Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 683
Filtrar
1.
Kardiologiia ; 60(9): 102-109, 2020 Oct 14.
Artigo em Russo | MEDLINE | ID: mdl-33131481

RESUMO

Aim To compare efficacy and safety of direct oral anticoagulants (DOACs) for prevention of stroke in patients with nonvalvular atrial fibrillation and reduced creatinine clearance.Material and methods Systematic search for literature and indirect comparison of DOACs were performed.Results The indirect comparison included five randomized clinical trials. The DOACs were comparable by the efficacy of preventing stroke and systemic embolism. The safety profiles had differences. Apixaban significantly decreased the relative risk of major bleeding compared to rivaroxaban by 27 % (relative risk (RR) 0.73; 95 % confidence interval (CI): 0.55-0.98). The apixaban advantage was even greater in the group of patients with a creatinine clearance <50 ml/min: RR was reduced by 48 % compared to rivaroxaban (RR=0.52; 95 % CI: 0.32-0.84), by 50 % compared to dabigatran 300 mg/day (RR=0.50; 95 % CI: 0.31-0.81), and by 48 % compared to dabigatran 220 mg/day (RR=0.52; 95 % CI: 0.32-0.85)Conclusion The indirect comparison of DOACs showed that their efficacy was comparable. With respect of safety, apixaban is the preferrable DOAC for patients with atrial fibrillation and creatinine clearance below 50 ml/min.


Assuntos
Fibrilação Atrial , Insuficiência Renal Crônica , Acidente Vascular Cerebral , Administração Oral , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Dabigatrana/uso terapêutico , Humanos , Piridonas/efeitos adversos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do Tratamento
2.
Angiol Sosud Khir ; 26(3): 16-26, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33063748

RESUMO

The routine practice of a vascular surgeon is invariably associated with decreasing the risk of adverse cardiovascular events in patients presenting with either arterial or venous pathology. Antithrombotic therapy is one of the key approaches used to achieve this purpose. However, a wide variety of modern drugs inhibiting platelet aggregation and agents blocking the coagulation cascade, as well as their combinations makes the selection of the most appropriate treatment for a particular patient quite a difficult task. The choice should carefully be made taking into consideration the nosology, aetiology, accompanying diseases and therapy thereof, as well as the balance of the risk of ischaemic and haemorrhagic complications. Therefore, availability of modern antithrombotic drugs favourably contributing to a more personified approach to treatment is of utmost importance. Thus, for example, rivaroxaban, an anticoagulant belonging to the class of direct-acting oral factor Xa inhibitors, provides a possibility to select an optimal dosage and regimen for a particular patient with arterial or vascular pathology in practice of a cardiovascular surgeon.


Assuntos
Anticoagulantes , Inibidores da Agregação de Plaquetas , Anticoagulantes/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , Inibidores do Fator Xa/efeitos adversos , Humanos , Inibidores da Agregação de Plaquetas/efeitos adversos , Rivaroxabana/efeitos adversos
3.
An Sist Sanit Navar ; 43(2): 251-254, 2020 Aug 31.
Artigo em Espanhol | MEDLINE | ID: mdl-32865189

RESUMO

Infection caused by SARS-CoV-2 (COVID-19) is associated with an increased risk of thromboembolic disease. So-me authors recommend anticoagulation at therapeutic doses for, at least, the most severely ill patients; this practice is not free of risks, which is why only thromboembolic prophylaxis is recommended by other consensuses. In the case of previously anticoagulated patients, changing the oral anticoagulant for a low molecular weight heparin (LMWH) is generally recommended. We present the cases of two patients admitted due to COVID-19, without serious clinical data, in whom anticoagulation (acenocoumarol and rivaroxaban, respectively) was replaced by LMWH at therapeutic doses, both presenting abdominal bleeding. This type of bleeding is an infrequent complication in anticoagulated patients, but the concurrence of two cases in a short period of time in the context of the COVID-19 pandemic leads us to consider that there is not yet any clear evidence on therapeutic anticoagulation in SARS-CoV-2 infection.


Assuntos
Anticoagulantes/efeitos adversos , Betacoronavirus , Infecções por Coronavirus/complicações , Hematoma/induzido quimicamente , Pneumonia Viral/complicações , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/virologia , Abdome , Acenocumarol/efeitos adversos , Acenocumarol/uso terapêutico , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Feminino , Hematoma/diagnóstico , Heparina de Baixo Peso Molecular/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Pandemias , Rivaroxabana/efeitos adversos , Rivaroxabana/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico
4.
Medicine (Baltimore) ; 99(36): e22028, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899057

RESUMO

Comparison of different anticoagulants in blood management and complications with tranexamic acid (TXA) in total hip arthroplasty (THA) is unclear. Our aim was to compare the efficacy and safety among receiving nadroparin calcium, enoxaparin sodium or rivaroxaban after TXA in THA.150 patients undergoing primary unilateral THA were received 15 mg/kg intravenous TXA (IV-TXA) before skin incision, followed by 1 of nadroparin calcium (Group A), enoxaparin sodium (Group B), or rivaroxaban (Group C) randomly during hospitalization. The primary outcome was hidden blood loss (HBL). Other outcomes such as the maximum hemoglobin (Hb) drop, total blood loss (TBL), the volume of drainage, transfusion rate, length of hospital stay (LOS), and complications were also compared.There were no statistically significant differences in HBL, the maximum hemoglobin (Hb) drop, transfusion rate, and complications among 3 groups. LOS was significantly higher for patients in Group B than Group A (P = .026). Neither deep venous thrombosis (DVT) nor pulmonary embolism (PE) occurred in any group.There were no differences in efficacy and safety in patients undergoing THA receiving nadroparin calcium, enoxaparin sodium, or rivaroxaban after anti-fibrinolysis with TXA.


Assuntos
Anticoagulantes/efeitos adversos , Antifibrinolíticos/efeitos adversos , Perda Sanguínea Cirúrgica/prevenção & controle , Ácido Tranexâmico/efeitos adversos , Administração Intravenosa , Idoso , Anticoagulantes/administração & dosagem , Antifibrinolíticos/administração & dosagem , Artroplastia de Quadril/efeitos adversos , Transfusão de Sangue/estatística & dados numéricos , China/epidemiologia , Enoxaparina/administração & dosagem , Enoxaparina/efeitos adversos , Feminino , Hemoglobinas/análise , Hospitalização , Humanos , Tempo de Internação/tendências , Masculino , Pessoa de Meia-Idade , Nadroparina/administração & dosagem , Nadroparina/efeitos adversos , Sangue Oculto , Estudos Retrospectivos , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Segurança , Ácido Tranexâmico/administração & dosagem , Resultado do Tratamento
5.
Khirurgiia (Mosk) ; (7): 68-75, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32736466

RESUMO

The paper is a narrative review of the literature on the use of direct oral anticoagulants (DOACs) for the VTE treatment in challenging patients: senile age (≥75 years), impaired renal function (estimated glomerular filtration rate ≤50 ml/min), fragility (one of the previous characteristics and/or bodyweight ≤50 kg). The paper discusses the studies of EINSTEIN DVT and PE (rivaroxaban), AMPLIFY (apixaban), HOKUSAI-VTE (edoxaban), RE-COVER I and II (dabigatran) in the focus of the secondary analysis in the pre-specified patient's subgroups, as well as their pooled analyzes and meta-analyzes. Based on the results of this review, it was concluded that in a subgroup of senile age patients, dabigatran increases the risk of major bleeding by 4.8 times and has no advantages over vitamin K antagonists (VKA); rivaroxaban and apixaban retain superiority over VKA on the safety outcomes and reduce the risk of major bleeding by 73% and 77%. In the subgroup of patients with impaired renal function, the use of apixaban and dabigatran is associated with an increase in the risk of major bleeding by 6.5 and 7.3 times, and these DOACs do not have advantages over VKA; rivaroxaban retains its superiority over VKA and reduces the risk of major bleeding by 78%. For fragile patients, a secondary analysis is available only for rivaroxaban, which remains superior to VKA on safety endpoints and reduces the risk of major bleeding by 73%. In the absence of direct comparisons between the available DOACs, the presented data can be used as a rational approach for the choice of appropriate treatment for VTE in challenging patients.


Assuntos
Dabigatrana/efeitos adversos , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Insuficiência Renal/complicações , Rivaroxabana/efeitos adversos , Tromboembolia Venosa/tratamento farmacológico , Administração Oral , Fatores Etários , Idoso , Antitrombinas , Dabigatrana/administração & dosagem , Idoso Fragilizado , Humanos , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Rivaroxabana/administração & dosagem , Tromboembolia Venosa/complicações
6.
J Stroke Cerebrovasc Dis ; 29(8): 104936, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32689594

RESUMO

BACKGROUND: Non-stenotic intracranial and systemic atherosclerosis are associated with ischemic stroke. We report frequency and response to anticoagulant vs. antiplatelet prophylaxis of patients with embolic stroke of undetermined source (ESUS) who have non-stenotic intracranial atherosclerosis and/or systemic atherosclerosis. METHODS: Exploratory analysis of the international NAVIGATE ESUS randomized trial comparing rivaroxaban 15mg daily with aspirin 100mg daily in 7213 patients with recent ESUS. Among participants with results of intracranial arterial imaging with either computed tomographic angiography (CTA) or magnetic resonance angiography (MRA), the frequency and predictors of non-stenotic intracranial and systemic atherosclerosis and responses to antithrombotic therapy were assessed. RESULTS: Among 4723 participants with available intracranial CTA or MRA results (65% of the trial cohort), the prevalence of intracranial atherosclerosis was 16% (n=739). Patient features independently associated with intracranial atherosclerosis included East Asian region (odds ratio 2.7, 95%CI 2.2,3.3) and cervical carotid plaque (odds ratio 2.3, 95%CI 1.9,2.7), among others. The rate of recurrent ischemic stroke averaged 4.8%/year among those with intracranial atherosclerosis vs. 5.0.%/year for those without (HR 0.95, 95%CI 0.65, 1.4). Among those with intracranial atherosclerosis, the recurrent ischemic stroke rate was higher if assigned to rivaroxaban (5.8%/year) vs. aspirin (3.7%/year), but the difference was not statistically significant (HR 1.6, 95%CI 0.78, 3.3). There was trend for the effect of antithrombotic treatments to be different according to the presence or absence of intracranial atherosclerosis (pinteraction=0.09). Among participants with evidence of systemic atherosclerosis by either history or imaging (n=3820), recurrent ischemic stroke rates were similar among those assigned to rivaroxaban (5.5%/year) vs. aspirin (4.9%/year)(HR 1.1, 95%CI 0.84, 1.5). CONCLUSIONS: East Asia region was the strongest factor associated with intracranial atherosclerosis. There were no statistically significant differences between rivaroxaban and aspirin prophylaxis for recurrent ischemic stroke in patients with non-stenotic intracranial atherosclerosis and/or systemic atherosclerosis.


Assuntos
Aspirina/administração & dosagem , Inibidores do Fator Xa/administração & dosagem , Fibrinolíticos/administração & dosagem , Arteriosclerose Intracraniana/tratamento farmacológico , Embolia Intracraniana/prevenção & controle , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/administração & dosagem , Rivaroxabana/administração & dosagem , Acidente Vascular Cerebral/prevenção & controle , Idoso , Aspirina/efeitos adversos , Método Duplo-Cego , Inibidores do Fator Xa/efeitos adversos , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/epidemiologia , Embolia Intracraniana/diagnóstico por imagem , Embolia Intracraniana/epidemiologia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/epidemiologia , Inibidores da Agregação de Plaquetas/efeitos adversos , Prevalência , Recidiva , Medição de Risco , Fatores de Risco , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo , Resultado do Tratamento
7.
Artigo em Inglês | MEDLINE | ID: mdl-32604907

RESUMO

The management of patients under treatment with Direct Oral Anticoagulants (DOACs) has led clinicians to deal with two clinical issues, such as the hemorrhagic risk in case of non-interruption or the risk of thromboembolism in case of suspension of the treatment. The primary aim of this retrospective study was to evaluate the incidence of perioperative bleeding events and healing complications in patients who were under treatment with Rivaroxaban and who received dental implants and immediate prosthetic restoration. Patients treated with Rivaroxaban (Xarelto 20 mg daily) and who needed implant rehabilitation were selected. Four to six implants were placed in mandibular healed sites or fresh extraction sockets. All patients, in agreement with their physicians, interrupted the medication for 24 h and received implants and immediate restorations. Twelve patients and 57 implants were analyzed in the study. No major postoperative bleeding events were reported. Three patients (25%) presented slight immediate postoperative bleeding controlled with compression only. The implant and prosthetic survival rate were both 100% after 1 year. Within the limitations of this study, multiple implant placement with an immediate loading can be performed without any significant complication with a 24 h discontinuation of Rivaroxaban, in conjunction with the patient's physician.


Assuntos
Carga Imediata em Implante Dentário , Rivaroxabana/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Falha de Restauração Dentária , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rivaroxabana/efeitos adversos , Extração Dentária , Alvéolo Dental/cirurgia , Resultado do Tratamento
8.
Clin Drug Investig ; 40(9): 839-845, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32607688

RESUMO

BACKGROUND AND OBJECTIVE: Current guidelines recommend anticoagulation with a vitamin K antagonist (warfarin) after a bioprosthetic valve replacement. There is minimal literature evaluating direct oral anticoagulants (DOACs) in patients who have just received a bioprosthetic aortic valve replacement (AVR) or mitral valve replacement (MVR). The purpose of this study was to investigate any differences in efficacy and safety for patients taking a DOAC, compared with warfarin, after a bioprosthetic AVR or MVR. METHODS: A retrospective cohort study was performed to evaluate anticoagulation in patients who received bioprosthetic valve replacements at a large teaching hospital from 2014 to 2018. Patients included in this study received either warfarin or a DOAC following bioprosthetic AVR or MVR, and were maintained on the same agent throughout the 6-month follow-up period. The primary efficacy outcome was the incidence of thromboembolic complications and the primary safety outcome was the incidence of major bleeding within 6 months following surgery. The rate of readmission was assessed as a secondary endpoint. RESULTS: A total of 197 patients were included; 70 patients received warfarin and 127 patients received a DOAC (apixaban, n = 86; rivaroxaban, n = 40; dabigatran, n = 1). Three patients experienced thromboembolic events, all of which occurred in the DOAC group (0% vs. 2.4%; p = 0.20). Major bleeding occurred in 11 patients-two in the warfarin group and nine in the DOAC group (2.9% vs. 7.1%; p = 0.22). Sixty-one patients were readmitted within the 6-month time frame, with 26 readmissions in the warfarin group and 35 readmissions in the DOAC group (37% vs. 27%; p = 0.16). CONCLUSIONS: This small, exploratory study found similar rates of thromboembolic complications and major bleeding events in patients who received a DOAC versus warfarin after a recent bioprosthetic AVR or MVR. This study was limited by its retrospective nature and its sample size. Larger, randomized controlled trials are needed to further determine the efficacy and safety of DOACs in this patient population.


Assuntos
Anticoagulantes/uso terapêutico , Bioprótese , Dabigatrana/uso terapêutico , Próteses Valvulares Cardíacas , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Rivaroxabana/uso terapêutico , Varfarina/uso terapêutico , Administração Oral , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Dabigatrana/administração & dosagem , Dabigatrana/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Estudos Retrospectivos , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Tromboembolia/induzido quimicamente , Varfarina/administração & dosagem , Varfarina/efeitos adversos
9.
Neurology ; 95(5): e480-e487, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32651298

RESUMO

OBJECTIVE: Subdural hematomas (SDHs) are an uncommon, but important, complication of anticoagulation therapy. We hypothesized that the risks of SDH would be similar during treatment with oral factor Xa inhibitors compared with aspirin. METHODS: We assessed the frequency and the effects of antithrombotic treatments on SDHs in the recent international Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) randomized trial comparing aspirin 100 mg daily, rivaroxaban 5 mg twice daily, and rivaroxaban 2.5 mg twice daily plus aspirin. A systematic review/meta-analysis of randomized trials comparing oral factor Xa inhibitors vs aspirin on SDH risk was undertaken. RESULTS: Among 27,395 COMPASS participants, 28 patients with SDHs were identified (mean age 72 years). SDH-associated mortality was 7%. Incidence was 0.06 per 100 patient-years (11 SDH/17,492 years observation) during the mean 23-month follow-up among aspirin-assigned patients and did not differ significantly between treatments. Three additional randomized controlled trials including 16,177 participants reported a total of 14 SDHs with an incidence ranging from 0.06 to 0.1 per 100 patient-years. Factor Xa inhibitor use was not associated with an increased risk of SDH compared to aspirin (odds ratio, 0.97; 95% confidence interval, 0.52-1.81; I2 = 0%). CONCLUSION: The frequency of SDH was similar in all 3 treatment arms of the COMPASS trial. The COMPASS trial results markedly increase the available evidence from randomized comparisons of oral factor Xa inhibitors with aspirin regarding SDH. From available, albeit limited, evidence from 4 randomized trials, therapeutic dosages of factor Xa inhibitors do not appear to increase the risk of SDH compared with aspirin. CLINICAL TRIAL IDENTIFIER NUMBER: NCT01776424.


Assuntos
Inibidores do Fator Xa/efeitos adversos , Hematoma Subdural Intracraniano/induzido quimicamente , Rivaroxabana/efeitos adversos , Idoso , Aspirina/uso terapêutico , Aterosclerose/tratamento farmacológico , Feminino , Hematoma Subdural Intracraniano/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Stroke ; 51(7): 2139-2147, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32517582

RESUMO

BACKGROUND AND PURPOSE: Risks, sites, and predictors of major bleeding during antithrombotic therapies have not been well defined for patients with recent embolic stroke of undetermined source. METHODS: Exploratory analysis of major bleeds defined by International Society of Thrombosis and Hemostasis criteria occurring among 7213 participants in international NAVIGATE (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial) embolic stroke of undetermined source randomized trial comparing rivaroxaban 15 mg daily with aspirin 100 mg daily. RESULTS: During a median follow-up of 11 months, 85 major bleeds occurred. The most frequent site was gastrointestinal (38%), followed by intracranial (29%). Assignment to rivaroxaban (hazard ratio [HR], 2.7 [95% CI, 1.7-4.3]), East Asia region (HR, 2.5 [95% CI, 1.6-3.9]), systolic blood pressure ≥160 mm Hg (HR, 2.2 [95% CI, 1.2-3.8]), and reduced estimated glomerular filtration rate (HR, 1.2 per 10 mL/min per 1.73 m2 decrease, [95% CI, 1.0-1.3]) were independently associated with presence of major bleeds. Five (6%) were fatal. Among 15 patients with intracerebral hemorrhage, 2 (13%) were fatal. There was no evidence of an early high-risk period following initiation of rivaroxaban. The annualized rate of intracerebral hemorrhage was 6-fold higher among East Asian participants (0.67%) versus all other regions (0.11%; HR, 6.3 [95% CI, 2.2-18.0]). Distribution of bleeding sites was similar for rivaroxaban and aspirin. CONCLUSIONS: Among embolic stroke of undetermined source patients participating in an international randomized trial, independent predictors of major bleeding were assignment to rivaroxaban, East Asia region, increased systolic blood pressure, and impaired renal function. East Asia as a region was strongly associated with risk of intracerebral hemorrhage. Estimated glomerular filtration rate should be a consideration for stratifying bleeding risk. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02313909.


Assuntos
Hemorragia Cerebral/induzido quimicamente , Inibidores do Fator Xa/efeitos adversos , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Método Duplo-Cego , Extremo Oriente , Feminino , Taxa de Filtração Glomerular , Hemorragia/induzido quimicamente , Humanos , Embolia Intracraniana/complicações , Masculino , Pessoa de Meia-Idade , Fatores de Risco
11.
Am Heart J ; 225: 69-77, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32474206

RESUMO

BACKGROUND: Rheumatic heart disease (RHD) is a neglected disease affecting 33 million people, mainly in low and middle income countries. Yet very few large trials or registries have been conducted in this population. The INVICTUS program of research in RHD consists of a randomized-controlled trial (RCT) of 4500 patients comparing rivaroxaban with vitamin K antagonists (VKA) in patients with RHD and atrial fibrillation (AF), a registry of 17,000 patients to document the contemporary clinical course of patients with RHD, including a focused sub-study on pregnant women with RHD within the registry. This paper describes the rationale, design, organization and baseline characteristics of the RCT and a summary of the design of the registry and its sub-study. Patients with RHD and AF are considered to be at high risk of embolic strokes, and oral anticoagulation with VKAs is recommended for stroke prevention. But the quality of anticoagulation with VKA is poor in developing countries. A drug which does not require monitoring, and which is safe and effective for preventing stroke in patients with valvular AF, would fulfill a major unmet need. METHODS: The INVestIgation of rheumatiC AF Treatment Using VKAs, rivaroxaban or aspirin Studies (INVICTUS-VKA) trial is an international, multicentre, randomized, open-label, parallel group trial, testing whether rivaroxaban 20 mg given once daily is non-inferior (or superior) to VKA in patients with RHD, AF, and an elevated risk of stroke (mitral stenosis with valve area ≤2 cm2, left atrial spontaneous echo-contrast or thrombus, or a CHA2DS2VASc score ≥2). The primary efficacy outcome is a composite of stroke or systemic embolism and the primary safety outcome is the occurrence of major bleeding. The trial has enrolled 4565 patients from 138 sites in 23 countries from Africa, Asia and South America. The Registry plans to enroll an additional 17,000 patients with RHD and document their treatments, and their clinical course for at least 2 years. The pregnancy sub-study will document the clinical course of pregnant women with RHD. CONCLUSION: INVICTUS is the largest program of clinical research focused on a neglected cardiovascular disease and will provide new information on the clinical course of patients with RHD, and approaches to anticoagulation in those with concomitant AF.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Embolia/prevenção & controle , Inibidores do Fator Xa/uso terapêutico , Cardiopatia Reumática/tratamento farmacológico , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Vitamina K/antagonistas & inibidores , Adulto , Idoso , Fibrilação Atrial/complicações , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Cardiopatia Reumática/complicações , Rivaroxabana/efeitos adversos
12.
Angiol Sosud Khir ; 26(2): 42-50, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32597884

RESUMO

Analysed herein is the incidence rate of decompensated forms of venous insufficiency in patients who endured lower limb deep vein thrombosis and were prescribed either warfarin, rivaroxaban in therapeutic doses or rivaroxaban in a preventive dose. The study enrolled a total of 129 patients presenting with thrombotic lesions of deep veins of the lower limbs. The patients were divided into three groups depending on the anticoagulant therapy prescribed. Patients of the first and second groups for 6 months received warfarin and rivaroxaban, respectively, in therapeutic doses, and group three patients continued taking rivaroxaban in a therapeutic dose for a long time. RESULTS: Eighteen (36%) patients from the first group and two (4.5%) patients from the second group discontinued taking the anticoagulant before the scheduled date. Relapses of venous thromboembolic complications were observed in 11 (22%) group one patients and in 7 (15.9%) group two patients, with no relapses observed in the third group. Negative dynamics of the ultrasonographic picture was observed in two groups: 16% of group one patients and 9.1% of group two patients were found to develop signs of damage of previously unaltered veins or occlusion of a previously patent vein after endured thrombosis without clinical manifestation. Trophic disorders were observed in a third of patients of the first group and in one patient of the second group by the fourth year of follow up. None of the third group patients developed trophic ulcers. Statistically significant differences in the examined groups were obtained for such parameters as adherence to treatment and the degree of severity of venous insufficiency, in favour of rivaroxaban, with quality of recanalization being significantly better in the third group. A conclusion was drawn that prolonged preventive administration of new oral anticoagulants did not lead to the development of decompensated forms of venous insufficiency.


Assuntos
Ultrassonografia Doppler Dupla , Trombose Venosa/diagnóstico , Anticoagulantes/efeitos adversos , Humanos , Extremidade Inferior , Rivaroxabana/efeitos adversos , Resultado do Tratamento
13.
Stroke ; 51(7): 2066-2075, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32539675

RESUMO

BACKGROUND AND PURPOSE: The effects of direct oral anticoagulants in nonvalvular atrial fibrillation should be assessed in actual conditions of use. France has near-universal healthcare coverage with a unified healthcare information system, allowing large population-based analyses. NAXOS (Evaluation of Apixaban in Stroke and Systemic Embolism Prevention in Patients With Nonvalvular Atrial Fibrillation) aimed to compare the safety, effectiveness, and mortality of apixaban with vitamin K antagonists (VKAs), rivaroxaban, and dabigatran, in oral anticoagulant-naive patients with nonvalvular atrial fibrillation. METHODS: This was an observational study using French National Health System claims data and including all adults with nonvalvular atrial fibrillation who initiated oral anticoagulant between 2014 and 2016. Outcomes of interest were major bleeding events leading to hospitalization (safety), stroke and systemic thromboembolic events (effectiveness), and all-cause mortality. Four approaches were used for comparative analyses: matching on propensity score (PS; 1:n); as a sensitivity analysis, matching on high-dimensional PS; adjustment on PS; and adjustment on known confounders. For each outcome, cumulative incidence rates accounting for competing risks of death were estimated. RESULTS: Overall, 321 501 patients were analyzed, of whom 35.0%, 27.2%, 31.1%, and 6.6% initiated VKAs, apixaban, rivaroxaban, and dabigatran, respectively. Apixaban was associated with a lower PS-matched risk of major bleeding compared with VKAs (hazard ratio [HR], 0.43 [95% CI, 0.40-0.46]) and rivaroxaban (HR, 0.67 [95% CI, 0.63-0.72]), but not dabigatran (HR, 0.93 [95% CI, 0.81-1.08]). Apixaban was associated with a lower risk of stroke and systemic thromboembolic event compared with VKAs (HR, 0.60 [95% CI, 0.56-0.65]), but not rivaroxaban (HR, 1.05 [95% CI, 0.97-1.15]) or dabigatran (HR, 0.93 [95% CI, 0.78-1.11]). All-cause mortality was lower with apixaban than with VKAs, but not lower than with rivaroxaban or dabigatran. CONCLUSIONS: Apixaban was associated with superior safety, effectiveness, and lower mortality than VKAs; with superior safety than rivaroxaban and similar safety to dabigatran; and with similar effectiveness when compared with rivaroxaban or dabigatran. These observational data suggest potentially important differences in outcomes between direct oral anticoagulants, which should be explored in randomized trials.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Adulto , Idoso , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Dabigatrana/efeitos adversos , Dabigatrana/uso terapêutico , Embolia/tratamento farmacológico , Embolia/epidemiologia , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rivaroxabana/efeitos adversos , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Varfarina/efeitos adversos , Varfarina/uso terapêutico
14.
Vascul Pharmacol ; 130: 106682, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32438078

RESUMO

No data are available on rivaroxaban use in renal transplant recipients and on its surmised interaction with immunosuppressants. The aim was to investigate potential interactions between rivaroxaban and immunosuppressants in this setting. Renal transplant recipients with a stable renal function treated with rivaroxaban and tacrolimus with or without everolimus were investigated. All drugs and creatinine concentrations were determined daily for 2 weeks after the start of anticoagulation. Blood samples were drawn at 8.00 am and 3-4 h later for trough and peak concentrations, respectively. Bleeding and thrombotic events were recorded during a minimum follow-up of 6 months. In 8 renal transplant patients, rivaroxaban levels showed a predictable pharmacokinetic trend, both at Ctrough (30-61 µg/L) and at Cpeak (143-449 µg/L), with limited variability in the 25th-75th percentile range. Tacrolimus (Ctrough 3-13 µg/L; Cpeak 3-16 µg/L), everolimus (Ctrough 3-11 µg/L; Cpeak 5-17 µg/L) and creatinine concentrations were stable as well. Immunosuppressors variability before and after rivaroxaban were 30% and 30% for tacrolimus, 27% and 29% for everolimus, respectively, as well as 14% and 3% for creatinine. For rivaroxaban monitoring, the reference change value better performed in identifying significant variations of its concentration. No patient had bleeding or thrombotic events, worsening of renal graft function, and signs of immunosuppressants toxicity during a mean follow-up of 23 (9-28) months. In conclusion, rivaroxaban does not seem to interact with tacrolimus and everolimus in renal transplant recipients. Both anticoagulant and immunosuppressive effects seem warranted, without major bleeding complications and effect on the graft function.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Everolimo/farmacocinética , Inibidores do Fator Xa/farmacocinética , Imunossupressores/farmacocinética , Transplante de Rim , Rivaroxabana/farmacocinética , Tacrolimo/farmacocinética , Trombose Venosa/tratamento farmacológico , Idoso , Fibrilação Atrial/sangue , Fibrilação Atrial/diagnóstico , Coagulação Sanguínea/efeitos dos fármacos , Interações Medicamentosas , Monitoramento de Medicamentos , Everolimo/efeitos adversos , Everolimo/sangue , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/sangue , Feminino , Sobrevivência de Enxerto/efeitos dos fármacos , Hemorragia/induzido quimicamente , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/sangue , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Rivaroxabana/efeitos adversos , Rivaroxabana/sangue , Tacrolimo/efeitos adversos , Tacrolimo/sangue , Resultado do Tratamento , Trombose Venosa/sangue , Trombose Venosa/diagnóstico
15.
Cochrane Database Syst Rev ; 5: CD005259, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-32374919

RESUMO

BACKGROUND: Knee arthroscopy (KA) is a routine orthopedic procedure recommended to repair cruciate ligaments and meniscus injuries and in eligible patients, to assist the diagnosis of persistent knee pain. KA is associated with a small risk of thromboembolic events. This systematic review aims to assess if pharmacological or non-pharmacological interventions may reduce this risk. This review is the second update of the review first published in 2007. OBJECTIVES: To assess the efficacy and safety of interventions, whether mechanical, pharmacological, or in combination, for thromboprophylaxis in adult patients undergoing KA. SEARCH METHODS: For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, the CENTRAL, MEDLINE, Embase and CINAHL databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registries, on 14 August 2019. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and controlled clinical trials (CCTs), whether blinded or not, of all types of interventions used to prevent deep vein thrombosis (DVT) in males and females aged 18 years and older undergoing KA. There were no restrictions on language or publication status. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies for inclusion, assessed trial quality with the Cochrane 'Risk of bias' tool, and extracted data. A third author addressed discrepancies. We contacted study authors for additional information when required. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: This update adds four new studies, bringing the total of included studies to eight and involving 3818 adult participants with no history of thromboembolic disease undergoing KA. Studies compared daily subcutaneous (sc) low-molecular-weight heparin (LMWH) versus control (five studies); oral rivaroxaban 10 mg versus placebo (one study); daily sc LMWH versus graduated compression stockings (GCS) (one study); and aspirin versus control (one study). The incidence of pulmonary embolism (PE) in all trials combined was low, with seven cases in 3818 participants.There were no deaths in any of the intervention or control groups. LMWH versus control When compared with control, LMWH probably results in little to no difference in the incidence of PE in patients undergoing KA (risk ratio (RR) 1.81, 95% confidence interval (CI) 0.49 to 6.65; 1820 participants; 3 studies; moderate-certainty evidence). LMWH showed no reduction of the incidence of symptomatic DVT (RR 0.61, 95% CI 0.18 to 2.03; 1848 participants; 4 studies; moderate-certainty evidence). LMWH may reduce the risk of asymptomatic DVT but the evidence is very uncertain (RR 0.14, 95% CI 0.03 to 0.61; 369 participants; 2 studies; very low-certainty evidence). There was no evidence of an increased risk of all adverse events combined (RR 1.85, 95% CI 0.95 to 3.59; 1978 participants; 5 studies; moderate-certainty evidence). No evidence of a clear effect on major bleeding (RR 0.98, 95% CI 0.06 to 15.72; 1451 participants; 1 study; moderate-certainty evidence), or minor bleeding was observed (RR 1.79, 95% CI 0.84 to 3.84; 1978 participants; 5 studies; moderate-certainty evidence). Rivaroxaban versus placebo One study with 234 participants compared oral rivaroxaban 10 mg versus placebo. No evidence of a clear impact on the risk of PE (no events in either group), symptomatic DVT (RR 0.16, 95% CI 0.02 to 1.29; moderate-certainty evidence); or asymptomatic DVT (RR 0.95, 95% CI 0.06 to 15.01; very low-certainty evidence) was detected. Only bleeding adverse events were reported. No major bleeds occurred in either group and there was no evidence of differences in minor bleeding between the groups (RR 0.63, 95% CI 0.18 to 2.19; moderate-certainty evidence). Aspirin versus control One study compared aspirin with control. No PE, DVT or asymptomatic events were detected in either group. Adverse events including pain and swelling were reported but it was not clear what groups these were in. No bleeds were reported. LMWH versus GCS One study with 1317 participants compared the use of LMWH versus GCS. There was no clear difference in the risk of PE (RR 1.00, 95% CI 0.14 to 7.05; low-certainty evidence). LMWH use did reduce the risk of DVT compared to people using GCS (RR 0.17, 95% CI 0.04 to 0.75; low-certainty evidence). No clear difference in effects was seen between the groups for asymptomatic DVT (RR 0.47, 95% CI 0.21 to 1.09; very low-certainty evidence); major bleeding (RR 3.01, 95% CI 0.61 to 14.88; moderate-certainty evidence) or minor bleeding (RR 1.16, 95% CI 0.64 to 2.08; moderate-certainty evidence). Levels of thromboembolic events were higher in the GCS group than in any other group. We downgraded the certainty of the evidence for imprecision resulting from overall small event numbers; risk of bias due to concerns about lack of blinding, and indirectness as we were uncertain about the direct clinical relevance of asymptomatic DVT detection. AUTHORS' CONCLUSIONS: There is a small risk that healthy adult patients undergoing KA will develop venous thromboembolism (PE or DVT). There is moderate- to low-certainty evidence of no benefit from the use of LMWH, aspirin or rivaroxaban in reducing this small risk of PE or symptomatic DVT. There is very low-certainty evidence that LMWH use may reduce the risk of asymptomatic DVT when compared to no treatment but it is uncertain how this directly relates to incidence of DVT or PE in healthy patients. No evidence of differences in adverse events (including major and minor bleeding) was seen, but data relating to this were limited due to low numbers of events in the studies reporting within the comparisons.


Assuntos
Anticoagulantes/uso terapêutico , Artroscopia/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Articulação do Joelho/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Trombose Venosa/prevenção & controle , Adulto , Anticoagulantes/efeitos adversos , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Hemorragia/induzido quimicamente , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Complicações Pós-Operatórias/induzido quimicamente , Embolia Pulmonar/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Meias de Compressão
16.
Am J Gastroenterol ; 115(9): 1513-1524, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32467502

RESUMO

INTRODUCTION: The risk of liver injury in patients with atrial fibrillation (AF) using nonvitamin K antagonist oral anticoagulants (NOACs) has not been previously examined using liver function tests as the primary outcome in the real-world setting. This study assessed the association between NOACs (dabigatran, rivaroxaban, and apixaban) and warfarin and the risk of liver injury, as defined by laboratory tests. METHODS: Patients newly diagnosed with AF and prescribed NOACs or warfarin between 2010 and 2016, identified using the Hong Kong Clinical Database and Reporting System, were matched on age, sex, health status scores, comorbidities, and medications by propensity score on a 1:1 ratio. Risk of liver injury, defined as laboratory test values >3 times the upper limit of normal of alanine aminotransferase or aspartate aminotransferase and >2 times the upper limit of normal of total bilirubin, was compared between NOAC and warfarin users using Cox proportional hazards regression. RESULTS: After propensity score matching, 13,698 patients were included, of which 141 (2.1%) NOAC users and 232 (3.4%) warfarin users developed liver injury. The hazard ratio (HR) for NOAC vs warfarin users was 0.71 (95% confidence interval: 0.58-0.89). When comparing individual NOACs, only dabigatran (hazard ratio: 0.63; 95% confidence interval: 0.48-0.82) was associated with a lower risk of liver injury. DISCUSSION: Among patients with AF, NOACs as a group, and dabigatran alone were associated with a significantly lower risk of laboratory-based liver injury when compared with warfarin. However, liver injury occurs more frequently in real-world practice than in NOAC randomized controlled trials.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Dabigatrana/efeitos adversos , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Rivaroxabana/efeitos adversos , Varfarina/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Dabigatrana/uso terapêutico , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Risco , Rivaroxabana/uso terapêutico , Varfarina/uso terapêutico
17.
Am J Hematol ; 95(7): 817-823, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32267011

RESUMO

Randomized controlled trials leading to the approval of apixaban and rivaroxaban for venous thromboembolism (VTE) did not include patients with upper extremity deep vein thrombosis (UE-DVT). We sought to evaluate the safety and effectiveness of rivaroxaban and apixaban for the treatment of acute UE-DVT. Consecutive patients with VTE enrolled into the Mayo Clinic VTE Registry, between March 1, 2013 and December 31, 2019, were followed prospectively. Clinical, demographic and imaging data were collected at the time of study recruitment. Patients with a diagnosis of acute UE-DVT who received rivaroxaban, apixaban, LMWH or warfarin were included. Recurrent VTE, major bleeding, clinical-relevant non-major bleeding (CRNMB), and death were assessed at 3-month intervals. During the study period, 210 patients with acute UE-DVT were included; 63 were treated with apixaban, 39 with rivaroxaban, and 108 with LWMH and/or warfarin. Overall 51% had catheter-associated UE-DVT, 60% had a diagnosis of malignancy, and 14% had concurrent pulmonary embolism. Malignancy was more common in patients treated with LMWH/warfarin (67% vs 52%, P = .03). At 3 months of follow up, one (0.9%) recurrent VTE occurred in a patient treated with LMWH/warfarin and one (1.0%) patient treated with apixaban or rivaroxaban (P = .97). Major bleeding occurred in three patients treated with LMWH/warfarin, and in none of those treated with apixaban or rivaroxaban (P = .09). Clinical-relevant non-major bleeding occurred in one patient (0.9%) treated with LWMH/warfarin and two patients (2.0%) treated with apixaban or rivaroxaban (P = .53). Treatment of UE-DVT with apixaban or rivaroxaban appears to be as safe and effective as LMWH/warfarin.


Assuntos
Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Sistema de Registros , Rivaroxabana/administração & dosagem , Extremidade Superior/irrigação sanguínea , Trombose Venosa/tratamento farmacológico , Idoso , Feminino , Seguimentos , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Rivaroxabana/efeitos adversos , Trombose Venosa/epidemiologia , Varfarina/administração & dosagem , Varfarina/efeitos adversos
18.
Am J Kidney Dis ; 76(3): 311-320, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32333946

RESUMO

RATIONALE & OBJECTIVE: Evidence for the efficacy of direct oral anticoagulants (DOACs) to prevent cardiovascular (CV) events and mortality in older individuals with a low estimated glomerular filtration rate (eGFR) is lacking. We sought to characterize the association of oral anticoagulant use with CV morbidity in elderly patients with or without reductions in eGFRs, comparing DOACs with vitamin K antagonists (VKAs). STUDY DESIGN: Population-based retrospective cohort study. SETTINGS & PARTICIPANTS: All individuals 66 years or older with an initial prescription for oral anticoagulants dispensed in Ontario, Canada, from 2009 to 2016. EXPOSURE: DOACs (apixaban, dabigatran, and rivaroxaban) compared with VKAs by eGFR group (≥60, 30-59, and<30mL/min/1.73m2). OUTCOMES: The primary outcome was a composite of a CV event (myocardial infarction, revascularization, or ischemic stroke) or mortality. Secondary outcomes were CV events alone, mortality, and hemorrhage requiring hospitalization. ANALYTICAL APPROACH: High-dimensional propensity score matching of DOAC to VKA users and Cox proportional hazards regression. RESULTS: 27,552 new DOAC users were matched to 27,552 new VKA users (median age, 78 years; 49% women). There was significantly lower risk for CV events or mortality among DOAC users compared with VKA users (event rates of 79.78 vs 99.77 per 1,000 person-years, respectively; HR, 0.82 [95% CI, 0.75-0.90]) and lower risk for hemorrhage (event rates of 10.35 vs 16.77 per 1,000 person-years, respectively; HR, 0.73 [95% CI, 0.58-0.91]). There was an interaction between eGFR and the association of anticoagulant class with the primary composite outcome (P<0.02): HRs of 1.01 [95% CI, 0.92-1.12], 0.83 [95% CI, 0.75-0.93], and 0.75 [95% CI, 0.51-1.10] for eGFRs of≥60, 30 to 59, and<30mL/min/1.73m2. No interaction was detected for the outcome of hemorrhage. LIMITATIONS: Retrospective observational study design limits causal inference; dosages of DOACs and international normalized ratio values were not available; low event rates in some subgroups limited statistical power. CONCLUSIONS: DOACs compared with VKAs were associated with lower risk for the composite of CV events or mortality, an association for which the strength was most apparent among those with reduced eGFRs. The therapeutic implications of these findings await further study.


Assuntos
Antitrombinas/uso terapêutico , Isquemia Encefálica/epidemiologia , Dabigatrana/uso terapêutico , Mortalidade , Infarto do Miocárdio/epidemiologia , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Insuficiência Renal Crônica/complicações , Rivaroxabana/uso terapêutico , Trombofilia/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antitrombinas/efeitos adversos , Isquemia Encefálica/prevenção & controle , Causas de Morte , Comorbidade , Dabigatrana/efeitos adversos , Feminino , Taxa de Filtração Glomerular , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Masculino , Infarto do Miocárdio/prevenção & controle , Revascularização Miocárdica , Ontário/epidemiologia , Utilização de Procedimentos e Técnicas , Pontuação de Propensão , Modelos de Riscos Proporcionais , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Rivaroxabana/efeitos adversos , Trombofilia/complicações , Vitamina K/antagonistas & inibidores
19.
Stroke ; 51(6): 1797-1804, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32295509

RESUMO

Background and Purpose- Emboli in embolic stroke of undetermined source (ESUS) may originate from various potential embolic sources (PES), some of which may respond better to anticoagulation, whereas others to antiplatelets. We analyzed whether rivaroxaban is associated with reduction of recurrent stroke compared with aspirin in patients with ESUS across different PES and by number of PES. Methods- We assessed the presence/absence of each PES (atrial cardiopathy, atrial fibrillation, arterial atherosclerosis, left ventricular dysfunction, cardiac valvulopathy, patent foramen ovale, cancer) in NAVIGATE-ESUS (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source) participants. Prevalence of each PES, as well as treatment effect and risk of event for each PES were determined. Results by number of PES were also determined. The outcomes were ischemic stroke, all-cause mortality, cardiovascular mortality, and myocardial infarction. Results- In 7213 patients (38% women, mean age 67years) followed for a median of 11 months, the 3 most prevalent PES were atrial cardiopathy (37%), left ventricular disease (36%), and arterial atherosclerosis (29%). Forty-one percent of all patients had multiple PES, with 15% having ≥3 PES. None or a single PES was present in 23% and 36%, respectively. Recurrent ischemic stroke risk was similar for rivaroxaban- and aspirin-assigned patients for each PES, except for those with cardiac valvular disease which was marginally higher in rivaroxaban-assigned patients (hazard ratio, 1.8 [95% CI, 1.0-3.0]). All-cause mortality risks were similar across treatment groups for each PES while too few myocardial infarctions and cardiovascular deaths occurred for meaningful assessment. Increasing number of PES was not associated with increased stroke recurrence nor all-cause mortality, and outcomes did not vary between rivaroxaban- and aspirin-assigned patients by number of PES. Conclusions- A large proportion of patients with ESUS had multiple PES which could explain the neutral results of NAVIGATE-ESUS. Recurrence rates between rivaroxaban- and aspirin-assigned patients were similar across the spectrum of PES. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02313909.


Assuntos
Anticoagulantes/administração & dosagem , Aspirina/administração & dosagem , Embolia Intracraniana , Inibidores da Agregação de Plaquetas/administração & dosagem , Rivaroxabana/administração & dosagem , Acidente Vascular Cerebral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Aspirina/efeitos adversos , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Embolia Intracraniana/tratamento farmacológico , Embolia Intracraniana/mortalidade , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/efeitos adversos , Prevalência , Fatores de Risco , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/mortalidade , Taxa de Sobrevida
20.
Circ Cardiovasc Qual Outcomes ; 13(4): e006058, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32283966

RESUMO

BACKGROUND: The comparative effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) is uncertain, as they have not been compared directly in randomized trials. Previous observational comparisons of NOACs are likely to be biased by unmeasured confounders. We sought to compare the efficacy and safety of rivaroxaban and apixaban for stroke prevention in patients with atrial fibrillation (AF), using practice variation in preference for NOAC as an instrumental variable. METHODS AND RESULTS: Patients started on apixaban or rivaroxaban after newly diagnosed AF were identified using Danish nationwide registries. Patients were categorized according to facility preferences for type of NOAC, independent of actual treatment, measured as fraction of the prior 20 patients with AF initiated on rivaroxaban in the same facility. Facility preference for NOAC was used as an instrumental variable. The occurrence of stroke/thromboembolism, major bleeding, myocardial infarction, and all-cause mortality over 2 years of follow-up were investigated using adjusted Cox regressions. We analyzed 6264 patients with AF initiated on rivaroxaban or apixaban. NOAC preference was strongly related to actual choice of treatment but not associated with any other measured baseline characteristics. Patients treated in facilities that had preference for rivaroxaban had more major bleeding: compared with patients treated in facilities that used rivaroxaban in 0% to 20% of cases, the adjusted hazard ratio for bleeding was 1.06 when treated in a facility with 25% to 40% use; 1.41 with 45% to 60% use; 1.51 with 65% to 80% use; and 1.81 with 0% to 100% use (Ptrend=0.01). Higher facility preference for rivaroxaban was not significantly associated with increased risk of stroke/thromboembolism (Ptrend=0.06), myocardial infarction (Ptrend=0.65), or all-cause mortality (Ptrend=0.89). When we used the instrumental variable to model the causal relationship between choice of NOAC and major bleeding, relative risk with rivaroxaban was 1.89 (95% CI, 1.06-2.72) compared with apixaban. CONCLUSIONS: Using instrumental variable estimation in a cohort of patients with AF, rivaroxaban was associated with higher risk of major bleeding compared with apixaban. No significant associations to other outcomes were found in main analyses.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Inibidores do Fator Xa/administração & dosagem , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Rivaroxabana/administração & dosagem , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Idoso , Fibrilação Atrial/mortalidade , Pesquisa Comparativa da Efetividade , Dinamarca/epidemiologia , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Sistema de Registros , Medição de Risco , Fatores de Risco , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/mortalidade , Fatores de Tempo , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA