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1.
Europace ; 26(7)2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38941511

RESUMO

AIMS: Anticoagulation can prevent stroke and prolong lives in patients with atrial fibrillation (AF). However, anticoagulated patients with AF remain at risk of death. The aim of this study was to investigate the causes of death and factors associated with all-cause and cardiovascular death in the XANTUS population. METHODS AND RESULTS: Causes of death occurring within a year after rivaroxaban initiation in patients in the XANTUS programme studies were adjudicated by a central adjudication committee and classified following international guidance. Baseline characteristics associated with all-cause or cardiovascular death were identified. Of 11 040 patients, 187 (1.7%) died. Almost half of these deaths were due to cardiovascular causes other than bleeding (n = 82, 43.9%), particularly heart failure (n = 38, 20.3%) and sudden or unwitnessed death (n = 24, 12.8%). Fatal stroke (n = 8, 4.3%), which was classified as a type of cardiovascular death, and fatal bleeding (n = 17, 9.1%) were less common causes of death. Independent factors associated with all-cause or cardiovascular death included age, AF type, body mass index, left ventricular ejection fraction, hospitalization at baseline, rivaroxaban dose, and anaemia. CONCLUSION: The overall risk of death due to stroke or bleeding was low in XANTUS. Anticoagulated patients with AF remain at risk of death due to heart failure and sudden death. Potential interventions to reduce cardiovascular deaths in anticoagulated patients with AF require further investigation, e.g. early rhythm control therapy and AF ablation. TRIAL REGISTRATION NUMBERS: NCT01606995, NCT01750788, NCT01800006.


Assuntos
Fibrilação Atrial , Causas de Morte , Inibidores do Fator Xa , Hemorragia , Rivaroxabana , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/mortalidade , Fibrilação Atrial/tratamento farmacológico , Rivaroxabana/uso terapêutico , Rivaroxabana/efeitos adversos , Feminino , Masculino , Idoso , Inibidores do Fator Xa/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Fatores de Risco , Hemorragia/induzido quimicamente , Hemorragia/mortalidade , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/mortalidade , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Resultado do Tratamento , Insuficiência Cardíaca/mortalidade , Fatores de Tempo , Medição de Risco , Anticoagulantes/uso terapêutico , Anticoagulantes/efeitos adversos
2.
Diabetes Obes Metab ; 25(10): 3040-3053, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37435777

RESUMO

AIMS: This study aims to describe both management and prognosis of patients with diabetes mellitus (DM) and newly diagnosed atrial fibrillation (AF), overall as well as by antidiabetic treatment, and to assess the influence of oral anticoagulation (OAC) on outcomes by DM status. METHODS: The study population comprised 52 010 newly diagnosed patients with AF, 11 542 DM and 40 468 non-DM, enrolled in the GARFIELD-AF registry. Follow-up was truncated at 2 years after enrolment. Comparative effectiveness of OAC versus no OAC was assessed by DM status using a propensity score overlap weighting scheme and weights were applied to Cox models. RESULTS: Patients with DM [39.3% oral antidiabetic drug (OAD), 13.4% insulin ± OAD, 47.2% on no antidiabetic drug] had higher risk profile, OAC use, and rates of clinical outcomes compared with patients without DM. OAC use was associated in patients without DM and patients with DM with lower risk of all-cause mortality [hazard ratio 0.75 (0.69-0.83), 0.74 (0.64-0.86), respectively] and stroke/systemic embolism (SE) [0.69 (0.58-0.83), 0.70 (0.53-0.93), respectively]. The risk of major bleeding with OAC was similarly increased in patients without DM and those with DM [1.40 (1.14-1.71), 1.37 (0.99-1.89), respectively]. Patients with insulin-requiring DM had a higher risk of all-cause mortality and stroke/SE [1.91 (1.63-2.24)], [1.57 (1.06-2.35), respectively] compared with patients without DM, and experienced significant risk reductions of all-cause mortality and stroke/SE with OAC [0.73 (0.53-0.99); 0.50 (0.26-0.97), respectively]. CONCLUSIONS: In both patients with DM and patients without DM with AF, OAC was associated with lower risk of all-cause mortality and stroke/SE. Patients with insulin-requiring DM derived significant benefit from OAC.


Assuntos
Fibrilação Atrial , Diabetes Mellitus , Insulinas , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Anticoagulantes/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Sistema de Registros , Administração Oral , Fatores de Risco
3.
JAMA ; 327(2): 129-137, 2022 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-35015038

RESUMO

Importance: Among patients younger than 21 years of age, the optimal duration of anticoagulant therapy for venous thromboembolism is unknown. Objective: To test the hypothesis that a 6-week duration of anticoagulant therapy for provoked venous thromboembolism is noninferior to a conventional 3-month therapy duration in patients younger than 21 years of age. Design, Setting, and Participants: Randomized clinical trial involving 417 patients younger than 21 years of age with acute, provoked venous thromboembolism enrolled at 42 centers in 5 countries from 2008-2021. The main exclusions were severe anticoagulant deficiencies or prior venous thromboembolism. Patients without persistent antiphospholipid antibodies and whose thrombi were resolved or not completely occlusive upon repeat imaging at 6 weeks after diagnosis underwent randomization. The final visit for the primary end points occurred in January 2021. Interventions: Total duration for anticoagulant therapy of 6 weeks (n = 207) vs 3 months (n = 210) for provoked venous thromboembolism. Main Outcomes and Measures: The primary efficacy and safety end points were centrally adjudicated symptomatic recurrent venous thromboembolism and clinically relevant bleeding events within 1 year blinded to treatment group. The primary analysis was noninferiority in the per-protocol population. The noninferiority boundary incorporated a bivariate trade-off that included an absolute increase of 0% in symptomatic recurrent venous thromboembolism with an absolute risk reduction of 4% in clinically relevant bleeding events (1 of 3 points on the bivariate noninferiority boundary curve). Results: Among 417 randomized patients, 297 (median age, 8.3 [range, 0.04-20.9] years; 49% female) met criteria for the primary per-protocol population analysis. The Kaplan-Meier estimate for the 1-year cumulative incidence of the primary efficacy outcome was 0.66% (95% CI, 0%-1.95%) in the 6-week anticoagulant therapy group and 0.70% (95% CI, 0%-2.07%) in the 3-month anticoagulant therapy group, and for the primary safety outcome, the incidence was 0.65% (95% CI, 0%-1.91%) and 0.70% (95% CI, 0%-2.06%). Based on absolute risk differences in recurrent venous thromboembolism and clinically relevant bleeding events between groups, noninferiority was demonstrated. Adverse events occurred in 26% of patients in the 6-week anticoagulant therapy group and in 32% of patients in the 3-month anticoagulant therapy group; the most common adverse event was fever (1.9% and 3.4%, respectively). Conclusions and Relevance: Among patients younger than 21 years of age with provoked venous thromboembolism, anticoagulant therapy for 6 weeks compared with 3 months met noninferiority criteria based on the trade-off between recurrent venous thromboembolism risk and bleeding risk. Trial Registration: ClinicalTrials.gov Identifier: NCT00687882.


Assuntos
Anticoagulantes/administração & dosagem , Hemorragia/induzido quimicamente , Tromboembolia Venosa/tratamento farmacológico , Adolescente , Fatores Etários , Anticoagulantes/efeitos adversos , Criança , Pré-Escolar , Esquema de Medicação , Feminino , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Recidiva , Terapêutica , Fatores de Tempo , Tromboembolia Venosa/etiologia , Adulto Jovem
4.
Circulation ; 139(6): 787-798, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30586740

RESUMO

BACKGROUND: Atrial fibrillation is associated with increased risks of death, stroke/systemic embolism, and bleeding (incurred by antithrombotic therapy), which may occur early after diagnosis. METHODS: We assessed the risk of early events (death, stroke/systemic embolism, and major bleeding) over 12 months and their relation to the time after diagnosis of atrial fibrillation in 52 014 patients prospectively enrolled in the GARFIELD-AF registry (Global Anticoagulant Registry in the FIELD-Atrial Fibrillation) between March 2010 and August 2016. RESULTS: Over 12 months, 2140 patients died (mortality rate, 4.3; 95% CI, 4.2-4.5 per 100 person-years), of whom 288 (13.5%) died in the first month (6.8; 95% CI, 6.1-7.6). Over 12 months, 657 patients had a stroke/systemic embolism (1.3; 95% CI, 1.2-1.4) and 411 had a major bleeding (0.8; 95% CI, 0.8-0.9). During the first month, the rates (per 100 person-years) of stroke/systemic embolism and major bleed were 2.3 (95% CI, 1.9-2.8) and 1.5 (95% CI, 1.2-1.9), respectively. The elevated 1-month mortality rate was mostly attributable to cardiovascular mortality (3.5; 95% CI, 3.0-4.1), in particular, heart failure, sudden death, and acute coronary syndromes (1.0 [95% CI, 0.8-1.4], 0.6 [95% CI, 0.4-0.8], and 0.5 [95% CI, 0.3-0.8], respectively). Age, heart failure, prior stroke, history of cirrhosis, vascular disease, moderate-to-severe kidney disease, diabetes mellitus, and living in North or Latin America were independent predictors of a higher risk of early death, whereas anticoagulation and living in Europe or Asia were independent predictors of a lower risk of early death. A predictive model developed for the 1-month risk of death had a C-statistic of 0.81 (95% CI, 0.78-0.83). CONCLUSIONS: The increased hazard of early events, in particular, cardiovascular mortality, in newly diagnosed atrial fibrillation points to the importance of comprehensive care for such patients and should alert clinicians to detect warning signs of possible early mortality. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01090362.


Assuntos
Fibrilação Atrial/epidemiologia , Embolia/epidemiologia , Hemorragia/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Idoso , Fibrilação Atrial/mortalidade , Estudos de Coortes , Embolia/mortalidade , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Hemorragia/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Risco , Acidente Vascular Cerebral/mortalidade , Análise de Sobrevida
5.
Europace ; 22(2): 195-204, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31747004

RESUMO

AIMS: Guidelines do not recommend to take pattern of atrial fibrillation (AF) into account for the indication of anticoagulation (AC). We assessed AF pattern and the risk of cardiovascular events during 2-years of follow-up. METHODS AND RESULTS: We categorized AF as paroxysmal, persistent, or permanent in 29 181 patients enrolled (2010-15) in the Global Anticoagulant Registry In the FIELD of AF (GARFIELD-AF). We used multivariable Cox regression to assess the risks of stroke/systemic embolism (SE) and death across patterns of AF, and whether this changed with AC on outcomes. Atrial fibrillation pattern was paroxysmal in 14 344 (49.2%), persistent in 8064 (27.6%), and permanent 6773 (23.2%) patients. Median CHA2DS2-VASc, GARFIELD-AF, and HAS-BLED scores assessing the risk of stroke/SE and/or bleeding were similar across AF patterns, but the risk of death, as assessed by the GARFIELD-AF risk calculator, was higher in non-paroxysmal than in paroxysmal AF patterns. During 2-year follow-up, after adjustment, non-paroxysmal AF patterns were associated with significantly higher rates of all-cause death, stroke/SE, and new/worsening congestive heart failure (CHF) than paroxysmal AF in non-anticoagulated patients only. In anticoagulated patients, a significantly higher risk of death but not of stroke/SE and new/worsening CHF persisted in non-paroxysmal compared with paroxysmal AF patterns. CONCLUSION: In non-anticoagulated patients, non-paroxysmal AF patterns were associated with higher risks of stroke/SE, new/worsening HF and death than paroxysmal AF. In anticoagulated patients, the risk of stroke/SE and new/worsening HF was similar across all AF patterns. Thus AF pattern is no longer prognostic for stroke/SE when patients are treated with anticoagulants. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Anticoagulantes/efeitos adversos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Hemorragia , Humanos , Sistema de Registros , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do Tratamento
6.
J Thromb Thrombolysis ; 50(2): 267-277, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32583306

RESUMO

Venous thromboembolism (VTE) is common in cancer patients and is an important cause of morbidity and mortality. The Global Anticoagulant Registry in the FIELD (GARFIELD)-VTE (ClinicalTrials.gov: NCT02155491) is a prospective, observational study of 10,684 patients with objectively diagnosed VTE from 415 sites in 28 countries. We compared baseline characteristics, VTE treatment patterns, and 1-year outcomes (mortality, recurrent VTE and major bleeding) in 1075 patients with active cancer, 674 patients with a history of cancer, and 8935 patients without cancer. Patients with active cancer and history of cancer were older than cancer-free patients, with median ages of 64.8, 68.9, and 58.4 years, respectively. The most common sites of active cancer were lung (14.5%), colorectal (11.0%), breast (10.6%), and gynaecological (10.3%). Active cancer patients had a higher incidence of upper limb and vena cava thrombosis than cancer-free patients (9.0% vs 4.8% and 5.1% vs 1.4%, respectively), and were more likely to receive parenteral anticoagulation as monotherapy than cancer-free patients (57.8% vs 12.1%), and less likely to receive DOACs (14.2% vs 50.6%). Rates of death, recurrent VTE, and major bleeding were higher in active cancer patients than in cancer-free patients, with hazard ratios (95% confidence intervals) of 14.2 (12.1-16.6), 1.6 (1.2-2.0) and 3.8 (2.9-5.0), respectively. VTE was the second most common cause of death in patients with active cancer or history of cancer. In patients with VTE, those with active cancer are at higher risk of death, recurrence, and major bleeding than those without cancer.


Assuntos
Neoplasias/epidemiologia , Embolia Pulmonar/epidemiologia , Tromboembolia Venosa/epidemiologia , Trombose Venosa/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Causas de Morte , Feminino , Fibrinolíticos/uso terapêutico , Hemorragia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/mortalidade , Estudos Prospectivos , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/mortalidade , Recidiva , Sistema de Registros , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/mortalidade , Trombose Venosa/diagnóstico , Trombose Venosa/tratamento farmacológico , Trombose Venosa/mortalidade
7.
Am Heart J ; 213: 35-46, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31128503

RESUMO

INTRODUCTION: A principal aim of the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) was to document changes in treatment practice for patients with newly diagnosed atrial fibrillation during an era when non-vitamin K antagonist oral anticoagulants (NOACs) were becoming more widely adopted. In these analyses, the key factors which determined the choice between NOACs and vitamin K antagonists (VKAs) are explored. METHODS: Logistic least absolute shrinkage and selection operator regression determined predictors of NOAC and VKA use. Data were collected from 24,137 patients who were initiated on AC ±â€¯antiplatelet (AP) therapy (NOAC [51.4%] or VKA [48.6%]) between April 2013 and August 2016. RESULTS: The most significant predictors of AC therapy were country, enrolment year, care setting at diagnosis, AF type, concomitant AP, and kidney disease. Patients enrolled in emergency care or in the outpatient setting were more likely to receive a NOAC than those enrolled in hospital (OR 1.16 [95% CI: 1.04-1.30], OR: 1.15 [95% CI: 1.05-1.25], respectively). NOAC prescribing seemed to be favored in lower-risk groups, namely, patients with paroxysmal AF, normotensive patients, and those with moderate alcohol consumption, but also the elderly and patients with acute coronary syndrome. By contrast, VKAs were preferentially used in patients with permanent AF, moderate to severe kidney disease, heart failure, vascular disease, and diabetes and with concomitant AP. CONCLUSION: GARFIELD-AF data highlight marked heterogeneity in stroke prevention strategies globally. Physicians are adopting an individualized approach to stroke prevention where NOACs are favored in patients with a lower stroke risk but also in the elderly and patients with acute coronary syndrome.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Inibidores da Agregação Plaquetária/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Vitamina K/antagonistas & inibidores , Administração Oral , Idoso , Fibrilação Atrial/etnologia , Feminino , Humanos , Masculino , Estudos Prospectivos , Sistema de Registros , Acidente Vascular Cerebral/etnologia
8.
Europace ; 21(3): 421-427, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30052894

RESUMO

AIMS: Based on Phase III data, non-vitamin K antagonist oral anticoagulants are recommended for stroke prevention in patients with atrial fibrillation. To determine whether trial outcomes translate into similar event rates in unselected patients, this analysis compared outcomes from the real-world XANTUS study with those from the Phase III ROCKET AF study. METHODS AND RESULTS: Individual patient data from 4020 XANTUS patients were re-weighted to match the proportion of selected baseline characteristics in 7061 rivaroxaban-treated patients from ROCKET AF, using the matching-adjusted indirect comparison (MAIC) method. For the primary analysis, CHADS2 scores and gender were selected as relevant variables. Adjusted annualized incidence rates for XANTUS were calculated and compared with incidence rates from ROCKET AF-the ratio of these rates ('MAIC ratio') was used as a relative effect estimate. Rates of major bleeding [3.10%/year vs. 3.60%/year; MAIC ratio 0.86; 95% confidence interval (CI) 0.67-1.12] and stroke/non-central nervous system systemic embolism (1.54%/year vs. 1.70%/year; MAIC ratio 0.91; 95% CI 0.62-1.32) were similar between XANTUS and ROCKET AF. The rate of all-cause death was higher in XANTUS (3.22%/year vs. 1.87%/year; MAIC ratio 1.72; 95% CI 1.31-2.27), but the rates of vascular death were similar (1.83%/year vs. 1.53%/year; MAIC ratio 1.19; 95% CI 0.84-1.70). Sensitivity analyses weighted by different baseline characteristics supported these results. CONCLUSION: The low rates of major bleeding and stroke in XANTUS were consistent with results from ROCKET AF. All-cause death, but not vascular death, was higher in XANTUS, as expected in an unselected real-world population.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Inibidores do Fator Xa/uso terapêutico , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/mortalidade , Causas de Morte , Ensaios Clínicos Fase III como Assunto , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Rivaroxabana/efeitos adversos , Fatores Sexuais , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/mortalidade , Fatores de Tempo , Resultado do Tratamento
9.
Thromb J ; 17: 7, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31169831

RESUMO

BACKGROUND: Real-world data on non-vitamin K oral anticoagulants (NOACs) are essential in determining whether evidence from randomised controlled clinical trials translate into meaningful clinical benefits for patients in everyday practice. RIVER (RIVaroxaban Evaluation in Real life setting) is an ongoing international, prospective registry of patients with newly diagnosed non-valvular atrial fibrillation (NVAF) and at least one investigator-determined risk factor for stroke who received rivaroxaban as an initial treatment for the prevention of thromboembolic stroke. The aim of this paper is to describe the design of the RIVER registry and baseline characteristics of patients with newly diagnosed NVAF who received rivaroxaban as an initial treatment. METHODS AND RESULTS: Between January 2014 and June 2017, RIVER investigators recruited 5072 patients at 309 centres in 17 countries. The aim was to enroll consecutive patients at sites where rivaroxaban was already routinely prescribed for stroke prevention. Each patient is being followed up prospectively for a minimum of 2-years. The registry will capture data on the rate and nature of all thromboembolic events (stroke / systemic embolism), bleeding complications, all-cause mortality and other major cardiovascular events as they occur. Data quality is assured through a combination of remote electronic monitoring and onsite monitoring (including source data verification in 10% of cases). Patients were mostly enrolled by cardiologists (n = 3776, 74.6%), by internal medicine specialists 14.2% (n = 718) and by primary care/general practice physicians 8.2% (n = 417). The mean (SD) age of the population was 69.5 (11.0) years, 44.3% were women. Mean (SD) CHADS2 score was 1.9 (1.2) and CHA2DS2-VASc scores was 3.2 (1.6). Almost all patients (98.5%) were prescribed with once daily dose of rivaroxaban, most commonly 20 mg (76.5%) and 15 mg (20.0%) as their initial treatment; 17.9% of patients received concomitant antiplatelet therapy. Most patients enrolled in RIVER met the recommended threshold for AC therapy (86.6% for 2012 ESC Guidelines, and 79.8% of patients according to 2016 ESC Guidelines). CONCLUSIONS: The RIVER prospective registry will expand our knowledge of how rivaroxaban is prescribed in everyday practice and whether evidence from clinical trials can be translated to the broader cross-section of patients in the real world. TRIAL REGISTRATION: Unique identifier: NCT02444221. Registerd 14 May 2015; Retrospectively Registered.

10.
Br J Haematol ; 183(3): 457-465, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30123981

RESUMO

Venous thromboembolism (VTE)-BLEED, a decision tool for predicting major bleeding during chronic anticoagulation for VTE has not yet been validated in practice-based conditions. We calculated the prognostic indices of VTE-BLEED for major bleeding after day 30 and day 90, as well as for recurrent VTE and all-cause mortality, in 4457 patients enrolled in the international, prospective XALIA study. The median at-risk time was 190 days (interquartile range 106-360). The crude hazard ratio (HR) for major bleeding after day 30 was 2·6 [95% confidence interval (CI) 1·3-5·2] and the treatment-adjusted HR was 2·3 (95% CI 1·1-4·5) for VTE-BLEED high (versus low) risk patients: the corresponding values for major bleeding after day 90 were 3·8 (95% CI 1·6-9·3) and 3·2 (95% CI 1·3-7·7), respectively. The predictive value of VTE-BLEED was similar in selected patients with unprovoked VTE or those treated with rivaroxaban. High VTE-BLEED score was associated with higher incidence of all-cause mortality (treatment-adjusted HR 11, 95% CI 4·8-23), but not evidently with recurrent VTE (treatment-adjusted HR 1·5; 95% CI 0·85-2·7). These results confirm the predictive value of VTE-BLEED in practice-based data in patients treated with rivaroxaban or conventional anticoagulation, supporting the hypothesis that VTE-BLEED may be useful for making management decisions on the duration of anticoagulant therapy.


Assuntos
Hemorragia , Rivaroxabana/administração & dosagem , Tromboembolia Venosa , Adulto , Intervalo Livre de Doença , Feminino , Hemorragia/tratamento farmacológico , Hemorragia/etiologia , Hemorragia/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Rivaroxabana/efeitos adversos , Taxa de Sobrevida , Tromboembolia Venosa/complicações , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/mortalidade , Adulto Jovem
11.
Lancet ; 400(10368): 2047-2048, 2022 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-36502840
12.
N Engl J Med ; 373(9): 823-33, 2015 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-26095867

RESUMO

BACKGROUND: It is uncertain whether bridging anticoagulation is necessary for patients with atrial fibrillation who need an interruption in warfarin treatment for an elective operation or other elective invasive procedure. We hypothesized that forgoing bridging anticoagulation would be noninferior to bridging with low-molecular-weight heparin for the prevention of perioperative arterial thromboembolism and would be superior to bridging with respect to major bleeding. METHODS: We performed a randomized, double-blind, placebo-controlled trial in which, after perioperative interruption of warfarin therapy, patients were randomly assigned to receive bridging anticoagulation therapy with low-molecular-weight heparin (100 IU of dalteparin per kilogram of body weight) or matching placebo administered subcutaneously twice daily, from 3 days before the procedure until 24 hours before the procedure and then for 5 to 10 days after the procedure. Warfarin treatment was stopped 5 days before the procedure and was resumed within 24 hours after the procedure. Follow-up of patients continued for 30 days after the procedure. The primary outcomes were arterial thromboembolism (stroke, systemic embolism, or transient ischemic attack) and major bleeding. RESULTS: In total, 1884 patients were enrolled, with 950 assigned to receive no bridging therapy and 934 assigned to receive bridging therapy. The incidence of arterial thromboembolism was 0.4% in the no-bridging group and 0.3% in the bridging group (risk difference, 0.1 percentage points; 95% confidence interval [CI], -0.6 to 0.8; P=0.01 for noninferiority). The incidence of major bleeding was 1.3% in the no-bridging group and 3.2% in the bridging group (relative risk, 0.41; 95% CI, 0.20 to 0.78; P=0.005 for superiority). CONCLUSIONS: In patients with atrial fibrillation who had warfarin treatment interrupted for an elective operation or other elective invasive procedure, forgoing bridging anticoagulation was noninferior to perioperative bridging with low-molecular-weight heparin for the prevention of arterial thromboembolism and decreased the risk of major bleeding. (Funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health; BRIDGE ClinicalTrials.gov number, NCT00786474.).


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Procedimentos Cirúrgicos Eletivos , Heparina de Baixo Peso Molecular/administração & dosagem , Tromboembolia/prevenção & controle , Adulto , Anticoagulantes/efeitos adversos , Método Duplo-Cego , Feminino , Hemorragia/induzido quimicamente , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Masculino , Período Perioperatório , Complicações Pós-Operatórias/prevenção & controle , Varfarina/administração & dosagem , Varfarina/efeitos adversos
13.
Europace ; 20(6): e87-e95, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29016755

RESUMO

Aims: In patients with atrial fibrillation, catheter ablation and cardioversion carry a risk of peri-procedural thromboembolic events; current guidelines recommend anticoagulation in these settings. This study aimed to report the baseline demographics and clinical characteristics of patients enrolled in the prospective, observational XANTUS study who underwent catheter ablation or cardioversion, and adverse outcomes with each of these procedures in patients treated with rivaroxaban. Methods and results: Data collected included information on catheter ablation and cardioversion, and adverse outcomes occurring within 30 days of these procedures: incidence of treatment-emergent adjudicated symptomatic thromboembolic events and major bleeding; and cardiovascular and all-cause death. Incidence of these adverse outcomes at 42 days after cardioversion was also analysed. Patients undergoing either procedure had significantly lower mean CHA2DS2-VASc and HAS-BLED scores than those who did not, and were more frequently hospitalized at study baseline. Within a period of 30 days after intervention, symptomatic thromboembolic events were reported in 1.2% and 0.6% of patients undergoing ablation or cardioversion, respectively; major bleeding events were reported in 2.9% and 0.4% of patients undergoing ablation or cardioversion, respectively. No patients died within 30 days of intervention. Incidence of symptomatic thromboembolic and major bleeding events remained low at 42 days after cardioversion. Conclusion: Similar to the results of prospective and non-interventional studies, the low rates of symptomatic thromboembolic events and major bleeding in patients with atrial fibrillation undergoing ablation or cardioversion and treated with rivaroxaban in XANTUS suggest that its use is associated with an acceptable benefit-risk profile in this setting. Trial registration number: Clinicaltrials.gov: NCT01606995.


Assuntos
Fibrilação Atrial/terapia , Ablação por Cateter , Cardioversão Elétrica , Hemorragia , Rivaroxabana , Tromboembolia , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Ablação por Cateter/estatística & dados numéricos , Cardioversão Elétrica/efeitos adversos , Cardioversão Elétrica/métodos , Cardioversão Elétrica/estatística & dados numéricos , Europa (Continente)/epidemiologia , Feminino , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Medição de Risco , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Tromboembolia/epidemiologia , Tromboembolia/etiologia , Tromboembolia/prevenção & controle
14.
J Thromb Thrombolysis ; 46(3): 339-345, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29881958

RESUMO

A paucity of real-world data evaluating rivaroxaban in provoked venous thromboembolism (VTE) exists. We assessed the effectiveness and safety of rivaroxaban versus warfarin in provoked VTE patients treated in routine practice. Using MarketScan claims data from 1/2012 to 12/2016, we identified adults who had ≥ 1 primary hospitalization/emergency department discharge diagnosis code for VTE (index event) and a provoking factor, received rivaroxaban or warfarin as their first outpatient oral anticoagulant within 30-days of the index event and had ≥ 12-month of insurance coverage prior the index VTE. Provoking factors included cancer, hospital admission for ≥ 3-consecutive days over the prior 3-months, major surgery, trauma or fracture within 90-days or pregnancy within 42-weeks of the index VTE. Differences in baseline covariates between cohorts were adjusted using inverse probability-of-treatment weights based on propensity-scores (residual standardized differences < 0.1 achieved for all covariates after adjustment). The incidence of the composite endpoint of recurrent VTE or major bleeding at 3- and 6-months was compared using Cox regression and reported as hazard ratios (HRs) and 95% confidence intervals (CIs). We included 4454 rivaroxaban and 13,164 warfarin users with provoked VTE. At 3- and 6-months, rivaroxaban was associated with a reduced hazard of the composite endpoint (HR 0.72, 95% CI 0.61-0.84 and HR 0.69, 95% CI 0.60-0.80) and recurrent VTE (HR 0.70, 95% CI 0.59-0.84 and HR 0.71, 95% CI 0.60-0.84) versus warfarin. Major bleeding was non-significantly reduced at 3-months (HR 0.77, 95% CI 0.57-1.06) and significantly reduced at 6-months (HR 0.68, 95% CI 0.53-0.88) with rivaroxaban. Rivaroxaban reduces recurrent VTE and major bleeding risk versus warfarin in provoked VTE patients treated in routine practice.


Assuntos
Rivaroxabana/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Varfarina/uso terapêutico , Adulto , Idoso , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Feminino , Hemorragia/induzido quimicamente , Hospitalização , Humanos , Seguro Saúde , Masculino , Pessoa de Meia-Idade , Recidiva , Rivaroxabana/efeitos adversos , Prevenção Secundária/métodos , Resultado do Tratamento , Tromboembolia Venosa/complicações , Tromboembolia Venosa/etiologia , Varfarina/efeitos adversos
15.
Am Heart J ; 194: 132-140, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29223431

RESUMO

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the world. We aimed to provide comprehensive data on international patterns of AF stroke prevention treatment. METHODS: Demographics, comorbidities, and stroke risk of the patients in the GARFIELD-AF (n=51,270), ORBIT-AF I (n=10,132), and ORBIT-AF II (n=11,602) registries were compared (overall N=73,004 from 35 countries). Stroke prevention therapies were assessed among patients with new-onset AF (≤6 weeks). RESULTS: Patients from GARFIELD-AF were less likely to be white (63% vs 89% for ORBIT-AF I and 86% for ORBIT-AF II) or have coronary artery disease (19% vs 36% and 27%), but had similar stroke risk (85% CHA2DS2-VASc ≥2 vs 91% and 85%) and lower bleeding risk (11% with HAS-BLED ≥3 vs 24% and 15%). Oral anticoagulant use was 46% and 57% for patients with a CHA2DS2-VASc=0 and 69% and 87% for CHA2DS2-VASc ≥2 in GARFIELD-AF and ORBIT-AF II, respectively, but with substantial geographic heterogeneity in use of oral anticoagulant (range: 31%-93% [GARFIELD-AF] and 66%-100% [ORBIT-AF II]). Among patients with new-onset AF, non-vitamin K antagonist oral anticoagulant use increased over time to 43% in 2016 for GARFIELD-AF and 71% for ORBIT-AF II, whereas use of antiplatelet monotherapy decreased from 36% to 17% (GARFIELD-AF) and 18% to 8% (ORBIT-AF I and II). CONCLUSIONS: Among new-onset AF patients, non-vitamin K antagonist oral anticoagulant use has increased and antiplatelet monotherapy has decreased. However, anticoagulation is used frequently in low-risk patients and inconsistently in those at high risk of stroke. Significant geographic variability in anticoagulation persists and represents an opportunity for improvement.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Sistema de Registros , Medição de Risco , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Idoso , Fibrilação Atrial/complicações , Feminino , Saúde Global , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia
16.
Eur Heart J ; 37(14): 1145-53, 2016 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-26330425

RESUMO

AIMS: Although non-vitamin K antagonist oral anticoagulants are recommended for stroke prevention in patients with non-valvular atrial fibrillation (NVAF) based on clinical trial results, there is a need for safety and efficacy data from unselected patients in everyday clinical practice. XANTUS investigated the safety and efficacy of the Factor Xa inhibitor rivaroxaban in routine clinical use in the NVAF setting. METHODS AND RESULTS: Consecutive consenting patients with NVAF newly started on rivaroxaban were eligible and were followed up at ∼3-month intervals for 1 year, or for at least 30 days after permanent discontinuation. All adverse events (AEs) were recorded as AEs or serious AEs; major outcomes (including major bleeding, symptomatic thromboembolic events [stroke, systemic embolism, transient ischaemic attack, and myocardial infarction], and all-cause death) were centrally adjudicated. There were 6784 patients treated with rivaroxaban at 311 centres in Europe, Israel, and Canada. Mean patient age was 71.5 years (range 19-99), 41% were female, and 9.4% had documented severe or moderate renal impairment (creatinine clearance <50 mL/min). The mean CHADS2 and CHA2DS2-VASc scores were 2.0 and 3.4, respectively; 859 (12.7%) patients had a CHA2DS2-VASc score of 0 or 1. The mean treatment duration was 329 days. Treatment-emergent major bleeding occurred in 128 patients (2.1 events per 100 patient-years), 118 (1.9 events per 100 patient-years) died, and 43 (0.7 events per 100 patient-years) suffered a stroke. CONCLUSION: XANTUS is the first international, prospective, observational study to describe the use of rivaroxaban in a broad NVAF patient population. Rates of stroke and major bleeding were low in patients receiving rivaroxaban in routine clinical practice. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT01606995.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Inibidores do Fator Xa/uso terapêutico , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
17.
Eur Heart J ; 37(38): 2882-2889, 2016 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-27357359

RESUMO

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362.


Assuntos
Fibrilação Atrial , Idoso , Anticoagulantes , Feminino , Hemorragia , Humanos , Masculino , Fatores de Risco , Acidente Vascular Cerebral
18.
Br J Haematol ; 174(4): 610-23, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27071942

RESUMO

Vitamin K antagonist (VKA) therapy for stroke prevention in atrial fibrillation (AF) requires monitoring of the international normalized ratio (INR). We evaluated the agreement between two INR audit parameters, frequency in range (FIR) and proportion of time in the therapeutic range (TTR), using data from a global population of patients with newly diagnosed non-valvular AF, the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF). Among 17 168 patients with 1-year follow-up data available at the time of the analysis, 8445 received VKA therapy (±antiplatelet therapy) at enrolment, and of these patients, 5066 with ≥3 INR readings and for whom both FIR and TTR could be calculated were included in the analysis. In total, 70 905 INRs were analysed. At the patient level, TTR showed higher values than FIR (mean, 56·0% vs 49·8%; median, 59·7% vs 50·0%). Although patient-level FIR and TTR values were highly correlated (Pearson correlation coefficient [95% confidence interval; CI], 0·860 [0·852-0·867]), estimates from individuals showed widespread disagreement and variability (Lin's concordance coefficient [95% CI], 0·829 [0·821-0·837]). The difference between FIR and TTR explained 17·4% of the total variability of measurements. These results suggest that FIR and TTR are not equivalent and cannot be used interchangeably.


Assuntos
Fibrilação Atrial/complicações , Coeficiente Internacional Normatizado/métodos , Acidente Vascular Cerebral/prevenção & controle , Vitamina K/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Sistemas de Apoio a Decisões Clínicas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Varfarina/uso terapêutico
19.
Br J Clin Pharmacol ; 81(4): 724-34, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26580706

RESUMO

AIM: The aim of the present study was to analyse concomitant drug use and its association with outcome in patients (N = 17 701) receiving rivaroxaban or standard of care (SOC) for the prevention of venous thromboembolism after major orthopaedic surgery in the non-interventional, phase IV XAMOS (Xarelto® in the prophylaxis of post-surgical venous thromboembolism after elective major orthopaedic surgery of hip or knee) study. METHODS: Concomitant drug use was at the discretion of the treating physician. Prespecified co-medications of interest were cytochrome P450 (CYP) 3A4/P-glycoprotein inhibitors/inducers, platelet aggregation inhibitors (PAIs) and nonsteroidal anti-inflammatory drugs (NSAIDs). Crude event incidences were compared between rivaroxaban and SOC groups. RESULTS: CYP3A4/P-glycoprotein inhibitor/inducer use was infrequent, in contrast to PAI (~7%) and NSAID (~52%) use. Rivaroxaban was associated with a lower incidence of overall symptomatic thromboembolic events compared with SOC, regardless of co-medication use. In both treatment groups, PAI users, with higher age and prevalence of cardiovascular co-morbidities, had similar higher (>7-fold) incidences of symptomatic arterial but not venous thromboembolic events compared with non-users. NSAID use had no influence on thromboembolic events. However, odds ratios (ORs) for major bleeding events (European Medicines Agency definition) were higher in NSAID users compared with non-users in rivaroxaban [OR = 1.50; 95% confidence interval (CI) 1.06, 2.13] and SOC (OR = 1.70; CI 1.16, 2.49) groups. In PAI users, ORs for major bleeding events were no different from those of non-users in both the rivaroxaban (OR = 1.49; CI 0.84, 2.65) and SOC (OR = 1.46; CI 0.82, 2.62) groups. CONCLUSIONS: Use of NSAIDs in XAMOS was frequent and associated with a higher frequency of bleeding events in patients receiving rivaroxaban or SOC, although the benefit-risk profile of rivaroxaban compared with SOC was maintained.


Assuntos
Anticoagulantes/uso terapêutico , Artroplastia de Quadril/métodos , Artroplastia do Joelho/métodos , Rivaroxabana/uso terapêutico , Tromboembolia Venosa/prevenção & controle , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Estudos de Coortes , Interações Medicamentosas , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos
20.
N Engl J Med ; 366(7): 601-9, 2012 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-22335737

RESUMO

BACKGROUND: Patients receiving chemotherapy for cancer are at increased risk for venous thromboembolism. Limited data support the clinical benefit of antithrombotic prophylaxis. METHODS: In this double-blind, multicenter trial, we evaluated the efficacy and safety of the ultra-low-molecular-weight heparin semuloparin for prevention of venous thromboembolism in patients receiving chemotherapy for cancer. Patients with metastatic or locally advanced solid tumors who were beginning to receive a course of chemotherapy were randomly assigned to receive subcutaneous semuloparin, 20 mg once daily, or placebo until there was a change of chemotherapy regimen. The primary efficacy outcome was the composite of any symptomatic deep-vein thrombosis, any nonfatal pulmonary embolism, and death related to venous thromboembolism. Clinically relevant bleeding (major and nonmajor) was the main safety outcome. RESULTS: The median treatment duration was 3.5 months. Venous thromboembolism occurred in 20 of 1608 patients (1.2%) receiving semuloparin, as compared with 55 of 1604 (3.4%) receiving placebo (hazard ratio, 0.36; 95% confidence interval [CI], 0.21 to 0.60; P<0.001), with consistent efficacy among subgroups defined according to the origin and stage of cancer and the baseline risk of venous thromboembolism. The incidence of clinically relevant bleeding was 2.8% and 2.0% in the semuloparin and placebo groups, respectively (hazard ratio, 1.40; 95% CI, 0.89 to 2.21). Major bleeding occurred in 19 of 1589 patients (1.2%) receiving semuloparin and 18 of 1583 (1.1%) receiving placebo (hazard ratio, 1.05; 95% CI, 0.55 to 1.99). Incidences of all other adverse events were similar in the two study groups. CONCLUSIONS: Semuloparin reduces the incidence of thromboembolic events in patients receiving chemotherapy for cancer, with no apparent increase in major bleeding. (Funded by Sanofi; ClinicalTrials.gov number, NCT00694382.).


Assuntos
Fibrinolíticos/uso terapêutico , Fibrinopeptídeo A/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Neoplasias/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle , Adulto , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Método Duplo-Cego , Fibrinolíticos/efeitos adversos , Fibrinopeptídeo A/efeitos adversos , Hemorragia/epidemiologia , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Incidência , Estimativa de Kaplan-Meier , Neoplasias/complicações , Fatores de Risco , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia
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