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1.
JAMA Neurol ; 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31058947

RESUMO

Importance: Translating evidence into clinical practice in the management of acute ischemic stroke (AIS) and transient ischemic attack (TIA) is challenging, especially in low- and middle-income countries. Objective: To assess the effect of a multifaceted quality improvement intervention on adherence to evidence-based therapies for care of patients with AIS and TIA. Design, Setting and Participants: This 2-arm cluster-randomized clinical trial assessed 45 hospitals and 2336 patients with AIS and TIA for eligibility before randomization. Eligible hospitals were able to provide care for patients with AIS and TIA in Brazil, Argentina, and Peru. Recruitment started September 12, 2016, and ended February 26, 2018; follow-up ended June 29, 2018. Data were analyzed using the intention-to-treat principle. Interventions: The multifaceted quality improvement intervention included case management, reminders, a roadmap and checklist for the therapeutic plan, educational materials, and periodic audit and feedback reports to each intervention cluster. Main Outcomes and Measures: The primary outcome was a composite adherence score for AIS and TIA performance measures. Secondary outcomes included an all-or-none composite end point of performance measures, the individual process measure components of the composite end points, and clinical outcomes at 90 days after admission (stroke recurrence, death, and disability measured by the modified Rankin scale). Results: A total of 36 hospitals and 1624 patients underwent randomization. Nineteen hospitals were randomized to the quality improvement intervention and 17 to routine care. The overall mean (SD) age of patients enrolled in the study was 69.4 (13.5) years, and 913 (56.2%) were men. Overall mean (SD) composite adherence score for the 10 performance measures in the intervention group hospitals compared with control group hospitals was 85.3% (20.1%) vs 77.8% (18.4%) (mean difference, 4.2%; 95% CI, -3.8% to 12.2%). As a secondary end point, 402 of 817 patients (49.2%) at intervention hospitals received all the therapies that they were eligible for vs 203 of 807 (25.2%) in the control hospitals (odds ratio, 2.59; 95% CI, 1.22-5.53; P = .01). Conclusions and Relevance: A multifaceted quality improvement intervention did not result in a significant increase in composite adherence score for evidence-based therapies in patients with AIS or TIA. However, when using an all-or-none approach, the intervention resulted in improved adherence to evidence-based therapies. Trial Registration: ClinicalTrials.gov Identifier: NCT02223273.

2.
N Engl J Med ; 380(16): 1509-1524, 2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-30883055

RESUMO

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


Assuntos
Síndrome Coronariana Aguda/complicações , Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Intervenção Coronária Percutânea , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Vitamina K/antagonistas & inibidores , Síndrome Coronariana Aguda/terapia , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Aspirina/efeitos adversos , Fibrilação Atrial/complicações , Método Duplo-Cego , Quimioterapia Combinada , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Pirazóis/efeitos adversos , Piridonas/efeitos adversos
3.
Circulation ; 139(20): 2292-2300, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-30773022

RESUMO

BACKGROUND: Guidelines caution against the use of non-vitamin K antagonist oral anticoagulants in patients with extremely high (>120 kg) or low (≤60 kg) body weight because of a lack of data in these populations. METHODS: In a post hoc analysis of ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation; n=18 201), a randomized trial comparing apixaban with warfarin for the prevention of stroke in patients with atrial fibrillation, we estimated the randomized treatment effect (apixaban versus warfarin) stratified by body weight (≤60, >60-120, >120 kg) using a Cox regression model and tested the interaction between body weight and randomized treatment. The primary efficacy and safety outcomes were stroke or systemic embolism and major bleeding. RESULTS: Of the 18 139 patients with available weight and outcomes data, 1985 (10.9%) were in the low-weight group (≤60 kg), 15 172 (83.6%) were in the midrange weight group (>60-120 kg), and 982 (5.4%) were in the high-weight group (>120 kg). The treatment effect of apixaban versus warfarin for the efficacy outcomes of stroke/systemic embolism, all-cause death, or myocardial infarction was consistent across the weight spectrum (interaction P value>0.05). For major bleeding, apixaban had a better safety profile than warfarin in all weight categories and even showed a greater relative risk reduction in patients in the low (≤60 kg; HR, 0.55; 95% CI, 0.36-0.82) and midrange (>60-120 kg) weight groups (HR, 0.71; 95% CI, 0.61-0.83; interaction P value=0.016). CONCLUSIONS: Our findings provide evidence that apixaban is efficacious and safe across the spectrum of weight, including in low- (≤60 kg) and high-weight patients (>120 kg). The superiority on efficacy and safety outcomes of apixaban compared with warfarin persists across weight groups, with even greater reductions in major bleeding in patients with atrial fibrillation with low to normal weight as compared with high weight. The superiority of apixaban over warfarin in regard to efficacy and safety for stroke prevention seems to be similar in patients with atrial fibrillation across the spectrum of weight, including in low- and very high-weight patients. Thus, apixaban appears to be appropriate for patients with atrial fibrillation irrespective of body weight. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00412984.

4.
Int J Cardiol ; 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31932116

RESUMO

BACKGROUND: Variation in patient characteristics and practice patterns may influence outcomes at a regional level. METHODS: We assessed differences in demographics, practice patterns, outcomes, and the effect of apixaban compared with warfarin in ARISTOTLE (n = 18,201) by prespecified regions: North America, Latin America, Europe, and Asia Pacific. The primary outcomes were stroke/systemic embolism and major bleeding. RESULTS: Compared with other regions, patients from Asia Pacific were younger, more women were enrolled in Latin America. Coronary artery disease was more prevalent in Europe and Asia Pacific had the highest rate of prior stroke and renal impairment. Over 50% of patients in North America were taking ≥9 drugs at randomization, compared with 10% in Latin America. North America had the highest rates of temporary study drug discontinuation and procedures. Time in therapeutic range (INR 2.0-3.0) on warfarin was highest in North America and lowest in Asia Pacific. After adjustment and compared with Europe, patients in Asia Pacific had 2-fold higher risk of stroke/systemic embolism and 3-fold higher risk of intracranial hemorrhage. Patients in Latin America had 2-fold increased risk of all-cause death compared with Europe. The benefits of apixaban compared with warfarin were consistent across regions; there was a pronounced reduction in major bleeding in patients from Asia Pacific compared with other regions (p-interaction = 0.03). CONCLUSIONS: Patients with AF enrolled in prespecified regions in ARISTOTLE had differences in clinical baseline characteristics and practice patterns. After adjustment, patients in Asia Pacific and Latin America had worse outcomes than patients from other regions. The relative benefits of apixaban compared with warfarin were consistent across regions with an even greater treatment effect in the reduction of bleeding in patients from Asia Pacific.

5.
JACC Heart Fail ; 6(3): 179-186, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29496021

RESUMO

Heart failure (HF) complicating myocardial infarction (MI) is common and may be present at admission or develop during the hospitalization. Among patients with MI, there is a strong relationship between degree of HF and mortality. The optimal management of the patient with HF complicating MI varies according to time since the onset of infarction. Medical therapy for HF after MI includes early (within 24 h) initiation of angiotensin-converting enzyme inhibitors and early (within 7 days) use of aldosterone antagonists. Alternatively, in patients with MI and ongoing HF, early use (<24 h) of beta-blockers is associated with an increased risk of cardiogenic shock and death. Long-term beta-blocker use after MI is associated with a reduced risk of reinfarction and death. Thus, it is critical to frequently re-evaluate beta-blocker eligibility among patients after MI with HF. Cardiogenic shock is an extreme presentation of HF after MI and is a leading cause of death in the MI setting. The only therapy proven to reduce mortality for patients with cardiogenic shock is early revascularization. Several studies are examining new approaches to mitigate the occurrence and adverse impact of post-MI HF. These studies are testing drugs for HF and diabetes and are evaluating mechanical support devices to bridge patients to recovery or transplantation.


Assuntos
Insuficiência Cardíaca/etiologia , Infarto do Miocárdio/complicações , Antagonistas Adrenérgicos beta/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Pesquisa Biomédica/tendências , Previsões , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Coração Auxiliar , Humanos , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/mortalidade , Prognóstico
6.
Am Heart J ; 197: 133-141, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29447773

RESUMO

BACKGROUND: We assessed antiplatelet therapy use and outcomes in patients undergoing percutaneous coronary intervention (PCI) during the ARISTOTLE trial. METHODS: Patients were categorized based on the occurrence of PCI during follow-up (median 1.8 years); PCI details and outcomes post-PCI are reported. Of the 18,201 trial participants, 316 (1.7%) underwent PCI (152 in apixaban group, 164 in warfarin group). RESULTS: At the time of PCI, 84% (267) were on study drug (either apixaban or warfarin). Of these, 19% did not stop study drug during PCI, 49% stopped and restarted <5 days post-PCI, and 30% stopped and restarted >5 days post-PCI. At 30 days post-PCI, 35% of patients received dual -antiplatelet therapy (DAPT), 23% received aspirin only, and 13% received a P2Y12 inhibitor only; 29% received no antiplatelet therapy. Triple therapy (DAPT + oral anticoagulant [OAC]) was used in 21% of patients, 23% received OAC only, 15% received OAC plus aspirin, and 9% received OAC plus a P2Y12 inhibitor; 32% received antiplatelet agents without OAC. Post-PCI, patients assigned to apixaban versus warfarin had numerically similar rates of major bleeding (5.93 vs 6.73 events/100 patient-years; P = .95) and stroke (2.74 vs 1.84 events/100 patient-years; P = .62). CONCLUSIONS: PCI occurred infrequently during follow-up. Most patients on study drug at the time of PCI remained on study drug in the peri-PCI period; 19% continued the study drug without interruption. Antiplatelet therapy use post-PCI was variable, although most patients received DAPT. Additional data are needed to guide the use of antithrombotics in patients undergoing PCI.


Assuntos
Fibrilação Atrial , Doença da Artéria Coronariana/cirurgia , Hemorragia , Intervenção Coronária Percutânea , Complicações Pós-Operatórias , Pirazóis , Piridonas , Acidente Vascular Cerebral/prevenção & controle , Varfarina , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/mortalidade , Monitoramento de Medicamentos/métodos , Feminino , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Humanos , Coeficiente Internacional Normatizado/métodos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/prevenção & controle , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Modelos de Riscos Proporcionais , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Acidente Vascular Cerebral/etiologia , Varfarina/administração & dosagem , Varfarina/efeitos adversos
7.
Lancet ; 390(10104): 1737-1746, 2017 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-28859942

RESUMO

BACKGROUND: Oral anticoagulation is underused in patients with atrial fibrillation. We assessed the impact of a multifaceted educational intervention, versus usual care, on oral anticoagulant use in patients with atrial fibrillation. METHODS: This study was a two-arm, prospective, international, cluster-randomised, controlled trial. Patients were included who had atrial fibrillation and an indication for oral anticoagulation. Clusters were randomised (1:1) to receive a quality improvement educational intervention (intervention group) or usual care (control group). Randomisation was carried out centrally, using the eClinicalOS electronic data capture system. The intervention involved education of providers and patients, with regular monitoring and feedback. The primary outcome was the change in the proportion of patients treated with oral anticoagulants from baseline assessment to evaluation at 1 year. The trial is registered at ClinicalTrials.gov, number NCT02082548. FINDINGS: 2281 patients from five countries (Argentina, n=343; Brazil, n=360; China, n=586; India, n=493; and Romania, n=499) were enrolled from 48 clusters between June 11, 2014, and Nov 13, 2016. Follow-up was at a median of 12·0 months (IQR 11·8-12·2). Oral anticoagulant use increased in the intervention group from 68% (804 of 1184 patients) at baseline to 80% (943 of 1184 patients) at 1 year (difference 12%), whereas in the control group it increased from 64% (703 of 1092 patients) at baseline to 67% (732 of 1092 patients) at 1 year (difference 3%). Absolute difference in the change between groups was 9·1% (95% CI 3·8-14·4); odds ratio of change in the use of oral anticoagulation between groups was 3·28 (95% CI 1·67-6·44; adjusted p value=0·0002). Kaplan-Meier estimates showed a reduction in the secondary outcome of stroke in the intervention versus control groups (HR 0·48, 95% CI 0·23-0·99; log-rank p value=0·0434). INTERPRETATION: A multifaceted and multilevel educational intervention, aimed to improve use of oral anticoagulation in patients with atrial fibrillation and at risk for stroke, resulted in a significant increase in the proportion of patients treated with oral anticoagulants. Such an intervention has the potential to improve stroke prevention around the world for patients with atrial fibrillation. FUNDING: Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Uso de Medicamentos/tendências , Educação Médica Continuada , Educação de Pacientes como Assunto , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Idoso , Anticoagulantes , Argentina/epidemiologia , Fibrilação Atrial/epidemiologia , Brasil/epidemiologia , China/epidemiologia , Retroalimentação , Feminino , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Índia/epidemiologia , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Romênia/epidemiologia , Acidente Vascular Cerebral/epidemiologia
8.
Lancet ; 389(10081): 1799-1808, 2017 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-28325638

RESUMO

BACKGROUND: Dual antiplatelet therapy (DAPT), aspirin plus a P2Y12 inhibitor, is the standard antithrombotic treatment following acute coronary syndromes. The factor Xa inhibitor rivaroxaban reduced mortality and ischaemic events when added to DAPT, but caused increased bleeding. The safety of a dual pathway antithrombotic therapy approach combining low-dose rivaroxaban (in place of aspirin) with a P2Y12 inhibitor has not been assesssed in acute coronary syndromes. We aimed to assess rivaroxaban 2·5 mg twice daily versus aspirin 100 mg daily, in addition to clopidogrel or ticagrelor (chosen at investigator discretion before randomisation), for patients with acute coronary syndromes started within 10 days after presentation and continued for 6-12 months. METHODS: In this double-blind, multicentre, randomised trial (GEMINI-ACS-1) done at 371 clinical centres in 21 countries, eligible patients were older than 18 years with unstable angina, non-ST segment elevation myocardial infarction (NSTEMI) or ST segment elevation myocardial infarction (STEMI), with positive cardiac biomarkers and either ischaemic electrocardiographic changes or an atherosclerotic culprit lesion identified during angiography. Participants were randomly assigned (1:1) within 10 days after admission for the index acute coronary syndromes event to either aspirin or rivaroxaban based on a computer-generated randomisation schedule. Randomisation was balanced by using randomly permuted blocks with size of four and was stratified based on the background P2Y12 inhibitor (clopidogrel or ticagrelor) intended to be used at the time of randomisation. Investigators and patients were masked to treatment assignment. Patients received a minimum of 180 days of double-blind treatment with rivaroxaban 2·5 mg twice daily or aspirin 100 mg daily. The choice of clopidogrel or ticagrelor during trial conduct was not randomised and was based on investigator preference. The primary endpoint was thrombolysis in myocardial infarction (TIMI) clinically significant bleeding not related to coronary artery bypass grafting (CABG; major, minor, or requiring medical attention) up to day 390. Primary analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02293395. FINDINGS: Between April 22, 2015, and Oct 14, 2016, 3037 patients with acute coronary syndromes were randomly assigned; 1518 to receive aspirin and 1519 to receive rivaroxaban. 1704 patients (56%) were in the ticagrelor and 1333 (44%) in the clopidogrel strata. Median duration of treatment was 291 days (IQR 239-354). TIMI non-CABG clinically significant bleeding was similar with rivaroxaban versus aspirin therapy (total 154 patients [5%]; 80 participants [5%] of 1519 vs 74 participants [5%] of 1518; HR 1·09 [95% CI 0·80-1·50]; p=0·5840). INTERPRETATION: A dual pathway antithrombotic therapy approach combining low-dose rivaroxaban with a P2Y12 inhibitor for the treatment of patients with acute coronary syndromes had similar risk of clinically significant bleeding as aspirin and a P2Y12 inhibitor. A larger, adequately powered trial would be required to definitively assess the efficacy and safety of this approach. FUNDING: Janssen Research & Development and Bayer AG.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Aspirina/uso terapêutico , Hemorragia/induzido quimicamente , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Rivaroxabana/uso terapêutico , Adenosina/administração & dosagem , Adenosina/análogos & derivados , Adenosina/uso terapêutico , Idoso , Aspirina/administração & dosagem , Clopidogrel , Angiografia Coronária/métodos , Método Duplo-Cego , Quimioterapia Combinada/métodos , Eletrocardiografia/métodos , Inibidores do Fator Xa/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/fisiopatologia , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Rivaroxabana/administração & dosagem , Terapia Trombolítica/métodos , Ticagrelor , Ticlopidina/administração & dosagem , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico , Resultado do Tratamento
9.
Heart ; 103(8): 623-628, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27798052

RESUMO

OBJECTIVE: We describe the incidence, location and management of non-major bleeding, and assess the association between non-major bleeding and clinical outcomes in patients with atrial fibrillation (AF) receiving anticoagulation therapy enrolled in Apixaban for Reduction in Stroke and other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE). METHODS: We included patients who received ≥1 dose of study drug (n=18 140). Non-major bleeding was defined as the first bleeding event considered to be clinically relevant non-major (CRNM) or minor bleeding, and not preceded by a major bleeding event. RESULTS: Non-major bleeding was three times more common than major bleeding (12.1% vs 3.8%). Like major bleeding, non-major bleeding was less frequent with apixaban (6.4 per 100 patient-years) than warfarin (9.4 per 100 patient-years) (adjusted HR 0.69, 95% CI 0.63 to 0.75). The most frequent sites of non-major bleeding were haematuria (16.4%), epistaxis (14.8%), gastrointestinal (13.3%), haematoma (11.5%) and bruising/ecchymosis (10.1%). Medical or surgical intervention was similar among patients with non-major bleeding on warfarin versus apixaban (24.7% vs 24.5%). A change in antithrombotic therapy (58.6% vs 50.0%) and permanent study drug discontinuation (5.1% (61) vs 3.6% (30), p=0.10) was numerically higher with warfarin than apixaban. CRNM bleeding was independently associated with an increased risk of overall death (adjusted HR 1.70, 95% CI 1.32 to 2.18) and subsequent major bleeding (adjusted HR 2.18, 95% CI 1.56 to 3.04). CONCLUSIONS: In ARISTOTLE, non-major bleeding was common and substantially less frequent with apixaban than with warfarin. CRNM bleeding was independently associated with a higher risk of death and subsequent major bleeding. Our results highlight the importance of any severity of bleeding in patients with AF treated with anticoagulation therapy and suggest that non-major bleeding, including minor bleeding, might not be minor. TRIAL REGISTRATION NUMBER: NCT00412984; post-results.


Assuntos
Anticoagulantes/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Inibidores do Fator Xa/efeitos adversos , Hemorragia/induzido quimicamente , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Acidente Vascular Cerebral/prevenção & controle , Tromboembolia/prevenção & controle , Varfarina/efeitos adversos , Idoso , Ásia , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/mortalidade , Substituição de Medicamentos , Europa (Continente) , Feminino , Hemorragia/mortalidade , Hemorragia/terapia , Humanos , Incidência , América Latina , Masculino , Pessoa de Meia-Idade , América do Norte , Segurança do Paciente , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade , Tromboembolia/diagnóstico , Tromboembolia/etiologia , Tromboembolia/mortalidade , Fatores de Tempo , Resultado do Tratamento
10.
Am Heart J ; 175: 175-83, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27179738

RESUMO

AIMS: History of bleeding strongly influences decisions for anticoagulation in atrial fibrillation (AF). We analyzed outcomes in relation to history of bleeding and randomization in ARISTOTLE trial patients. METHODS AND RESULTS: The on-treatment safety population included 18,140 patients receiving at least 1 dose of study drug (apixaban) or warfarin. Centrally adjudicated outcomes in relation to bleeding history were analyzed using a Cox proportional hazards model adjusted for randomized treatment and established risk factors. Efficacy end points were analyzed on the randomized (intention to treat) population. A bleeding history was reported at baseline in 3,033 patients (16.7%), who more often were male, with a history of prior stroke/transient ischemic attack/systemic embolism and diabetes; higher CHADS2 scores, age, and body weight; and lower creatinine clearance and mean systolic blood pressure. Major (but not intracranial) bleeding occurred more frequently in patients with versus without a history of bleeding (adjusted hazard ratio 1.35, 95% CI 1.14-1.61). There were no significant interactions between bleeding history and treatment for stroke/systemic embolism, hemorrhagic stroke, death, or major bleeding, with fewer outcomes with apixaban versus warfarin for all of these outcomes independent of the presence/absence of a bleeding history. CONCLUSION: In patients with AF in a randomized clinical trial of oral anticoagulants, a history of bleeding is associated with several risk factors for stroke and portends a higher risk of major-but not intracranial-bleeding, during anticoagulation. However, the beneficial effects of apixaban over warfarin for stroke, hemorrhagic stroke, death, or major bleeding remains consistent regardless of history of bleeding.


Assuntos
Fibrilação Atrial/complicações , Hemorragia , Pirazóis , Piridonas , Acidente Vascular Cerebral/prevenção & controle , Tromboembolia/prevenção & controle , Varfarina , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Monitoramento de Medicamentos , Feminino , Hemorragia/induzido quimicamente , Hemorragia/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Acidente Vascular Cerebral/etiologia , Tromboembolia/etiologia , Varfarina/administração & dosagem , Varfarina/efeitos adversos
11.
Stroke ; 47(6): 1640-2, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27217510

RESUMO

BACKGROUND AND PURPOSE: Epidemiological data about stroke are scarce in low- and middle-income Latin-American countries. We investigated annual incidence of first-ever stroke and transient ischemic attack (TIA) and 30-day case-fatality rates in a population-based setting in Tandil, Argentina. METHODS: We prospectively identified all first-ever stroke and TIA cases from overlapping sources between January 5, 2013, and April 30, 2015, in Tandil, Argentina. We calculated crude and standardized incidence rates. We estimated 30-day case-fatality rates. RESULTS: We identified 334 first-ever strokes and 108 TIAs. Age-standardized incidence rate per 100 000 for Segi's World population was 76.5 (95% confidence interval [CI], 67.8-85.9) for first-ever stroke and 25.1 (95% CI, 20.2-30.7) for first-ever TIA, 56.1 (95% CI, 48.8-64.2) for ischemic stroke, 13.5 (95% CI, 9.9-17.9) for intracerebral hemorrhage, and 4.9 (95% CI, 2.7-8.1) for subarachnoid hemorrhage. Stroke incidence was slightly higher for men (87.8; 95% CI, 74.6-102.6) than for women (73.2; 95% CI, 61.7-86.1) when standardized for the Argentinean population. Thirty-day case-fatality rate was 14.7% (95% CI, 10.8-19.5) for ischemic stroke, 24.1% (95% CI, 14.2-36.6) for intracerebral hemorrhage, and 1.9% (95% CI, 0.4-5.8) for TIA. CONCLUSIONS: This study provides the first prospective population-based stroke and TIA incidence and case-fatality estimate in Argentina. First-ever stroke incidence was lower than that reported in previous Latin-American studies, but first-ever TIA incidence was higher. Thirty-day case-fatality rates were similar to those of other population-based Latin-American studies.


Assuntos
Hemorragia Cerebral/epidemiologia , Ataque Isquêmico Transitório/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Argentina/epidemiologia , Hemorragia Cerebral/mortalidade , Feminino , Humanos , Incidência , Ataque Isquêmico Transitório/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Acidente Vascular Cerebral/mortalidade , Fatores de Tempo , Adulto Jovem
12.
J Am Heart Assoc ; 4(12)2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26627878

RESUMO

BACKGROUND: Patients with atrial fibrillation (AF) and hypertension are at high risk for stroke. Previous studies have shown elevated risk of stroke in patients with AF who have a history of hypertension (regardless of blood pressure [BP] control) and in patients with elevated BP. We assessed the association of hypertension and BP control on clinical outcomes. METHODS AND RESULTS: In ARISTOTLE (n=18 201), BP was evaluated as history of hypertension requiring treatment and elevated BP (systolic ≥140 and/or diastolic ≥90 mm Hg) at study entry and any point during the trial. Hazard ratios (HRs) were derived from Cox proportional hazards models including BP as a time-dependent covariate. A total of 15 916 (87.5%) patients had a history of hypertension requiring treatment. In patients with elevated BP measurement at any point during the trial, the rate of stroke or systemic embolism was significantly higher (HR, 1.53; 95% confidence interval [CI], 1.25-1.86), as was hemorrhagic stroke (HR 1.85; 95% CI, 1.26-2.72) and ischemic stroke (HR, 1.50; 95% CI, 1.18-1.90). Rates of major bleeding were lower in patients with a history of hypertension (HR, 0.80; 95% CI, 0.66-0.98) and nonsignificantly lower in patients with elevated BP at study entry (HR, 0.89; 95% CI, 0.77-1.03). The benefit of apixaban versus warfarin on preventing stroke or systemic embolism was consistent among patients with and without a history of hypertension (P interaction=0.27), BP control at baseline (P interaction=0.43), and BP control during the trial (P interaction=0.97). CONCLUSIONS: High BP measurement at any point during the trial was independently associated with a substantially higher risk of stroke or systemic embolism. These results strongly support efforts to treat elevated BP as an important strategy to optimally lower risk of stroke in patients with AF. CLINICAL TRIAL REGISTRATION: URL: https://ClinicalTrials.gov/. Unique identifier: NCT00412984.


Assuntos
Fibrilação Atrial/complicações , Inibidores do Fator Xa/uso terapêutico , Hipertensão/prevenção & controle , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Tromboembolia/prevenção & controle , Idoso , Isquemia Encefálica/etiologia , Isquemia Encefálica/prevenção & controle , Método Duplo-Cego , Feminino , Humanos , Hemorragias Intracranianas/etiologia , Hemorragias Intracranianas/prevenção & controle , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Tromboembolia/etiologia , Resultado do Tratamento
13.
Circulation ; 132(8): 624-32, 2015 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-26106009

RESUMO

BACKGROUND: Apixaban is approved for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. However, the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial included a substantial number of patients with valvular heart disease and only excluded patients with clinically significant mitral stenosis or mechanical prosthetic heart valves. METHODS AND RESULTS: We compared the effect of apixaban and warfarin on rates of stroke or systemic embolism, major bleeding, and death in patients with and without moderate or severe valvular heart disease using Cox proportional hazards modeling. Of the 18 201 patients enrolled in ARISTOTLE, 4808 (26.4%) had a history of moderate or severe valvular heart disease or previous valve surgery. Patients with valvular heart disease had higher rates of stroke or systemic embolism and bleeding than patients without valvular heart disease. There was no evidence of a differential effect of apixaban over warfarin in patients with and without valvular heart disease in reducing stroke and systemic embolism (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.51-0.97 and HR, 0.84; 95%, CI 0.67-1.04; interaction P=0.38), causing less major bleeding (HR, 0.79; 95% CI, 0.61-1.04 and HR, 0.65; 95% CI, 0.55-0.77; interaction P=0.23), and reducing mortality (HR, 1.01; 95% CI, 0.84-1.22 and HR, 0.84; 95% CI, 0.73-0.96; interaction P=0.10). CONCLUSIONS: More than a quarter of the patients in ARISTOTLE with nonvalvular atrial fibrillation had moderate or severe valvular heart disease. There was no evidence of a differential effect of apixaban over warfarin in reducing stroke or systemic embolism, causing less bleeding, and reducing death in patients with and without valvular heart disease. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Doenças das Valvas Cardíacas/tratamento farmacológico , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Tromboembolia/tratamento farmacológico , Varfarina/uso terapêutico , Idoso , Anticoagulantes/uso terapêutico , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Feminino , Doenças das Valvas Cardíacas/diagnóstico , Doenças das Valvas Cardíacas/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Tromboembolia/diagnóstico , Tromboembolia/epidemiologia
15.
Am Heart J ; 169(1): 25-30, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25497244

RESUMO

BACKGROUND: We sought to assess the occurrence of events after blinded study drug discontinuation and transition to open-label vitamin K antagonist (VKA) in ARISTOTLE. METHODS: At the end of ARISTOTLE, blinded study drug was stopped, and open-label VKA was recommended. For patients completing the trial on blinded study drug, a 2-day bridging period with apixaban or apixaban placebo was recommended (while beginning open-label VKA). Outcomes were assessed during the 30 days after stopping blinded study drug. RESULTS: Of the 6,809 patients in the apixaban group and 6,588 in the warfarin group who completed the trial on study drug, there were 21 strokes or systemic emboli (4.02%/year) and 26 major bleeding (4.97%/year) events in the apixaban group (transitioning to VKA) and 5 strokes or systemic emboli (0.99%/year) and 10 major bleeding (1.97%/year) events in the warfarin group (continuing on VKA), with most of the imbalance between groups being after the first week. Similar results were seen in the first 30 days of the trial where warfarin-naive patients starting warfarin had a higher rate of stroke or systemic emboli (5.41%/year) than warfarin-experienced patients (1.42%/year), a pattern not seen when starting apixaban. No similar increase in events with apixaban versus warfarin was seen during temporary or permanent study drug discontinuation during the trial. CONCLUSIONS: The excess in thrombotic and bleeding events in the apixaban group after study drug discontinuation appears to be related to an increased risk associated with the initiation of a VKA rather than a direct effect of apixaban. Whether ≥2 days of apixaban bridging improves outcomes during VKA transition is unknown and deserves further evaluation.


Assuntos
Anticoagulantes/uso terapêutico , Inibidores do Fator Xa/uso terapêutico , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Varfarina/uso terapêutico , Fibrilação Atrial/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Vitamina K/antagonistas & inibidores
16.
Circulation ; 132(8): 624-632, 2015. ilus
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: ses-32361

RESUMO

Apixaban is approved for the prevention of stroke and systemic embolism in patients with nonvalvular atrialfibrillation. However, the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation(ARISTOTLE) trial included a substantial number of patients with valvular heart disease and only excluded patients withclinically significant mitral stenosis or mechanical prosthetic heart valves.Methods and Results—We compared the effect of apixaban and warfarin on rates of stroke or systemic embolism, majorbleeding, and death in patients with and without moderate or severe valvular heart disease using Cox proportional hazardsmodeling. Of the 18 201 patients enrolled in ARISTOTLE, 4808 (26.4%) had a history of moderate or severe valvular heartdisease or previous valve surgery. Patients with valvular heart disease had higher rates of stroke or systemic embolismand bleeding than patients without valvular heart disease. There was no evidence of a differential effect of apixaban overwarfarin in patients with and without valvular heart disease in reducing stroke and systemic embolism (hazard ratio [HR],0.70; 95% confidence interval [CI], 0.51–0.97 and HR, 0.84; 95%, CI 0.67–1.04; interaction P=0.38), causing less majorbleeding (HR, 0.79; 95% CI, 0.61–1.04 and HR, 0.65; 95% CI, 0.55–0.77; interaction P=0.23), and reducing mortality(HR, 1.01; 95% CI, 0.84–1.22 and HR, 0.84; 95% CI, 0.73–0.96; interaction P=0.10).Conclusions—More than a quarter of the patients in ARISTOTLE with nonvalvular atrial fibrillation had moderate or severevalvular heart disease. There was no evidence of a differential effect of apixaban over warfarin in reducing stroke orsystemic embolism, causing less bleeding, and reducing death in patients with and without valvular heart disease. (AU)


Assuntos
Fibrilação Atrial , Doenças Cardiovasculares , Inibidor de Coagulação do Lúpus , Acidente Vascular Cerebral
17.
Am Heart J ; 168(3): 303-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25173541

RESUMO

BACKGROUND: The perceived risk of serious bleeding is an obstacle to the use of oral anticoagulation in East Asia. The efficacy and safety of apixaban in East Asian patients with atrial fibrillation are unknown. METHODS: ARISTOTLE included 18,201 patients with nonvalvular atrial fibrillation randomized to apixaban 5mg twice daily or warfarin. The efficacy and safety of apixaban and warfarin among patients recruited from East Asia (n = 1,993) were compared with those recruited from outside East Asia (n = 16,208). RESULTS: Compared with warfarin, apixaban resulted in a consistent reduction in stroke or systemic embolism in East Asian (hazard ratio [HR] 0.74, 95% CI 0.50-1.10) and non-East Asian (HR 0.81, 95% CI 0.66-0.99) patients (interaction P = .70). Consistent benefits of apixaban over warfarin were also seen for major bleeding in East Asian (HR 0.53, 95% CI 0.35-0.80) and non-East Asian (HR 0.72, 95% CI 0.62-0.83) patients (interaction P = .17). There was a greater reduction in major or clinically relevant nonmajor bleeding with apixaban compared with warfarin in East Asian (HR 0.49, 95% CI 0.35-0.67) than in non-East Asian (HR 0.71, 95% CI 0.63-0.79) patients (interaction P = .03). Numerically higher rates of intracranial bleeding were seen in East Asian patients with warfarin but not with apixaban. CONCLUSIONS: Apixaban resulted in similar reductions in stroke or systemic embolism and major bleeding and greater reductions in major or clinically relevant nonmajor bleeding in patients from East Asia. Warfarin is associated with more intracranial bleeding, particularly in patients from East Asia.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Varfarina/uso terapêutico , Idoso , Fibrilação Atrial/etnologia , Extremo Oriente/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/etnologia
18.
Int J Stroke ; 8(7): 591-7, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24024917

RESUMO

The availability of population-based epidemiological data on the incident risk of stroke is very scarce in Argentina and other Latin American countries. In response to the priorities established by the World Health Organization and the United Nations, PREVISTA was envisaged as a population-based program to determine the risk of first-ever and recurrent stroke and transient ischemic attack incidence and mortality in Tandil, Buenos Aires, Argentina. The study will be conducted according to Standardized Tools for Stroke Surveillance (STEPS Stroke) methodology and will enroll all new (incident) and recurrent consecutive cases of stroke and transient ischemic attack in the City of Tandil between May 1st, 2013 and April 30, 2015. The study will include patients with ischemic stroke, non-traumatic primary intracerebral hemorrhage, subarachnoid hemorrhage, and transient ischemic attack. To ensure the inclusion of every cerebrovascular event during an observation period of two years, we will instrument an 'intensive screening program', consisting of a comprehensive daily tracking of every potential event of stroke or transient ischemic attack using multiple overlapping sources. Mortality would be determined during follow-up for every enrolled patient. Also, fatal community events would be screened daily through revision of death certificates at funeral homes and local offices of vital statistics. All causes of death will be adjudicated by an ad-hoc committee. The close population of Tandil is representative of a large proportion of Latin-American countries with low- and middle-income economies. The findings and conclusions of PREVISTA may provide data that could support future health policy decision-making in the region.


Assuntos
Acidente Vascular Cerebral/epidemiologia , Argentina/epidemiologia , Humanos , Incidência , Projetos de Pesquisa
19.
Neurology ; 80(20): 1834-40, 2013 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-23596075

RESUMO

BACKGROUND: Based on the higher frequency of paroxysmal atrial fibrillation during night and early morning hours, we sought to analyze the association between newly diagnosed atrial fibrillation and wake-up ischemic cerebrovascular events. METHODS: We prospectively assessed every acute ischemic stroke and TIA patient admitted to our hospital between 2008 and 2011. We used a forward step-by-step multiple logistic regression analysis to assess the relationship between newly diagnosed atrial fibrillation and wake-up ischemic stroke or TIA, after adjusting for significant covariates. RESULTS: The study population comprised 356 patients, 274 (77.0%) with a diagnosis of acute ischemic stroke and 82 (23.0%) with TIA. A total of 41 (11.5%) of these events occurred during night sleep. A newly diagnosed atrial fibrillation was detected in 27 patients of 272 without known atrial fibrillation (9.9%). We found an independent association between newly diagnosed atrial fibrillation and wake-up ischemic stroke and TIA (odds ratio 3.6, 95% confidence interval 1.2-7.7, p = 0.019). CONCLUSIONS: The odds of detecting a newly diagnosed atrial fibrillation were 3-fold higher among wake-up cerebrovascular events than among non-wake-up events. The significance of this independent association between newly diagnosed atrial fibrillation and wake-up ischemic stroke and TIA and the role of other comorbidities should be investigated in future studies.


Assuntos
Fibrilação Atrial/diagnóstico , Ataque Isquêmico Transitório/diagnóstico , Acidente Vascular Cerebral/diagnóstico , Vigília , Idoso , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/fisiopatologia , Feminino , Humanos , Ataque Isquêmico Transitório/epidemiologia , Ataque Isquêmico Transitório/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/fisiopatologia , Vigília/fisiologia
20.
Lancet ; 380(9855): 1749-58, 2012 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-23036896

RESUMO

BACKGROUND: The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial showed that apixaban is better than warfarin at prevention of stroke or systemic embolism, causes less bleeding, and results in lower mortality. We assessed in this trial's participants how results differed according to patients' CHADS(2), CHA(2)DS(2)VASc, and HAS-BLED scores, used to predict the risk of stroke and bleeding. METHODS: ARISTOTLE was a double-blind, randomised trial that enrolled 18,201 patients with atrial fibrillation in 39 countries. Patients were randomly assigned apixaban 5 mg twice daily (n=9120) or warfarin (target international normalised ratio 2·0-3·0; n=9081). The primary endpoint was stroke or systemic embolism. The primary safety outcome was major bleeding. We calculated CHADS(2), CHA(2)DS(2)VASc, and HAS-BLED scores of patients at randomisation. Efficacy analyses were by intention to treat, and safety analyses were of the population who received the study drug. ARISTOTLE is registered with ClinicalTrials.gov, number NCT00412984. FINDINGS: Apixaban significantly reduced stroke or systemic embolism with no evidence of a differential effect by risk of stroke (CHADS(2) 1, 2, or ≥3, p for interaction=0·4457; or CHA(2)DS(2)VASc 1, 2, or ≥3, p for interaction=0·1210) or bleeding (HAS-BLED 0-1, 2, or ≥3, p for interaction=0·9422). Patients who received apixaban had lower rates of major bleeding than did those who received warfarin, with no difference across all score categories (CHADS(2), p for interaction=0·4018; CHA(2)DS(2)VASc, p for interaction=0·2059; HAS-BLED, p for interaction=0·7127). The relative risk reduction in intracranial bleeding tended to be greater in patients with HAS-BLED scores of 3 or higher (hazard ratio [HR] 0·22, 95% CI 0·10-0·48) than in those with HAS-BLED scores of 0-1 (HR 0·66, 0·39-1·12; p for interaction=0·0604). INTERPRETATION: Because apixaban has benefits over warfarin that are consistent across patient risk of stroke and bleeding as assessed by the CHADS2, CHA2DS2VASc, and HAS-BLED scores, these scores might be less relevant when used to tailor apixaban treatment to individual patients than they are for warfarin. Further improvement in risk stratification for both stroke and bleeding is needed, particularly for patients with atrial fibrillation at low risk for these events. FUNDING: Bristol-Myers Squibb and Pfizer.


Assuntos
Anticoagulantes/uso terapêutico , Hemorragia/prevenção & controle , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Varfarina/uso terapêutico , Idoso , Fibrilação Atrial/complicações , Método Duplo-Cego , Embolia/prevenção & controle , Humanos , Hemorragias Intracranianas/prevenção & controle , Masculino , Pessoa de Meia-Idade , Medição de Risco/métodos , Resultado do Tratamento
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