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1.
Kyobu Geka ; 73(12): 1015-1017, 2020 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-33268753

RESUMO

A 57-year-old man on maintenance hemodialysis was admitted to a hospital after suffering from cardiac arrest. He had collapsed soon after hemodialysis and was restored to sinus rhythm after receiving direct-current shocks. Further examination revealed old myocardial infarction with triple-vessel disease, and he was referred to our hospital for surgical treatment. Soon after performing coronary artery bypass grafting, we started the patient on intravenous amiodarone for frequent ventricular tachycardia. However, incessant ventricular tachycardia occurred frequently which necessitated several countershocks. Although ventricular tachycardia disappeared by replacing intravenous amiodarone with intravenous nifekalant, it reappeared when we initiated oral amiodarone instead of intravenous nifekalant. So therefore, we stopped using any anti-arrhythmic drug except bisoprolol fumarate, whereby ventricular tachycardia ceased once again. Amiodarone is known as relatively safe anti-arrhythmic drug that is often used after cardiovascular surgery. However, we should pay close attention to the possibility of amiodarone-induced arrhythmia.


Assuntos
Amiodarona , Taquicardia Ventricular , Amiodarona/efeitos adversos , Antiarrítmicos/efeitos adversos , Ponte de Artéria Coronária , Humanos , Masculino , Pessoa de Meia-Idade , Taquicardia Ventricular/induzido quimicamente
2.
Kardiologiia ; 60(10): 4-12, 2020 Sep 16.
Artigo em Russo | MEDLINE | ID: mdl-33228499

RESUMO

Recommendation provides information to employees of medical departments at any level and primarily primary care about the possible proarrhythmic and adverse effects of drugs used for the treatment of COVID-19 patients and the features of therapy for COVID-19 patients with heart rhythm and conduction disorders receiving permanent antiarrhythmic therapy.


Assuntos
Antiarrítmicos , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Antiarrítmicos/efeitos adversos , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/terapia , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Humanos
3.
Rev Cardiovasc Med ; 21(3): 419-432, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33070546

RESUMO

Several observational studies have shown a survival benefit for patients with atrial fibrillation (AF) who are treated with catheter ablation (CA) rather than medical management (MM). However, data from randomized controlled trials (RCTs) are uncertain. Therefore, we performed a meta-analysis of RCTs that compared the benefits of CA and MM in treatment of AF. We searched the Cochrane Library, PubMed, and EMBASE databases for RCTs that compared AF ablation with MM from the time of database establishment up to January 2020. The risk ratio (RR) with a 95% confidence interval (CI) was used as a measure treatment effect. Twenty-six RCTs that enrolled a total of 5788 patients were included in the meta-analysis. In this meta-analysis, the effect of AF ablation depended on the baseline level of left ventricular ejection fraction (LVEF) in the heart failure (HF) patients. AF ablation appears to be of benefit to patients with a lesser degree of advanced HF and better LVEF by reducing mortality. Meanwhile, this mortality advantage was manifested in long-term follow-up. CA increased the risk for hospitalization when it was used as first-line therapy and decreased the risk when used as second-line therapy. CA reduced recurrence of atrial arrhythmia for different types of AF (paroxysmal or persistent AF) and CA-related complications were non-negligible. There was no convincing evidence for a reduction in long-term stroke risk after AF ablation, and additional high quality RCTs are needed to address that issue.


Assuntos
Antiarrítmicos/uso terapêutico , Fibrilação Atrial/terapia , Ablação por Cateter , Frequência Cardíaca/efeitos dos fármacos , Adulto , Idoso , Antiarrítmicos/efeitos adversos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/mortalidade , Fibrilação Atrial/fisiopatologia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/prevenção & controle , Fatores de Tempo , Resultado do Tratamento
4.
N Engl J Med ; 383(14): 1305-1316, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32865375

RESUMO

BACKGROUND: Despite improvements in the management of atrial fibrillation, patients with this condition remain at increased risk for cardiovascular complications. It is unclear whether early rhythm-control therapy can reduce this risk. METHODS: In this international, investigator-initiated, parallel-group, open, blinded-outcome-assessment trial, we randomly assigned patients who had early atrial fibrillation (diagnosed ≤1 year before enrollment) and cardiovascular conditions to receive either early rhythm control or usual care. Early rhythm control included treatment with antiarrhythmic drugs or atrial fibrillation ablation after randomization. Usual care limited rhythm control to the management of atrial fibrillation-related symptoms. The first primary outcome was a composite of death from cardiovascular causes, stroke, or hospitalization with worsening of heart failure or acute coronary syndrome; the second primary outcome was the number of nights spent in the hospital per year. The primary safety outcome was a composite of death, stroke, or serious adverse events related to rhythm-control therapy. Secondary outcomes, including symptoms and left ventricular function, were also evaluated. RESULTS: In 135 centers, 2789 patients with early atrial fibrillation (median time since diagnosis, 36 days) underwent randomization. The trial was stopped for efficacy at the third interim analysis after a median of 5.1 years of follow-up per patient. A first-primary-outcome event occurred in 249 of the patients assigned to early rhythm control (3.9 per 100 person-years) and in 316 patients assigned to usual care (5.0 per 100 person-years) (hazard ratio, 0.79; 96% confidence interval, 0.66 to 0.94; P = 0.005). The mean (±SD) number of nights spent in the hospital did not differ significantly between the groups (5.8±21.9 and 5.1±15.5 days per year, respectively; P = 0.23). The percentage of patients with a primary safety outcome event did not differ significantly between the groups; serious adverse events related to rhythm-control therapy occurred in 4.9% of the patients assigned to early rhythm control and 1.4% of the patients assigned to usual care. Symptoms and left ventricular function at 2 years did not differ significantly between the groups. CONCLUSIONS: Early rhythm-control therapy was associated with a lower risk of adverse cardiovascular outcomes than usual care among patients with early atrial fibrillation and cardiovascular conditions. (Funded by the German Ministry of Education and Research and others; EAST-AFNET 4 ISRCTN number, ISRCTN04708680; ClinicalTrials.gov number, NCT01288352; EudraCT number, 2010-021258-20.).


Assuntos
Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/cirurgia , Doenças Cardiovasculares/prevenção & controle , Ablação por Cateter , Síndrome Coronariana Aguda/epidemiologia , Idoso , Antiarrítmicos/efeitos adversos , Fibrilação Atrial/complicações , Doenças Cardiovasculares/mortalidade , Feminino , Seguimentos , Insuficiência Cardíaca/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Tempo de Internação , Masculino , Risco , Prevenção Secundária , Método Simples-Cego , Função Ventricular Esquerda/efeitos dos fármacos
7.
Am J Cardiol ; 135: 77-83, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-32861738

RESUMO

The antiarrhythmic drug dronedarone was designed to reduce the extra-cardiac adverse effects associated with amiodarone use in treatment of patients with atrial fibrillation / atrial flutter (AF/AFL). This epidemiological study used a retrospective cohort design to compare risk of cardiovascular-related hospitalizations and death in AF/AFL patients treated with dronedarone versus other antiarrhythmic drugs (AADs). AF/AFL patients with incident dronedarone fills were matched by propensity score (PS) to incident users of other AADs. The primary study outcome was hospitalization for cardiovascular (CV) causes within 24 months after the first study drug fill. A secondary composite outcome comprised hospitalization for CV causes or all-cause mortality during follow-up. In the AF/AFL patient cohort meeting eligibility criteria, 6,964 incident users of dronedarone and 25 607 incident users of other AADs were identified. The PS-matched cohort comprised 6,349 Dronedarone users (91.2% of all eligible) and 12,698 other AAD users. Dronedarone patients had a significantly lower risk of hospitalization for a CV event compared to Other AAD users (hazard ratio = 0.87; 95% confidence interval = 0.79 to 0.96). This was consistent with results for the composite outcome (hazard ratio=0.86; 95% confidence interval = 0.78 to 0.95). In conclusion, AF/AFL patients initiated on dronedarone versus other AADs had significantly lower risk of CV hospitalizations as well as the composite CV hospitalization / death from any cause.


Assuntos
Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Flutter Atrial/tratamento farmacológico , Dronedarona/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antiarrítmicos/efeitos adversos , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/mortalidade , Estudos de Coortes , Dronedarona/efeitos adversos , Estudos Epidemiológicos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Resultado do Tratamento
8.
Ther Adv Cardiovasc Dis ; 14: 1753944720926824, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32633682

RESUMO

INTRODUCTION: Current atrial fibrillation (AF) guidelines recommend flecainide as a first-line rhythm control option in patients without structural heart disease. While there is proven efficacy in clinical trials and guideline support, it is hypothesized that flecainide may be underutilized due to negative outcomes in the CAST trial and that adverse effects are less common than previously perceived. METHODS: This retrospective chart review evaluated patients ⩾18 years initiated on flecainide for AF from August 2011 to October 2016 by a cardiology provider at the study site. Exclusion criteria included: <5 days of flecainide therapy, AF due to a reversible cause, and inadequate documentation. The primary outcome was efficacy of flecainide at maintaining symptomatic control at 6 and 12 months. Secondary outcomes included characterization of alterations in rhythm control strategies and documented normal sinus rhythm per electrocardiogram at 6 and 12 months. RESULTS: Of the 326 patients identified, 144 patients were included. After 6 and 12 months, 102 patients (70.8%) and 89 patients (61.8%) of the 144 were symptomatically controlled. Atenolol use (p = 0.024), female sex (p = 0.006), hypertension (p = 0.040), and dronedarone failure (p = 0.012) were associated with flecainide discontinuation at 6 months. At 12 months, only previous propafenone failure (p = 0.032) was significant. Of the 144 patients, 16 (11.1%) reported adverse effects with dizziness, hot flashes, bradycardia, and headache (1.4% each) being the most common. CONCLUSION: Flecainide is a well-tolerated medication, even at 12 months, with very minor adverse effects. These results support the utility of flecainide in guideline recommended patient populations.


Assuntos
Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Flecainida/uso terapêutico , Frequência Cardíaca/efeitos dos fármacos , Idoso , Antiarrítmicos/efeitos adversos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Feminino , Flecainida/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
9.
J Am Heart Assoc ; 9(14): e017529, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32515253

RESUMO

Atrial fibrillation is a common clinical manifestation in hospitalized patients with coronavirus disease 2019 (COVID-19). Medications used to treat atrial fibrillation, such as antiarrhythmic drugs and anticoagulants, may have significant drug interactions with emerging COVID-19 treatments. Common unintended nontherapeutic target effects of COVID-19 treatment include potassium channel blockade, cytochrome P 450 isoenzyme inhibition or activation, and P-glycoprotein inhibition. Drug-drug interactions with antiarrhythmic drugs and anticoagulants in these patients may lead to significant bradycardia, ventricular arrhythmias, or severe bleeding. It is important for clinicians to be aware of these interactions, drug metabolism changes, and clinical consequences when choosing antiarrhythmic drugs and anticoagulants for COVID-19 patients with atrial fibrillation. The objective of this review is to provide a practical guide for clinicians who are managing COVID-19 patients with concomitant atrial fibrillation.


Assuntos
Antiarrítmicos/uso terapêutico , Anticoagulantes/uso terapêutico , Antivirais/uso terapêutico , Fibrilação Atrial/terapia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Antiarrítmicos/efeitos adversos , Antiarrítmicos/farmacocinética , Anticoagulantes/efeitos adversos , Anticoagulantes/farmacocinética , Antivirais/efeitos adversos , Antivirais/farmacocinética , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Interações Medicamentosas , Interações entre Hospedeiro e Microrganismos , Humanos , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Medição de Risco , Fatores de Risco , Resultado do Tratamento
10.
J Am Coll Cardiol ; 75(25): 3105-3118, 2020 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-32586583

RESUMO

BACKGROUND: The CABANA (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation) trial randomized 2,204 patients with atrial fibrillation (AF) to catheter ablation or drug therapy. Analysis by intention-to-treat showed a nonsignificant 14% relative reduction in the primary outcome of death, disabling stroke, serious bleeding, or cardiac arrest. OBJECTIVES: The purpose of this study was to assess recurrence of AF in the CABANA trial. METHODS: The authors prospectively studied CABANA patients using a proprietary electrocardiogram recording monitor for symptom-activated and 24-h AF auto detection. The AF recurrence endpoint was any post-90-day blanking atrial tachyarrhythmias lasting 30 s or longer. Biannual 96-h Holter monitoring was used to assess AF burden. Patients who used the CABANA monitors and provided 90-day post-blanking recordings qualified for this analysis (n = 1,240; 56% of CABANA population). Treatment comparisons were performed using a modified intention-to-treat approach. RESULTS: Median age of the 1,240 patients was 68 years, 34.4% were women, and AF was paroxysmal in 43.0%. Over 60 months of follow-up, first recurrence of any symptomatic or asymptomatic AF (hazard ratio: 0.52; 95% confidence interval: 0.45 to 0.60; p < 0.001) or first symptomatic-only AF (hazard ratio: 0.49; 95% confidence interval: 0.39 to 0.61; p < 0.001) were both significantly reduced in the catheter ablation group. Baseline Holter AF burden in both treatment groups was 48%. At 12 months, AF burden in ablation patients averaged 6.3%, and in drug-therapy patients, 14.4%. AF burden was significantly less in catheter ablation compared with drug-therapy patients across the 5-year follow-up (p < 0.001). These findings were not sensitive to the baseline pattern of AF. CONCLUSIONS: Catheter ablation was effective in reducing recurrence of any AF by 48% and symptomatic AF by 51% compared with drug therapy over 5 years of follow-up. Furthermore, AF burden was also significantly reduced in catheter ablation patients, regardless of their baseline AF type. (Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial [CABANA]; NCT00911508).


Assuntos
Antiarrítmicos , Fibrilação Atrial , Ablação por Cateter , Eletrocardiografia Ambulatorial , Análise de Intenção de Tratamento/estatística & dados numéricos , Idoso , Antiarrítmicos/administração & dosagem , Antiarrítmicos/efeitos adversos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Ablação por Cateter/estatística & dados numéricos , Eletrocardiografia Ambulatorial/métodos , Eletrocardiografia Ambulatorial/estatística & dados numéricos , Feminino , Humanos , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Recidiva , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Tempo
11.
J Cardiovasc Pharmacol Ther ; 25(5): 425-437, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32500725

RESUMO

BACKGROUND: Switching between antiarrhythmic drugs is timed to minimize arrhythmia recurrence and adverse reactions. Dronedarone and amiodarone have similar electrophysiological profiles; however, little is known about the optimal timing of switching, given the long half-life of amiodarone. METHODS: The ARTEMIS atrial fibrillation (AF) Loading and Long-term studies evaluated switching patients with paroxysmal/persistent AF from amiodarone to dronedarone. Patients were randomized based on the timing of the switch: immediate, after a 2-week, or after a 4-week washout of amiodarone. Patients who did not convert to sinus rhythm after amiodarone loading underwent electrical cardioversion. The primary objectives were, for the Loading study, to evaluate recurrence of AF ≤60 days; and for the Long-term study, to profile the pharmacokinetics of dronedarone and its metabolite according to different timings of dronedarone initiation. RESULTS: In ARTEMIS AF Loading, 176 were randomized (planned 768) after a 28 ± 2 days load of oral amiodarone. Atrial fibrillation recurrence trended less in the immediate switch versus 4-week washout group (hazard ratio [HR] = 0.65 [97.5% CI: 0.34-1.23]; P = .14) and in the 2-week washout versus the 4-week washout group (HR = 0.75 [97.5% CI: 0.41-1.37]; P = .32). In ARTEMIS AF Long-term, 108 patients were randomized (planned 105). Pharmacokinetic analyses (n = 97) showed no significant differences for dronedarone/SR35021 exposures in the 3 groups. CONCLUSION: The trial was terminated early due to poor recruitment and so our findings are limited by low numbers. However, immediate switching from amiodarone to dronedarone appeared to be well tolerated and safe.


Assuntos
Amiodarona/administração & dosagem , Antiarrítmicos/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Dronedarona/administração & dosagem , Substituição de Medicamentos , Idoso , Amiodarona/efeitos adversos , Amiodarona/farmacocinética , Antiarrítmicos/efeitos adversos , Antiarrítmicos/farmacocinética , Fibrilação Atrial/diagnóstico , Dronedarona/efeitos adversos , Dronedarona/farmacocinética , Substituição de Medicamentos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Resultado do Tratamento
12.
Circ Arrhythm Electrophysiol ; 13(7): e008168, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32538135

RESUMO

BACKGROUND: Dofetilide is one of the only anti-arrhythmic agents approved for atrial fibrillation (AF) in patients with reduced left ventricular ejection fraction (LVEF). However, postapproval data and safety outcomes are limited. In this study, we assessed the incidence and predictors of LVEF improvement, safety, and outcomes in patients with AF with LVEF ≤35% without prior implantable cardioverter defibrillator, cardiac resynchronization therapy, or AF ablation. METHODS: An analysis of 168 consecutive patients from 2007 to 2016 was performed. Incidences of adverse events, drug continuation, implantable cardioverter defibrillator and cardiac resynchronization therapy implantation, LVEF improvement (>35%) and recovery (≥50%), AF recurrence, and AF ablation were determined. Multivariable regression analysis to identify predictors of LVEF improvement/recovery was performed. RESULTS: The mean age was 64±12 years. Dofetilide was discontinued before hospital discharge in 46 (27%) because of QT prolongation (14%), torsades de pointe or polymorphic ventricular tachycardia/fibrillation (6% [sustained 3%, nonsustained 3%]), ineffectiveness (5%), or other causes (3%). At 1 year, 43% remained on dofetilide. Freedom from AF was 42% at 1 year, and 40% underwent future AF ablation. LVEF recovered (≥50%) in 45% and improved to >35% in 73%. Predictors of LVEF improvement included presence of AF during echocardiogram (odds ratio, 4.22 [95% CI, 1.71-10.4], P=0.002), coronary artery disease (odds ratio, 0.35 [95% CI, 0.16-0.79], P=0.01), left atrial diameter (odds ratio, 0.52 per 1 cm increase [95% CI, 0.30-0.90], P=0.01), and LVEF (odds ratio, per 1% increase, 1.09 [95% CI, 1.02-1.16], P=0.006). The C statistic was 0.78. CONCLUSIONS: In patients with LVEF ≤35%, who are potential implantable cardioverter defibrillator candidates, treated with dofetilide as an initial anti-arrhythmic strategy for AF, drug discontinuation rates were high, and many underwent future AF ablation. However, most patients had improvement in LVEF, obviating the need for primary prevention implantable cardioverter defibrillator.


Assuntos
Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Frequência Cardíaca/efeitos dos fármacos , Fenetilaminas/uso terapêutico , Volume Sistólico/efeitos dos fármacos , Sulfonamidas/uso terapêutico , Disfunção Ventricular Esquerda/terapia , Função Ventricular Esquerda/efeitos dos fármacos , Idoso , Antiarrítmicos/efeitos adversos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Bases de Dados Factuais , Desfibriladores Implantáveis , Cardioversão Elétrica/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenetilaminas/efeitos adversos , Recuperação de Função Fisiológica , Recidiva , Estudos Retrospectivos , Sulfonamidas/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/fisiopatologia
14.
J Cardiovasc Pharmacol ; 76(2): 138-145, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32453074

RESUMO

Coronavirus disease 2019 (COVID-19) outbreak is a public health emergency of international concerns because of a highly pathogenic human coronavirus (HCoV), actually named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite much emerging data about the epidemiological association between cardiovascular diseases and COVID-19, little is still known about atrial fibrillation and its optimal management in this clinical contest. The aim of our review is to describe the pharmacological interactions between cardiovascular drugs more commonly used in atrial fibrillation management and experimental COVID-19 therapies, based on EU and US summaries of product characteristics.


Assuntos
Antiarrítmicos/uso terapêutico , Anticoagulantes/uso terapêutico , Antivirais/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Antiarrítmicos/efeitos adversos , Antiarrítmicos/farmacocinética , Anticoagulantes/efeitos adversos , Anticoagulantes/farmacocinética , Antivirais/efeitos adversos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Interações Medicamentosas , Interações Hospedeiro-Patógeno , Humanos , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Fatores de Risco , Resultado do Tratamento
15.
Sci Rep ; 10(1): 8397, 2020 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-32439959

RESUMO

The 'translational therapeutic index' (TTI) is a drug's ratio of nonclinical threshold dose (or concentration) for significant benefit versus threshold for adversity. In early nonclinical research, discovery and safety studies are normally undertaken separately. Our aim was to evaluate a novel integrated approach for generating a TTI for drugs intended for prevention of ischaemia-induced ventricular fibrillation (VF). We templated the current best available class 1b antiarrhythmic, mexiletine, using the rat Langendorff preparation. Mexiletine's beneficial effects on the incidence of VF caused by 120 min regional ischaemia were contrasted with its concurrent adverse effects (on several variables) in the same hearts, to generate a TTI. Mexiletine 0.1 and 0.5 µM had no adverse effects, but did not reduce VF incidence. Mexiletine 1 µM reduced VF incidence to 0% but had adverse effects on atrioventricular conduction and ventricular repolarization. Separate studies undertaken using an intraventricular balloon revealed no detrimental effects of mexiletine (1 and 5 µM) on mechanical function, or any benefit against reperfusion-related dysfunction. Mexiletine's TTI was found to be less than two, which accords with its clinical therapeutic index. Although non-cardiac adversity, identifiable from additional in vivo studies, may reduce the TTI further, it cannot increase it. Our experimental approach represents a useful early-stage integrated risk/benefit method that, when TTI is found to be low, would eliminate unsuitable class 1b drugs prior to next stage in vivo work, with mexiletine's TTI defining the gold standard that would need to be bettered.


Assuntos
Antiarrítmicos/farmacologia , Mexiletina/farmacologia , Isquemia Miocárdica/complicações , Fibrilação Ventricular/tratamento farmacológico , Animais , Antiarrítmicos/administração & dosagem , Antiarrítmicos/efeitos adversos , Relação Dose-Resposta a Droga , Eletrocardiografia , Coração/efeitos dos fármacos , Masculino , Mexiletina/administração & dosagem , Mexiletina/efeitos adversos , Isquemia Miocárdica/fisiopatologia , Técnicas de Cultura de Órgãos , Ratos Wistar , Fibrilação Ventricular/etiologia
17.
Vasc Health Risk Manag ; 16: 111-123, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32308404

RESUMO

Background: Landiolol hydrochloride, a highly cardio-selective beta-1 blocker with an ultra-short-acting half-life of 4 minutes, was originally approved by Japan for treatment of intraoperative tachyarrhythmias. This review aims to provide an integrated overview of the current state of knowledge of landiolol hydrochloride in the management of arrhythmia in critical settings. Methods: We searched MEDLINE, EMBASE, and the Cochrane Library to retrieve relevant articles with a total of 65 records identified. Results: The high ß1 selectivity (ß1/ß2 ratio of 255:1) of landiolol causes a more rapid heart rate (HR) decrease compared to esmolol while avoiding decreases in mean arterial blood pressure. Recently, it has been found useful in left ventricular dysfunction patients and fatal arrhythmia requiring emergency treatment. Recent random clinical trials (RCT) have revealed therapeutic and prophylactic effects on arrhythmia, and very low-dose landiolol might be effective for preventing postoperative atrial fibrillation (POAF) and sinus tachycardia. Likewise, landiolol is an optimal choice for perioperative tachycardia treatment during cardiac surgery. The high ß1 selectivity of landiolol is useful in heart failure patients as a first-line therapy for tachycardia and arrhythmia as it avoids the typical depression of cardiac function seen in other ß-blockers. Application in cardiac injury after percutaneous coronary intervention (PCI), protection for vital organs (lung, kidney, etc.) during sepsis, and stabilizing hemodynamics in pediatric patients are becoming the new frontier of landiolol use. Conclusion: Landiolol is useful as a first-line therapy for the prevention of POAF after cardiac/non-cardiac surgery, fatal arrhythmias in heart failure patients and during PCI. Moreover, the potential therapeutic effect of landiolol for sepsis in pediatric patients is currently being explored. As positive RCT results continue to be published, new clinical uses and further clinical studies in various settings by cardiologists, intensivists and pediatric cardiologists are being conducted.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Antiarrítmicos/uso terapêutico , Arritmias Cardíacas/prevenção & controle , Frequência Cardíaca/efeitos dos fármacos , Morfolinas/uso terapêutico , Ureia/análogos & derivados , Antagonistas de Receptores Adrenérgicos beta 1/efeitos adversos , Antagonistas de Receptores Adrenérgicos beta 1/farmacocinética , Adulto , Antiarrítmicos/efeitos adversos , Antiarrítmicos/farmacocinética , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Cuidados Críticos , Feminino , Humanos , Masculino , Morfolinas/efeitos adversos , Morfolinas/farmacocinética , Fatores de Risco , Resultado do Tratamento , Ureia/efeitos adversos , Ureia/farmacocinética , Ureia/uso terapêutico , Adulto Jovem
20.
Cardiovasc Drugs Ther ; 34(3): 383-389, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32236859

RESUMO

PURPOSE: Atrial fibrillation (AF) is the most common cardiac arrhythmia with a considerable impact on patients' quality of life (QoL). METHODS: This prospective, multicenter, observational study aimed to evaluate the effect of oral treatment with controlled-release (CR) flecainide on AF patients' QoL and treatment compliance during a 12-week period. A total of 70 sites enrolled consecutive patients with paroxysmal (PAF) or persistent AF (PerAF), treated with flecainide CR in the context of a rhythm control strategy. The effect on QoL was assessed by the Canadian Cardiovascular Society Severity of Atrial Fibrillation scale (CCS-SAF). RESULTS: In total, 679 patients (53.2% females, 66 ± 11.7 years, 86.9% PAF) were included. Prior antiarrhythmic medication had been administered in 43.8% of patients. A daily dose of 200 mg was administered to 66.4% of patients by the end of study. Flecainide CR resulted in a significant reduction in the CCS-SAF score (mean (SD)) at the end of the study as compared with baseline (1.32 (0.57) vs 1.64 (0.73), p < 0.0001). Flecainide CR significantly reduced the CCS-SAF score both in PAF (1.27 (0.52) vs 1.61 (0.72), p < 0.0001) as well as in PerAF (1.63(0.77) vs 1.84(0.81), p = 0.017). Overall, 4 (0.6%) patients experienced a total of 6 adverse events during the study period. The compliance to flecainide CR treatment was very high with 93.6% of patients responding that they had not missed any dose during the study period. CONCLUSION: Treatment with flecainide CR significantly improves QoL in both paroxysmal as well as persistent AF patients, with an excellent safety profile and associated patient compliance.


Assuntos
Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Flecainida/uso terapêutico , Frequência Cardíaca/efeitos dos fármacos , Qualidade de Vida , Idoso , Antiarrítmicos/efeitos adversos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/psicologia , Preparações de Ação Retardada , Feminino , Flecainida/efeitos adversos , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Segurança do Paciente , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
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