ABSTRACT
Importance: Diltiazem, a commonly prescribed ventricular rate-control medication for patients with atrial fibrillation, inhibits apixaban and rivaroxaban elimination, possibly causing overanticoagulation. Objective: To compare serious bleeding risk for new users of apixaban or rivaroxaban with atrial fibrillation treated with diltiazem or metoprolol. Design, Setting, and Participants: This retrospective cohort study included Medicare beneficiaries aged 65 years or older with atrial fibrillation who initiated apixaban or rivaroxaban use and also began treatment with diltiazem or metoprolol between January 1, 2012, and November 29, 2020. Patients were followed up to 365 days through November 30, 2020. Data were analyzed from August 2023 to February 2024. Exposures: Diltiazem and metoprolol. Main Outcomes and Measures: The primary outcome was a composite of bleeding-related hospitalization and death with recent evidence of bleeding. Secondary outcomes were ischemic stroke or systemic embolism, major ischemic or hemorrhagic events (ischemic stroke, systemic embolism, intracranial or fatal extracranial bleeding, or death with recent evidence of bleeding), and death without recent evidence of bleeding. Hazard ratios (HRs) and rate differences (RDs) were adjusted for covariate differences with overlap weighting. Results: The study included 204â¯155 US Medicare beneficiaries, of whom 53â¯275 received diltiazem and 150â¯880 received metoprolol. Study patients (mean [SD] age, 76.9 [7.0] years; 52.7% female) had 90â¯927 person-years (PY) of follow-up (median, 120 [IQR, 59-281] days). Patients receiving diltiazem treatment had increased risk for the primary outcome (RD, 10.6 [95% CI, 7.0-14.2] per 1000 PY; HR, 1.21 [95% CI, 1.13-1.29]) and its components of bleeding-related hospitalization (RD, 8.2 [95% CI, 5.1-11.4] per 1000 PY; HR, 1.22 [95% CI, 1.13-1.31]) and death with recent evidence of bleeding (RD, 2.4 [95% CI, 0.6-4.2] per 1000 PY; HR, 1.19 [95% CI, 1.05-1.34]) compared with patients receiving metoprolol. Risk for the primary outcome with initial diltiazem doses exceeding 120 mg/d (RD, 15.1 [95% CI, 10.2-20.1] per 1000 PY; HR, 1.29 [95% CI, 1.19-1.39]) was greater than that for lower doses (RD, 6.7 [95% CI, 2.0-11.4] per 1000 PY; HR, 1.13 [95% CI, 1.04-1.24]). For doses exceeding 120 mg/d, the risk of major ischemic or hemorrhagic events was increased (HR, 1.14 [95% CI, 1.02-1.27]). Neither dose group had significant changes in the risk for ischemic stroke or systemic embolism or death without recent evidence of bleeding. When patients receiving high- and low-dose diltiazem treatment were directly compared, the HR for the primary outcome was 1.14 (95% CI, 1.02-1.26). Conclusions and Relevance: In Medicare patients with atrial fibrillation receiving apixaban or rivaroxaban, diltiazem was associated with greater risk of serious bleeding than metoprolol, particularly for diltiazem doses exceeding 120 mg/d.
Subject(s)
Atrial Fibrillation , Diltiazem , Hemorrhage , Pyrazoles , Pyridones , Rivaroxaban , Humans , Atrial Fibrillation/drug therapy , Atrial Fibrillation/complications , Diltiazem/adverse effects , Diltiazem/therapeutic use , Aged , Female , Male , Rivaroxaban/adverse effects , Rivaroxaban/therapeutic use , Retrospective Studies , Pyridones/adverse effects , Pyridones/therapeutic use , Pyridones/administration & dosage , Hemorrhage/chemically induced , Pyrazoles/adverse effects , Pyrazoles/therapeutic use , Aged, 80 and over , Factor Xa Inhibitors/adverse effects , Factor Xa Inhibitors/therapeutic use , Metoprolol/adverse effects , Metoprolol/therapeutic use , Metoprolol/administration & dosage , United States , Hospitalization/statistics & numerical data , Embolism/prevention & control , Medicare , Drug Therapy, CombinationABSTRACT
Aging, polypharmacy (concurrent use of ≥ 5 medications), and functional impairment are global healthcare challenges. However, knowledge of the age/sex-specific effects of polypharmacy is limited, particularly on daily physical activities. Using continuous monitoring, we demonstrated how polypharmacy with high Drug Burden Index (DBI-cumulative anticholinergic/sedative exposure) affected behaviors over 23 h in male/female, young/old mice. For comparison, we also evaluated how different drug regimens (polypharmacy/monotherapy) influenced activities in young mice. We found that after 4 weeks of treatment, high DBI (HDBI) polypharmacy decreased exploration (reduced mean gait speed and climbing) during the habituation period, but increased it during other periods, particularly in old mice during the transition to inactivity. After HDBI polypharmacy, mean gait speed consistently decreased throughout the experiment. Some behavioral declines after HDBI were more marked in females than males, indicating treatment × sex interactions. Metoprolol and simvastatin monotherapies increased activities in young mice, compared to control/polypharmacy. These findings highlight that in mice, some polypharmacy-associated behavioral changes are greater in old age and females. The observed diurnal behavioral changes are analogous to drug-induced delirium and sundowning seen in older adults. Future mechanistic investigations are needed to further inform considerations of age, sex, and polypharmacy to optimize quality use of medicines.
Subject(s)
Aging , Behavior, Animal , Circadian Rhythm , Locomotion , Polypharmacy , Age Factors , Animals , Cholinergic Antagonists/administration & dosage , Exploratory Behavior , Female , Hypnotics and Sedatives/administration & dosage , Male , Metoprolol/administration & dosage , Mice , Sex Factors , Simvastatin/administration & dosageABSTRACT
BACKGROUND/PURPOSE: To describe a patient with visually symptomatic circumscribed choroidal hemangioma (CCH) treated successfully with intravitreal beta-blocker. METHODS: This is an interventional single case report of a 63 year-old man with a juxtafoveal CCH and extensive subretinal fluid (SRF) unsuccessfully treated with intravitreal anti-VEGF. Off-label intravitreal use of metoprolol (50µg/0.05 ml) was then performed. Main outcome measures were resolution or decreased subretinal fluid on OCT, visual stability or improvement, lack of retinal/ocular toxicity. RESULTS: Following 2 intravitreal injections of metoprolol (1 month apart), significant response was observed with decrease of SRF and visual improvement to 20/400 during a 9-week follow-up after the injections. CONCLUSION: These preliminary findings suggest that intravitreal metoprolol can be a safe alternative treatment for patients with CCH. This off-label therapy could represent another option for patients with this condition.
Subject(s)
Choroid Neoplasms , Hemangioma , Metoprolol , Off-Label Use , Angiogenesis Inhibitors/administration & dosage , Choroid Neoplasms/drug therapy , Hemangioma/drug therapy , Humans , Intravitreal Injections , Male , Metoprolol/administration & dosage , Middle Aged , Treatment OutcomeABSTRACT
BACKGROUND: Beta-blockers have become the cornerstone for medical management in patients with chronic type B aortic dissection (TBAD). However, the effect of being on and/or receiving intravenous beta-blockers during hospitalization on outcomes of surgical repair of TBAD is not fully described. We sought to investigate this association during open surgical repair (OSR) and endovascular (Endo) intervention for nontraumatic TBAD. METHODS: The Premier Healthcare Database was inquired (June/2009-March/2015). Patients with nontraumatic isolated TBAD were identified via ICD-9-CM diagnosis and procedural codes. Patients with codes that indicated TAAD were excluded. In-hospital mortality, cardiac complications (CHF, MI, arrythmia) and stroke were evaluated. Log binomial regression analyses with bootstrapping were performed to assess the relative risk of adverse outcomes. RESULTS: A total of 1,752 were admitted for OSR (54.3%) and Endo (45.7%) TBAD repair. Use of oral beta blocker (BB) was 16.0% in OSR and 56.4% in Endo groups. In each arm, patients on BB were more likely to be diabetic, on aspirin or statin and more likely to receive additional IV BB than nonBB patients. There was no significant difference in age, sex, race, or prior history of CHF between BB and nonBB groups. Mortality was proportionally lower in patients on BB in OSR group (7.9% vs. 16.7%; P = 0.006) and Endo (3.3% vs. 9.2%; P < 0.001). The adjusted relative risk for mortality and stroke were significantly lower in oral BB recipients compared with none [aRR (95% CI): 0.53 (0.32-0.90) and 0.46 (0.25-0.87); both P ≤ 0.02]. IV metoprolol was the only IV BB that reduced mortality [aRR (95% CI): 0.62 (0.46-0.85); P = 0.003]. A dose of ≤10 mg was associated with significant mortality reduction: 6.3% (3.0-9.5%) compared with 8.1% (4.6-11.6%) in no IV BB group. Cardiac complications were not affected by BB use. CONCLUSIONS: For patients with nontraumatic TBAD, use of oral BB was associated with significant protection against in-hospital mortality and stroke following repair. Metoprolol was the only Intravenous BB type associated with improved survival. Further research is warranted to elucidate the effect of beta-blockers on the long-term surgical outcomes of TBAD.
Subject(s)
Adrenergic beta-Antagonists/administration & dosage , Aortic Aneurysm, Thoracic/surgery , Aortic Dissection/surgery , Metoprolol/administration & dosage , Administration, Oral , Databases, Factual , Endovascular Procedures , Female , Hospital Mortality , Humans , Infusions, Intravenous , Male , Middle Aged , Stroke/prevention & control , Survival RateABSTRACT
BACKGROUND: Intravenous [IV] esmolol, an alternative to IV metoprolol for coronary computed tomography angiography [CCTA], has shorter half-life that decreases the risk of prolonged hypotension. The primary aim was to prospectively compare IV esmolol alone to IV metoprolol alone for effectiveness in achieving heart rate [HR] of 60 beats per minute[bpm] during CCTA. The secondary aim was to compare hemodynamic response, image quality, radiation dose and cost. MATERIALS AND METHODS: Institutional Review Board approved prospective randomized study of 28 CCTA patients medicated in a 1:1 blinded match with IV esmolol or IV metoprolol to achieve HR of 60 bpm. Serial hemodynamic response was measured at 6 specified times. Two cardiac radiologists independently scored the image quality. RESULTS: Both IV esmolol and IV metoprolol achieved the target HR. IV esmolol resulted in significantly less profound and shorter duration of reduction in systolic blood pressure [BP] than IV metoprolol with a difference of -10, -14 and -9 mm Hg compared to -20, -26 and -25 mmHg at 2, 15 & 30 min respectively. No significant difference in HR at image acquisition, exposure window, radiation dose and image quality. Although IV esmolol was expensive, the overall cost of care was comparable to IV metoprolol due to shortened post CCTA observation period consequent to faster restoration of hemodynamic status. CONCLUSION: Comparison of IV esmolol and IV metoprolol demonstrate that both are effective in achieving the target HR but significantly faster recovery of HR and BP in patients who receive IV esmolol was found.
Subject(s)
Computed Tomography Angiography/methods , Coronary Angiography/methods , Coronary Artery Disease/diagnostic imaging , Hemodynamics/drug effects , Metoprolol/administration & dosage , Propanolamines/administration & dosage , Administration, Intravenous , Adrenergic beta-1 Receptor Antagonists/administration & dosage , Adrenergic beta-1 Receptor Antagonists/economics , Computed Tomography Angiography/economics , Coronary Angiography/economics , Cost-Benefit Analysis/economics , Female , Heart Rate/drug effects , Humans , Male , Metoprolol/economics , Middle Aged , Propanolamines/economics , Prospective Studies , Single-Blind MethodABSTRACT
BACKGROUND: Intravenous diltiazem and metoprolol are both commonly used to treat atrial fibrillation (AF) with rapid ventricular rate (RVR) in the emergency department (ED), but the advantages and disadvantages of these drugs cannot be verified. This meta-analysis aimed to assess the efficacy and safety of intravenous diltiazem versus metoprolol for AF with RVR. METHOD: We systematically searched PubMed, Web of Science, Embase, Cochrane library, the China National Knowledge Infrastructure (CNKI), Wanfang, China Biology Medicine disc (CBM) and the WeiPu (VIP). Meta-analysis was performed using weighted mean difference (WMD), relative risk (RR) and 95% confidence interval (CI). Statistical analysis was performed using Review Manager 5.4.1. RESULTS: Seventeen studies involving 1214 patients in nine randomized controlled trials (RCTs) and eight cohort studies were included in meta-analysis, including 643 patients in the intravenous diltiazem group and 571 patients group in the intravenous metoprolol. The results of the meta-analysis showed that compared with intravenous metoprolol, intravenous diltiazem was found higher efficacy (RR =1.11; 95% CI = 1.06 to 1.16, p < 0.00001), shorter average onset time (RR = -1.13; 95% CI = -1.97 to -0.28, p = 0.009), lower ventricular rate (RR = -9.48; 95% CI = -12.13 to -6.82, p<0.00001), less impact on systolic blood pressure (WMD = 3.76; 95% CI: 0.20 to 7.33, P = 0.04), and no significant difference in adverse events (RR = 0.80, 95% CI = 0.55 to 1.14, P = 0.22) and diastolic blood pressure (WMD = -1.20; 95% CI: -3.43 to 1.04, P = 0.29) was found between intravenous diltiazem and metoprolol. CONCLUSION: Intravenous diltiazem has higher efficacy, shorter average onset time, lower ventricular rate, less impact on blood pressure, and with no increase in adverse events compared to intravenous metoprolol.
Subject(s)
Atrial Fibrillation/drug therapy , Diltiazem/therapeutic use , Heart Rate/drug effects , Metoprolol/therapeutic use , Administration, Intravenous , Blood Pressure/drug effects , Diltiazem/administration & dosage , Humans , Metoprolol/administration & dosage , Randomized Controlled Trials as TopicSubject(s)
Ascites , Heart Failure , Hyperthyroidism , Methimazole/administration & dosage , Metoprolol/administration & dosage , Abdominal Pain/diagnosis , Abdominal Pain/etiology , Antithyroid Agents/administration & dosage , Ascites/diagnostic imaging , Ascites/etiology , Ascites/therapy , Atrial Fibrillation/diagnosis , Diagnosis, Differential , Echocardiography, Transesophageal/methods , Electrocardiography/methods , Female , Heart Failure/diagnosis , Heart Failure/physiopathology , Heart Failure/therapy , Humans , Hyperthyroidism/blood , Hyperthyroidism/complications , Hyperthyroidism/drug therapy , Hyperthyroidism/physiopathology , Magnetic Resonance Imaging, Cine/methods , Medication Adherence , Middle Aged , Paracentesis/methods , Thyroid Function Tests/methodsABSTRACT
BACKGROUND: Severe coronavirus disease-2019 (COVID-19) can progress to an acute respiratory distress syndrome (ARDS), which involves alveolar infiltration by activated neutrophils. The beta-blocker metoprolol has been shown to ameliorate exacerbated inflammation in the myocardial infarction setting. OBJECTIVES: The purpose of this study was to evaluate the effects of metoprolol on alveolar inflammation and on respiratory function in patients with COVID-19-associated ARDS. METHODS: A total of 20 COVID-19 patients with ARDS on invasive mechanical ventilation were randomized to metoprolol (15 mg daily for 3 days) or control (no treatment). All patients underwent bronchoalveolar lavage (BAL) before and after metoprolol/control. The safety of metoprolol administration was evaluated by invasive hemodynamic and electrocardiogram monitoring and echocardiography. RESULTS: Metoprolol administration was without side effects. At baseline, neutrophil content in BAL did not differ between groups. Conversely, patients randomized to metoprolol had significantly fewer neutrophils in BAL on day 4 (median: 14.3 neutrophils/µl [Q1, Q3: 4.63, 265 neutrophils/µl] vs median: 397 neutrophils/µl [Q1, Q3: 222, 1,346 neutrophils/µl] in the metoprolol and control groups, respectively; P = 0.016). Metoprolol also reduced neutrophil extracellular traps content and other markers of lung inflammation. Oxygenation (PaO2:FiO2) significantly improved after 3 days of metoprolol treatment (median: 130 [Q1, Q3: 110, 162] vs median: 267 [Q1, Q3: 199, 298] at baseline and day 4, respectively; P = 0.003), whereas it remained unchanged in control subjects. Metoprolol-treated patients spent fewer days on invasive mechanical ventilation than those in the control group (15.5 ± 7.6 vs 21.9 ± 12.6 days; P = 0.17). CONCLUSIONS: In this pilot trial, intravenous metoprolol administration to patients with COVID-19-associated ARDS was safe, reduced exacerbated lung inflammation, and improved oxygenation. Repurposing metoprolol for COVID-19-associated ARDS appears to be a safe and inexpensive strategy that can alleviate the burden of the COVID-19 pandemic.
Subject(s)
COVID-19/transmission , Critical Illness/therapy , Metoprolol/administration & dosage , Pandemics , Respiration, Artificial/methods , SARS-CoV-2 , Adrenergic beta-1 Receptor Antagonists/administration & dosage , Adult , Aged , COVID-19/epidemiology , Female , Humans , Injections, Intravenous , Male , Middle Aged , Pilot Projects , Prospective StudiesABSTRACT
BACKGROUND: Inappropriate sinus tachycardia (IST) is an arrhythmic complication observed after coronary artery bypass graft (CABG) surgery which left untreated, commonly increases chances of postoperative stroke. The primary study objective was comparing effectiveness of beta blocker-metoprolol; a specific If blocker-ivabradine and its combination in patients who develop IST as a complication following CABG. MATERIALS AND METHODS: An open-labeled, investigator initiated, clinical study was conducted on 150 patients who developed IST (heart rate [HR] >100 beats/min) following elective CABG surgery. The patients were randomized into three treatment groups. Group I - received ivabradine (5 mg), Group II - metoprolol (25 mg), and Group III - ivabradine (5 mg) and metoprolol (25 mg). Treatment was given orally, twice a day for 7 days in all the three groups postoperatively. Primary endpoints were comparative effectiveness in HR and blood pressure reduction following treatment. RESULTS: IST was diagnosed by an electrocardiogram (12-lead) considering morphological features of P-wave and with 32% increase from baseline HR in all the three groups. Compared to IST arrthymic rate, HR was reduced in all groups following respective treatment (P = 0.05). Reduction in HR was significant (P < 0.05) in combination group followed by ivabradine which was significantly greater than metoprolol treated group. None of the treatments clinically changed the systolic, diastolic and mean blood pressure till discharge. No surgery/treatment-related complications were observed in any groups. CONCLUSION: Ivabradine stands as a pharmacological option for controlling HR and rhythm without associated side effects in postoperative CABG patients with IST.
Subject(s)
Coronary Artery Bypass/adverse effects , Ivabradine/therapeutic use , Metoprolol/therapeutic use , Tachycardia, Sinus/drug therapy , Aged , Drug Therapy, Combination , Heart Rate/drug effects , Humans , Ivabradine/administration & dosage , Ivabradine/adverse effects , Metoprolol/administration & dosage , Metoprolol/adverse effects , Middle AgedABSTRACT
BACKGROUND: The existing meta-analyses and randomized studies on comparing the effects of carvedilol and metoprolol are of poor quality, with small sample sizes, and involve a homogeneous population. Therefore, to provide new evidence-based medical evidence for clinical treatment, we undertook a systematic review and meta-analysis to compare the mortality benefits of carvedilol with metoprolol head to head and determine the better beta-blocker in acute myocardial infarction (AMI) setting. METHODS: Seven electronic databases including Web of Science, Embase, PubMed, Wanfang Data, Scopus, Science Direct, Cochrane Library will be searched in May 2021 by 2 independent reviewers. The protocol was written following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement guidelines. The primary outcome is all-cause mortality; secondary outcomes include complex cardiovascular events, sudden death, cardiovascular death, reinfarction, revascularization, readmission, ventricular arrhythmias, and drug withdrawal for all causes except death. All outcomes are pooled on random-effect model. A P value of <.05 is considered to be statistically significant. RESULTS: The review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/VSTJC.
Subject(s)
Arrhythmias, Cardiac/epidemiology , Carvedilol/administration & dosage , Death, Sudden, Cardiac/epidemiology , Metoprolol/administration & dosage , Myocardial Infarction/drug therapy , Arrhythmias, Cardiac/etiology , Arrhythmias, Cardiac/prevention & control , Death, Sudden, Cardiac/prevention & control , Humans , Meta-Analysis as Topic , Myocardial Infarction/complications , Myocardial Infarction/mortality , Patient Readmission/statistics & numerical data , Randomized Controlled Trials as Topic , Recurrence , Systematic Reviews as Topic , Treatment OutcomeABSTRACT
The practice of prescribing ß-blockers to lower blood pressure and mitigate perioperative cardiovascular events has been questioned because of reports of an increased risk of stroke. The benefit of ß-blocker therapy primarily relies on preventing activation of cardiac ß1-adrenergic receptors (ARs). However, we reported that ß1ARs also mediate vasodilator responses of rat cerebral arteries (CAs), implying that ß-blockers may impair cerebral blood flow under some conditions. Here, we defined the impact of metoprolol (MET), a widely prescribed ß1AR-selective antagonist, on adrenergic-elicited diameter responses of rat CAs ex vivo and in vivo. MET (1-10 µmol/l) prevented ß1AR-mediated increases in diameter elicited by dobutamine in cannulated rat CAs. The ß1AR-mediated dilation elicited by the endogenous adrenergic agonist norepinephrine (NE) was reversed to a sustained constriction by MET. Acute oral administration of MET (30 mg/kg) to rats in doses that attenuated resting heart rate and dobutamine-induced tachycardia also blunted ß1AR-mediated dilation of CAs. In the same animals, NE-induced dilation of CAs was reversed to sustained constriction. Administration of MET for 2 weeks in drinking water (2 mg/ml) or subcutaneously (15 mg/kg per day) also resulted in NE-induced constriction of CAs in vivo. Thus, doses of MET that protect the heart from adrenergic stimulation also prevent ß1AR-mediated dilation of CAs and favor anomalous adrenergic constriction. Our findings raise the possibility that the increased risk of ischemic stroke in patients on ß-blockers relates in part to adrenergic dysregulation of cerebrovascular tone. SIGNIFICANCE STATEMENT: ß-Blocker therapy using second-generation, cardioselective ß-blockers is associated with an increased risk of stroke, but the responsible mechanisms are unclear. Here, we report that either acute or chronic systemic administration of a cardioselective ß-blocker, metoprolol, mitigates adrenergic stimulation of the heart as an intended beneficial action. However, metoprolol concomitantly eliminates vasodilator responses to adrenergic stimuli of rat cerebral arteries in vivo as a potential cause of dysregulated cerebral blood flow predisposing to ischemic stroke.
Subject(s)
Adrenergic beta-1 Receptor Antagonists/pharmacology , Cardiotonic Agents/pharmacology , Cerebral Arteries/drug effects , Metoprolol/pharmacology , Receptors, Adrenergic, beta-1/metabolism , Vasodilation , Adrenergic beta-1 Receptor Agonists/pharmacology , Adrenergic beta-1 Receptor Antagonists/administration & dosage , Adrenergic beta-1 Receptor Antagonists/adverse effects , Animals , Cardiotonic Agents/administration & dosage , Cardiotonic Agents/adverse effects , Cerebral Arteries/physiology , Dobutamine/pharmacology , Heart Rate/drug effects , Male , Metoprolol/administration & dosage , Metoprolol/adverse effects , Norepinephrine/pharmacology , Rats , Rats, Sprague-DawleyABSTRACT
BACKGROUND: Coronary CT angiography (CCTA) is increasing seen as a first line investigation in patients with suspected coronary artery disease. Heart-rate control improves the image quality and diagnostic accuracy of CCTA. Typically, beta-blockers are administered to induce sinus bradycardia. Sinus bradycardia may also be induced by ivabradine. We hypothesized that in a real-world population ivabradine would be an effective alternative to metoprolol at heart rate lowering for CCTA. METHODS: This was a retrospective analysis of consecutive patients who were exposed to an ivabradine-based (IB) versus a metoprolol-only (MO) protocol to achieve a target heart rate = 65bpm. Hemodynamic responses to both strategies were compared along with differences in cost and the time expired from medication administration to CCTA. RESULTS: 5955 consecutive patients were included in the analysis: 3211 were imaged during an era of a metoprolol only strategy (MO) and 2744 CCTA following an ivabradine based (IB) strategy. 2676 patients had heart rates >65 and received heart-rate lowering medication: 1958 patients had MO, and 718 received IB protocol. Target heart rate of = 65bpm was achieved in 77% of MO and 89% of IB patients (p < 0.01). The time from initial medication administration to CCTA was longer in the IB versus MO patients (77 versus 48 min, p < 0.01). CONCLUSIONS: Introduction of a novel single dose ivabradine-based protocol to control heart rate for CCTA was more successful in achieving target heart rate than a metoprolol-only strategy. The use of ivabradine however incurred a 1.6-fold increase in the time delay from medication administration and imaging compared to a metoprolol only protocol.
Subject(s)
Cardiovascular Agents/administration & dosage , Computed Tomography Angiography , Coronary Angiography , Coronary Artery Disease/diagnostic imaging , Heart Rate/drug effects , Ivabradine/administration & dosage , Multidetector Computed Tomography , Point-of-Care Testing , Administration, Oral , Adrenergic beta-1 Receptor Antagonists/administration & dosage , Aged , Female , Humans , Male , Metoprolol/administration & dosage , Middle Aged , Predictive Value of Tests , Retrospective Studies , Time Factors , WorkflowABSTRACT
OBJECTIVE: The objective of this study was to compare sustained rate control with intravenous (IV) diltiazem vs. IV metoprolol in acute treatment of atrial fibrillation (AF) with rapid ventricular rate (RVR) in the emergency department (ED). METHODS: This retrospective chart review at a large, academic medical center identified patients with AF with RVR diagnosis who received IV diltiazem or IV metoprolol in the ED. The primary outcome was sustained rate control defined as heart rate (HR) < 100 beats per minute without need for rescue IV medication for 3 h following initial rate control attainment. Secondary outcomes included time to initial rate control, HR at initial control and 3 h, time to oral dose, admission rates, and safety outcomes. RESULTS: Between January 1, 2016 and November 1, 2018, 51 patients met inclusion criteria (diltiazem n = 32, metoprolol n = 19). No difference in sustained rate control was found (diltiazem 87.5% vs. metoprolol 78.9%, p = 0.45). Time to rate control was significantly shorter with diltiazem compared to metoprolol (15 min vs. 30 min, respectively, p = 0.04). Neither hypotension nor bradycardia were significantly different between groups. CONCLUSIONS: Choice of rate control agent for acute management of AF with RVR did not significantly influence sustained rate control success. Safety outcomes did not differ between treatment groups.
Subject(s)
Anti-Arrhythmia Agents/therapeutic use , Atrial Fibrillation/drug therapy , Cardiovascular Agents/therapeutic use , Diltiazem/therapeutic use , Emergency Service, Hospital , Heart Rate/drug effects , Metoprolol/therapeutic use , Anti-Arrhythmia Agents/administration & dosage , Cardiovascular Agents/administration & dosage , Diltiazem/administration & dosage , Female , Humans , Male , Metoprolol/administration & dosage , Middle Aged , Retrospective Studies , TexasABSTRACT
OBJECTIVE: The effect of early intravenous (IV) beta-blockers (BBs) administration in patients undergoing primary percutaneous coronary intervention (pPCI) on ST-segment deviation is unknown. We undertook a prespecified secondary analysis of the Early Beta-blocker Administration before primary PCI in patients with ST-elevation Myocardial Infarction (EARLY-BAMI) trial to investigate the effect of early IV BB on ST-segment deviation. METHODS: The EARLY-BAMI trial randomised patients with ST-elevation myocardial infarction (STEMI) to IV metoprolol (2×5 mg bolus) or matched placebo before pPCI. The prespecified outcome, evaluated by an independent core laboratory blinded to study treatment, was the residual ST-segment deviation 1 hour after pPCI (ie, the percentage of patients with >3 mm cumulative ST deviation at 1 hour after pPCI). RESULTS: An ECG for the evaluation of residual ST-segment deviation 1 hour after pPCI was available in 442 out of 683 randomised patients. The BB group had a lower heart rate after pPCI compared with placebo (71.2±13.2 vs 74.3±13.6, p=0.016); however, no differences were noted in the percentages of patients with >3 mm cumulative ST deviation at 1 hour after pPCI (58.6% vs 54.1%, p=0.38, in BB vs placebo, respectively) neither a significant difference was found for the percentages of patients in each of the four prespecified groups (normalised ST-segment; 1-3 mm; 4-6 mm;>6 mm residual ST-deviation). CONCLUSIONS: In patients with STEMI, who were being transported for primary PCI, early IV BB administration did not significantly affect ST-segment deviation after pPCI compared with placebo. The neutral result of early IV BB administration on an early marker of pharmacological effect is consistent with the absence of subsequent improvement of clinical outcomes.
Subject(s)
Electrocardiography/drug effects , Metoprolol/administration & dosage , Percutaneous Coronary Intervention/methods , ST Elevation Myocardial Infarction/therapy , Adrenergic beta-1 Receptor Antagonists/administration & dosage , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Male , Middle Aged , ST Elevation Myocardial Infarction/diagnosis , Treatment OutcomeABSTRACT
Fundamento: Durante o ecocardiograma sob estresse com dobutamina, podem ocorrer efeitos adversos e exames inconclusivos. Objetivo: Avaliar em uma grande população geral a segurança e a exequibilidade do ecocardiograma sob estresse com dobutamina. Métodos: Estudo de 10.006 ecocardiogramas sob estresse com dobutamina realizados no período de julho de 1996 a setembro de 2007. A dobutamina foi administrada em quatro estágios (10, 20, 30 e 40 µcg.kg-1.min-1) para pesquisa de isquemia miocárdica e iniciada com 5 µcg.kg- ¹.min-1 apenas na análise de viabilidade miocárdica. A atropina foi iniciada conforme os protocolos vigentes. Foram verificados dados clínicos, hemodinâmicos e efeitos adversos associados ao ecocardiograma sob estresse com dobutamina. Resultados: Durante os ecocardiogramas sob estresse com dobutamina, ocorreu angina típica (8,9%), pico hipertensivo (1,7%), ectopias ventriculares isoladas (31%), taquiarritmia supraventricular (1,89%), fibrilação atrial (0,76%) e taquicardia ventricular não sustentada (0,6%). Os efeitos adversos citados foram mais frequentes nos pacientes com ecocardiogramas sob estresse com dobutamina positivos para isquemia. A desaceleração sinusal paradoxal (0,16%) não ocorreu em ecocardiogramas sob estresse com dobutamina positivo. As três complicações graves ocorreram em ecocardiogramas sob estresse com dobutamina positivos para isquemia. Foram dois casos (0,02%) com fibrilação ventricular e um caso de síndrome coronariana aguda (0,01%). Não houve caso de taquicardia ventricular sustentada, ruptura cardíaca, assistolia ou óbito. Comparados aos exames concluídos, nos inconclusivos, os pacientes usaram menos atropina (81,5% versus 49,9%; p< 0,001) e mais betabloqueador (4,7% versus 19%; p< 0,001), apresentando mais pico hipertensivo (1,1% versus 14,2%; p = 0,0001) e taquicardia ventricular não sustentada (0,5% versus 2,2%; p< 0,001). Conclusão: O ecocardiograma sob estresse com dobutamina realizado de forma apropriada é seguro e apresenta elevada exequibilidade.
Background: Adverse effects and inconclusive results may occur on dobutamine stress echocardiography. Objective: To assess the safety and feasibility of dobutamine stress echocardiography in a large general population. Methods: A total of 10,006 dobutamine stress echocardiographies were performed between July 1996 and September 2007. Dobutamine was administered in four stages (10, 20, 30, and 40 µcg·kg-1·min-1) to research myocardial ischemia starting with 5 µcg·kg- ¹·min-1 to analyze myocardial viability. Atropine administration was initiated according to current protocols. Clinical, hemodynamic, and adverse effect data associated with dobutamine stress echocardiography findings were verified. Results: Typical angina (8.9%), hypertensive peak (1.7%), isolated ventricular ectopias (31%), supraventricular tachyarrhythmia (1.89%), atrial
Subject(s)
Humans , Male , Female , Aged , Coronary Disease/diagnosis , Drug-Related Side Effects and Adverse Reactions , Atropine/administration & dosage , Retrospective Studies , Risk Factors , Echocardiography, Stress/adverse effects , Echocardiography, Stress/drug effects , Dobutamine/administration & dosage , Dobutamine/adverse effects , Electrocardiography/methods , Hypertension/complications , Metoprolol/administration & dosageABSTRACT
Recent CYP2D6 phenotype standardization efforts by CYP2D6 activity score (AS) are based on limited pharmacokinetic (PK) and pharmacodynamic (PD) data. Using data from two independent clinical trials of metoprolol, we compared metoprolol PK and PD across CYP2D6 AS with the goal of determining whether the PK and PD data support the new phenotype classification. S-metoprolol apparent oral clearance (CLo), adjusted for clinical factors, was correlated with CYP2D6 AS (P < 0.001). The natural log of CLo was lower with an AS of 1 (7.6 ± 0.4 mL/minute) vs. 2-2.25 (8.3 ± 0.6 mL/minute; P = 0.012), similar between an AS of 1 and 1.25-1.5 (7.8 ± 0.5 mL/minute; P = 0.702), and lower with an AS of 1.25-1.5 vs. 2-2.25 (P = 0.03). There was also a greater reduction in heart rate with metoprolol among study participants with AS of 1 (-10.8 ± 5.5) vs. 2-2.25 (-7.1 ± 5.6; P < 0.001) and no significant difference between those with an AS of 1 and 1.25-1.5 (-9.2 ± 4.7; P = 0.095). These data highlight linear trends among CYP2D6 AS and metoprolol PK and PD, but inconsistencies with the phenotypes assigned by AS based on the current standards. Overall, this case study with metoprolol suggests that utilizing CYP2D6 AS, instead of collapsing AS into phenotype categories, may be the most precise approach for utilizing CYP2D6 pharmacogenomics in clinical practice.
Subject(s)
Adrenergic beta-1 Receptor Antagonists/pharmacokinetics , Cytochrome P-450 CYP2D6/genetics , Genotype , Metoprolol/pharmacokinetics , Administration, Oral , Adrenergic beta-1 Receptor Antagonists/administration & dosage , Adult , Aged , Blood Pressure/drug effects , Female , Heart Rate/drug effects , Humans , Male , Metoprolol/administration & dosage , Middle Aged , Pharmacogenetics , Phenotype , Polymorphism, Single Nucleotide , Prospective StudiesABSTRACT
Coronary artery fistulas (CAFs) are described as abnormal communications between a coronary artery and cardiac chambers, or other vascular structures. The two types of CAFs are defined as type I (singular fistula) and type II (microfistulas). Even though various electrocardiographic changes have been previously described in CAF patients, coronary-artery microfistulas causing ST-segment elevation in diverse locations have not been reported. We describe a case report of an adult patient who presented with acute inferior myocardial infarction due to coronary-artery microfistulas. During the hospital stay, the patient re-experienced chest pain, and control electrocardiography revealed ST-segment elevation in the I and AVL leads along with reciprocal ST-segment depression in the inferior precordial leads. Although CAFs are clinically rare, they can have important clinical consequences. Microfistulas should be kept in mind as a cause of ST elevation myocardial infarction in some patients.
Subject(s)
Coronary Vessel Anomalies/complications , ST Elevation Myocardial Infarction/etiology , Vascular Fistula/complications , Aspirin/administration & dosage , Coronary Angiography , Coronary Vessel Anomalies/diagnosis , Electrocardiography , Humans , Male , Metoprolol/administration & dosage , Middle Aged , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/drug therapy , Vascular Fistula/diagnosisABSTRACT
PURPOSE: To assess gender-, age-, and the dose-related influence of metoprolol on cardiac function, motor function, quality-of-life (QoL), and mental status in Chinese chronic heart failure (CHF) patients. PATIENTS AND METHODS: This single-center, prospective study enrolled CHF patients with resting heart rate (HR) >80 bpm and used metoprolol continuous release tablets. Patients were initiated with 12.5-mg metoprolol. All patients were assessed for change in cardiac function, motor function, QoL, and mental status according to gender (men vs women), age (<60 vs ≥60 years), and metoprolol dose administered (47.5 mg [n=37], 71.25 mg [n=7], 118.75 [n=74], and 142.5 mg [n=19]). RESULTS: Overall, 154 CHF patients (101 men and 53 women), with median age 66.39 years, were enrolled. In total, 116 and 38 patients were aged ≥60 and <60 years, respectively. We observed a slight decrease in systolic blood pressure (SBP) in women compared with men. HR had increased with an increase in ejection fraction (EF) from baseline to 1 month (35.24±6.15 and 34.79±6.25) and increased to 50.00±4.45 and 50.72±4.09 among both the genders. Cardiac index (CI) and motor function had improved along with better QoL after metoprolol treatment in both the genders. In both age groups (<60 and ≥60 years), improvement in cardiac function, motor function, and QoL was observed; however, there was a difference in mental status. The dose effect of metoprolol on cardiac function, motor function, QoL, and mental status showed a gradual decrease in EF with dose increments, with no change in CI. Motor function, QoL, and mental status did not show much difference with uptitration of metoprolol dose. CONCLUSION: Psychological responses to metoprolol treatment differ with gender, with no age-related changes in terms of cardiac function, motor function, QoL, or mental status, except increases in depression, burnout, and anxiety.
Subject(s)
Heart Failure/drug therapy , Metoprolol/pharmacology , Motor Activity/drug effects , Stroke Volume/drug effects , Administration, Oral , Aged , Asian People , Chronic Disease , Female , Humans , Male , Metoprolol/administration & dosage , Prospective Studies , Quality of Life , Surveys and QuestionnairesABSTRACT
OBJECTIVE: Intravenous push (IVP) diltiazem and metoprolol are commonly used for management of atrial fibrillation (AF) with rapid ventricular rate (RVR) in the emergency department (ED). This study's objective was to determine if there was a significant difference in blood pressure reduction between agents. METHODS: This was a single-center, retrospective study of adult patients initially treated with IVP diltiazem or metoprolol in the ED from 2008 to 2018. Primary endpoint was mean reduction in systolic blood pressure (SBP) from baseline to nadir during the study period. Study period was defined as time from first dose of IVP intervention to 30 min after last dose of IVP intervention or first dose of maintenance therapy, whichever came first. RESULTS: A total of 63 diltiazem patients and 45 metoprolol patients met eligibility criteria. Baseline characteristics were similar except for initial ventricular rate (VR) and home beta-blocker use. Median dose of initial intervention was 10 [10-20] mg and 5 [5-5] mg for diltiazem and metoprolol respectively. Mean SBP reduction was 18 ± 22 mmHg for diltiazem compared to 14 ± 15 mmHg for metoprolol (p = .33). Clinically relevant hypotension was similar between groups 14% vs. 16% (p = .86). Rate control was achieved in 35 (56%) of the diltiazem group and 16 (36%) of the metoprolol group (p = .04). CONCLUSION: IVP diltiazem and metoprolol caused similar SBP reduction and hypotension when used for initial management of AF with RVR in the ED. However, rate control was achieved more often with diltiazem.
Subject(s)
Anti-Arrhythmia Agents/therapeutic use , Atrial Fibrillation/drug therapy , Diltiazem/therapeutic use , Hemodynamics/drug effects , Metoprolol/therapeutic use , Administration, Intravenous , Aged , Anti-Arrhythmia Agents/administration & dosage , Blood Pressure/drug effects , Diltiazem/administration & dosage , Female , Humans , Male , Metoprolol/administration & dosage , Middle Aged , Retrospective Studies , Treatment OutcomeABSTRACT
Early metoprolol administration protects against myocardial ischemia-reperfusion injury, but its effect on infarct size progression (ischemic injury) is unknown. Eight groups of pigs (total n = 122) underwent coronary artery occlusion of varying duration (20, 25, 30, 35, 40, 45, 50, or 60 min) followed by reperfusion. In each group, pigs were randomized to i.v. metoprolol (0.75 mg/kg) or vehicle (saline) 20 min after ischemia onset. The primary outcome measure was infarct size (IS) on day7 cardiac magnetic resonance (CMR) normalized to area at risk (AAR, measured by perfusion computed tomography [CT] during ischemia). Metoprolol treatment reduced overall mortality (10% vs 26%, p = 0.03) and the incidence and number of primary ventricular fibrillations during infarct induction. In controls, IS after 20-min ischemia was ≈ 5% of the area AAR. Thereafter, IS progressed exponentially, occupying almost all the AAR after 35 min of ischemia. Metoprolol injection significantly reduced the slope of IS progression (p = 0.004 for final IS). Head-to-head comparison (metoprolol treated vs vehicle treated) showed statistically significant reductions in IS at 30, 35, 40, and 50-min reperfusion. At 60-min reperfusion, IS was 100% of AAR in both groups. Despite more prolonged ischemia, metoprolol-treated pigs reperfused at 50 min had smaller infarcts than control pigs undergoing ischemia for 40 or 45 min and similar-sized infarcts to those undergoing 35-min ischemia. Day-45 LVEF was higher in metoprolol-treated vs vehicle-treated pigs (41.6% vs 36.5%, p = 0.008). In summary, metoprolol administration early during ischemia attenuates IS progression and reduces the incidence of primary ventricular fibrillation. These data identify metoprolol as an intervention ideally suited to the treatment of STEMI patients identified early in the course of infarction and requiring long transport times before primary angioplasty.