane was found to affect the drug release from the developed formulations. Drug release was inversely proportional to the membrane weight but directly related to the level of pore former. Burst strength of the exhausted shell was inversely proportional to the level of pore former, but directly affected by the membrane weight. Results of scanning electron microscopy (SEM) studies showed the formation of pores in the membrane from where the drug release occurred. Dissolution models were applied to drug release data in order to establish the mechanism of drug release kinetics. In vitro release kinetics was subjected to superposition method to predict in vivo performance of the developed formulation.
CONCLUSION
The developed osmotic system is effective in the multi-drug therapy of hypertension by delivering both drugs in a controlled manner.
Topics: Drug Delivery Systems; Metoprolol; Nifedipine; Porosity; Tablets
PubMed: 21477386
DOI: 10.1186/1476-511X-10-51 -
JACC. Cardiovascular Imaging Jul 2019
Topics: Heart Ventricles; Humans; Magnetic Resonance Spectroscopy; Metoprolol; ST Elevation Myocardial Infarction; Ventricular Function, Left
PubMed: 30219409
DOI: 10.1016/j.jcmg.2018.08.009 -
Brazilian Journal of Anesthesiology... 2015Injection pain after propofol administration is common and may disturb patients' comfort. The aim of this study was to compare effectiveness of intravenous (iv)...
BACKGROUND AND OBJECTIVES
Injection pain after propofol administration is common and may disturb patients' comfort. The aim of this study was to compare effectiveness of intravenous (iv) nitroglycerin, lidocaine and metoprolol applied through the veins on the dorsum of hand or antecubital vein on eliminating propofol injection pain.
METHOD
There were 147 patients and they were grouped according to the analgesic administered. Metoprolol (n=31, Group M), lidocaine (n=32, Group L) and nitroglycerin (n=29, Group N) were applied through iv catheter at dorsum hand vein or antecubital vein. Pain was evaluated by 4 point scale (0 - no pain, 1 - light pain, 2 - mild pain, 3 - severe pain) in 5, 10, 15 and 20th seconds. ASA, BMI, patient demographics, education level and the effect of pathways for injection and location of operations were analyzed for their effect on total pain score.
RESULTS
There were no differences between the groups in terms of total pain score (p=0.981). There were no differences in terms of total pain score depending on ASA, education level, location of operation. However, lidocaine was more effective when compared with metoprolol (p=0.015) and nitroglycerin (p=0.001) among groups. Although neither lidocaine nor metoprolol had any difference on pain management when applied from antecubital or dorsal hand vein (p>0.05), nitroglycerin injection from antecubital vein had demonstrated statistically lower pain scores (p=0.001).
CONCLUSION
We found lidocaine to be the most effective analgesic in decreasing propofol related pain. We therefore suggest iv lidocaine for alleviating propofol related pain at operations.
Topics: Adult; Aged; Female; Humans; Injections; Lidocaine; Male; Metoprolol; Middle Aged; Nitroglycerin; Pain; Propofol
PubMed: 26323730
DOI: 10.1016/j.bjane.2014.01.006 -
Indian Journal of Pharmacology 2014To estimate and compare the cost-effectiveness and safety of nebivolol with sustained-release metoprolol in reducing blood pressure by 1 mm of Hg per day in hypertensive... (Comparative Study)
Comparative Study Randomized Controlled Trial
OBJECTIVE
To estimate and compare the cost-effectiveness and safety of nebivolol with sustained-release metoprolol in reducing blood pressure by 1 mm of Hg per day in hypertensive patients.
MATERIALS AND METHODS
This was a prospective, randomized, open label, observational analysis of cost-effectiveness, in a questionnaire-based fashion to compare the cost of nebivolol (2.5 mg, 5 mg, 10 mg) and sustained released metoprolol succinate (25 mg, 50 mg, 100 mg) in hypertensive patients using either of the two drugs. A total of 60 newly detected drug naïve hypertensive patients were considered for the comparison, of which 30 patients were prescribed nebivolol and the other 30 were prescribed metoprolol succinate as per the recommended dosage. Based on the data, statistical analysis was carried out using GraphPad Prism 5 and MS Excel Spreadsheet 2007.
RESULT
The cost of reducing 1 mm of Hg blood pressure per day with nebivolol was 0.60, 0.70, and 1.06 INR, whereas that of metoprolol succinate was 0.93, 1.18, and 1.25 INR at their respective equivalent doses, hence significantly lower with the nebivolol group as compared to the metoprolol group (P < 0.05).
CONCLUSION
This pharmacoeconomic analysis shows that nebivolol is more cost-effective as compared to metoprolol when the cost per reduction in blood pressure per day is considered. This may affect the patients economically during their long-term use of these molecules for the treatment of hypertension.
Topics: Adrenergic beta-Antagonists; Adult; Antihypertensive Agents; Benzopyrans; Blood Pressure; Cost-Benefit Analysis; Delayed-Action Preparations; Dose-Response Relationship, Drug; Economics, Pharmaceutical; Essential Hypertension; Ethanolamines; Female; Humans; Hypertension; Male; Metoprolol; Middle Aged; Nebivolol; Prospective Studies; Surveys and Questionnaires; Treatment Outcome
PubMed: 25298575
DOI: 10.4103/0253-7613.140577