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The New England Journal of Medicine Dec 2019Observational studies suggest that beta-blockers may reduce the risk of exacerbations and death in patients with moderate or severe chronic obstructive pulmonary disease... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Observational studies suggest that beta-blockers may reduce the risk of exacerbations and death in patients with moderate or severe chronic obstructive pulmonary disease (COPD), but these findings have not been confirmed in randomized trials.
METHODS
In this prospective, randomized trial, we assigned patients between the ages of 40 and 85 years who had COPD to receive either a beta-blocker (extended-release metoprolol) or placebo. All the patients had a clinical history of COPD, along with moderate airflow limitation and an increased risk of exacerbations, as evidenced by a history of exacerbations during the previous year or the prescribed use of supplemental oxygen. We excluded patients who were already taking a beta-blocker or who had an established indication for the use of such drugs. The primary end point was the time until the first exacerbation of COPD during the treatment period, which ranged from 336 to 350 days, depending on the adjusted dose of metoprolol.
RESULTS
A total of 532 patients underwent randomization. The mean (±SD) age of the patients was 65.0±7.8 years; the mean forced expiratory volume in 1 second (FEV) was 41.1±16.3% of the predicted value. The trial was stopped early because of futility with respect to the primary end point and safety concerns. There was no significant between-group difference in the median time until the first exacerbation, which was 202 days in the metoprolol group and 222 days in the placebo group (hazard ratio for metoprolol vs. placebo, 1.05; 95% confidence interval [CI], 0.84 to 1.32; P = 0.66). Metoprolol was associated with a higher risk of exacerbation leading to hospitalization (hazard ratio, 1.91; 95% CI, 1.29 to 2.83). The frequency of side effects that were possibly related to metoprolol was similar in the two groups, as was the overall rate of nonrespiratory serious adverse events. During the treatment period, there were 11 deaths in the metoprolol group and 5 in the placebo group.
CONCLUSIONS
Among patients with moderate or severe COPD who did not have an established indication for beta-blocker use, the time until the first COPD exacerbation was similar in the metoprolol group and the placebo group. Hospitalization for exacerbation was more common among the patients treated with metoprolol. (Funded by the Department of Defense; BLOCK COPD ClinicalTrials.gov number, NCT02587351.).
Topics: Adrenergic beta-1 Receptor Antagonists; Aged; Aged, 80 and over; Disease Progression; Female; Forced Expiratory Volume; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Metoprolol; Middle Aged; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Treatment Failure
PubMed: 31633896
DOI: 10.1056/NEJMoa1908142 -
Journal of the American College of... Dec 2021The use of β-adrenergic receptor blocking agents in symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM) rests on clinical experience and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The use of β-adrenergic receptor blocking agents in symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM) rests on clinical experience and observational cohort studies.
OBJECTIVES
This study aimed to investigate the effects of metoprolol on left ventricular outflow tract (LVOT) obstruction, symptoms, and exercise capacity in patients with obstructive HCM.
METHODS
This double-blind, placebo-controlled, randomized crossover trial enrolled 29 patients with obstructive HCM and New York Heart Association (NYHA) functional class II or higher symptoms from May 2018 to September 2020. Patients received metoprolol or placebo for 2 consecutive 2-week periods in random order. The effect parameters were LVOT gradients, NYHA functional class, Canadian Cardiovascular Society (CCS) angina class, Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), and cardiopulmonary exercise testing.
RESULTS
Compared with placebo, the LVOT gradient during metoprolol was lower at rest (25 mm Hg [interquartile range (IQR): 15-58 mm Hg] vs 72 mm Hg [IQR: 28-87 mm Hg]; P = 0.007), at peak exercise (28 mm Hg [IQR: 18-40 mm Hg] vs 62 mm Hg [IQR: 31-113 mm Hg]; P < 0.001), and postexercise (45 mm Hg [IQR: 24-100 mm Hg] vs 115 mm Hg [IQR: 55-171 mm Hg]; P < 0.0001). During metoprolol treatment, 14% of patients were in NYHA functional class III or higher compared with 38% of patients receiving placebo (P < 0.01). Similarly, no patients were in CCS class III or higher during metoprolol treatment compared with 10% during placebo treatment (P < 0.01). These findings were confirmed by higher KCCQ-OSS during metoprolol treatment (76.2 ± 16.2 vs 73.8 ± 19.5; P = 0.039). Measures of exercise capacity, peak oxygen consumption, and N-terminal pro-B-type natriuretic peptide did not differ between the study arms.
CONCLUSIONS
Compared with placebo, metoprolol reduced LVOT obstruction at rest and during exercise, provided symptom relief, and improved quality of life in patients with obstructive HCM. Maximum exercise capacity remained unchanged. (The Effect of Metoprolol in Patients with Hypertrophic Obstructive Cardiomyopathy [TEMPO]; NCT03532802).
Topics: Adrenergic beta-1 Receptor Antagonists; Aged; Cardiomyopathy, Hypertrophic; Cross-Over Studies; Double-Blind Method; Exercise Tolerance; Female; Humans; Male; Metoprolol; Middle Aged; Ventricular Outflow Obstruction
PubMed: 34915981
DOI: 10.1016/j.jacc.2021.07.065 -
The Journal of Experimental Medicine Nov 2023Chimeric antigen receptor (CAR) T therapies have achieved remarkable success for treating hematologic malignancies, yet are often accompanied by severe cytokine release...
Chimeric antigen receptor (CAR) T therapies have achieved remarkable success for treating hematologic malignancies, yet are often accompanied by severe cytokine release syndrome (CRS). Here, an accidental clinical observation raised the possibility that metoprolol, an FDA-approved β1 adrenergic receptor blocker widely used for cardiovascular conditions, may alleviate CAR T-induced CRS. Metoprolol effectively blocked IL-6 production in human monocytes through unexpected mechanisms of action of targeting IL-6 protein translation but not IL6 mRNA expression. Mechanistically, metoprolol diminished IL-6 protein synthesis via attenuating eEF2K-eEF2 axis-regulated translation elongation. Furthermore, an investigator-initiated phase I/II clinical trial demonstrated a favorable safety profile of metoprolol in CRS management and showed that metoprolol significantly alleviated CAR T-induced CRS without compromising CAR T efficacy. These results repurposed metoprolol, a WHO essential drug, as a potential therapeutic for CRS and implicated IL-6 translation as a mechanistic target of metoprolol, opening venues for protein translation-oriented drug developments for human inflammatory diseases.
Topics: Humans; Receptors, Chimeric Antigen; Interleukin-6; Cytokine Release Syndrome; Cytokines; Metoprolol; Immunotherapy, Adoptive
PubMed: 37584653
DOI: 10.1084/jem.20230577 -
Lancet (London, England) May 2008Trials of beta blockers in patients undergoing non-cardiac surgery have reported conflicting results. This randomised controlled trial, done in 190 hospitals in 23... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Trials of beta blockers in patients undergoing non-cardiac surgery have reported conflicting results. This randomised controlled trial, done in 190 hospitals in 23 countries, was designed to investigate the effects of perioperative beta blockers.
METHODS
We randomly assigned 8351 patients with, or at risk of, atherosclerotic disease who were undergoing non-cardiac surgery to receive extended-release metoprolol succinate (n=4174) or placebo (n=4177), by a computerised randomisation phone service. Study treatment was started 2-4 h before surgery and continued for 30 days. Patients, health-care providers, data collectors, and outcome adjudicators were masked to treatment allocation. The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal cardiac arrest. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00182039.
FINDINGS
All 8351 patients were included in analyses; 8331 (99.8%) patients completed the 30-day follow-up. Fewer patients in the metoprolol group than in the placebo group reached the primary endpoint (244 [5.8%] patients in the metoprolol group vs 290 [6.9%] in the placebo group; hazard ratio 0.84, 95% CI 0.70-0.99; p=0.0399). Fewer patients in the metoprolol group than in the placebo group had a myocardial infarction (176 [4.2%] vs 239 [5.7%] patients; 0.73, 0.60-0.89; p=0.0017). However, there were more deaths in the metoprolol group than in the placebo group (129 [3.1%] vs 97 [2.3%] patients; 1.33, 1.03-1.74; p=0.0317). More patients in the metoprolol group than in the placebo group had a stroke (41 [1.0%] vs 19 [0.5%] patients; 2.17, 1.26-3.74; p=0.0053).
INTERPRETATION
Our results highlight the risk in assuming a perioperative beta-blocker regimen has benefit without substantial harm, and the importance and need for large randomised trials in the perioperative setting. Patients are unlikely to accept the risks associated with perioperative extended-release metoprolol.
Topics: Adrenergic beta-Antagonists; Aged; Blood Pressure; Cardiovascular Diseases; Delayed-Action Preparations; Female; Humans; Intraoperative Complications; Male; Metoprolol; Middle Aged; Perioperative Care; Preoperative Care; Risk Factors
PubMed: 18479744
DOI: 10.1016/S0140-6736(08)60601-7 -
Journal of the American College of... Apr 2022The relationship between exercise hemodynamics, loading conditions, and medical treatment in patients with obstructive hypertrophic cardiomyopathy (HCM) is incompletely... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The relationship between exercise hemodynamics, loading conditions, and medical treatment in patients with obstructive hypertrophic cardiomyopathy (HCM) is incompletely understood.
OBJECTIVES
This study aimed to investigate the effect of metoprolol on invasive hemodynamic parameters at rest and during exercise in patients with obstructive HCM.
METHODS
This randomized, double-blind, placebo-controlled crossover trial enrolled 28 patients with obstructive HCM and New York Heart Association functional class ≥II. Patients were randomized to initiate either metoprolol 150 mg or placebo for 2 consecutive 2-week periods. Right-heart catheterization and echocardiography were performed at rest and during exercise at the end of each treatment period. The primary outcome was the difference in pulmonary capillary wedge pressure (ΔPCWP) between peak exercise and rest.
RESULTS
No treatment effect on ΔPCWP was observed between metoprolol and placebo treatment (21 ± 9 mm Hg vs 23 ± 9 mm Hg; P = 0.12). At rest, metoprolol lowered heart rate (P < 0.0001), left ventricular outflow tract (LVOT) gradient (P = 0.01), and increased left ventricular end-diastolic volume (P = 0.02) and stroke volume (SV) (+6.4; 95% CI: 0.02-17.7; P = 0.049). During peak exercise, metoprolol was associated with a lower heart rate (P < 0.0001), a lower LVOT gradient (P = 0.0005), lesser degree of mitral regurgitation (P = 0.004), and increased SV (+9 mL; 95% CI: 2-15 mL; P = 0.008).
CONCLUSIONS
In patients with obstructive HCM, exercise was associated with an abnormal rise in PCWP, which was unaffected by metoprolol. However, metoprolol increased SV at rest and peak exercise following changes in end-diastolic volume, LVOT gradient, and degree of mitral regurgitation. (The Effect of Metoprolol in Patients With Hypertrophic Obstructive Cardiomyopathy [TEMPO]; NCT03532802).
Topics: Cardiomyopathy, Hypertrophic; Hemodynamics; Humans; Metoprolol; Mitral Valve Insufficiency; Stroke Volume
PubMed: 35450573
DOI: 10.1016/j.jacc.2022.02.024 -
Oxidative Medicine and Cellular... 2022The harm of heart failure mainly causes patients to develop dyspnea, fatigue, fluid retention, and other symptoms, which impair patients' activity tolerance and lead to...
The harm of heart failure mainly causes patients to develop dyspnea, fatigue, fluid retention, and other symptoms, which impair patients' activity tolerance and lead to a dramatic decrease in patients' quality of life. The purpose of this study was to verify whether metoprolol regulates AKAP5 expression and test the role of AKAP5 postinjury in mitigating cardiac infarction-associated tissue remodeling and fibrosis. Sprague-Dawley (SD) rats underwent coronary artery ligation (CAL), which was followed immediately with metoprolol daily. And western blot and coimmunoprecipitation experiments were performed to detect the expression of related proteins in the sham-operated group, model group, and drug-treated group. HW/BW ratio and cardiac expression of COL1 and COL3 were increased in rats following CAL compared with shams. Treatment with metoprolol postinjury was associated with a decrease in HW/BW ratio and COL1/COL3 expression compared to uncontrolled rats. CAL resulted in decreased cardiac AKAP5 expression compared to the control group, while metoprolol treatment restored levels compared to baseline shams. Cardiac expression levels of NFATc3/p-NFATc3 and GATA4 were modest at baseline and increased with injury, whereas metoprolol suppressed gene expression to below injury-associated changes. Immunoprecipitation indicated that AKAP5 could bind and regulate PP2B. In summary, we know that metoprolol alleviates ischemic cardiac remodeling and fibrosis, and the mechanism of alleviating remodeling may improve cardiac AKAP5 expression and AKAP5-PP2B interaction.
Topics: A Kinase Anchor Proteins; Animals; Fibrosis; Heart; Heart Failure; Metoprolol; Quality of Life; Rats; Rats, Sprague-Dawley
PubMed: 36238650
DOI: 10.1155/2022/5993459 -
Pharmacoepidemiology and Drug Safety Jun 2018Co-prescription of paroxetine/fluoxetine (a strong CYP2D6 inhibitor) in metoprolol (a CYP2D6 substrate) users is common, but data on the clinical consequences of this...
PURPOSE
Co-prescription of paroxetine/fluoxetine (a strong CYP2D6 inhibitor) in metoprolol (a CYP2D6 substrate) users is common, but data on the clinical consequences of this drug-drug interaction are limited and inconclusive. Therefore, we assessed the effect of paroxetine/fluoxetine initiation on the existing treatment with metoprolol on the discontinuation and dose adjustment of metoprolol among elderly.
METHODS
We performed a cohort study using the University of Groningen IADB.nl prescription database (www.IADB.nl). We selected all elderly (≥60 years) who had ever been prescribed metoprolol and had a first co-prescription of paroxetine/fluoxetine, citalopram (weak CYP2D6 inhibitor), or mirtazapine (negative control) from 1994 to 2015. The exposure group was metoprolol and paroxetine/fluoxetine co-prescription, and the other groups acted as controls. The outcomes were early discontinuation and dose adjustment of metoprolol. Logistic regression was applied to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI).
RESULTS
Combinations of metoprolol-paroxetine/fluoxetine, metoprolol-citalopram, and metoprolol-mirtazapine were started in 528, 673, and 625 patients, respectively. Compared with metoprolol-citalopram, metoprolol-paroxetine/fluoxetine was not significantly associated with the early discontinuation and dose adjustment of metoprolol (OR = 1.07, 95% CI:0.77-1.48; OR = 0.87, 95% CI:0.57-1.33, respectively). In comparison with metoprolol-mirtazapine, metoprolol-paroxetine/fluoxetine was associated with a significant 43% relative increase in early discontinuation of metoprolol (OR = 1.43, 95% CI:1.01-2.02) but no difference in the risk of dose adjustment. Stratified analysis by gender showed that women have a significantly high risk of metoprolol early discontinuation (OR = 1.62, 95% CI:1.03-2.53).
CONCLUSION
Paroxetine/fluoxetine initiation in metoprolol prescriptions, especially for female older patients, is associated with the risk of early discontinuation of metoprolol.
Topics: Aged; Aged, 80 and over; Citalopram; Cohort Studies; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP2D6 Inhibitors; Dose-Response Relationship, Drug; Drug Interactions; Drug Prescriptions; Drug Therapy, Combination; Female; Fluoxetine; Humans; Male; Metoprolol; Middle Aged; Mirtazapine; Netherlands; Paroxetine
PubMed: 29575226
DOI: 10.1002/pds.4422 -
Journal of Healthcare Engineering 2022In China, the incidence of arrhythmia has also increased to approximately 20% of all cardiovascular diseases. The incidence of cardiovascular diseases in China has...
In China, the incidence of arrhythmia has also increased to approximately 20% of all cardiovascular diseases. The incidence of cardiovascular diseases in China has certain characteristics, which are generally low in the south and high in the north, and they tend to be younger and growing. Permanent pacemaker implantation is currently the most effective means of treating arrhythmia and preventing sudden death. To explore the clinical application value of metoprolol in patients after permanent pacemaker implantation. Ninety patients with permanent dual-chamber pacemaker implantation in our hospital are selected and divided into a metoprolol group and a control group according to whether metoprolol is used one week after the operation and 45 patients in each group. After one postoperative week, the LVEF%, LVEDd, LAD, and E/A of the metoprolol and the control groups had no statistically significant differences ( > 0.05). Twelve months postoperatively, the E/A of the metoprolol group is higher than that of the control group ( < 0.05), and LVEDd and LAD are lower than those of the control group ( < 0.05). The NT-proBNP and hs-CRP levels between the metoprolol and control groups had no significant differences ( > 0.05) in the values recorded immediately postoperatively. The NT-proBNP of the metoprolol group is lower than that of the control group ( < 0.05) at 12 months following pacemaker implantation. At one week after surgery, QTd, Pd, and Tp-Te are not significantly different ( > 0.05) between the metoprolol group and the control group, whereas the QTd and Pd times in the metoprolol group are lower than those in the control group ( < 0.05) at the 12-month follow-up. At one week postoperatively, the SDNN, SDANN, and RMSSD between the metoprolol and control groups did not show any statistically significant differences ( > 0.05). The SDANN of the metoprolol group is higher than that in the control group ( < 0.05) in the 12-month evaluation. One week after the operation, the serum IL-6 and TNF- levels are not significantly different between the metoprolol and control groups ( > 0.05). At 12 months after surgery, the serum IL-6 and TNF- levels in the metoprolol group are lower than those in the control group ( < 0.05). The incidence of adverse events in the metoprolol group is 9.30% lower than 26.83% in the control group within 12 months after the operation ( < 0.05). The use of metoprolol in patients with permanent pacemaker implantation after surgery can reduce the expansionary remodeling of the left atrium and have less impact on the QT-dispersion and Pd time.
Topics: Arrhythmias, Cardiac; Cardiovascular Diseases; Humans; Interleukin-6; Metoprolol; Pacemaker, Artificial; Tumor Necrosis Factor-alpha
PubMed: 35449861
DOI: 10.1155/2022/7340992 -
Medicine Sep 2022This meta-analysis aimed to systematically and comprehensively assess the effectiveness and safety of wenxin granule (WXG) and metoprolol in the treatment of elderly... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This meta-analysis aimed to systematically and comprehensively assess the effectiveness and safety of wenxin granule (WXG) and metoprolol in the treatment of elderly patients with coronary heart disease (CHD) and arrhythmia.
METHODS
We searched the electronic databases of the Cochrane Library, PUBMED, EMBASE, CNKI, Wangfang, and CBM from initiation to May 1, 2022, and selected a set of clinical indicators for WXG and metoprolol for CHD and arrhythmia. The methodological quality of the included studies was analyzed using the Cochrane risk-of-bias tool. Data were pooled using a fixed-effects or random-effects model, and a meta-analysis was conducted.
RESULTS
Eight randomized controlled trials involving 722 patients with CHD and arrhythmia were included. Our findings showed that WXG and metoprolol showed better effects than metoprolol alone on electrocardiogram change (odds ratio [OR] = 7.21, 95% confidence interval [CI] [1.48, 35.07]), clinical symptom improvement (OR = 5.83, 95% CI [1.52, 22.35]), overall clinical effect (OR = 5.51, 95% CI [2.65, 11.44], P < .001), atrial premature beat (mean difference [MD] = -109.85, 95% CI [-171.25, -48.46], P < .001), ventricular premature beat (MD = -195.43, 95% CI [-334.09, -56.77], P < .001), borderline premature beat (MD = -42.92, 95% CI [-77.18, -8.67], P = .01), short-burst ventricular tachycardia (MD = -35.98, 95% CI [-39.66, -32.30], P < .001), ST segment reduction (MD = -0.47, 95% CI [-0.54, -0.40], P < .001), ST segment decrease duration (MD = -0.76, 95% CI [-0.95, -0.57], P < .001). However, no significant differences were observed in adverse reactions (OR = 0.54, 95% CI [0.27, 1.09], P = .09).
CONCLUSION
Compared to metoprolol alone, WXG and metoprolol can more effectively manage patients with CHD and arrhythmia. However, additional large-scale, multicenter, rigorous, and high-quality randomized controlled trials are warranted to verify the present findings.
Topics: Aged; Coronary Disease; Drugs, Chinese Herbal; Humans; Metoprolol; Multicenter Studies as Topic; Ventricular Premature Complexes
PubMed: 36107542
DOI: 10.1097/MD.0000000000030250 -
Indian Heart Journal 2022Intravenous calcium channel blockers or beta-blockers are the preferred rate control medications for hemodynamically stable patients with atrial fibrillation with rapid... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intravenous calcium channel blockers or beta-blockers are the preferred rate control medications for hemodynamically stable patients with atrial fibrillation with rapid ventricular rate (AF-RVR) in the emergency department.
OBJECTIVES
To compare the efficacy of intravenous diltiazem and metoprolol for rate control and safety with respect to development of hypotension and bradycardia in patients with AF-RVR.
METHODS
For this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane databases, and the clinicaltrials.gov registry between database inception and 30th May 2021. Articles were included if they compared efficacy and safety of diltiazem versus metoprolol in critically ill adult patients hospitalized with AF-RVR. Outcome measures were achievement of rate control, development of new hypotension, and bradycardia after drug administration.
RESULTS
Of 86 records identified, 14 were eligible, all of which had a low to moderate risk of overall bias. The meta-analysis (Mantel-Haenszel, random-effects model) showed that diltiazem use was associated with increased achievement of rate control target compared to metoprolol [14 studies, n = 1732, Odds Ratio (OR): 1.92; 95% Confidence Intervals (CI):1.26 to 2.90; I = 61%]. In the pooled analysis, no differences were seen in hypotension using diltiazem vs metoprolol [12 studies, n = 1477, OR: 0.96; 95% CI:0.61 to 1.52; I = 35%] or bradycardia [9 studies, n = 1203, OR: 2.44; 95% CI: 0.82 to 7.31; I = 48%].
CONCLUSIONS
Intravenous diltiazem is associated with increased achievement of rate control target in patients with AF-RVR compared to metoprolol, while both medications are associated with similar incidence of hypotension and bradycardia.
Topics: Adult; Humans; Diltiazem; Atrial Fibrillation; Metoprolol; Bradycardia; Hypotension; Heart Rate
PubMed: 36334652
DOI: 10.1016/j.ihj.2022.10.195