Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.223
Filtrar
1.
JAMA ; 323(2): 130-139, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31935028

RESUMO

Importance: The efficacy of factor XIa inhibition for thromboprophylaxis is unknown. Osocimab is a long-acting, fully human monoclonal antibody that inhibits factor XIa. Objective: To compare different doses of osocimab with enoxaparin and apixaban for thromboprophylaxis in patients who have undergone knee arthroplasty. Design, Setting, and Participants: Randomized, open-label, adjudicator-blinded, phase 2 noninferiority trial with observer blinding for osocimab doses, conducted at 54 hospitals in 13 countries. Adult patients undergoing unilateral knee arthroplasty were randomized from October 2017 through August 2018 and followed up until January 2019. Interventions: Single intravenous osocimab postoperative doses of 0.3 mg/kg (n = 107), 0.6 mg/kg (n = 65), 1.2 mg/kg (n = 108), or 1.8 mg/kg (n = 106); preoperative doses of 0.3 mg/kg (n = 109) or 1.8 mg/kg (n = 108); or 40 mg of subcutaneous enoxaparin once daily (n = 105) or 2.5 mg of oral apixaban twice daily (n = 105) for at least 10 days or until venography. Main Outcomes and Measures: The primary outcome was venous thromboembolism incidence between 10 and 13 days postoperatively (assessed by mandatory bilateral venography performed 10 to 13 days after surgery or confirmed symptomatic deep vein thrombosis or pulmonary embolism). A 5% noninferiority margin compared with enoxaparin was chosen. The primary safety outcome of major or clinically relevant nonmajor bleeding was assessed until 10 to 13 days postoperatively. Results: Of 813 randomized participants (mean [SD] age, 66.5 years [8.2 years]; body mass index, 32.7 [5.7]; and 74.2% women), 600 were included in the per-protocol population used for the primary analysis. The primary outcome occurred in 18 patients (23.7%) receiving 0.3 mg/kg, 8 (15.7%) receiving 0.6 mg/kg, 13 (16.5%) receiving 1.2 mg/kg, and 14 (17.9%) receiving 1.8 mg/kg of osocimab postoperatively; 23 (29.9%) receiving 0.3 mg/kg and 9 (11.3%) receiving 1.8 mg/kg of osocimab preoperatively; 20 (26.3%) receiving enoxaparin; and 12 (14.5%) receiving apixaban. Osocimab given postoperatively met criteria for noninferiority compared with enoxaparin with risk differences (1-sided 95% CIs) of 10.6% (95% CI, -1.2% to ∞) at the 0.6-mg/kg dose; 9.9% (95% CI, -0.9% to ∞) at the 1.2-mg/kg dose, and 8.4% (95% CI, -2.6 to ∞) at the 1.8-mg/kg dose. The preoperative dose of 1.8 mg/kg of osocimab met criteria for superiority compared with enoxaparin with a risk difference of 15.1%; 2-sided 90% CI, 4.9% to 25.2%). Postoperative and preoperative doses of 0.3 mg/kg of osocimab did not meet the prespecified criteria for noninferiority, with risk differences (1-sided 95% CIs) of 2.6% (95% CI, -8.9% to ∞) and -3.6% (95% CI, -15.5% to ∞), respectively. Major or clinically relevant nonmajor bleeding was observed in up to 4.7% of those receiving osocimab, 5.9% receiving enoxaparin, and 2% receiving apixaban. Conclusions and Relevance: Among patients undergoing knee arthroplasty, postoperative osocimab 0.6 mg/kg, 1.2 mg/kg, and 1.8 mg/kg met criteria for noninferiority compared with enoxaparin, and the preoperative 1.8-mg/kg dose of osocimab met criteria for superiority compared with enoxaparin for the primary outcome of incidence of venous thromboembolism at 10 to 13 days postoperatively. Further studies are needed to establish efficacy and safety of osocimab relative to standard thromboprophylaxis. Trial Registration: ClinicalTrials.gov Identifier: NCT03276143.


Assuntos
Anticoagulantes/administração & dosagem , Artroplastia do Joelho , Inibidores do Fator Xa/administração & dosagem , Hemorragia/induzido quimicamente , Complicações Pós-Operatórias/prevenção & controle , Tromboembolia Venosa/prevenção & controle , Idoso , Anticoagulantes/efeitos adversos , Relação Dose-Resposta a Droga , Enoxaparina/administração & dosagem , Enoxaparina/efeitos adversos , Inibidores do Fator Xa/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Embolia Pulmonar/prevenção & controle , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Método Simples-Cego , Trombose Venosa/prevenção & controle
2.
Gynecol Oncol ; 155(3): 420-428, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31623857

RESUMO

OBJECTIVE: We sought to determine safety and efficacy of the AKT inhibitor, GSK2141795, combined with the MEK inhibitor, trametinib, in endometrial cancer. METHODS: Patients with measurable recurrent endometrial cancer were eligible. One to two prior cytotoxic regimens were allowed; prior use of a MEK or PI3K pathway inhibitor was excluded. Initial trial design consisted of a KRAS mutation stratified randomized phase II with a safety lead-in evaluating the combination. For the safety lead in, the previously recommended phase 2 dose (RP2D; trametinib 1.5 mg, GSK2141795 50 mg) was chosen for Dose Level 1 (DL1). RESULTS: Of 26 enrolled patients, 14 were treated on DL1 and 12 were treated on DL-1 (trametinib 1.5 mg, GSK2141795 25 mg). Most common histologies were endometrioid (58%) and serous (27%). Four of 25 (16%) patients were KRAS mutant. Dose limiting toxicities (DLTs) were assessed during cycle 1. DL1 had 8 DLTs (hypertension (n = 2), mucositis (2), rash (2), dehydration, stroke/acute kidney injury). DL1 was deemed non-tolerable so DL-1 was explored. DL-1 had no DLTs. Sixty-five percent of patients had ≥ grade 3 toxicity. There were no responses in DL1 (0%, 90%CI 0-15%) and 1 response in DL-1 (8.3%, 90%CI 0.4-33.9%). Proportion PFS at 6 months for DL1 is 14%, and 25% for DL-1. CONCLUSION: The combination of trametinib and GSK2141795 had high levels of toxicity in endometrial cancer at the previously RP2D but was tolerable at a reduced dose. Due to insufficient preliminary efficacy at a tolerable dose, the Phase II study was not initiated.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Endométrio/tratamento farmacológico , MAP Quinase Quinase Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Diaminas/administração & dosagem , Diaminas/efeitos adversos , Neoplasias do Endométrio/enzimologia , Feminino , Humanos , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Pirimidinonas/administração & dosagem , Pirimidinonas/efeitos adversos
3.
Expert Opin Drug Saf ; 18(12): 1119-1125, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31580164

RESUMO

Introduction: The non-vitamin K antagonist oral anticoagulants (NOACs) are changing the landscape for stroke prevention in atrial fibrillation (AF) and prevention or treatment of venous thromboembolism (VTE). In patients with AF and concomitant acute coronary syndrome (ACS), the treatment regimen of combined NOACs and P2Y12 inhibitors is gaining popularity.Areas covered: We conducted a review of safety evaluation and effectiveness of apixaban for AF and ACS treatment, both alone and in combination with different antiplatelet treatment regimens. The aim was to provide an overview of apixaban including mechanism of action, indications, adverse events and tolerability.Expert opinion: Apixaban is recommended as a safe, well tolerated and effective oral anticoagulant for reducing the risk of ischemic events among AF patients. It is of value in prevention and treatment of VTE and pulmonary embolism. Comparing to VKA, apixaban was superior in preventing stroke or systemic embolism with lower major bleeding events among AF patients. When combined with dual antiplatelet therapy apixaban may cause dose-related increase in bleeding which reduces the benefit of this treatment regimen among ACS patients but without AF. In those with ACS and concomitant AF, the combination of apixaban with P2Y12 inhibitor appears to be safe and effective.


Assuntos
Inibidores do Fator Xa/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Síndrome Coronariana Aguda/tratamento farmacológico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Quimioterapia Combinada , Inibidores do Fator Xa/efeitos adversos , Humanos , Intervenção Coronária Percutânea/métodos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
4.
Medicine (Baltimore) ; 98(42): e17171, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626082

RESUMO

Mesial temporal lobe epilepsy (MTLE) is a common epilepsy syndrome often refractory to antiepileptic drug (AED) treatment. The purpose of this study was to evaluate the effectiveness and tolerability of perampanel (PER) as add-on treatment for patients of MTLE.We pooled retrospective data from adult patients with MTLE, from a tertiary center in Taiwan, who were prescribed PER between March 2016 and December 2016. The retention, responder, and seizure-free rate as well as the treatment emergent adverse events were assessed after 6 months of PER adjunctive treatment in this single-center postmarketing study.Review of medical records revealed that adequate data were available for 44 patients who were being administered PER (mean age: 42.0 ±â€Š13.3 years, 24 females; baseline mean seizure frequency: 5.4 per 28 days). Twelve patients exhibited hippocampal sclerosis (HS). Open-label PER was added to ongoing medications. Twelve patients withdrew because of ineffectiveness (n = 6) or adverse effects (n = 6). The retention rate was 72.7% at 6 months. On final evaluation, with a mean PER dose of 5.7 mg/day for 6 months, a ≥50% reduction in seizure frequency was observed in 46.9% of the patients, and 5 patients became seizure-free. The effectiveness was similar for patients with or without HS. Twenty-three patients (52.3%) experienced adverse effects. The most common adverse effects were dizziness, ataxia, and irritability.Our results suggest that PER, at doses of 2 to 12 mg/day, reduces seizure frequency effectively with acceptable safety profiles for adults with MTLE.


Assuntos
Anticonvulsivantes/administração & dosagem , Epilepsia do Lobo Temporal/tratamento farmacológico , Piridonas/administração & dosagem , Adulto , Anticonvulsivantes/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância de Produtos Comercializados , Piridonas/efeitos adversos , Estudos Retrospectivos , Taiwan , Resultado do Tratamento
5.
Int J Mycobacteriol ; 8(3): 298-301, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31512609

RESUMO

We report a case of idiopathic pulmonary fibrosis (IPF) treated with pirfenidone who developed tuberculosis (TB) and later had exfoliative dermatitis secondary to an interaction between pirfenidone and rifampicin. This case report highlights the possible risk of developing TB in patients diagnosed with IPF and on antifibrotic therapy like pirfenidone. Furthermore, this case report documents a previously unreported adverse reaction due to the interaction of rifampicin with pirfenidone.


Assuntos
Eritema/induzido quimicamente , Fibrose Pulmonar Idiopática/tratamento farmacológico , Piridonas/efeitos adversos , Rifampina/efeitos adversos , Tuberculose/tratamento farmacológico , Tuberculose/etiologia , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Antibióticos Antituberculose/efeitos adversos , Interações de Medicamentos , Humanos , Fibrose Pulmonar Idiopática/complicações , Índia , Masculino , Piridonas/uso terapêutico , Tomografia Computadorizada por Raios X , Resultado do Tratamento
7.
Sr Care Pharm ; 34(8): 514-519, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31462355

RESUMO

OBJECTIVE: The aim of this study was to evaluate prescribing practices for elderly patients started on apixaban in multiple practice settings.
DESIGN: Retrospective, chart review.
SETTING: One outpatient and three inpatient settings in Arizona and Massachusetts.
PATIENT, PARTICIPANTS: Patients who received a new order for apixaban between July 1, 2015, and December 31, 2016. Inclusion criteria included adults 65 years of age and older who were receiving apixaban for atrial fibrillation or venous thromboembolism (VTE) at a current treatment dose.
There were 1,045 patients included, the average age was 78 years, 52% were male, and 90% had atrial fibrillation.
MAIN OUTCOME MEASURE: Appropriate prescribing of apixaban based on Food and Drug Administration (FDA)-labeling (age, weight, serum creatinine).
RESULTS: Six patients who were on hemodialysis were excluded from the analysis, leaving 1,039 patients to be analyzed. 16.2% (168/1,039) of patients had an incorrect dose of apixaban prescribed based on their indication. Of those, 75% (126/168) were taking the medication for atrial fibrillation and 25% (42/168) for VTE. For those with atrial fibrillation (n = 126), the majority of inappropriate orders resulted from doses that were lower than indicated (113/126).
CONCLUSION: This research suggests that elderly patients may receive inappropriately lower doses of apixaban than indicated, which may decrease the effectiveness of the medication. This research supports the fact that pharmacists can play a vital role in anticoagulation stewardship by verifying apixaban doses for accuracy.


Assuntos
Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Idoso , Anticoagulantes , Arizona , Feminino , Humanos , Masculino , Massachusetts , Estudos Retrospectivos
8.
Ann Saudi Med ; 39(4): 265-278, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31381381

RESUMO

BACKGROUND: Apixaban, an oral anticoagulant for stroke and systemic embolism prevention in non-valvular atrial fibrillation (NVAF), was superior to warfarin in prevention of stroke and systemic embolism, bleeding outcomes and mortality (ARISTOTLE trial), and substantially reduced stroke risk, with no significant increase in major or intracranial bleeding risk versus aspirin (AVERROES trial). OBJECTIVE: Estimate cost-effectiveness of apixaban versus other anticoagulants for NVAF treatment in Saudi Arabia. DESIGN: Lifetime Markov model. SETTING: A published model was adapted from the United Kingdom (UK) to the Saudi Arabia setting. PATIENTS AND METHODS: The model enabled pairwise comparisons of apixaban against other anticoagulants, aspirin, and aspirin+clopidogrel. Apart from warfarin and aspirin, comparisons were indirect. Subpopulations included vitamin K antagonist (VKA) suitable and unsuitable patients. Medication and physician visit costs were from published lists. A cost ratio (0.533), from comparison of UK and Saudi physician visit costs, was applied to UK model inputs to estimate local event costs. Background life expectancy was from Saudi life tables. Model structure, treatment comparators, patient characteristics, event rates, and utilities were unchanged. Costs and health benefits were discounted by 3.5% annually. MAIN OUTCOME MEASURE: Incremental cost-effectiveness ratio of cost per quality-adjusted life-year (QALY) gained. SAMPLE SIZE: Model cohort of 1000 NVAF patients, for VKA suitable and VKA unsuitable populations. RESULTS: Apixaban was dominant versus warfarin (VKA suitable) and rivaroxaban (VKA suitable and unsuitable). Compared against dabigatran (110mg, 150 mg, 110/150mg), the cost/QALY gained for apixaban was $5166, $11 143, $10 849 (VKA suitable) and $5 157, $14 424, $14 134 (VKA unsuitable), respectively. Cost/QALY for apixaban versus aspirin and aspirin+clopidogrel was $14 805 and $5784 (VKA suitable); and $10 564 and $4203 (VKA unsuitable), respectively. Sensitivity analyses demonstrated consistency of findings across varying inputs. CONCLUSIONS: Apixaban was found to be cost-effective for stroke prevention among Saudi NVAF patients, when assessed using a US$20 000 willingness-to-pay threshold. LIMITATIONS: Lack of robust local clinical, cost and utility data for model inputs. Lack of head-to-head clinical trial data for rivaroxaban, dabigatran, and clopidogrel plus aspirin comparators. CONFLICT OF INTEREST: Study was funded by Pfizer Inc. and Bristol Myers-Squibb. KO, RS, SAK and AAA received salaries from their respective employers, but did not receive direct financial compensation for participation in or authorship of this study.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Idoso , Anticoagulantes/efeitos adversos , Anticoagulantes/economia , Fibrilação Atrial/complicações , Fibrilação Atrial/economia , Análise Custo-Benefício , Embolia/etiologia , Embolia/prevenção & controle , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/economia , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Cadeias de Markov , Pirazóis/efeitos adversos , Pirazóis/economia , Piridonas/efeitos adversos , Piridonas/economia , Anos de Vida Ajustados por Qualidade de Vida , Arábia Saudita , Acidente Vascular Cerebral/economia , Acidente Vascular Cerebral/etiologia , Vitamina K/antagonistas & inibidores
9.
Expert Opin Pharmacother ; 20(14): 1755-1765, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31264486

RESUMO

Introduction: Antiseizure drugs (ASDs) play a central and crucial role in the treatment of epilepsy patients, as the majority require anticonvulsant treatment for an extended period of time. Since up to 30% of patients are refractory to medical treatment, new therapeutic options are necessary. Perampanel (PER) and brivaracetam (BRV) are the latest approved ASDs that may be considered in a variety of epilepsy syndromes. PER has a distinct and selective mode of action on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and is licensed for use in focal and generalized epilepsies. BRV is a derivative of levetiracetam but exhibits a 20-fold higher affinity and a faster brain entry time as a synaptic vesicle glycoprotein 2A (SV2A) ligand. Areas covered: This article reviews the advances in the epileptic treatment and provides a comparison of PER and BRV. Both drugs have shown comparable results in randomized controlled trials, and both are well tolerated. Expert opinion: PER and BRV have the potential to perform as important, broad-spectrum ASDs with significant market shares. BRV's intravenous formulation and fast penetration into the brain and PER's unique mode of action will result in the more frequent use of both drugs in status epilepticus.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Piridonas/uso terapêutico , Pirrolidinonas/uso terapêutico , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/farmacocinética , Ensaios Clínicos como Assunto , Epilepsia/patologia , Meia-Vida , Humanos , Piridonas/efeitos adversos , Piridonas/farmacocinética , Pirrolidinonas/efeitos adversos , Pirrolidinonas/farmacocinética , Receptores de AMPA/química , Receptores de AMPA/metabolismo , Estado Epiléptico/tratamento farmacológico , Resultado do Tratamento
10.
BMJ Case Rep ; 12(6)2019 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-31256051

RESUMO

Direct oral anticoagulants (DOACs)-dabigatran, rivaroxaban, apixaban and edoxaban-are changing the landscape of clinical practice for patients requiring short and long-term anticoagulation. We report a patient with no history of kidney disease developing acute interstitial nephritis (AIN) after starting a DOAC, apixaban. To date, this is the first biopsy proven case of apixaban-induced AIN.


Assuntos
Anticoagulantes/efeitos adversos , Inibidores do Fator Xa/efeitos adversos , Nefrite Intersticial/induzido quimicamente , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Doença Aguda , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/tratamento farmacológico , Lesão Renal Aguda/patologia , Idoso , Biópsia , Glucocorticoides/uso terapêutico , Humanos , Rim/patologia , Masculino , Nefrite Intersticial/tratamento farmacológico , Nefrite Intersticial/patologia , Prednisolona/uso terapêutico
11.
N Engl J Med ; 381(7): 626-636, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31166680

RESUMO

BACKGROUND: Patients who have unresectable or metastatic melanoma with a BRAF V600E or V600K mutation have prolonged progression-free survival and overall survival when receiving treatment with BRAF inhibitors plus MEK inhibitors. However, long-term clinical outcomes in these patients remain undefined. To determine 5-year survival rates and clinical characteristics of the patients with durable benefit, we sought to review long-term data from randomized trials of combination therapy with BRAF and MEK inhibitors. METHODS: We analyzed pooled extended-survival data from two trials involving previously untreated patients who had received BRAF inhibitor dabrafenib (at a dose of 150 mg twice daily) plus MEK inhibitor trametinib (2 mg once daily) in the COMBI-d and COMBI-v trials. The median duration of follow-up was 22 months (range, 0 to 76). The primary end points in the COMBI-d and COMBI-v trials were progression-free survival and overall survival, respectively. RESULTS: A total of 563 patients were randomly assigned to receive dabrafenib plus trametinib (211 in the COMBI-d trial and 352 in the COMBI-v trial). The progression-free survival rates were 21% (95% confidence interval [CI], 17 to 24) at 4 years and 19% (95% CI, 15 to 22) at 5 years. The overall survival rates were 37% (95% CI, 33 to 42) at 4 years and 34% (95% CI, 30 to 38) at 5 years. In multivariate analysis, several baseline factors (e.g., performance status, age, sex, number of organ sites with metastasis, and lactate dehydrogenase level) were significantly associated with both progression-free survival and overall survival. A complete response occurred in 109 patients (19%) and was associated with an improved long-term outcome, with an overall survival rate of 71% (95% CI, 62 to 79) at 5 years. CONCLUSIONS: First-line treatment with dabrafenib plus trametinib led to long-term benefit in approximately one third of the patients who had unresectable or metastatic melanoma with a BRAF V600E or V600K mutation. (Funded by GlaxoSmithKline and Novartis; COMBI-d ClinicalTrials.gov number, NCT01584648; COMBI-v ClinicalTrials.gov number, NCT01597908.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imidazóis/administração & dosagem , Melanoma/tratamento farmacológico , Oximas/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Piridonas/administração & dosagem , Pirimidinonas/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Seguimentos , Humanos , Imidazóis/efeitos adversos , MAP Quinase Quinase Quinases/antagonistas & inibidores , Masculino , Melanoma/genética , Melanoma/mortalidade , Melanoma/secundário , Pessoa de Meia-Idade , Mutação , Oximas/efeitos adversos , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genética , Piridonas/efeitos adversos , Pirimidinonas/efeitos adversos , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Taxa de Sobrevida , Adulto Jovem
12.
Crit Care Nurse ; 39(3): e1-e8, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31154337

RESUMO

Intracerebral hemorrhage is a major source of morbidity and mortality, accounting for 10% of all strokes. Oral anticoagulation therapy, while necessary to prevent thromboembolic complications, increases the risk of intracerebral hemorrhage and can potentially worsen bleeding in cases of acute hemorrhage. Before the introduction of direct oral anticoagulant agents in 2010, warfarin was the only option for oral anticoagulation. These new agents have an improved safety profile compared with warfarin but require different reversal strategies. Anticoagulation reversal in the setting of acute intracerebral hemorrhage is an evolving field. This article covers the most common direct oral anticoagulant medications, various available anticoagulant reversal strategies, and the latest guidelines for anticoagulation reversal in patients with acute intracranial hemorrhage.


Assuntos
Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Hemorragias Intracranianas/induzido quimicamente , Tromboembolia/prevenção & controle , Administração Oral , Anticoagulantes/farmacocinética , Antitrombinas/administração & dosagem , Antitrombinas/efeitos adversos , Benzamidas/administração & dosagem , Benzamidas/efeitos adversos , Dabigatrana/administração & dosagem , Dabigatrana/efeitos adversos , Humanos , Hemorragias Intracranianas/prevenção & controle , Guias de Prática Clínica como Assunto , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Medição de Risco , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Resultado do Tratamento
13.
J Dermatol ; 46(8): 716-719, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31180164

RESUMO

Pyrexia is the most common adverse event in patients with melanoma or other solid organ malignancies that are treated with the combination of dabrafenib and trametinib (combi-DT). Given the expanded indication for combi-DT, management of pyrexia is a high priority. No previous case series has revealed which blood markers reflect the course of pyrexia and there is no consensus on the management strategy for pyrexia. The current case series study describes the utility of neutrophil count (NC), neutrophil ratio (NR) and C-reactive protein (CRP) in 11 patients with metastatic melanoma and BRAF V600 mutations who experienced pyrexia during combi-DT in our department. We also described the clinical course of pyrexia episodes that were managed with the concomitant use of oral prednisolone and immediate withdrawal of combi-DT. Consequently, the analysis of 37 pyrexia episodes in 11 patients showed that the differences in NC, NR and CRP at the onset of pyrexia were significantly different from those at pyretolysis (P = 0.01, 0.006 and 0.03, respectively). Additionally, in the 24 pyrexia episodes treated with the concomitant use of oral prednisolone and the immediate withdrawal of combi-DT, the mean duration of pyrexia and the mean time to restart combi-DT were 3 and 6 days, respectively. Therefore, the blood markers that reflect the course of pyrexia during combi-DT may be helpful for the appropriate management of pyrexia; also, our management strategy for pyrexia successfully reduced the duration of pyrexia and did not require a long-term drug holiday. Further large-scale studies are required to verify our results.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Proteína C-Reativa/análise , Febre/diagnóstico , Imidazóis/efeitos adversos , Neutrófilos , Oximas/efeitos adversos , Piridonas/efeitos adversos , Pirimidinonas/efeitos adversos , Administração Oral , Adulto , Idoso , Biomarcadores/sangue , Estudos de Viabilidade , Feminino , Febre/sangue , Febre/induzido quimicamente , Febre/tratamento farmacológico , Humanos , Contagem de Leucócitos , Masculino , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
14.
Gynecol Oncol ; 154(1): 95-101, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31118140

RESUMO

BACKGROUND: Improved treatment for advanced cervical cancer is needed; currently, treatment options include combined chemotherapy and bevacizumab or pembrolizumab monotherapy for PD-L1 positive disease. PIK3CA and KRAS mutations have been reported in cervical cancers; this study therefore tested dual inhibition of PI3K and RAS signaling by combining the MEK inhibitor trametinib and the AKT inhibitor GSK2141795 in recurrent cervical cancer. METHODS: This was an investigator-initiated phase II study combining trametinib and GSK2141795 in patients with recurrent cervical cancer. Primary endpoint was best tumor response; secondary endpoints included progression free survival, overall survival, and safety assessment. Translational objectives included characterization of molecular alterations in PI3K and RAS signaling pathway genes. RESULTS: Planned accrual was 35 patients; 14 patients were enrolled and received at least one dose of study drug before the study was terminated due to discontinuation of GSK2141795 development. There were no confirmed responses; 1 patient had an unconfirmed PR, 8 had stable disease, 3 had progression as best response, and 2 were unevaluable. Toxicities were mostly grade 1 and 2, although 57% of patients experienced grade 3/4 adverse events and 50% patients required a dose reduction. CONCLUSIONS: The combination of trametinib and GSK2141795 was feasible but required dose holds and modifications for adverse events; however, anti-cancer activity was minimal, even in patients with PI3K or RAS pathway alterations. Although the study was terminated early after GSK2141795 development was halted, the findings in these 14 patients do not support further development of this combination in cervical cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias do Colo do Útero/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Diaminas/administração & dosagem , Diaminas/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , MAP Quinase Quinase Quinases/antagonistas & inibidores , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/enzimologia , Intervalo Livre de Progressão , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Pirimidinonas/administração & dosagem , Pirimidinonas/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Neoplasias do Colo do Útero/enzimologia
15.
Lancet Haematol ; 6(7): e359-e365, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31133411

RESUMO

BACKGROUND: Because studies of direct oral anticoagulants in patients with venous thromboembolism and non-valvular atrial fibrillation have had minimal representation of morbidly obese patients (ie, body-mass index [BMI] ≥40 kg/m2), their efficacy and safety in this population are unclear. We investigated whether apixaban and rivaroxaban are as effective and safe as warfarin in morbidly obese patients. METHODS: We did a single-centre, retrospective analysis of chart data for all adult patients aged at least 18 years at Montefiore Medical Center (Bronx, NY, USA) with a BMI of at least 40 kg/m2 who were prescribed apixaban, rivaroxaban, or warfarin for either venous thromboembolism or atrial fibrillation between March 1, 2013, and March 1, 2017. Patients who had both venous thromboembolism and atrial fibrillation were excluded, as were patients with indications other than atrial fibrillation and venous thromboembolism. Outcomes of recurrent venous thromboembolism, stroke, and bleeding were measured from the first prescription date to the earliest of a thrombotic event, medication discontinuation, death, or end of study on June 30, 2017. Analyses were stratified by anticoagulation indication and adjusted for comorbidities, CHA2DS2-VASc score, and age where appropriate. Outcome rates were compared using Pearson's χ2 or Fisher's exact test. Time-to-event analyses accounting for length of follow-up were used to compare risks of outcomes. FINDINGS: We obtained data for 795 patients: 150 prescribed apixaban, 326 rivaroxaban, and 319 warfarin. In 366 patients prescribed an anticoagulant for venous thromboembolism, the incidence of recurrent venous thromboembolism was similar between the apixaban, rivaroxaban, and warfarin cohorts (1/47 [2·1%, 95% CI 0·0-6·3], 3/152 [2·0%, 0·0-4·2], and 2/167 [1·2%, 0·0-2·9], respectively; p=0·74). Incidence of major bleeding in this patient group was also similar between the treatment cohorts (1/47 patients on apixaban [2·1%, 95% CI 0·0-6·3], 2/152 on rivaroxaban [1·3%, 0·0-3·1], and 4/167 on warfarin [2·4%, 0·1-4·7]; p=0·77). In 429 patients prescribed an anticoagulant for atrial fibrillation, incidence of stroke was similar between the treatment cohorts (1/103 patients on apixaban [1·0%, 95% CI 0·0-2·9], 4/174 on rivaroxaban [2·3%, 0·1-4·5], and 2/152 on warfarin [1·3%, 0·0-3·1], p=0·71). In this patient group, major bleeding occurred in 3/103 patients on apixaban (2·9%, 95% CI 0·0-6·2), 5/174 on rivaroxaban (2·9%, 0·4-5·4), and 12/152 on warfarin (7·9%, 3·6-12·2); p=0·063. Time-to-event analyses showed that risk of all outcomes in patients with venous thromboembolism, and stroke and composite bleeding in patients with atrial fibrillation, were similar between the anticoagulant cohorts. INTERPRETATION: Our retrospective study provides further evidence of similar efficacy and safety between the direct oral anticoagulants apixaban and rivaroxaban, and warfarin in morbidly obese patients with atrial fibrillation and venous thromboembolism. These data, if confirmed in prospective studies, might enable patients with a BMI of at least 40 kg/m2 to benefit from more convenient, and possibly safer, anticoagulants. FUNDING: None.


Assuntos
Anticoagulantes/uso terapêutico , Inibidores do Fator Xa/uso terapêutico , Obesidade Mórbida/tratamento farmacológico , Varfarina/uso terapêutico , Adulto , Idoso , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Índice de Massa Corporal , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/epidemiologia , Hemorragia/etiologia , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/patologia , Modelos de Riscos Proporcionais , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Piridonas/efeitos adversos , Piridonas/uso terapêutico , Recidiva , Estudos Retrospectivos , Rivaroxabana/efeitos adversos , Rivaroxabana/uso terapêutico , Tromboembolia Venosa/complicações , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/epidemiologia , Varfarina/efeitos adversos
16.
BMC Pulm Med ; 19(1): 78, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30975118

RESUMO

BACKGROUND: Current clinical practice guidelines for idiopathic pulmonary fibrosis (IPF) conditionally recommend use of pirfenidone and nintedanib. However, an optimal treatment sequence has not been established, and the data of treatment sequence from pirfenidone to nintedanib are limited. This study aimed to evaluate safety, tolerability and efficacy of nintedanib switched from pirfenidone in patients with IPF. METHODS: Thirty consecutive IPF cases, which discontinued pirfenidone because of a decline in forced vital capacity (FVC) or intolerable adverse event (AE), and newly started nintedanib (150 mg twice daily) from September 2015 to August 2017 (switch-group) were retrospectively reviewed. Subsequently, we compared the characteristics, treatment status, and AEs between the switch-group and other 64 IPF patients newly started nintedanib during the same period without any prior anti-fibrotic treatment (pirfenidone-naïve group). RESULTS: In the switch group, median age, body weight, body mass index (BMI), and %FVC were 72 years old, 54.9 kg, 21.0 kg/m2, and 52.9%, respectively. Most common AE of nintedanib was aspartate aminotransferase/alanine aminotransferase elevation (71.9%), followed by anorexia (46.7%) and diarrhea (46.7%); whereas, anorexia (63.3%) and ≥ 5% weight loss from baseline (56.7%) were common during pirfenidone administration. Sixteen patients (53.3%) discontinued nintedanib within 6 months (early termination). Multivariate logistic regression analysis revealed a significant association between low BMI and early nintedanib termination in the switch-group (p = 0.0239). Nintedanib suppressed FVC decline as compared with that during administration period of pirfenidone in 70% of the patients who could undergo lung function before and after switching to nintedanib. The incidence of early termination of nintedanib was higher in the switch-group than in the pirfenidone-naïve group, whereas body-weight, BMI, absolute FVC values, and %FVC were significantly lower in the switch-group (just before nintedanib initiation) than in the pirfenidone-naïve group. Nintedanib-induced anorexia was more frequent and severer in the switch-group than in the pirfenidone-naïve group, but no significant differences were observed in terms of other AEs. CONCLUSIONS: A high incidence of early termination of nintedanib was noted when patients were switched from pirfenidone. Anorexia and weight loss during prior pirfenidone administration may increase the rate of the early termination of subsequent nintedanib treatment.


Assuntos
Anorexia/induzido quimicamente , Fibrose Pulmonar Idiopática/tratamento farmacológico , Indóis/administração & dosagem , Piridonas/efeitos adversos , Idoso , Feminino , Humanos , Fibrose Pulmonar Idiopática/fisiopatologia , Indóis/efeitos adversos , Japão , Modelos Logísticos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Resultado do Tratamento , Capacidade Vital/efeitos dos fármacos , Perda de Peso/efeitos dos fármacos
17.
PLoS One ; 14(4): e0214884, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30939167

RESUMO

Panniculitis and vitiligo-like lesions have been recently identified as rare cutaneous side effects of the combination of BRAF and MEK inhibitors, a standard of care in metastatic and locally advanced BRAF V600 mutated melanoma. An immune-mediated mechanism has been advocated in the pathogenesis of these skin lesions. Herein we retrospectively reviewed our institutional experience with the aim to explore the association between the occurrence of panniculitis and vitiligo-like lesions during combination therapy with dabrafenib (D) and trametinib (T) and outcome of advanced melanoma patients. Among 52 consecutive BRAF V600 mutated melanoma patients submitted to DT in our center, 12 (23%) developed immune related skin lesions (IRSLs): 8 panniculitis and 4 vitiligo. Patients with IRSLs diagnosis obtained a better disease response (83% versus 25%) (p = 0.001) than their counterpart and had a longer progression free survival and overall survival. The association of IRSLs and lower risk of disease progression (HR 0.19; CI 95% 0.04-0.90; p = 0.043) was confirmed after adjusting for major prognostic factors in multivariate analysis. IRSLs might represent an easy predictive surrogate marker for treatment response and favourable outcome in melanoma patients submitted to DT combination therapy.


Assuntos
Antineoplásicos/efeitos adversos , Melanoma/tratamento farmacológico , Paniculite/induzido quimicamente , Inibidores de Proteínas Quinases/efeitos adversos , Neoplasias Cutâneas/tratamento farmacológico , Vitiligo/induzido quimicamente , Adulto , Idoso , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Feminino , Humanos , Imidazóis/administração & dosagem , Imidazóis/efeitos adversos , Estimativa de Kaplan-Meier , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Melanoma/genética , Melanoma/mortalidade , Pessoa de Meia-Idade , Mutação , Oximas/administração & dosagem , Oximas/efeitos adversos , Paniculite/patologia , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/administração & dosagem , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genética , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Pirimidinonas/administração & dosagem , Pirimidinonas/efeitos adversos , Estudos Retrospectivos , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/mortalidade , Resultado do Tratamento , Vitiligo/patologia
18.
Arch Cardiovasc Dis ; 112(6-7): 400-409, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31014991

RESUMO

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs), including apixaban, are recommended for prevention of stroke and systemic embolism in non-valvular atrial fibrillation (NVAF). AIMS: To describe the characteristics of patients starting anticoagulant treatment, identify the characteristics associated with apixaban prescription, and describe apixaban use in France. METHODS: This was a non-interventional multicentre French study. Patients with NVAF (aged≥18 years) with anticoagulant treatment started in the preceding 3 months were evaluated in four groups (NOAC [apixaban, dabigatran or rivaroxaban] or vitamin K antagonist [VKA]). RESULTS: Data from 2027 patients were eligible for analysis. Mean age was 73.0±11.2 years, 56.6% were men and 80.2% were anticoagulant naïve. Stage≥4 chronic kidney disease was present in 2.2% of patients prescribed apixaban, none of those prescribed dabigatran or rivaroxaban, and 16.8% of those prescribed VKAs. The median CHA2DS2-VASc score was 3 for all three NOACs and 4 for VKAs; the median HAS-BLED score was≥3 for 2.5-5.9% of patients prescribed NOACs and 12.0% of those prescribed VKAs. Apixaban was more likely to be prescribed than other NOACs in older patients with higher bleeding risk and decreased renal function, and VKAs in patients with lower bleeding risk and better renal function. Patients received a reduced dose (5mg/day; 30.4% patients) or a full dose (10mg/day; 69.6% patients) of apixaban. Only 79.3% of patients prescribed apixaban had doses consistent with the summary of product characteristics; underdosing was more frequent than overdosing. Off-label use of apixaban was observed, mainly in elderly patients, despite normal renal function and weight. CONCLUSIONS: Initiation of apixaban versus NOACs was more common among patients with increased age, higher bleeding risk and decreased renal function, whereas initiation of apixaban versus VKAs was more common among patients with lower bleeding risk and better renal function.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Embolia/prevenção & controle , Inibidores do Fator Xa/administração & dosagem , Padrões de Prática Médica/tendências , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Estudos Transversais , Uso de Medicamentos/tendências , Embolia/diagnóstico , Embolia/epidemiologia , Inibidores do Fator Xa/efeitos adversos , Feminino , França/epidemiologia , Fidelidade a Diretrizes/tendências , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Uso Off-Label , Guias de Prática Clínica como Assunto , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
19.
Yakugaku Zasshi ; 139(3): 461-467, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-30828024

RESUMO

Direct oral anticoagulants (DOACs) are safe and efficacious when compared to warfarin for patients with venous thromboembolism (VTE). However, bleeding is a major side effect of anticoagulant therapy in VTE patients. Discontinuation of the DOACs associated to adverse events such as bleeding. The HAS-BLED score predicts warfarin-associated hemorrhage. However, little is known about risk factors for DOAC-associated minor bleeding in VTE patients. We aimed to identify risk factors for minor bleeding in VTE patients that were treated with edoxaban, rivaroxaban, or apixaban. We retrospectively evaluated the data of 212 VTE patients who received treatment with a DOAC. The study endpoint was defined as the occurrence of minor bleeding. Logistic regression analysis was used to determine risk factors that were significantly associated with minor bleeding. A total of 36 (17.0%) patients experienced minor bleeding, with rates of 15.7%, 0%, and 21.3% for edoxaban, rivaroxaban, and apixaban, respectively. In the multivariate analysis, bleeding history or predisposition [odds ratio (OR) 6.083, 95% confidence interval (CI) 2.131-17.364, p=0.001] and cancer (OR 6.397, 95% CI 2.858-14.317, p<0.001) were significantly associated with minor bleeding. Bleeding history or predisposition and cancer were the most important risk factors for DOAC-induced minor bleeding in VTE patients in this study. To continue anticoagulant therapy of the DOACs, further management systems by minor bleeding risk factors for patients with VTE will be required.


Assuntos
Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/etiologia , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Tiazóis/administração & dosagem , Tiazóis/efeitos adversos , Tromboembolia Venosa/tratamento farmacológico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença
20.
N Engl J Med ; 380(16): 1509-1524, 2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-30883055

RESUMO

BACKGROUND: Appropriate antithrombotic regimens for patients with atrial fibrillation who have an acute coronary syndrome or have undergone percutaneous coronary intervention (PCI) are unclear. METHODS: In an international trial with a two-by-two factorial design, we randomly assigned patients with atrial fibrillation who had an acute coronary syndrome or had undergone PCI and were planning to take a P2Y12 inhibitor to receive apixaban or a vitamin K antagonist and to receive aspirin or matching placebo for 6 months. The primary outcome was major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and a composite of ischemic events. RESULTS: Enrollment included 4614 patients from 33 countries. There were no significant interactions between the two randomization factors on the primary or secondary outcomes. Major or clinically relevant nonmajor bleeding was noted in 10.5% of the patients receiving apixaban, as compared with 14.7% of those receiving a vitamin K antagonist (hazard ratio, 0.69; 95% confidence interval [CI], 0.58 to 0.81; P<0.001 for both noninferiority and superiority), and in 16.1% of the patients receiving aspirin, as compared with 9.0% of those receiving placebo (hazard ratio, 1.89; 95% CI, 1.59 to 2.24; P<0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the vitamin K antagonist group (23.5% vs. 27.4%; hazard ratio, 0.83; 95% CI, 0.74 to 0.93; P = 0.002) and a similar incidence of ischemic events. Patients in the aspirin group had an incidence of death or hospitalization and of ischemic events that was similar to that in the placebo group. CONCLUSIONS: In patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, an antithrombotic regimen that included apixaban, without aspirin, resulted in less bleeding and fewer hospitalizations without significant differences in the incidence of ischemic events than regimens that included a vitamin K antagonist, aspirin, or both. (Funded by Bristol-Myers Squibb and Pfizer; AUGUSTUS ClinicalTrials.gov number, NCT02415400.).


Assuntos
Síndrome Coronariana Aguda/complicações , Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Intervenção Coronária Percutânea , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Vitamina K/antagonistas & inibidores , Síndrome Coronariana Aguda/terapia , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Aspirina/efeitos adversos , Fibrilação Atrial/complicações , Método Duplo-Cego , Quimioterapia Combinada , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Pirazóis/efeitos adversos , Piridonas/efeitos adversos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA