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1.
Cardiovasc Diabetol ; 20(1): 176, 2021 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-34481513

RESUMO

BACKGROUND: It remains uncertain if prior use of oral anticoagulants (OACs) in COVID-19 outpatients with multimorbidity impacts prognosis, especially if cardiometabolic diseases are present. Clinical outcomes 30-days after COVID-19 diagnosis were compared between outpatients with cardiometabolic disease receiving vitamin K antagonist (VKA) or direct-acting OAC (DOAC) therapy at time of COVID-19 diagnosis. METHODS: A study was conducted using TriNetX, a global federated health research network. Adult outpatients with cardiometabolic disease (i.e. diabetes mellitus and any disease of the circulatory system) treated with VKAs or DOACs at time of COVID-19 diagnosis between 20-Jan-2020 and 15-Feb-2021 were included. Propensity score matching (PSM) was used to balance cohorts receiving VKAs and DOACs. The primary outcomes were all-cause mortality, intensive care unit (ICU) admission/mechanical ventilation (MV) necessity, intracranial haemorrhage (ICH)/gastrointestinal bleeding, and the composite of any arterial or venous thrombotic event(s) at 30-days after COVID-19 diagnosis. RESULTS: 2275 patients were included. After PSM, 1270 patients remained in the study (635 on VKAs; 635 on DOACs). VKA-treated patients had similar risks and 30-day event-free survival than patients on DOACs regarding all-cause mortality, ICU admission/MV necessity, and ICH/gastrointestinal bleeding. The risk of any arterial or venous thrombotic event was 43% higher in the VKA cohort (hazard ratio 1.43, 95% confidence interval 1.03-1.98; Log-Rank test p = 0.029). CONCLUSION: In COVID-19 outpatients with cardiometabolic diseases, prior use of DOAC therapy compared to VKA therapy at the time of COVID-19 diagnosis demonstrated lower risk of arterial or venous thrombotic outcomes, without increasing the risk of bleeding.


Assuntos
Assistência Ambulatorial/métodos , Anticoagulantes/administração & dosagem , COVID-19/tratamento farmacológico , Cardiopatias/tratamento farmacológico , Doenças Metabólicas/tratamento farmacológico , Vitamina K/antagonistas & inibidores , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , COVID-19/diagnóstico , COVID-19/mortalidade , Inibidores do Fator Xa/administração & dosagem , Feminino , Seguimentos , Cardiopatias/diagnóstico , Cardiopatias/mortalidade , Hemorragia/induzido quimicamente , Hemorragia/mortalidade , Humanos , Unidades de Terapia Intensiva/tendências , Masculino , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/mortalidade , Pessoa de Meia-Idade , Mortalidade/tendências , Resultado do Tratamento
2.
Isr Med Assoc J ; 23(9): 595-600, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34472236

RESUMO

BACKGROUND: Limited data exist regarding the safety of ultrasound-guided femoral nerve blockade (US-FNB) in patients with hip fractures treated with anti-Xa direct oral anticoagulants (DOAC). OBJECTIVES: To compare the safety outcomes of US-FNB to conventional analgesia in patients with hip fractures treated with anti-Xa DOAC. METHODS: This observational exploratory prospective study included 69 patients who presented to our emergency department (ED) in 3 years with hip fracture and who were treated with apixaban or rivaroxaban. Patients received either a US-FNB (n=19) or conventional analgesics (n=50) based on their preference and, and the presence of a trained ED physician qualified in performing US-FNB. Patients were observed for major bleeding events during and 30 days after hospitalization. The degree of preoperative pain and opioid use were also observed. RESULTS: We found no significant difference in the number of major bleeding events between groups (47.4% vs. 54.0%, P = 0.84). Degree of pain measured 3 and 12 hours after presentation was found to be lower in the US-FNB group (median visual analog scale of pain improvement from baseline of -5 vs. -3 (P = 0.002) and -5 vs.-4 (P = 0.023), respectively. Opioid administration pre-surgery was found to be more than three times more common in the conventional analgesia group (26.3% vs.80%, P < 0.0001). CONCLUSIONS: Regarding patients treated with Anti-Xa DOAC, US-FNB was not associated with an increase in major bleeding events compared to conventional analgesia, although it was an effective means of pain alleviation. Larger scale randomized controlled trials are required to determine long-term safety and efficacy.


Assuntos
Inibidores do Fator Xa/administração & dosagem , Fraturas do Quadril/cirurgia , Bloqueio Nervoso/métodos , Dor Pós-Operatória/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Analgésicos/administração & dosagem , Analgésicos Opioides/administração & dosagem , Estudos de Coortes , Serviço Hospitalar de Emergência , Inibidores do Fator Xa/efeitos adversos , Feminino , Nervo Femoral/diagnóstico por imagem , Hemorragia/epidemiologia , Hemorragia/etiologia , Humanos , Masculino , Bloqueio Nervoso/efeitos adversos , Medição da Dor , Projetos Piloto , Estudos Prospectivos , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Ultrassonografia de Intervenção
3.
J Am Coll Cardiol ; 78(1): 14-23, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34210409

RESUMO

BACKGROUND: The combination of 2.5 mg rivaroxaban twice daily and 100 mg aspirin once daily compared with 100 mg aspirin once daily reduces major adverse cardiovascular (CV) events in patients with chronic coronary artery disease (CAD) or peripheral artery disease (PAD). OBJECTIVES: The aim of this work was to report the effects of the combination on overall and cause-specific mortality. METHODS: The COMPASS trial enrolled 27,395 patients of whom 18,278 were randomized to the combination (n = 9,152) or aspirin alone (n = 9,126). Deaths were adjudicated by a committee blinded to treatment allocation. Previously identified high-risk baseline features were polyvascular disease, chronic kidney disease, mild or moderate heart failure, and diabetes. RESULTS: During a median of 23 months of follow-up (maximum 47 months), 313 patients (3.4%) allocated to the combination and 378 patients (4.1%) allocated to aspirin alone died (hazard ratio [HR]: 0.82; 95% confidence interval [CI]: 0.71-0.96; P = 0.01). Compared with aspirin, the combination reduced CV death (160 [1.7%] vs 203 [2.2%]; HR: 0.78; 95% CI: 0.64-0.96; P = 0.02) but not non-CV death. There were fewer deaths following MI, stroke, and CV procedures, as well as fewer sudden cardiac, other, and unknown causes of CV deaths and coronary heart disease deaths. Patients with 0, 1, 2, and 3 or 4 high-risk features at baseline had 4.2, 4.8, 25.0, and 53.9 fewer deaths, respectively, per 1000 patients treated for 30 months. CONCLUSIONS: The combination of rivaroxaban and aspirin compared with aspirin reduced overall and CV mortality with consistent reductions in cause specific CV mortality in patients with chronic CAD or PAD. The absolute mortality benefits are greater with increasing baseline risk. (Cardiovascular Outcomes for People Using Anticoagulant Strategies [COMPASS]; NCT01776424).


Assuntos
Aspirina , Doença da Artéria Coronariana , Doença Arterial Periférica , Rivaroxabana , Idoso , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/mortalidade , Diabetes Mellitus/epidemiologia , Quimioterapia Combinada , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Feminino , Insuficiência Cardíaca/epidemiologia , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/tratamento farmacológico , Doença Arterial Periférica/mortalidade , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Medição de Risco , Fatores de Risco , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Índice de Gravidade de Doença
4.
Pan Afr Med J ; 38: 333, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34285756

RESUMO

We reported an anaphylactic reaction following ingestion of rivaroxaban in a 48-years-old male, who was recently discharged from the hospital as a case of deep vein thrombosis. At home, the patient developed a diffuse itchy skin rash, shortness of breath, and vomiting 30 minutes after rivaroxaban ingestion. Emergency Medical Service found that the patient had severe dyspnea, low blood pressure, and decreased blood oxygen saturation. The patient was given oxygen, intramuscular epinephrine, intravenous hydrocortisone, diphenhydramine, salbutamol nebulizer, and was immediately transferred to the emergency department of Hamad General Hospital. Subcutaneous enoxaparin was initiated, while hydrocortisone and salbutamol nebulizer continued. On the next day, his vital signs had stabilized, and intravenous hydrocortisone was switched to prednisolone tablets, and salbutamol nebulizer was switched to budesonide/salmeterol inhaler, whereas enoxaparin was overlapped with warfarin. After achieving the target international normalized ratio (INR), enoxaparin was discontinued and the patient was discharged with significant clinical and laboratory improvement.


Assuntos
Anafilaxia/induzido quimicamente , Inibidores do Fator Xa/efeitos adversos , Rivaroxabana/efeitos adversos , Anafilaxia/terapia , Anticoagulantes/administração & dosagem , Broncodilatadores/administração & dosagem , Inibidores do Fator Xa/administração & dosagem , Glucocorticoides/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Rivaroxabana/administração & dosagem , Trombose Venosa/tratamento farmacológico
5.
Am J Cardiol ; 152: 69-77, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34162485

RESUMO

Low dose direct acting oral anticoagulants (LDDOACS) were approved for elderly atrial Fibrillation (AF) patients with limited information. A retrospective analysis collecting baseline characteristics and outcomes in AF patients ≥ 80 prescribed LDDOAC or warfarin (W), from a multidisciplinary practice between 1/1/11 (First LDDOAC available) and 5/31/17 was conducted. From 9660 AF patients, 514 ≥ 80 received a LDDOAC and 422 W. A multivariable comparison found LDDOAC patients were older (p <0.001), had lower creatinine clearance (CrCl) (p = 0.006), used more anti-platelet drugs (p <0.001), and more often had new onset AF verses those prescribed W (p <0.001). There were no clinically significant differences among those patients receiving Dabigatran 75 mgs BID (D), Rivaroxaban 15mgs (R) or Apixaban 2.5mgs BID (A). Forty-eight and 50% of the patients remained on their LDDOAC or W for the observation period (p = 0.55). Stroke/systemic embolism (SSE) and CNS bleeds were 1.16 vs 2.22%/yr., (p = 0.143) and 1.46 vs 0.93%/yr., (p = 0.24). Mortality and major bleeds were 6.26 vs 1.67%/yr., and 12.3vs 3.77%/yr. (p <0.001). SSE were 1.1%/yr for D, R, and A (p = 0.94). CNS bleeds were 2.2 for D, 1.7 for R and 0.8%/yr. for A: p = 0.53. Major bleeding was: 14.3 for D, 14.1 for R and 9.1%/yr. for A, p = 0.048 (with A < R, p = 0.01). Mortality was 5.5 for D, 4.2 for R and 9.5% for A, p = 0.031. In conclusion, half the patients remained on their assigned anti-coagulant. SSE and intracranial bleed rates were similar and low. Major bleeds and deaths were different between groups emphasizing the need for prospective randomized trials in this growing population with AF.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Inibidores do Fator Xa/administração & dosagem , Acidente Vascular Cerebral/prevenção & controle , Varfarina/uso terapêutico , Fatores Etários , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Dabigatrana/administração & dosagem , Dabigatrana/uso terapêutico , Embolia/etiologia , Embolia/prevenção & controle , Inibidores do Fator Xa/uso terapêutico , Feminino , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/epidemiologia , Masculino , Análise Multivariada , Inibidores da Agregação Plaquetária/uso terapêutico , Pirazóis/administração & dosagem , Pirazóis/uso terapêutico , Piridonas/administração & dosagem , Piridonas/uso terapêutico , Estudos Retrospectivos , Rivaroxabana/administração & dosagem , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/etiologia
6.
Expert Rev Clin Pharmacol ; 14(9): 1153-1163, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34058934

RESUMO

BACKGROUND: Rivaroxaban is an oral anticoagulant widely used for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). During long-term anticoagulant therapy, delayed or missed doses are common. This study aimed to explore appropriate remedial dosing regimens for non-adherent rivaroxaban-treated patients. METHODS: Monte Carlo simulation based on a previously established rivaroxaban population pharmacokinetic/pharmacodynamic (PK/PD) model for patients with NVAF was employed to design remedial dosing regimens. The proposed regimens were compared with remedial strategies in the European Heart Rhythm Association (EHRA) guide by assessing deviation time in terms of drug concentration, factor Xa activity, and prothrombin time. RESULTS: The proposed remedial dosing regimens were dependent on delay duration. The missed dose should be taken immediately when the delay does not exceed 6 h; a half dose is advisable when the delay is between 6 and 20 h. A missed dose should be skipped if less than 4 h remains before the next dose. The proposed regimens resulted in shorter deviation time than that of the EHRA guide. CONCLUSION: PK/PD modeling and simulation provide valid evidence on the remedial dosing regimen of rivaroxaban, which could help to minimize the risk of bleeding and thromboembolism.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Inibidores do Fator Xa/administração & dosagem , Modelos Biológicos , Rivaroxabana/administração & dosagem , Idoso , Fibrilação Atrial/complicações , Simulação por Computador , Relação Dose-Resposta a Droga , Inibidores do Fator Xa/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Adesão à Medicação , Pessoa de Meia-Idade , Método de Monte Carlo , Rivaroxabana/efeitos adversos , Tromboembolia/etiologia , Tromboembolia/prevenção & controle , Fatores de Tempo
7.
Medicine (Baltimore) ; 100(23): e26137, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34114997

RESUMO

RATIONALE: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with increased morbidity, especially stroke and heart failure. There is also increasing awareness that atrial fibrillation is a major cause of embolic events which in 75% of cases are complicated by cerebrovascular accidents. PATIENT CONCERNS: A 50-year-old woman with mitral bioprosthesis under warfarin for nonvalvular atrial fibrillation was referred to our Coronary Intensive Care Unit due to acute myocardial infarction without evidence of significant coronary artery stenosis. DIAGNOSES: Cardiovascular examination showed an irregular pulse and a grade II diastolic murmur was audible at the apical area. The patient underwent coronary angiography showing absence of obstructive coronary artery disease. We decided to replace Warfarin with direct oral anticoagulants as anticoagulant therapy. INTERVENTIONS: Transoesophageal echocardiography revealed a thrombus in left atrial appendage that was treated by replacing warfarin with an oral direct thrombin inhibitor. OUTCOMES: At 2-month follow-up, the therapy showed to be effective for thrombus resolution. LESSONS: Our case demonstrated how AF has high risk of thromboembolic complications, not only in terms of stroke but also of myocardial infarction and death.The use of direct oral anticoagulants in AF patients with bioprosthetic heart valves is still debated due to an unclear definition of "nonvalvular" AF.


Assuntos
Apêndice Atrial/diagnóstico por imagem , Fibrilação Atrial , Substituição de Medicamentos/métodos , Inibidores do Fator Xa/administração & dosagem , Trombose , Varfarina/uso terapêutico , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Bioprótese , Ecocardiografia Transesofagiana/métodos , Feminino , Próteses Valvulares Cardíacas , Humanos , Pessoa de Meia-Idade , Valva Mitral/cirurgia , Trombose/diagnóstico por imagem , Trombose/tratamento farmacológico , Trombose/fisiopatologia , Resultado do Tratamento
8.
Medicine (Baltimore) ; 100(23): e26272, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34115024

RESUMO

ABSTRACT: East Asians are reportedly at high risk of anticoagulant-related bleeding; therefore, some physicians prefer to prescribe low-dose direct oral anticoagulants (DOACs). Little is known about the therapeutic effectiveness and safety of off-label reduced-dose apixaban in East Asians with nonvalvular atrial fibrillation (AF). We aimed to investigate the effectiveness and safety of off-label reduced-dose apixaban in Taiwanese patients with nonvalvular AF.This retrospective cohort study enrolled 1073 patients with nonvalvular AF who took apixaban between July 2014 and October 2018 from 4 medical centers in southern Taiwan. The primary outcomes included thromboembolic events (stroke/transient ischemic attack or systemic embolism), major bleeding, and all-cause mortality.Among all patients, 826 (77%) patients were classified as the "per-label adequate-dose" treatment group (i.e., consistent with the Food and Drug Administration label recommendations) while 247 (23%) patients were the "off-label reduced-dose" treatment group. The mean follow-up period was 17.5 ±â€Š13 months. The "off-label reduced-dose" group did not have a lower major bleeding rate than the "per-label adequate-dose" group (4.8% vs 3.8%, adjusted hazard ratio [HR] 1.20, 95% confidence interval [CI] 0.69-2.09), but had a nonsignificantly higher incidence of thromboembolic events (4.23% vs 3.05%, adjusted HR: 1.29, 95% CI: 0.71-2.34).An off-label reduced-dose apixaban treatment strategy may not provide incremental benefits or safety for Taiwanese patients with nonvalvular AF.


Assuntos
Fibrilação Atrial , Hemorragia , Uso Off-Label/estatística & dados numéricos , Pirazóis , Piridonas , Tromboembolia , Anticoagulantes , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Hemorragia/diagnóstico , Hemorragia/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Taiwan/epidemiologia , Tromboembolia/epidemiologia , Tromboembolia/etiologia , Tromboembolia/prevenção & controle
9.
Isr Med Assoc J ; 23(6): 353-358, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34155848

RESUMO

BACKGROUND: Real-world information regarding the use of direct oral anticoagulants therapy and the outcome in patients with renal dysfunction is limited. OBJECTIVES: To evaluate the clinical characteristics and outcomes of patients with atrial fibrillation (AF) and severe renal dysfunction who are treated with apixaban. METHODS: A sub-analysis was conducted within a multicenter prospective cohort study. The study included consecutive eligible apixaban- or warfarin-treated patients with non-valvular AF and renal impairment (estimated glomerular filtration rate [eGFR] modification of diet in renal disease [MDRD] < 60 ml/min/BSA) were registered. All patients were prospectively followed for clinical events and over a mean period of 1 year. Our sub-analysis included the patients with 15 < eGFR MDRD < 30 ml/min/BSA. The primary outcomes at 1 year were recorded. They included mortality, stroke or systemic embolism, major bleeding, and myocardial infarction as well as their composite occurrence. RESULTS: The sub-analysis included 155 warfarin-treated patients and 97 apixaban-treated ones. All had 15 < eGFR MDRD < 30 ml/min/BSA. When comparing outcomes for propensity matched groups (n=76 per group) of patients treated by reduced dose apixaban or warfarin, the rates of the 1-year composite endpoint as well as mortality alone were higher among the warfarin group (30 [39.5%] vs. 14 [18.4%], P = 0.007 and 28 [36.8%] vs.12 [15.8%], P = 0.006), respectively. There was no significant difference in the rates of stroke, systemic embolism, or major bleeding. CONCLUSIONS: Apixaban might be a reasonable alternative to warfarin in patients with severe renal impairment.


Assuntos
Fibrilação Atrial , Hemorragia , Infarto do Miocárdio , Insuficiência Renal , Acidente Vascular Cerebral , Varfarina , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/mortalidade , Estudos de Coortes , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos/métodos , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Israel/epidemiologia , Testes de Função Renal/métodos , Testes de Função Renal/estatística & dados numéricos , Masculino , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Avaliação de Resultados em Cuidados de Saúde , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Insuficiência Renal/complicações , Insuficiência Renal/diagnóstico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Análise de Sobrevida , Varfarina/administração & dosagem , Varfarina/efeitos adversos
10.
Eur J Epidemiol ; 36(8): 793-812, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33993379

RESUMO

PURPOSE: To systematically review available evidence of indirect comparisons from RCTs and direct comparisons from observational studies regarding the comparative effectiveness and safety of DOACs in patients with AF. METHODS: Electronic databases including EMBASE, MEDLINE, and PUBMED were searched up to June 5th, 2020. Primary endpoints included effectiveness (stroke or systemic embolism [SE]) and safety (major bleeding) outcomes. Bucher methods and random-effects models were conducted for indirect and direct comparisons among DOACs, respectively. Ranking probability analyses and the number needed to treat for net effect (NNTnet) were applied. RESULTS: A total of 36 studies, involving 7 RCTs (n = 60,292 patients) and 29 observational studies (n = 1,164,821 patients), were included for analyses. Regarding the risk of stroke/SE, no significant differences were found from indirect comparisons of RCTs among the DOACs. For major bleeding, apixaban tended to be safer than rivaroxaban and dabigatran based on both direct and indirect comparisons (all p < 0.05; evidence quality: very low to moderate). Ranking probability analysis showed that apixaban had a high probability of being the best treatment in decreased risk of stroke/SE and major bleeding (80.30% and 91.30%, respectively). Likewise, apixaban was found to have the highest net clinical benefit (0.02, 95% CI: 0.014-0.029) and smallest NNTnet (48, 95% CI: 35-74). CONCLUSIONS: Apixaban appeared to have a favorable effectiveness-safety profile compared with the other DOACs in AF for stroke prevention, based on evidence from both direct and indirect comparisons. However, additional high-quality evidence is needed to support firm recommendations on clinical decision-making.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Hemorragia/prevenção & controle , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Humanos , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Resultado do Tratamento
12.
Neurologist ; 26(3): 108-111, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33942794

RESUMO

INTRODUCTION: The coronavirus disease 2019 (COVID-19) has been associated with a hypercoagulable state, increasing the risk for ischemic stroke. In select cases, patients are already on anticoagulation therapy. Such examples highlight the severity of COVID-19's hyperthrombotic state, and raise questions regarding optimal stroke prevention in these patients. CASE REPORT: An 84-year-ool male with past medical history of chronic obstructive pulmonary disease, hypertension, and paroxysmal atrial fibrillation was admitted for respiratory failure secondary to COVID-19 pneumonia. He was continued on his home apixaban 5 mg twice daily. On day 2 of admission, he developed a new aphasia, and right-sided facial droop. Computed tomography (CT) head was unrevealing. CT angiography did not show large vessel occlusion. CT perfusion demonstrated a left middle cerebral artery ischemic penumbra, without core. He was not eligible for thrombolysis or thrombectomy interventions. Later CT head confirmed L middle cerebral artery infarct. The patient's D-dimer was 1,184 ng/mL on day 1 of admission, and increased to 111,574 by day 4. His hypoxia worsened, requiring intubation and transfer to the ICU. He experienced further clinical decline and eventual demise. CONCLUSION: Ischemic stroke in anticoagulated patients with COVID-19 has been previously reported. Such cases emphasize the severity of the coronavirus virus associated hypercoagulable state. A majority of reported cases have occurred in patients continuing their ambulatory therapy. Overall, such cases are likely underreported. There are current trials comparing therapeutic versus prophylactic dose anticoagulation in patients with COVID-19. There are no studies specifically addressing anticoagulation agent failure in these patients. Further research is required this area to determine the optimal therapy for patients with COVID-19.


Assuntos
COVID-19/complicações , Inibidores do Fator Xa/administração & dosagem , AVC Isquêmico/etiologia , Idoso de 80 Anos ou mais , Fibrilação Atrial/tratamento farmacológico , Evolução Fatal , Humanos , Hipertensão/tratamento farmacológico , Masculino , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Pirazóis/administração & dosagem , Piridonas/administração & dosagem
13.
AAPS PharmSciTech ; 22(4): 147, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33948767

RESUMO

The present study was conducted to formulate ethosomal thermoreversible in situ gel of apixaban, an anticoagulant drug, for nasal delivery. Ethosomes were formed, of lecithin, cholesterol, and ethanol, by using thin-film hydration method. The prepared ethosomes were characterized by Zetasizer, transmission electron microscope, entrapment efficiency, and in vitro study. The selected ethosomal formula (API-ETHO2) was incorporated in gel using P407 and P188 as thermoreversible agents and carbopol 934 as mucoadhesive agent. Box-Behnken design was used to study the effect of independent variables (concentration of P407, P188, and carbopol 934) on gelation temperature, mucoadhesive strength, and in vitro cumulative percent drug released at 12h (response variables). The optimized formulation was subjected to compatibility study, ex vivo permeation, histopathological examination for the nasal mucosa, and in vivo study. API-ETHO2 was spherical with an average size of 145.1±12.3 nm, zeta potential of -20±4 mV, entrapment efficiency of 67.11%±3.26, and in vitro % release of 79.54%±4.1. All gel formulations exhibited an acceptable pH and drug content. The optimum gel offered 32.3°C, 1226.3 dyne/cm2, and 53.50% for gelation temperature, mucoadhesive strength, and in vitro percent released, respectively. Apixaban ethosomal in situ gel evolved higher ex vivo permeation (1.499±0.11 µg/cm2h) through the nasal mucosa than pure apixaban gel. Histopathological study assured that there is no necrosis or tearing of the nasal mucosa happened by ethosomal gel. The pharmacokinetic parameters in rabbit plasma showed that intranasal administration of optimized API-ethosomal in situ gel achieved higher Cmax and AUC0-∞ than unprocessed API nasal gel, nasal suspension, and oral suspension. The ethosomal thermoreversible nasal gel established its potential to improve nasal permeation and prolong anticoagulant effect of apixaban.


Assuntos
Géis/administração & dosagem , Géis/síntese química , Nanosferas/química , Mucosa Nasal/metabolismo , Pirazóis/administração & dosagem , Pirazóis/síntese química , Piridonas/administração & dosagem , Piridonas/síntese química , Administração Intranasal , Animais , Búfalos , Avaliação Pré-Clínica de Medicamentos/métodos , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/síntese química , Inibidores do Fator Xa/farmacocinética , Géis/farmacocinética , Nanosferas/administração & dosagem , Mucosa Nasal/efeitos dos fármacos , Pirazóis/farmacocinética , Piridonas/farmacocinética , Coelhos
15.
Mar Drugs ; 19(4)2021 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-33920475

RESUMO

dHG-5 (Mw 5.3 kD) is a depolymerized glycosaminoglycan from sea cucumber Holothuria fuscopunctata. As a selective inhibitor of intrinsic Xase (iXase), preclinical study showed it was a promising anticoagulant candidate without obvious bleeding risk. In this work, two bioanalytical methods based on the anti-iXase and activated partial thromboplastin time (APTT) prolongation activities were established and validated to determine dHG-5 concentrations in plasma and urine samples. After single subcutaneous administration of dHG-5 at 5, 9, and 16.2 mg/kg to rats, the time to peak concentration (Tmax) was at about 1 h, and the peak concentration (Cmax) was 2.70, 6.50, and 10.11 µg/mL, respectively. The plasma elimination half-life(T1/2ß) was also about 1 h and dHG-5 could be almost completely absorbed after s.c. administration. Additionally, the pharmacodynamics of dHG-5 was positively correlated with its pharmacokinetics, as determined by rat plasma APTT and anti-iXase method, respectively. dHG-5 was mainly excreted by urine as the unchanged parent drug and about 60% was excreted within 48 h. The results suggested that dHG-5 could be almost completely absorbed after subcutaneous injection and the pharmacokinetics of dHG-5 are predictable. Studying pharmacokinetics of dHG-5 could provide valuable information for future clinical studies.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Inibidores do Fator Xa/farmacocinética , Glicosaminoglicanos/farmacocinética , Holothuria/metabolismo , Animais , Biotransformação , Monitoramento de Medicamentos , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/isolamento & purificação , Glicosaminoglicanos/administração & dosagem , Glicosaminoglicanos/isolamento & purificação , Meia-Vida , Injeções Intravenosas , Injeções Subcutâneas , Masculino , Tempo de Tromboplastina Parcial , Ratos Sprague-Dawley , Eliminação Renal
16.
Am Heart J ; 237: 68-78, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33676886

RESUMO

BACKGROUND: Improving adherence to direct oral anticoagulants (DOAC) is challenging, and simple text messaging reminders have not been effective. METHODS: SmartADHERE was a randomized trial that tested a personalized digital and human direct oral anticoagulant adherence intervention compared to usual care. Eligibility required age ≥ 18, newly-prescribed (≤90 days) rivaroxaban for atrial fibrillation (AF), 1 of 4 at-risk criteria for nonadherence, and a smartphone. The intervention consisted of combination of a medication management smartphone app, daily app-based reminders, adaptive text messaging, and phone-based counseling for severe nonadherence. The primary outcome was the proportion of days covered by rivaroxaban (PDC) at 6 months. There were 25 U.S. sites, all cardiology and electrophysiology outpatient practices, activated for a target sample size of 378, but the study was terminated by the sponsor prior to reaching target enrollment. RESULTS: There were 139 participants (age 65±9.6 years, 30% female, median CHA2DS2-VASc score 3 with IQR 2 to 4, mean total medication burden 7.7±4.4). DOAC adherence was high in both arms with no difference in the primary outcome (PDC 0.86±0.25 intervention vs 0.88±0.25 control, p=0.62) or in secondary outcomes including PDC ≥ 0.80 and medication persistence. Per protocol analyses had similar results. Because of the high overall PDC, the likelihood to answer the primary hypothesis was only 51% even if target enrollment were achieved. There were no study-related adverse events. CONCLUSIONS: The use of a centralized digital and human adherence intervention was feasible across multiple sites. Overall adherence was much higher than expected despite prescreening for at-risk individuals. SmartADHERE illustrates the challenges of trials of behavioral and technology interventions, where enrollment itself may lead to selection bias or treatment effects. Pragmatic study designs, such as cluster randomization or stepped-wedge implementation, should be considered to improve enrollment and generalizability.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Eletrônica , Rivaroxabana/administração & dosagem , Smartphone , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Idoso , Fibrilação Atrial/complicações , Relação Dose-Resposta a Droga , Esquema de Medicação , Inibidores do Fator Xa/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia
17.
Am Heart J ; 236: 59-68, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33657403

RESUMO

BACKGROUND: In the AFIRE trial, rivaroxaban monotherapy was noninferior to combination therapy with rivaroxaban and an antiplatelet agent for thromboembolic events or death, and superior for major bleeding in patients with atrial fibrillation (AF) and stable coronary artery disease. Little is known about impacts of stroke and bleeding risks on the efficacy and safety of rivaroxaban monotherapy. METHODS: In this subanalysis of the AFIRE trial, we assessed the risk of stroke and bleeding by the CHADS2, CHA2DS2-VASc, and HAS-BLED scores. The primary efficacy end point was the composite of stroke, systemic embolism, myocardial infarction (MI), unstable angina requiring revascularization, or death from any cause. The primary safety end point was major bleeding defined by the International Society on Thrombosis and Haemostasis. RESULTS: Rivaroxaban monotherapy significantly reduced the primary efficacy and safety end points with no evidence of differential effects by stroke risk (CHADS2, p for interaction = 0.727 for efficacy, 0.395 for safety; CHA2DS2-VASc, p for interaction = 0.740 for efficacy, 0.265 for safety) or bleeding risk (HAS-BLED, p for interaction = 0.581 for efficacy, 0.225 for safety). There was also no evidence of statistical heterogeneity across patient risk categories for other end points; stroke or systemic embolism, ischemic stroke, hemorrhagic stroke, MI, MI or unstable angina, death from any cause, any bleeding, or net adverse clinical events. CONCLUSIONS: The advantages of rivaroxaban monotherapy compared with those of combination therapy with respect to all prespecified end points, including thromboembolism, bleeding, and mortality were similar across patients with AF and stable coronary artery disease, irrespective of their risk for stroke and bleeding. CLINICAL TRIAL REGISTRATION: UMIN Clinical Trials Registry number, UMIN000016612, and ClinicalTrials.gov number, NCT02642419.


Assuntos
Fibrilação Atrial , Doença da Artéria Coronariana , Hemorragia , Inibidores da Agregação Plaquetária , Rivaroxabana , Acidente Vascular Cerebral/prevenção & controle , Idoso , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Clopidogrel/administração & dosagem , Clopidogrel/efeitos adversos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/tratamento farmacológico , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Humanos , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Cloridrato de Prasugrel/administração & dosagem , Cloridrato de Prasugrel/efeitos adversos , Risco Ajustado/métodos , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/etiologia
18.
Am Heart J ; 238: 12-15, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33762178

RESUMO

Reduced-dose apixaban is recommended in patients fulfilling 2 of 3 criteria: age ≥80 years, body weight ≤60 kg, and serum creatinine ≥1.5 mg/dL. However, patient weight is often not available in electronic health data. We examined the validity of alternative definitions based on age and renal function alone using an observational dataset of patients with atrial fibrillation and chronic kidney disease which included weight measurements.


Assuntos
Fatores Etários , Fibrilação Atrial/complicações , Peso Corporal , Creatinina/sangue , Inibidores do Fator Xa/administração & dosagem , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Insuficiência Renal Crônica/complicações , Idoso de 80 Anos ou mais , Colúmbia Britânica , Redução da Medicação , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Insuficiência Renal Crônica/sangue , Fatores Sexuais , Tromboembolia/etiologia , Tromboembolia/prevenção & controle
19.
Am J Cardiol ; 149: 64-71, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33757781

RESUMO

Considering that there is a lack of evidence and guideline-based recommendations on the best preoperative oral anticoagulation management (OAC) for transcatheter aortic valve implantation (TAVI), this cohort study aimed to evaluate bleeding, access site complications, and early safety in patients undergoing TAVI on continued OAC therapy vs no-OAC therapy. Three-hundred forty-four patients submitted to a TAVI procedure (66.3% no-OAC vs 33.7% OAC) were consecutively enrolled. Primary endpoint was defined as in-hospital VARC-2 life-threatening or disabling bleeding. Secondary endpoints were in-hospital VARC-2 major vascular complications and VARC-2 early safety at 30 days. Propensity score matching analysis was performed to reduce potential distribution bias, resulting in 2 well-balanced groups (92 patients in each arm). In the overall cohort, mean age, median EuroScore II, and STS-score were 78.7±7.6 years, 2.9% (1.7-5.9), and 2.3% (1.6-3.6), respectively. Despite being older (78 ± 8 vs 80 ± 6, p = 0.004) and having higher STS score (2.1 vs 2.6, p = 0.001), patients on OAC had similar incidence of in-hospital VARC-2 life-threatening or disabling bleeding (1.3% vs. 0.9%, p = 0.711), major vascular complications (4.8% vs 5.2%, p = 0.888), and VARC-2 early safety at 30 days (10.1% vs 12.1%, p = 0.575). No significant differences in the main outcomes were observed when propensity score matching was applied. In conclusion, the management of patients on OAC submitted to a TAVI procedure is challenging and requires balancing the risk of bleeding with the risk of thromboembolic events. The present study suggests that continued OAC was not associated with increased in-hospital VARC-2 life-threatening or disabling bleeding, major vascular complications, and VARC-2 early safety at 30 days.


Assuntos
Anticoagulantes/administração & dosagem , Estenose da Valva Aórtica/cirurgia , Inibidores do Fator Xa/administração & dosagem , Hemorragia Pós-Operatória/epidemiologia , Cuidados Pré-Operatórios/métodos , Tromboembolia/epidemiologia , Substituição da Valva Aórtica Transcateter , Varfarina/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Insuficiência da Valva Aórtica/cirurgia , Fibrilação Atrial/tratamento farmacológico , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/epidemiologia , Hemorragia Pós-Operatória/induzido quimicamente , Pontuação de Propensão
20.
Am Heart J ; 236: 4-12, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33571477

RESUMO

BACKGROUND: ROCKET AF demonstrated the efficacy and safety of rivaroxaban compared with warfarin for the prevention of stroke and systemic embolism (SE) in patients with atrial fibrillation (AF). We examined baseline characteristics and outcomes in patients enrolled in Latin America compared with the rest of the world (ROW). METHODS: ROCKET AF enrolled 14,264 patients from 45 countries. Of these, 1,878 (13.2%) were from 7 Latin American countries. The clinical characteristics and outcomes (adjusted by baseline characteristics) of these patients were compared with 12,293 patients from the ROW. Treatment outcomes of rivaroxaban compared with warfarin were also stratified by region. RESULTS: The annual rate of stroke/SE was similar in those from Latin American and ROW (P= .63), but all-cause and vascular death were significantly higher than in ROW (HR 1.40, 95% CI 1.20-1.64; HR 1.38, 95% CI 1.14-1.68; P< .001). Rates of major or nonmajor clinically relevant bleeding tended to be lower in Latin America (HR 0.89, 95% CI 0.80-1.0; P= .05). Rates of stroke and/or SE were similar with rivaroxaban and warfarin in patients from Latin America and ROW (HR 0.83, 95% CI 0.54-1.29 vs HR 0.89, 95% CI 0.75-1.07; interaction P= .77). CONCLUSIONS: Patients with AF in Latin America had similar rates of stroke and/or SE, higher rates of vascular death, and lower rates of bleeding compared with patients in the ROW. The effect of rivaroxaban compared with warfarin in Latin America was similar to the ROW. Further studies analyzing patient- and country-specific determinants of these regional differences in Latin America are warranted.


Assuntos
Fibrilação Atrial , Embolia , Hemorragia , Rivaroxabana , Acidente Vascular Cerebral , Varfarina , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Método Duplo-Cego , Embolia/etnologia , Embolia/etiologia , Embolia/prevenção & controle , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Hemorragia/diagnóstico , Hemorragia/etnologia , Humanos , América Latina , Masculino , Mortalidade , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/etnologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do Tratamento , Varfarina/administração & dosagem , Varfarina/efeitos adversos
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