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1.
JAMA ; 324(3): 279-290, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32692391

RESUMO

Importance: Perioperative cardiovascular complications occur in 3% of hospitalizations for noncardiac surgery in the US. This review summarizes evidence regarding cardiovascular risk assessment prior to noncardiac surgery. Observations: Preoperative cardiovascular risk assessment requires a focused history and physical examination to identify signs and symptoms of ischemic heart disease, heart failure, and severe valvular disease. Risk calculators, such as the Revised Cardiac Risk Index, identify individuals with low risk (<1%) and higher risk (≥1%) for perioperative major adverse cardiovascular events during the surgical hospital admission or within 30 days of surgery. Cardiovascular testing is rarely indicated in patients at low risk for major adverse cardiovascular events. Stress testing may be considered in patients at higher risk (determined by the inability to climb ≥2 flights of stairs, which is <4 metabolic equivalent tasks) if the results from the testing would change the perioperative medical, anesthesia, or surgical approaches. Routine coronary revascularization does not reduce perioperative risk and should not be performed without specific indications independent of planned surgery. Routine perioperative use of low-dose aspirin (100 mg/d) does not decrease cardiovascular events but does increase surgical bleeding. Statins are associated with fewer postoperative cardiovascular complications and lower mortality (1.8% vs 2.3% without statin use; P < .001) in observational studies, and should be considered preoperatively in patients with atherosclerotic cardiovascular disease undergoing vascular surgery. High-dose ß-blockers (eg, 100 mg of metoprolol succinate) administered 2 to 4 hours prior to surgery are associated with a higher risk of stroke (1.0% vs 0.5% without ß-blocker use; P = .005) and mortality (3.1% vs 2.3% without ß-blocker use; P = .03) and should not be routinely used. There is a greater risk of perioperative myocardial infarction and major adverse cardiovascular events in adults aged 75 years or older (9.5% vs 4.8% for younger adults; P < .001) and in patients with coronary stents (8.9% vs 1.5% for those without stents; P < .001) and these patients warrant careful preoperative consideration. Conclusions and Relevance: Comprehensive history, physical examination, and assessment of functional capacity during daily life should be performed prior to noncardiac surgery to assess cardiovascular risk. Cardiovascular testing is rarely indicated in patients with a low risk of major adverse cardiovascular events, but may be useful in patients with poor functional capacity (<4 metabolic equivalent tasks) undergoing high-risk surgery if test results would change therapy independent of the planned surgery. Perioperative medical therapy should be prescribed based on patient-specific risk.


Assuntos
Doenças Cardiovasculares/etiologia , Complicações Pós-Operatórias/etiologia , Medição de Risco/métodos , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/efeitos adversos , Fatores Etários , Idoso , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Biomarcadores/sangue , Angiografia Coronária , Ecocardiografia Transesofagiana , Eletrocardiografia/métodos , Fibrinolíticos/administração & dosagem , Fibrinolíticos/efeitos adversos , Insuficiência Cardíaca/diagnóstico , Doenças das Valvas Cardíacas/diagnóstico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/etiologia , Isquemia Miocárdica/diagnóstico , Revascularização Miocárdica , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios/métodos , Stents/efeitos adversos , Acidente Vascular Cerebral/induzido quimicamente , Fatores de Tempo , Estados Unidos/epidemiologia
2.
Isr Med Assoc J ; 7(22): 375-379, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32692500

RESUMO

BACKGROUND: Heart failure (HF) patients with reduced ejection fraction (HFrEF) are frequently treated with sub-optimal doses of angiotensin converting enzyme-inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and beta blockers (BBs). OBJECTIVES: To determine factors associated with attaining upper-range doses in patients with HFrEF. METHODS: We examined treatment in patients with left ventricular ejection fraction (LVEF) ≤ 40% in a community-based, dedicated heart-failure clinic. Upper-range doses were defined as ≥ 75% of target recommended doses by heart failure society guidelines. RESULTS: The majority of the 215 patients were men (82%); median age at presentation 73 years (interquartile range [IQR] 65-78) and LVEF of 30% (IQR 25-35%). Following the up-titration program, 41% and 35% of patients achieved upper-range doses of ACE-Is/ARBs and BBs, respectively. Higher body mass index (BMI) was the only parameter found to be associated with achieving upper-range doses of ACE-I/ARBs (odds ratio [OR] 1.13, 95% confidence interval [95%CI] 1.05-1.22, P = 0.001). More patients achieved this target as BMI increased, with a sharp decline in the highest obesity category (BMI ≥ 40 m2/kg). Attaining upper-range doses of BBs was associated with pre-existing diabetes mellitus (DM) (OR 2.6, 95%CI 1.34-5.19, P = 0.005); women were associated with attaining lower BBs doses (OR 0.34, 95%CI 0.13-0.90, P = 0.031). CONCLUSIONS: Achieving upper-range doses of ACE-Is/ARBs and BBs in HFrEF outpatients in a treatment up-titration program were associated with greater BMI and DM, respectively. These findings may serve as benchmarks for up-titration programs.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas de Receptores de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Disfunção Ventricular Esquerda/tratamento farmacológico , Idoso , Benchmarking , Índice de Massa Corporal , Diabetes Mellitus/epidemiologia , Relação Dose-Resposta a Droga , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Volume Sistólico/fisiologia , Função Ventricular Esquerda/efeitos dos fármacos
5.
N Engl J Med ; 382(25): 2441-2448, 2020 06 18.
Artigo em Inglês | MEDLINE | ID: covidwho-155188

RESUMO

BACKGROUND: There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2). METHODS: We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as a substantial difference. RESULTS: Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness. A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness. There was no association between any single medication class and an increased likelihood of a positive test. None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive. CONCLUSIONS: We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas de Receptores de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Bloqueadores dos Canais de Cálcio/administração & dosagem , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Inibidores de Simportadores de Cloreto de Sódio/administração & dosagem , Antagonistas Adrenérgicos beta/efeitos adversos , Adulto , Idoso , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Teorema de Bayes , Betacoronavirus , Bloqueadores dos Canais de Cálcio/efeitos adversos , Feminino , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , New York , Pandemias , Pontuação de Propensão , Sistema Renina-Angiotensina/efeitos dos fármacos , Fatores de Risco , Inibidores de Simportadores de Cloreto de Sódio/efeitos adversos
6.
N Engl J Med ; 382(25): 2441-2448, 2020 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-32356628

RESUMO

BACKGROUND: There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2). METHODS: We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as a substantial difference. RESULTS: Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness. A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness. There was no association between any single medication class and an increased likelihood of a positive test. None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive. CONCLUSIONS: We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas de Receptores de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Bloqueadores dos Canais de Cálcio/administração & dosagem , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Inibidores de Simportadores de Cloreto de Sódio/administração & dosagem , Antagonistas Adrenérgicos beta/efeitos adversos , Adulto , Idoso , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Teorema de Bayes , Betacoronavirus , Bloqueadores dos Canais de Cálcio/efeitos adversos , Feminino , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , New York , Pandemias , Pontuação de Propensão , Sistema Renina-Angiotensina/efeitos dos fármacos , Fatores de Risco , Inibidores de Simportadores de Cloreto de Sódio/efeitos adversos
7.
Life Sci ; 252: 117649, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32275936

RESUMO

Chronic obstructive pulmonary disease (COPD) with cardiovascular complications is very common. Due to fear of exacerbating airway spasm, ß-blockers are rarely used in such patients. Many observational studies suggest that ß-blockers can reduce the disease progression and the risk of mortality in patients with COPD, but lack of confirmation from randomized controlled trials. This article reviews the application of ß-blockers in patients with COPD based on the results of the latest published randomized controlled trials.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Doenças Cardiovasculares/prevenção & controle , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Antagonistas Adrenérgicos beta/efeitos adversos , Progressão da Doença , Humanos , Doença Pulmonar Obstrutiva Crônica/mortalidade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Int Heart J ; 61(2): 384-389, 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32132321

RESUMO

Tachycardia and supraventricular tachyarrhythmias often impair cardiovascular capacity in patients with decompensated heart failure (dHF) treated with inotropes. Normalization of heart rhythm or rate typically improves diastolic filling and stroke volume (SV). Thus, isochronal administration of an ultra-short-acting and highly selective ß1-blockers, such as landiolol, along with inotropic calcium-sensitizer medications, such as levosimendan, could benefit patients with dHF.We present a case series of three patients with severe dHF and low ejection fraction who were successfully treated with a combination of landiolol and levosimendan. The co-administration of landiolol and levosimendan was well tolerated, improved cardiac function, normalized SV, and enabled the reduction of norepinephrine dosing in all patients. Additionally, the combination improved the vectorcardiographic spatial QRS-T angle and decreased the corrected QT interval. All patients were successfully discharged from the intensive care unit (ICU).A combination of levosimendan and landiolol was safe and well-tolerated. This combination may be a new option for successful treatment of patients with acute dHF complicated by sinus or supraventricular tachycardias.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Cardiotônicos/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Morfolinas/administração & dosagem , Simendana/administração & dosagem , Taquicardia/tratamento farmacológico , Ureia/análogos & derivados , Idoso , Quimioterapia Combinada , Feminino , Insuficiência Cardíaca/complicações , Humanos , Masculino , Taquicardia/etiologia , Ureia/administração & dosagem
9.
Int J Surg ; 76: 153-162, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32169568

RESUMO

BACKGROUND: It remains uncertain whether there is a benefit to perioperative beta-blocker use on outcomes after non-cardiac surgery. This meta-analysis aims to update the evidence regarding the associations between beta-blocker exposure and patient major short-term outcomes following non-cardiac surgery. METHODS: Pubmed, Embase, and the Cochrane Central Register from their inception to May 2019 were searched by two independent authors. Observational studies reporting associations between perioperative beta-blocker treatment and short-term outcomes including 30-day all-cause mortality (ACM), 30-day major adverse cardiovascular events (MACE) and 30-day stroke risk were selected for inclusion. Meta-analyses were carried out by using random effects models. RESULTS: Nineteen studies with a total of 1,711,766 participants were identified. Beta-blocker exposure was associated with reduced 30-day all-cause mortality (ACM) (RR 0.83, 95% CI 0.72 to 0.96). No evidence of publication bias was observed. Subgroup analyses revealed that significant 30-day survival benefits were observed in prospective, population-based studies, drug exposure period last till 1-2 months after surgery, patients having abdominal gastrointestinal surgery or having 3-4 cardiac risk factors. Beta-blocker exposure was associated with increased 30-day ACM among patients with no cardiac risk factors (RR 1.30, 95% CI 1.19 to 1.43). However, meta-analysis demonstrated a non-significant risk reduction in 30-day MACE (RR 1.03; 95% CI 0.85 to 1.25) or 30-day stroke risk (RR 0.86; 95% CI 0.44 to 1.68) with beta-blocker exposure. CONCLUSIONS: The results of the current meta-analysis indicate beta-blocker exposure may be a significant indicator for 30-day ACM, but not for 30-day MACE or 30-day stroke risk. The association between beta-blocker exposure and long-term outcomes deserves further investigation.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Doenças Cardiovasculares , Complicações Pós-Operatórias , Procedimentos Cirúrgicos Operatórios , Antagonistas Adrenérgicos beta/uso terapêutico , Doenças Cardiovasculares/etiologia , Humanos , Estudos Prospectivos , Fatores de Risco
11.
An Bras Dermatol ; 95(2): 207-209, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32061465

RESUMO

Infantile hemangioma is the most common pediatric vascular tumor, with the following risk factors: low birth weight, prematurity, white skin, female gender, multiparity and advanced maternal age. The use of oral and topical beta-blockers, although recent, has emerged as the first line of treatment, with superior safety and efficacy to previously used therapies, such as corticosteroids and surgeries. This report describes two cases of nasal tip infantile hemangioma, treated with oral propranolol. Both presented excellent therapeutic responses.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Hemangioma/tratamento farmacológico , Neoplasias Nasais/tratamento farmacológico , Propranolol/administração & dosagem , Administração Oral , Feminino , Hemangioma/patologia , Humanos , Lactente , Neoplasias Nasais/patologia , Resultado do Tratamento
12.
Anesthesiology ; 132(2): 267-279, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31939841

RESUMO

BACKGROUND: For cardiac surgery patients under chronic ß-blocker therapy, guidelines recommend their early postoperative reintroduction to decrease the incidence of postoperative atrial fibrillation. The authors hypothesized that the timing of ß-blocker reintroduction affects their effectiveness on the incidence of postoperative atrial fibrillation. METHODS: This multicenter prospective French cohort study included patients on ß-blockers (more than 30 days before surgery) in sinus rhythm without a pacemaker. The primary outcome, time sequence of ß-blocker reintroduction, was analyzed for 192 h after surgery. The secondary outcome, relationship between the occurrence of postoperative atrial fibrillation and timing of ß-blocker reintroduction, was analyzed based on pre- and intraoperative predictors (full and selected sets) according to landmark times (patients in whom atrial fibrillation occurred before a given landmark time were not analyzed). RESULTS: Of 663 patients, ß-blockers were reintroduced for 532 (80%) but for only 261 (39%) patients in the first 48 h after surgery. Median duration before reintroduction was 49.5 h (95% CI, 48 to 51.5 h). Postoperative atrial fibrillation or death (N = 4) occurred in 290 (44%) patients. After performing a landmark analysis to take into account the timing of ß-blocker reintroduction, the adjusted odds ratios (95% CI) for predictor full and selected (increased age, history of paroxysmal atrial fibrillation, and duration of aortic cross clamping) sets for the occurrence of postoperative atrial fibrillation were: adjusted odds ratio (full) = 0.87 (0.58 to 1.32; P = 0.517) and adjusted odds ratio (selected) = 0.84 (0.58 to 1.21; P = 0.338) at 48 h; adjusted odds ratio (full) = 0.64 (0.39 to 1.05; P = 0.076) and adjusted odds ratio (selected) = 0.58 (0.38 to 0.89; P = 0.013) at 72 h; adjusted odds ratio (full) = 0.58 (0.31 to 1.07; P = 0.079) and adjusted odds ratio (selected) = 0.53 (0.31 to 0.91; P = 0.021) at 96 h. CONCLUSIONS: ß-Blockers were reintroduced early (after less than 48 h) in fewer than half of the cardiac surgery patients. Reintroduction decreased postoperative atrial fibrillation occurrence only at later time points and only in the predictor selected set model. These results are an incentive to optimize (timing, doses, or titration) ß-blocker reintroduction after cardiac surgery.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/prevenção & controle , Procedimentos Cirúrgicos Cardíacos/tendências , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Antagonistas Adrenérgicos beta/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/diagnóstico , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Estudos de Coortes , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Estudos Prospectivos
13.
J Am Osteopath Assoc ; 120(2): 90-99, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31985768

RESUMO

Modern medical and technological advances provide highly effective management for the treatment of patients with heart failure with reduced ejection fraction (HFrEF). In this review, the authors propose a 2-step approach to treatment that is straightforward, practical, and thorough. For the patient whose life now includes HFrEF, the physician's first step is to ensure that the patient is taking the 3 key medications ([1] renin-angiotensin inhibitors (angiotensin receptor/neprilysin inhibitors, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers), [2] ß-blockers, and [3] mineralocorticoid receptor antagonists) recommended in guideline-directed doses to attain comprehensive receptor blockade. Significant coexisting medical issues are also characteristic in patients with HFrEF. Therefore, the physician's second step is to address the comorbidities of heart failure to fulfill comprehensive patient care. This review presents evidence to implement the management of HFrEF and heart failure comorbidities that will reduce cardiac mortality and hospitalization and to avoid treatments that are of no benefit or may cause harm.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas de Receptores de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Comorbidade , Humanos
14.
J Cardiovasc Pharmacol ; 75(3): 250-258, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31895871

RESUMO

Heart failure (HF) is highly prevalent and a major cause of death in the United States. The effect of HF medications on survival has been predicted by validated models studied in populations predominantly of European descent. This study aimed to identify medications associated with survival in a racially diverse HF population. Patients with HF were recruited and followed from 2001 to 2015. Data were collected from electronic health records and the Social Security Death Index. The primary analysis tested the association between medication dose and all-cause mortality, with a secondary analysis assessing the composite outcome of death or cardiac-related hospitalization. Circulating concentration of the fibrotic marker procollagen type III N-terminal peptide (PIIINP) was also compared with medication doses in patients with concentrations available. The study population consisted of 337 patients, of which 25.2% died and 46% were hospitalized. Increased beta-blocker (BB) dose was significantly associated with survival in the base model [hazard ratio (HR) = 0.71, P = 0.017] and marginally associated in the comprehensive model (HR = 0.75, P = 0.068). BB dose was also associated with decreased risk of the composite end point in the base model (HR = 0.80, P = 0.029) and to a lesser extent in the comprehensive model (HR = 0.83, P = 0.085). Furthermore, increased BB dose was inversely associated with circulating PIIINP concentration (P = 0.041). In conclusion, our study highlights the importance of BB dose escalation for survival and decreased hospitalization in patients with HF, regardless of race or HF type. It also suggests that benefits observed with high-dose BBs could be mediated, at least in part, by decreased cardiac fibrosis.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Antagonistas Adrenérgicos beta/efeitos adversos , Idoso , Biomarcadores/sangue , Causas de Morte , Chicago/epidemiologia , Feminino , Fibrose , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etnologia , Insuficiência Cardíaca/mortalidade , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Prevalência , Pró-Colágeno/sangue , Fatores de Proteção , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
15.
Clin Oral Investig ; 24(3): 1239-1247, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31317257

RESUMO

OBJECTIVES: Metoprolol is a cardioselective competitive beta-1 adrenergic receptor antagonist with antihypertensive properties, devoid of intrinsic sympathomimetic activity. Various studies have suggested the effect of beta-blockers on bone remodeling. We aimed to investigate whether metoprolol affects bone remodeling by altering anti-inflammatory and pro-inflammatory cytokines. MATERIALS AND METHODS: Surgical defects of 3 mm diameter were created in tibiae of 72 Sprague-Dawley rats. Rats were randomly assigned to a control group without metoprolol treatment (n = 36), and a test group treated with 0.1 mg/kg/day metoprolol (n = 36). Six rats from each group were sacrificed at days 0, 1, 3, 5, 7, and 14. The percentages of cells, which showed positive immunohistochemical staining for IL-1ß, IL-6, IL-10, and RANKL, were assessed in the defect area. Differences in percentages of stained cells within each of the test and control groups over various time intervals were tested using one-way ANOVA test. A P value of < 0.05 was considered statistically significant. RESULTS: No significant differences in IL-1ß, IL-10, IL-6, and RANKL expressions were found between test and control groups at the same interval. Significant reduction was observed at different time intervals in the same group (P < 0.05). CONCLUSION: Metoprolol did not reduce bone-active cytokine: IL-1ß, IL-6, and RANKL. It also did not elevate IL-10 expression levels. Thus, it does not appear to decrease osteoclastogenesis. CLINICAL RELEVANCE: Results from this animal model help us understand any effect of metoprolol on bone healing by potential contribution to different real-world clinical research.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Remodelação Óssea/efeitos dos fármacos , Metoprolol/administração & dosagem , Tíbia/efeitos dos fármacos , Animais , Injeções Intraperitoneais , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Projetos Piloto , Ligante RANK/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Tíbia/patologia
16.
Drugs Aging ; 37(2): 125-135, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31858449

RESUMO

BACKGROUND: Medications endorsed by clinical practice guidelines, such as cardiovascular medications, could still have risks that outweigh potential benefits, and could thus warrant deprescribing. OBJECTIVES: The objective of this study was to develop a framework of facilitators and barriers specific to deprescribing cardiovascular medications in the setting of uncertain benefit. Given the frequent use of ß-blockers in heart failure with preserved ejection fraction, and its uncertain benefits with potential for harm, we used this scenario as an example case for a cardiovascular medication that may be reasonable to deprescribe. METHODS: We conducted one-on-one, semi-structured interviews of older adults until we reached thematic saturation. Two coders independently reviewed each interview, and developed codes using deductive thematic analysis based on a prior conceptual framework for deprescribing. Subthemes and themes were finalized with a third coder. RESULTS: Ten participants were interviewed. We identified three key previously described patient-reported facilitators to deprescribing: (1) appropriateness of cessation; (2) process of cessation; and (3) dislike of medications; and identified three key previously described patient-reported barriers: (1) appropriateness of cessation; (2) process of cessation; and (3) fear. We found that these facilitators and barriers often co-occurred within the same individual. This observation, coupled with subthemes from our patient interviews, yielded two barriers to deprescribing specific to cardiovascular medications-uncertainty and conflicting attitudes. CONCLUSION: We adapted a new framework of patient-reported barriers and facilitators specific to deprescribing cardiovascular medications. In addition to addressing barriers previously described, future deprescribing interventions targeting cardiovascular medications must also address uncertainty and conflicting attitudes.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , Desprescrições , Insuficiência Cardíaca/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/efeitos adversos , Idoso , Fármacos Cardiovasculares/administração & dosagem , Fármacos Cardiovasculares/efeitos adversos , Feminino , Hospitalização , Humanos , Masculino , Segurança do Paciente , Inquéritos e Questionários
18.
Cardiovasc Diabetol ; 18(1): 163, 2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775749

RESUMO

BACKGROUND: Although beta blockers could increase the risk of hypoglycemia, the difference between subtypes on hypoglycemia and mortality have not been studied. This study sought to determine the relationship between type of beta blocker and incidence of hypoglycemia and mortality in hospitalized patients. METHODS: We retrospectively identified non-critically ill hospitalized insulin requiring patients who were undergoing bedside glucose monitoring and received either carvedilol or a selective beta blocker (metoprolol or atenolol). Patients receiving other beta blockers were excluded. Hypoglycemia was defined as any glucose < 3.9 mmol/L within 24 h of admission (Hypo1day) or throughout hospitalization (HypoT) and any glucose < 2.2 mmol/L throughout hospitalization (Hyposevere). RESULTS: There were 1020 patients on carvedilol, 886 on selective beta blockers, and 10,216 on no beta blocker at admission. After controlling for other variables, the odds of Hypo1day, HypoT and Hyposevere were higher for carvedilol and selective beta blocker recipients than non-recipients, but only in basal insulin nonusers. The odds of Hypo1day (odds ratio [OR] 1.99, 95% confidence interval [CI] 1.28, 3.09, p = 0.0002) and HypoT (OR 1.38, 95% CI 1.02, 1.86, p = 0.03) but not Hyposevere (OR 1.90, 95% CI 0.90, 4.02, p = 0.09) were greater for selective beta blocker vs. carvedilol recipients in basal insulin nonusers. Hypo1day, HypoT, and Hyposevere were all associated with increased mortality in adjusted models among non-beta blocker and selective beta blocker recipients, but not among carvedilol recipients. CONCLUSIONS: Beta blocker use is associated with increased odds of hypoglycemia among hospitalized patients not requiring basal insulin, and odds are greater for selective beta blockers than for carvedilol. The odds of hypoglycemia-associated mortality are increased with selective beta blocker use or nonusers but not in carvedilol users, warranting further study.


Assuntos
Antagonistas Adrenérgicos beta/efeitos adversos , Glicemia/efeitos dos fármacos , Carvedilol/efeitos adversos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Pacientes Internados , Insulina/efeitos adversos , Admissão do Paciente , Antagonistas Adrenérgicos beta/administração & dosagem , Idoso , Atenolol/administração & dosagem , Atenolol/efeitos adversos , Biomarcadores/sangue , Glicemia/metabolismo , Carvedilol/administração & dosagem , Feminino , Mortalidade Hospitalar , Humanos , Hipoglicemia/sangue , Hipoglicemia/diagnóstico , Hipoglicemia/mortalidade , Hipoglicemiantes/administração & dosagem , Incidência , Insulina/administração & dosagem , Masculino , Metoprolol/administração & dosagem , Metoprolol/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo
19.
Int Heart J ; 60(6): 1284-1292, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31735782

RESUMO

The efficacy of pre-procedural beta-blocker use in patients with acute coronary syndrome (ACS) is not well established in the current percutaneous coronary intervention (PCI) era. We investigate the effect of pre-procedural beta-blocker use on clinical outcomes in patients with ACS undergoing PCI. Among 44,967 consecutive cases of PCI enrolled in the nationwide, retrospective, multicenter registry (K-PCI registry), 31,040 patients with ACS were selected and analyzed. We classified patients into pre-procedural beta-blocker group (n = 8,678) and pre-procedural no-beta-blocker group (n = 22,362) according to the use of beta-blockers at least for two weeks before index PCI. Propensity score-matching analysis was performed and resulted in 7,445 pairs. The primary outcome was in-hospital cardiac death. In propensity score-matched populations, the pre-procedural beta-blocker group had a lower incidence of in-hospital cardiac death compared with the pre-procedural no-beta-blocker group (1.1% versus 2.0%, unadjusted odds ratio [OR]: 0.56, 95% confidence interval [CI]: 0.42-0.73, P < 0.01). In subgroup analysis, the pre-procedural beta-blocker group had a lower incidence of in-hospital cardiac death, compared with the pre-procedural no-beta-blocker group in ST-segment elevation myocardial infarction subpopulation (3.1% versus 6.1%, unadjusted OR: 0.49, 95% CI: 0.34-0.71, P < 0.01) and non-ST-segment elevation myocardial infarction subpopulation (1.5% versus 2.9%, unadjusted OR: 0.51, 95% CI: 0.33-0.79, P < 0.01). However, in unstable angina subpopulation, the in-hospital cardiac death rate was comparable between both groups. In conclusion, the use of pre-procedural beta-blocker was associated with a lower risk of in-hospital cardiac death in patients with ACS undergoing PCI. This result adds to the body of evidence that use of pre-procedural beta-blocker in patients with ACS might be reasonable.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/cirurgia , Antagonistas Adrenérgicos beta/administração & dosagem , Intervenção Coronária Percutânea , Pré-Medicação , Cuidados Pré-Operatórios , Síndrome Coronariana Aguda/mortalidade , Idoso , Esquema de Medicação , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Sistema de Registros , Estudos Retrospectivos , Resultado do Tratamento
20.
PLoS One ; 14(11): e0224674, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31682617

RESUMO

Catecholamine excess reflecting an adrenergic overdrive of the sympathetic nervous system (SNS) has been proposed to link to hyperleptinemia in obesity and may contribute to the development of metabolic disorders. However, relationship between the catecholamine level and plasma leptin in obesity has not yet been investigated. Moreover, whether pharmacological blockade of the adrenergic overdrive in obesity by the third-generation beta-blocker agents such as carvedilol could help to prevent metabolic disorders is controversial and remains to be determined. Using the high fat diet (HFD)-induced obese mouse model, we found that basal plasma norepinephrine, the principal catecholamine as an index of SNS activity, was persistently elevated and highly correlated with plasma leptin concentration during obesity development. Targeting the adrenergic overdrive from this chronic norepinephrine excess in HFD-induced obesity with carvedilol, a third-generation beta-blocker with vasodilating action, blunted the HFD-induced hepatic glucose over-production by suppressing the induction of gluconeogenic enzymes, and enhanced the muscular insulin signaling pathway. Furthermore, carvedilol treatment in HFD-induced obese mice decreased the enlargement of white adipose tissue and improved the glucose tolerance and insulin sensitivity without affecting body weight and blood glucose levels. Our results suggested that catecholamine excess in obesity might directly link to the hyperleptinemic condition and the therapeutic targeting of chronic adrenergic overdrive in obesity with carvedilol might be helpful to attenuate obesity-related metabolic disorders.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Carvedilol/administração & dosagem , Insulina/metabolismo , Norepinefrina/metabolismo , Obesidade/tratamento farmacológico , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Administração Oral , Adrenérgicos , Animais , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Glucose/metabolismo , Teste de Tolerância a Glucose , Humanos , Resistência à Insulina , Leptina/sangue , Leptina/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Norepinefrina/sangue , Obesidade/etiologia , Obesidade/metabolismo , Transdução de Sinais/efeitos dos fármacos
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