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1.
Medicine (Baltimore) ; 100(11): e25216, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33726018

RESUMO

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) have been widely used for stroke prevention in atrial fibrillation (AF) and the treatment and prevention of venous thromboembolism. There is an issue with safety, especially in clinically relevant bleeding. We performed a network meta-analysis to evaluate the risk of major gastrointestinal (GI) bleeding associated with NOACs. METHODS: Interventions were warfarin, enoxaparin, apixaban, dabigatran, edoxaban, and rivaroxaban. The primary outcome was the incidence of major GI bleeding. A subgroup analysis was performed according to the following indications: AF, deep venous thrombosis/pulmonary embolism, and postsurgical prophylaxis. RESULTS: A total of 29 randomized controlled trials (RCTs) and 4 large observation population studies were included. Compared with warfarin, apixaban showed a decreased the risk of major GI bleeding (relative risk [RR] 0.54, 95% confidence interval [CI] 0.25-0.76), and rivaroxaban tended to increase this risk (RR 1.40, 95% CI 1.06-1.85). Dabigatran (RR 1.25, 95% CI 0.98-1.60), edoxaban (RR 1.07, 95% CI 0.69-1.65), and enoxaparin (RR 1.24, 95% CI 0.63-2.43) did not significantly increase the risk of GI bleeding than did warfarin. In the subgroup analysis, according to indications, apixaban showed a decreased risk of major GI bleeding (RR 0.50, 95% CI 0.34-0.74) than did warfarin in AF studies. Dabigatran (RR 2.36, 95% CI 1.55-3.60, and rivaroxaban (RR 1.75, 95% CI 1.10-6.41) increased the risk of major GI bleeding than did apixaban. An analysis of studies on venous thromboembolism or pulmonary embolism showed that no individual NOAC or enoxaparin was associated with an increased risk of major GI bleeding compared to warfarin. CONCLUSION: Individual NOACs had varying profiles of GI bleeding risk. Results of analyses including only RCTs and those including both RCTs and population studies showed similar trends, but also showed several differences.


Assuntos
Anticoagulantes/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Hemorragia Gastrointestinal/induzido quimicamente , Embolia Pulmonar/tratamento farmacológico , Tromboembolia Venosa/tratamento farmacológico , Administração Oral , Adulto , Idoso , Fibrilação Atrial/complicações , Dabigatrana/efeitos adversos , Enoxaparina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metanálise em Rede , Estudos Observacionais como Assunto , Embolia Pulmonar/complicações , Pirazóis/efeitos adversos , Piridinas/efeitos adversos , Piridonas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Tiazóis/efeitos adversos , Tromboembolia Venosa/complicações , Varfarina/efeitos adversos
2.
Trials ; 22(1): 3, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397457

RESUMO

OBJECTIVES: To investigate the efficacy and safety of repurposed antiprotozoal and antiretroviral drugs, nitazoxanide and atazanavir/ritonavir, in shortening the time to clinical improvement and achievement of SARS-CoV-2 polymerase chain reaction (PCR) negativity in patients diagnosed with moderate to severe COVID-19. TRIAL DESIGN: This is a pilot phase 2, multicentre 2-arm (1:1 ratio) open-label randomised controlled trial. PARTICIPANTS: Patients with confirmed COVID-19 diagnosis (defined as SARS-CoV-2 PCR positive nasopharyngeal swab) will be recruited from four participating isolation and treatment centres in Nigeria: two secondary care facilities (Infectious Diseases Hospital, Olodo, Ibadan, Oyo State and Specialist State Hospital, Asubiaro, Osogbo, Osun State) and two tertiary care facilities (Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Osun State and Olabisi Onabanjo University Teaching Hospital, Sagamu, Ogun State). These facilities have a combined capacity of 146-bed COVID-19 isolation and treatment ward. INCLUSION CRITERIA: Confirmation of SARS-CoV-2 infection by PCR test within two days before randomisation and initiation of treatment, age bracket of 18 and 75 years, symptomatic, able to understand study information and willingness to participate. Exclusion criteria include the inability to take orally administered medication or food, known hypersensitivity to any of the study drugs, pregnant or lactating, current or recent (within 24 hours of enrolment) treatment with agents with actual or likely antiviral activity against SARS-CoV-2, concurrent use of agents with known or suspected interaction with study drugs, and requiring mechanical ventilation at screening. INTERVENTION AND COMPARATOR: Participants in the intervention group will receive 1000 mg of nitazoxanide twice daily orally and 300/100 mg of atazanvir/ritonavir once daily orally in addition to standard of care while participants in the control group will receive only standard of care. Standard of care will be determined by the physician at the treatment centre in line with the current guidelines for clinical management of COVID-19 in Nigeria. MAIN OUTCOME MEASURES: Main outcome measures are: (1) Time to clinical improvement (defined as time from randomisation to either an improvement of two points on a 10-category ordinal scale (developed by the WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection) or discharge from the hospital, whichever came first); (2) Proportion of participants with SARS-CoV-2 polymerase chain reaction (PCR) negative result at days 2, 4, 6, 7, 14 and 28; (3) Temporal patterns of SARS-CoV-2 viral load on days 2, 4, 6, 7, 14 and 28 quantified by RT-PCR from saliva of patients receiving standard of care alone versus standard of care plus study drugs. RANDOMISATION: Allocation of participants to study arm is randomised within each site with a ratio 1:1 based on randomisation sequences generated centrally at Obafemi Awolowo University. The model was implemented in REDCap and includes stratification by age, gender, viral load at diagnosis and presence of relevant comorbidities. BLINDING: None, this is an open-label trial. NUMBER TO BE RANDOMISED (SAMPLE SIZE): 98 patients (49 per arm). TRIAL STATUS: Regulatory approval was issued by the National Agency for Food and Drug Administration and Control on 06 October 2020 (protocol version number is 2.1 dated 06 August 2020). Recruitment started on 9 October 2020 and is anticipated to end before April 2021. TRIAL REGISTRATION: The trial has been registered on ClinicalTrials.gov (July 7, 2020), with identifier number NCT04459286 and on Pan African Clinical Trials Registry (August 13, 2020), with identifier number PACTR202008855701534 . FULL PROTOCOL: The full protocol is attached as an additional file which will be made available on the trial website. In the interest of expediting dissemination of this material, the traditional formatting has been eliminated, and this letter serves as a summary of the key elements in the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).


Assuntos
Antivirais/administração & dosagem , Sulfato de Atazanavir/administração & dosagem , Ritonavir/administração & dosagem , Tiazóis/administração & dosagem , Administração Oral , Adolescente , Adulto , Idoso , Antivirais/efeitos adversos , Sulfato de Atazanavir/efeitos adversos , /virologia , Ensaios Clínicos Fase II como Assunto , Esquema de Medicação , Combinação de Medicamentos , Reposicionamento de Medicamentos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Nigéria , Projetos Piloto , RNA Viral/isolamento & purificação , Ensaios Clínicos Controlados Aleatórios como Assunto , Ritonavir/efeitos adversos , /isolamento & purificação , Índice de Gravidade de Doença , Padrão de Cuidado , Tiazóis/efeitos adversos , Resultado do Tratamento , Carga Viral/efeitos dos fármacos , Adulto Jovem
4.
BMC Med ; 18(1): 401, 2020 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-33357217

RESUMO

BACKGROUND: Atrial fibrillation (AF) is common in older people with frailty and is associated with an increased risk of stroke and systemic embolism. Whilst oral anticoagulation is associated with a reduction in this risk, there is a lack of data on the safety and efficacy of direct oral anticoagulants (DOACs) in people with frailty. This study aims to report clinical outcomes of patients with AF in the Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) trial by frailty status. METHODS: Post hoc analysis of 20,867 participants in the ENGAGE AF-TIMI 48 trial, representing 98.8% of those randomised. This double-blinded double-dummy trial compared two once-daily regimens of edoxaban (a DOAC) with warfarin. Participants were categorised as fit, living with pre-frailty, mild-moderate, or severe frailty according to a standardised index, based upon the cumulative deficit model. The primary efficacy endpoint was stroke or systemic embolism and the safety endpoint was major bleeding. RESULTS: A fifth (19.6%) of the study population had frailty (fit: n = 4459, pre-frailty: n = 12,326, mild-moderate frailty: n = 3722, severe frailty: n = 360). On average over the follow-up period, the risk of stroke or systemic embolism increased by 37% (adjusted HR 1.37, 95% CI 1.19-1.58) and major bleeding by 42% (adjusted HR 1.42, 1.27-1.59) for each 0.1 increase in the frailty index (four additional health deficits). Edoxaban was associated with similar efficacy to warfarin in every frailty category, and a lower risk of bleeding than warfarin in all but those living with severe frailty. CONCLUSIONS: Edoxaban was similarly efficacious to warfarin across the frailty spectrum and was associated with lower rates of bleeding except in those with severe frailty. Overall, with increasing frailty, there was an increase in stroke and bleeding risk. There is a need for high-quality, frailty-specific population randomised control trials to guide therapy in this vulnerable population. TRIAL REGISTRATION: ClinicalTrials.gov NCT00781391 . First registered on 28 October 2008.


Assuntos
Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Fragilidade/diagnóstico , Fragilidade/tratamento farmacológico , Piridinas/administração & dosagem , Tiazóis/administração & dosagem , Varfarina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Coagulação Sanguínea/efeitos dos fármacos , Método Duplo-Cego , Esquema de Medicação , Inibidores do Fator Xa/uso terapêutico , Feminino , Seguimentos , Fragilidade/complicações , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/tratamento farmacológico , Prognóstico , Piridinas/efeitos adversos , Tiazóis/efeitos adversos , Resultado do Tratamento
6.
J Stroke Cerebrovasc Dis ; 29(11): 105216, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33066930

RESUMO

Convexity subarachnoid hemorrhage (cSAH) is typically due to head trauma, but it rarely occurs subsequent to acute ischemic stroke. Direct oral anticoagulants (DOACs) have favorable bleeding profiles as compared with warfarin, and, to our knowledge, no DOAC has been regarded as a causative agent for cSAH. Here, we reported 2 patients with cSAH apparently caused by starting DOAC therapy. No hemorrhage had been evident just prior to treatment initiation, but cSAH occurred so soon after DOAC therapy began. Each of our patients had occlusion or severe stenosis of a major artery due to emboligenic disease, and cSAH occurred in the territory of the affected artery. Reperfusion and dynamic changes in perfusion pressure due may trigger cSAH. Clinicians should remain alert for cSAH when starting DOAC for treatment of embolic ischemic stroke during the acute phase.


Assuntos
Infarto Encefálico/tratamento farmacológico , Inibidores do Fator Xa/efeitos adversos , Pirazóis/efeitos adversos , Piridinas/efeitos adversos , Piridonas/efeitos adversos , Hemorragia Subaracnóidea/induzido quimicamente , Tiazóis/efeitos adversos , Administração Oral , Idoso , Infarto Encefálico/diagnóstico por imagem , Substituição de Medicamentos , Inibidores do Fator Xa/administração & dosagem , Feminino , Humanos , Pirazóis/administração & dosagem , Piridinas/administração & dosagem , Piridonas/administração & dosagem , Hemorragia Subaracnóidea/diagnóstico por imagem , Tiazóis/administração & dosagem , Fatores de Tempo
7.
N Engl J Med ; 383(18): 1735-1745, 2020 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-32865374

RESUMO

BACKGROUND: Implementation of appropriate oral anticoagulant treatment for the prevention of stroke in very elderly patients with atrial fibrillation is challenging because of concerns regarding bleeding. METHODS: We conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled, event-driven trial to compare a once-daily 15-mg dose of edoxaban with placebo in elderly Japanese patients (≥80 years of age) with nonvalvular atrial fibrillation who were not considered to be appropriate candidates for oral anticoagulant therapy at doses approved for stroke prevention. The primary efficacy end point was the composite of stroke or systemic embolism, and the primary safety end point was major bleeding according to the definition of the International Society on Thrombosis and Haemostasis. RESULTS: A total of 984 patients were randomly assigned in a 1:1 ratio to receive a daily dose of 15 mg of edoxaban (492 patients) or placebo (492 patients). A total of 681 patients completed the trial, and 303 discontinued (158 withdrew, 135 died, and 10 had other reasons); the numbers of patients who discontinued the trial were similar in the two groups. The annualized rate of stroke or systemic embolism was 2.3% in the edoxaban group and 6.7% in the placebo group (hazard ratio, 0.34; 95% confidence interval [CI], 0.19 to 0.61; P<0.001), and the annualized rate of major bleeding was 3.3% in the edoxaban group and 1.8% in the placebo group (hazard ratio, 1.87; 95% CI, 0.90 to 3.89; P = 0.09). There were substantially more events of gastrointestinal bleeding in the edoxaban group than in the placebo group. There was no substantial between-group difference in death from any cause (9.9% in the edoxaban group and 10.2% in the placebo group; hazard ratio, 0.97; 95% CI, 0.69 to 1.36). CONCLUSIONS: In very elderly Japanese patients with nonvalvular atrial fibrillation who were not appropriate candidates for standard doses of oral anticoagulants, a once-daily 15-mg dose of edoxaban was superior to placebo in preventing stroke or systemic embolism and did not result in a significantly higher incidence of major bleeding than placebo. (Funded by Daiichi Sankyo; ELDERCARE-AF ClinicalTrials.gov number, NCT02801669.).


Assuntos
Fibrilação Atrial/tratamento farmacológico , Embolia/prevenção & controle , Inibidores do Fator Xa/administração & dosagem , Piridinas/administração & dosagem , Acidente Vascular Cerebral/prevenção & controle , Tiazóis/administração & dosagem , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Fibrilação Atrial/mortalidade , Método Duplo-Cego , Embolia/etiologia , Inibidores do Fator Xa/efeitos adversos , Feminino , Seguimentos , Hemorragia/induzido quimicamente , Humanos , Incidência , Masculino , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Piridinas/efeitos adversos , Acidente Vascular Cerebral/etiologia , Tiazóis/efeitos adversos
8.
Drugs Aging ; 37(9): 665-676, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32725584

RESUMO

BACKGROUND: In older patients with overactive bladder (OAB), mirabegron, a ß3-adrenoreceptor agonist, represents an alternative treatment that may have a favorable risk-benefit profile. OBJECTIVES: Our objective was to further examine the safety and tolerability of mirabegron versus placebo treatment in patients aged ≥ 65 years with OAB-wet. METHODS: We conducted a 12-week, double-blind, randomized, placebo-controlled phase IV study to compare mirabegron with placebo. Community-dwelling patients aged ≥ 65 years with OAB-wet (one or more incontinence episode and three or more urgency episodes, and an average of eight or more micturitions/24 h over a 3-day diary) were randomized to receive placebo or mirabegron 25 mg/day (optional dose escalation to 50 mg/day at week 4 or 8). Safety analyses were performed for adverse events (AEs) and vital signs on all randomized patients who received one or more dose of study drug. RESULTS: Treatment-emergent AEs (TEAEs), the majority mild or moderate in severity, were reported in 39.4% of placebo patients and 44.2 and 49.8% of those who received mirabegron 25 mg or 50 mg, respectively. The most common TEAEs in mirabegron-treated patients were urinary tract infection, headache, and diarrhea. The incidence of TEAEs was slightly higher in mirabegron patients aged ≥ 75 years than in those aged < 75 years. There were no clinically meaningful differences in changes in vital signs from baseline to end of treatment for any treatment group, and no differences were observed between mirabegron and placebo treatment groups. TEAEs tended to occur early post exposure and were not dose related. CONCLUSIONS: Mirabegron treatment was well-tolerated in older adults with OAB-wet. Safety and tolerability were consistent with the known mirabegron safety profile. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov: NCT02216214.


Assuntos
Acetanilidas/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 3/uso terapêutico , Tiazóis/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico , Incontinência Urinária/tratamento farmacológico , Acetanilidas/administração & dosagem , Acetanilidas/efeitos adversos , Agonistas de Receptores Adrenérgicos beta 3/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 3/efeitos adversos , Fatores Etários , Idoso , Diarreia/induzido quimicamente , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Cefaleia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Tiazóis/administração & dosagem , Tiazóis/efeitos adversos , Resultado do Tratamento , Bexiga Urinária Hiperativa/diagnóstico
9.
Cochrane Database Syst Rev ; 5: CD002309, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32356609

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with cough, sputum production or dyspnoea, and a reduction in lung function, quality of life, and life expectancy. Apart from smoking cessation, no other treatments that slow lung function decline are available. Roflumilast and cilomilast are oral phosphodiesterase-4 (PDE4) inhibitors proposed to reduce the airway inflammation and bronchoconstriction seen in COPD. This Cochrane Review was first published in 2011, and was updated in 2017 and 2020. OBJECTIVES: To evaluate the efficacy and safety of oral PDE4 inhibitors for management of stable COPD. SEARCH METHODS: We identified randomised controlled trials (RCTs) from the Cochrane Airways Trials Register (date of last search 9 March 2020). We found other trials at web-based clinical trials registers. SELECTION CRITERIA: We included RCTs if they compared oral PDE4 inhibitors with placebo in people with COPD. We allowed co-administration of standard COPD therapy. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Two independent review authors selected trials for inclusion, extracted data, and assessed risk of bias. We resolved discrepancies by involving a third review author. We assessed our confidence in the evidence by using GRADE recommendations. Primary outcomes were change in lung function (minimally important difference (MID) = 100 mL) and quality of life (scale 0 to 100; higher score indicates more limitations). MAIN RESULTS: We found 42 RCTs that met the inclusion criteria and were included in the analyses for roflumilast (28 trials with 18,046 participants) or cilomilast (14 trials with 6457 participants) or tetomilast (1 trial with 84 participants), with a duration between six weeks and one year or longer. These trials included people across international study centres with moderate to very severe COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades II to IV), with mean age of 64 years. We judged risks of selection bias, performance bias, and attrition bias as low overall amongst the 39 published and unpublished trials. Lung function Treatment with a PDE4 inhibitor was associated with a small, clinically insignificant improvement in forced expiratory volume in one second (FEV1) over a mean of 40 weeks compared with placebo (mean difference (MD) 49.33 mL, 95% confidence interval (CI) 44.17 to 54.49; participants = 20,815; studies = 29; moderate-certainty evidence). Forced vital capacity (FVC) and peak expiratory flow (PEF) were also improved over 40 weeks (FVC: MD 86.98 mL, 95% CI 74.65 to 99.31; participants = 22,108; studies = 17; high-certainty evidence; PEF: MD 6.54 L/min, 95% CI 3.95 to 9.13; participants = 4245; studies = 6; low-certainty evidence). Quality of life Trials reported improvements in quality of life over a mean of 33 weeks (St George's Respiratory Questionnaire (SGRQ) MD -1.06 units, 95% CI -1.68 to -0.43; participants = 7645 ; moderate-certainty evidence). Incidence of exacerbations Treatment with a PDE4 inhibitor was associated with a reduced likelihood of COPD exacerbation over a mean of 40 weeks (odds ratio (OR) 0.78, 95% CI 0.73 to 0.84; participants = 20,382; studies = 27; high-certainty evidence), that is, for every 100 people treated with PDE4 inhibitors, five more remained exacerbation-free during the study period compared with those given placebo (number needed to treat for an additional beneficial outcome (NNTB) 20, 95% CI 16 to 27). No change in COPD-related symptoms nor in exercise tolerance was found. Adverse events More participants in the treatment groups experienced an adverse effect compared with control participants over a mean of 39 weeks (OR 1.30, 95% CI 1.22 to 1.38; participants = 21,310; studies = 30; low-certainty evidence). Participants experienced a range of gastrointestinal symptoms such as diarrhoea, nausea, vomiting, or dyspepsia. Diarrhoea was more commonly reported with PDE4 inhibitor treatment (OR 3.20, 95% CI 2.74 to 3.50; participants = 20,623; studies = 29; high-certainty evidence), that is, for every 100 people treated with PDE4 inhibitors, seven more suffered from diarrhoea during the study period compared with those given placebo (number needed to treat for an additional harmful outcome (NNTH) 15, 95% CI 13 to 17). The likelihood of psychiatric adverse events was higher with roflumilast 500 µg than with placebo (OR 2.13, 95% CI 1.79 to 2.54; participants = 11,168; studies = 15 (COPD pool data); moderate-certainty evidence). Roflumilast in particular was associated with weight loss during the trial period and with an increase in insomnia and depressive mood symptoms. Participants treated with PDE4 inhibitors were more likely to withdraw from trial participation; on average, 14% in the treatment groups withdrew compared with 8% in the control groups. Mortality No effect on mortality was found (OR 0.98, 95% CI 0.77 to 1.24; participants = 19,786; studies = 27; moderate-certainty evidence), although mortality was a rare event during these trials. AUTHORS' CONCLUSIONS: For this current update, five new studies from the 2020 search contributed to existing findings but made little impact on outcomes described in earlier versions of this review. PDE4 inhibitors offered a small benefit over placebo in improving lung function and reducing the likelihood of exacerbations in people with COPD; however, they had little impact on quality of life or on symptoms. Gastrointestinal adverse effects and weight loss were common, and the likelihood of psychiatric symptoms was higher, with roflumilast 500 µg. The findings of this review provide cautious support for the use of PDE4 inhibitors in COPD. In accordance with GOLD 2020 guidelines, they may have a place as add-on therapy for a subgroup of people with persistent symptoms or exacerbations despite optimal COPD management (e.g. people whose condition is not controlled by fixed-dose long-acting beta2-agonist (LABA) and inhaled corticosteroid (ICS) combinations). More longer-term trials are needed to determine whether or not PDE4 inhibitors modify FEV1 decline, hospitalisation, or mortality in COPD.


Assuntos
Aminopiridinas/administração & dosagem , Benzamidas/administração & dosagem , Ácidos Cicloexanocarboxílicos/administração & dosagem , Nitrilos/administração & dosagem , Inibidores da Fosfodiesterase 4/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Tiazóis/administração & dosagem , Administração Oral , Aminopiridinas/efeitos adversos , Benzamidas/efeitos adversos , Ácidos Cicloexanocarboxílicos/efeitos adversos , Ciclopropanos/administração & dosagem , Ciclopropanos/efeitos adversos , Diarreia/induzido quimicamente , Progressão da Doença , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Nitrilos/efeitos adversos , Pico do Fluxo Expiratório/efeitos dos fármacos , Inibidores da Fosfodiesterase 4/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/mortalidade , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Tiazóis/efeitos adversos , Capacidade Vital/efeitos dos fármacos
10.
Clin Nucl Med ; 45(8): 628-631, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32453085

RESUMO

Brown adipose tissue (BAT), which produces energy and is known to play a role as a hibernating gland, is sometimes visualized on F-FDG PET in children or in slender young adults in a cold environment. Because BAT is activated by catecholamines, FDG uptake in BAT is also observed in patients with pheochromocytoma or paraganglioma. We present the case of an elderly woman with remarkable FDG uptake in BAT. Activation of BAT by a ß3-adrenergic receptor agonist (mirabegron) prescribed for overactive bladder was suspected as the cause of the marked visualization of BAT in this patient.


Assuntos
Acetanilidas/efeitos adversos , Tecido Adiposo Marrom/diagnóstico por imagem , Agonistas Adrenérgicos/efeitos adversos , Fluordesoxiglucose F18/farmacocinética , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/farmacocinética , Tiazóis/efeitos adversos , Acetanilidas/uso terapêutico , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Agonistas Adrenérgicos/uso terapêutico , Idoso de 80 Anos ou mais , Feminino , Humanos , Feocromocitoma/diagnóstico por imagem , Tiazóis/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico
11.
Clin Interv Aging ; 15: 575-581, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368024

RESUMO

Lower urinary tract symptoms, including urgency, urgency incontinence, frequency, and nocturia, are highly prevalent in older adults and are associated with significant morbidity and impairment in quality of life. When conservative measures such as bladder training fail to improve symptoms, pharmacological management is recommended by national and international guidelines. Mirabegron, an agonist of the ß3 adrenergic receptor, demonstrates similar efficacy to the anticholinergic drugs without the risk of anticholinergic effects, but experience and evidence in the very elderly population are limited. This narrative review examines the current evidence base for mirabegron in very elderly adults.


Assuntos
Acetanilidas/uso terapêutico , Segurança do Paciente , Tiazóis/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico , Agentes Urológicos/uso terapêutico , Acetanilidas/efeitos adversos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Noctúria/tratamento farmacológico , Tiazóis/efeitos adversos , Resultado do Tratamento , Bexiga Urinária Hiperativa/prevenção & controle , Incontinência Urinária/tratamento farmacológico , Agentes Urológicos/efeitos adversos
12.
Actas urol. esp ; 44(4): 224-232, mayo 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-199005

RESUMO

INTRODUCCIÓN Y OBJETIVO: El estudio BELIEVE es un estudio europeo, no intervencionista, con pacientes con vejiga hiperactiva que recibieron mirabegrón en condiciones de práctica clínica habitual. El presente estudio incluye datos de la subpoblación española, y evalúa su calidad de vida relacionada con la salud (CVRS) y su persistencia al tratamiento. MATERIALES Y MÉTODOS: Se analizaron los datos de los 11 centros españoles del estudio BELIEVE. La variable principal fue el cambio de la CVRS desde el estado basal, a partir del cuestionario OAB-q. Las variables secundarias incluyeron la persistencia al tratamiento, la CVRS mediante el EQ-5D-5L y los acontecimientos adversos. El periodo de seguimiento fue de 12 meses, con 2 ventanas a los 2-4 meses y a los 10-12 meses. RESULTADOS: Se incluyeron 153 pacientes españoles. En el Full Analysis Set (FAS), el 63,1% eran mujeres, con una edad media de 66 años. Las puntuaciones de la molestia de síntomas y la CVRS total mostraron una mejora hasta los 2-4 meses y los 10-12 meses. El EQ-5D-5L también mostró una mejora en la CVRS de estos pacientes. La persistencia fue elevada, ya que el 49% de los pacientes seguían recibiendo mirabegrón a los 10-12 meses. No se observaron problemas de seguridad inesperados y los acontecimientos adversos coincidieron con el perfil de seguridad conocido de mirabegrón. CONCLUSIONES: Los pacientes españoles que reciben mirabegrón en condiciones de práctica clínica real reportan mejoras en su CVRS, con una buena tolerabilidad y una persistencia aceptable al tratamiento


INTRODUCTION AND OBJECTIVE: The BELIEVE study is a European, non-interventional study which includes patients with overactive bladder who were prescribed mirabegron as part of routine clinical practice. Data from the Spanish subpopulation has been obtained for the present study, aiming to analyze health-related quality-of-life (HRQoL) and treatment persistence of these patients. MATERIALS AND METHODS: Data from 11 Spanish hospitals of the BELIEVE study were analyzed. The primary endpoint was to evaluate change of HRQoL from baseline with overactive bladder questionnaire (OAB-q). Secondary endpoints included treatment persistence, HRQoL based on the EQ-5D-5L questionnaire and adverse events. Study follow-up was 12 months, with two visit windows at 2-4 months and 10-12 months. RESULTS: 153 Spanish patients were enrolled in the study. In the Full Analysis Set (FAS), 63.1% were women, and the mean age was 66 years. Symptom bother and HRQoL improved from baseline to 2-4 months and 10-12 months. EQ-5D-5L questionnaire also showed an improved patients' HRQoL. Treatment persistence was high, as 49% of patients remained with mirabegron at 10-12 months. Adverse events were consistent with previous safety profile results of mirabegron, and no unexpected safety issues were observed. CONCLUSIONS: Spanish patients treated with mirabegron in real clinical practice reported improvements in HRQoL, with a good tolerability and persistence to treatment


Assuntos
Humanos , Masculino , Feminino , Idoso , Bexiga Urinária Hiperativa/tratamento farmacológico , Qualidade de Vida , Tiazóis/uso terapêutico , Cooperação e Adesão ao Tratamento , Seguimentos , Espanha , Densidade Demográfica , Inquéritos e Questionários , Tiazóis/efeitos adversos
13.
Pharmacotherapy ; 40(5): 416-437, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32259313

RESUMO

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into an emergent global pandemic. Coronavirus disease 2019 (COVID-19) can manifest on a spectrum of illness from mild disease to severe respiratory failure requiring intensive care unit admission. As the incidence continues to rise at a rapid pace, critical care teams are faced with challenging treatment decisions. There is currently no widely accepted standard of care in the pharmacologic management of patients with COVID-19. Urgent identification of potential treatment strategies is a priority. Therapies include novel agents available in clinical trials or through compassionate use, and other drugs, repurposed antiviral and immunomodulating therapies. Many have demonstrated in vitro or in vivo potential against other viruses that are similar to SARS-CoV-2. Critically ill patients with COVID-19 have additional considerations related to adjustments for organ impairment and renal replacement therapies, complex lists of concurrent medications, limitations with drug administration and compatibility, and unique toxicities that should be evaluated when utilizing these therapies. The purpose of this review is to summarize practical considerations for pharmacotherapy in patients with COVID-19, with the intent of serving as a resource for health care providers at the forefront of clinical care during this pandemic.


Assuntos
Antivirais/administração & dosagem , Antivirais/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Imunomodulação , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/análogos & derivados , Corticosteroides , Alanina/administração & dosagem , Alanina/efeitos adversos , Alanina/análogos & derivados , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Azetidinas/administração & dosagem , Azetidinas/efeitos adversos , Betacoronavirus , Cloroquina/administração & dosagem , Cloroquina/efeitos adversos , Infecções por Coronavirus/terapia , Combinação de Medicamentos , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Imunização Passiva , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Lopinavir/administração & dosagem , Lopinavir/efeitos adversos , Nelfinavir/administração & dosagem , Nelfinavir/efeitos adversos , Pandemias , Ribavirina/administração & dosagem , Ribavirina/efeitos adversos , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Tiazóis/administração & dosagem , Tiazóis/efeitos adversos
14.
J Thromb Haemost ; 18(6): 1320-1323, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32329231

RESUMO

BACKGROUND: Antiviral drugs are administered in patients with severe COVID-19 respiratory syndrome, including those treated with direct oral anticoagulants (DOACs). Concomitant administration of antiviral agents has the potential to increase their plasma concentration. A series of patients managed in the Cremona Thrombosis Center were admitted at Cremona Hospital for SARS-CoV-2 and started antiviral drugs without stopping DOAC therapy. DOAC plasma levels were measured in hospital and results compared with those recorded before hospitalization. METHODS: All consecutive patients on DOACs were candidates for administration of antiviral agents (lopinavir, ritonavir, or darunavir). Plasma samples for DOAC measurement were collected 2to 4 days after starting antiviral treatment, at 12 hours from the last dose intake in patients on dabigatran and apixaban, and at 24 hours in those on rivaroxaban and edoxaban. For each patient, C-trough DOAC level, expressed as ng/mL, was compared with the one measured before hospitalization. RESULTS: Of the 1039 patients hospitalized between February 22 and March 15, 2020 with COVID-19 pneumonia and candidates for antiviral therapy, 32 were on treatment with a DOAC. DOAC was stopped in 20 and continued in the remaining 12. On average, C-trough levels were 6.14 times higher during hospitalization than in the pre-hospitalization period. CONCLUSION: DOAC patients treated with antiviral drugs show an alarming increase in DOAC plasma levels. In order to prevent bleeding complications, we believe that physicians should consider withholding DOACs from patients with SARS-CoV-2 and replacing them with alternative parenteral antithrombotic strategies for as long as antiviral agents are deemed necessary and until discharge.


Assuntos
Antitrombinas/sangue , Antivirais/efeitos adversos , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Dabigatrana/sangue , Inibidores do Fator Xa/sangue , Pneumonia Viral/tratamento farmacológico , Pirazóis/sangue , Piridinas/sangue , Piridonas/sangue , Tiazóis/sangue , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Antitrombinas/administração & dosagem , Antitrombinas/efeitos adversos , Antivirais/administração & dosagem , Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Dabigatrana/administração & dosagem , Dabigatrana/efeitos adversos , Darunavir/efeitos adversos , Interações Medicamentosas , Monitoramento de Medicamentos , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Itália , Lopinavir/efeitos adversos , Masculino , Pandemias , Segurança do Paciente , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Medição de Risco , Fatores de Risco , Ritonavir/efeitos adversos , Índice de Gravidade de Doença , Tiazóis/administração & dosagem , Tiazóis/efeitos adversos
15.
J Clin Psychiatry ; 81(3)2020 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-32237292

RESUMO

OBJECTIVE: To compare longitudinal metabolic effects of 7 antipsychotics, including body mass index (BMI), waist circumference (WC), blood pressure (BP), glucose, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C); to investigate risk factors for metabolic syndrome (MetS); and to make recommendations on frequency and timing of monitoring metabolic measurements. METHODS: This randomized, open-label, pharmacologic trial was conducted among patients with schizophrenia (DSM-IV) in 32 hospitals across China. Patients were randomly assigned to 7 groups and assessed at baseline, 2, 4, and 6 weeks. Linear mixed-effect models were used to assess changes of metabolic measures over time. Multivariable logistic regression analysis was performed to investigate the risk factors for MetS. RESULTS: In total, 2,550 (718 drug-naïve) of 2,774 patients finished the study between July 6, 2010, and November 30, 2011. We found significant (P < .05) changes for BMI, WC, TG, and LDL-C, with TG and LDL-C reaching a plateau. Interactions between baseline metabolic condition and changes over time were observed for BMI (χ² = 43.11, P < .001), WC (χ² = 36.34, P < .001), systolic BP (χ² = 11.92, P = .002), glucose (χ² = 6.09, P = .01), and TG (χ² = 6.01, P = .01). Antipsychotics generally had greater adverse effects on patients who were initially screened as metabolically normal. After controlling for other associated factors, we found that antipsychotics resulted in differing risk for incident MetS, with a similar pattern to findings in other populations: olanzapine (odds ratio [OR] = 3.36, P < .001) > quetiapine (OR = 3.29, P < .001) > perphenazine (OR = 2.73, P = .007) > risperidone (OR = 2.21, P = .02) > aripiprazole (OR = 1.74, P = .15) ≈ haloperidol (OR = 1.75, P = .22) ≈ ziprasidone (OR = 1, reference). CONCLUSIONS: Metabolic traits should be monitored frequently in early stages of antipsychotic treatment due to rapid and substantial changes. Clinicians should not assume low risk for patients with normal metabolic parameters at baseline. TRIAL REGISTRATION: Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000934.


Assuntos
Antipsicóticos/efeitos adversos , Síndrome Metabólica/induzido quimicamente , Esquizofrenia/tratamento farmacológico , Adulto , Antipsicóticos/uso terapêutico , Aripiprazol/efeitos adversos , Aripiprazol/uso terapêutico , Glicemia/efeitos dos fármacos , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Masculino , Olanzapina/efeitos adversos , Olanzapina/uso terapêutico , Piperazinas/efeitos adversos , Piperazinas/uso terapêutico , Fumarato de Quetiapina/efeitos adversos , Fumarato de Quetiapina/uso terapêutico , Fatores de Risco , Risperidona/efeitos adversos , Risperidona/uso terapêutico , Esquizofrenia/metabolismo , Tiazóis/efeitos adversos , Tiazóis/uso terapêutico , Triglicerídeos/sangue
16.
An Bras Dermatol ; 95(2): 194-199, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32156503

RESUMO

BACKGROUND: Kathon CG, a combination of methylchloroisothiazolinone and methylisothiazolinone, is widely used as preservative in cosmetics, as well in household cleaning products, industrial products such as paints and glues. It has emerged as an important sensitizing agent in allergic contact dermatitis. OBJECTIVES: This study evaluated the reactivity to this substance in patients subjected to patch tests at the Dermatology Institute in Bauru, São Paulo from 2015 to 2017 and its correlation with other preservatives, the professional activity and location of the lesions. METHODS: The patients were submitted to standard series of epicutaneous tests, standardized by the Brazilian Group Studies on Contact Dermatitis. RESULTS: Out the 267 patients tested, 192 presented positivity to at least one substance and 29 of the patients (15.10%) presented reaction to Kathon CG, with predominance of the female gender (n=27); main professional activity associated with Kathon CG sensibilization was cleaning (17.24%), followed by aesthetic areas (13.79%) and health care (10.34%). The most prevalent sensitizations among the substances tested were nickel sulphate (56.3%), followed by cobalt chloride (23.4%), neomycin (18.2%), potassium dichromate (17.7%), thimerosal (14.5%), formaldehyde (13.2%), paraphenylenediamine (9.3%), and fragrance mix (8.3%). STUDY LIMITATIONS: We do not have data from patients that were submitted to patch test a decade ago in order to confront to current data and establish whether or no sensitization to Kathon CG has increased. CONCLUSION: High positivity to Kathon CG corroborates the recent findings in the literature, suggesting more attention to concentration of this substance, used in cosmetics and products for domestic use.


Assuntos
Dermatite Alérgica de Contato/diagnóstico , Testes do Emplastro/métodos , Tiazóis/análise , Adulto , Brasil , Cosméticos/efeitos adversos , Cosméticos/química , Dermatite Alérgica de Contato/etiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Testes do Emplastro/estatística & dados numéricos , Conservantes Farmacêuticos/efeitos adversos , Conservantes Farmacêuticos/química , Estudos Retrospectivos , Estatísticas não Paramétricas , Tiazóis/efeitos adversos
17.
BMC Geriatr ; 20(1): 109, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-32183741

RESUMO

BACKGROUND: Antimuscarinics are often used for treatment of overactive bladder (OAB), but exposure to medications such as antimuscarinics that have anticholinergic properties has been linked to adverse cognitive effects. A phase 4 placebo-controlled study (PILLAR; NCT02216214) described the efficacy and safety of mirabegron, a ß3-adrenoreceptor agonist, for treatment of wet OAB in patients aged ≥65 years. This pre-planned analysis aimed to measure differences in cognitive function between mirabegron and placebo, using a rapid screening instrument for mild cognitive impairment: the Montreal Cognitive Assessment (MoCA). METHODS: Outpatients aged ≥65 years with wet OAB were randomized 1:1 to mirabegron or placebo, stratified by age (<75/≥75 years). There were no exclusion criteria regarding cognitive status. Patients randomized to mirabegron initially received 25 mg/day with an optional increase to 50 mg/day after week 4/8 based on patient/investigator discretion. The MoCA was administered at baseline and end of treatment (EoT, week 12). The study protocol was Independent Ethics Committee/Institutional Review Board-approved. RESULTS: Of the 887 randomized patients who received ≥1 dose of study drug, 72.3% were female, 79.5% were white, and 28.1% were aged ≥75 years. All patients had ≥1 comorbidity and 94.3% were receiving ≥1 concomitant medication. One third of patients had a history of psychiatric disorders, the most common being depression (17.2%), insomnia (15.7%), and anxiety (11.4%). Baseline mean (standard error, SE) MoCA total scores were 26.9 (0.1) and 26.8 (0.1) in the mirabegron and placebo groups, respectively. Among patients with MoCA data available at baseline/EoT, 27.1% (115/425) and 25.8% (106/411) of mirabegron and placebo group patients, respectively, had impaired cognitive function at baseline (MoCA total score <26). There was no statistically significant change in adjusted mean (SE) MoCA total score from baseline to EoT in the mirabegron group (-0.2 [0.1]) or the placebo group (-0.1 [0.1]). CONCLUSIONS: Treatment with mirabegron for 12 weeks did not contribute to drug-related cognitive side effects in patients aged ≥65 years, as measured by the MoCA. Furthermore, the pattern of change in cognition over time in an older OAB trial population does not appear to differ from that of subjects receiving placebo. TRIAL REGISTRATION: NCT02216214 (prospectively registered August 13, 2014).


Assuntos
Acetanilidas/efeitos adversos , Cognição/efeitos dos fármacos , Tiazóis/efeitos adversos , Bexiga Urinária Hiperativa/tratamento farmacológico , Agentes Urológicos/efeitos adversos , Acetanilidas/uso terapêutico , Idoso , Feminino , Humanos , Masculino , Testes de Estado Mental e Demência , Tiazóis/uso terapêutico , Resultado do Tratamento , Bexiga Urinária Hiperativa/diagnóstico , Agentes Urológicos/uso terapêutico
19.
Sci Rep ; 10(1): 687, 2020 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-31959760

RESUMO

Induction of autophagy can have beneficial effects in several human diseases, e.g. cancer and neurodegenerative diseases (ND). Here, we therefore evaluated the potential of two novel autophagy-inducing compounds, i.e. STF-62247 and pimozide, to stimulate autophagy as well as autophagic cell death (ACD) using mouse embryonic fibroblasts (MEFs) as a cellular model. Importantly, both STF-62247 and pimozide triggered several hallmarks of autophagy in MEFs, i.e. enhanced levels of LC3B-II protein, its accumulation at distinct cytosolic sites and increase of the autophagic flux. Intriguingly, autophagy induction by STF-62247 and pimozide resulted in cell death that was significantly reduced in ATG5- or ATG7-deficient MEFs. Consistent with ACD induction, pharmacological inhibitors of apoptosis, necroptosis or ferroptosis failed to protect MEFs from STF-62247- or pimozide-triggered cell death. Interestingly, at subtoxic concentrations, pimozide stimulated fragmentation of the mitochondrial network, degradation of mitochondrial proteins (i.e. mitofusin-2 and cytochrome c oxidase IV (COXIV)) as well as a decrease of the mitochondrial mass, indicative of autophagic degradation of mitochondria by pimozide. In conclusion, this study provides novel insights into the induction of selective autophagy as well as ACD by STF-62247 and pimozide in MEFs.


Assuntos
Proteína 5 Relacionada à Autofagia/genética , Proteína 7 Relacionada à Autofagia/genética , Fibroblastos/citologia , Pimozida/efeitos adversos , Piridinas/efeitos adversos , Tiazóis/efeitos adversos , Animais , Morte Celular Autofágica , Autofagia , Proteína 5 Relacionada à Autofagia/metabolismo , Proteína 7 Relacionada à Autofagia/metabolismo , Linhagem Celular , Fibroblastos/metabolismo , Técnicas de Inativação de Genes , Camundongos , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Modelos Biológicos , Proteólise
20.
Sci Rep ; 10(1): 662, 2020 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-31959803

RESUMO

Warfarin care bundles (e.g. genotype-guided warfarin dosing, patient's self-testing [PST] or patient's self-management [PSM] and left atrial appendage closure) are based on the concept of combining several interventions to improve anticoagulation care. NOACs are also introduced for stroke prevention in atrial fibrillation (SPAF). However, these interventions have not been compared in head-to-head trials yet. We did a network meta-analysis based on a systematic review of randomized controlled trials comparing anticoagulant interventions for SPAF. Studies comparing these interventions in adults, whether administered alone or as care bundles were included in the analyses. The primary efficacy outcome was stroke and the primary safety outcome was major bleeding. Thirty-seven studies, involving 100,142 patients were assessed. Compared to usual care, PSM significantly reduced the risk of stroke (risk ratio [RR] 0.24, 95% CI 0.08-0.68). For major bleeding, edoxaban 60 mg (0.80, 0.71-0.90), edoxaban 30 mg (0.48, 0.42-0.56), and dabigatran 110 mg (0.81, 0.71-0.94) significantly reduced the risk of major bleeding compared with usual warfarin care. Cluster rank plot incorporating stroke and major bleeding outcomes indicates that some warfarin care bundles perform as well as NOACs. Both interventions are therefore viable options to be considered for SPAF. Additional studies including head-to-head trials and cost-effectiveness evaluation are still warranted.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Pacotes de Assistência ao Paciente/métodos , Varfarina/administração & dosagem , Idoso , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Dabigatrana/administração & dosagem , Dabigatrana/efeitos adversos , Feminino , Hemorragia/etiologia , Hemorragia/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Tiazóis/administração & dosagem , Tiazóis/efeitos adversos , Resultado do Tratamento , Varfarina/efeitos adversos
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