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INTRODUCTION: Studies of sex-based differences in atrial fibrillation (AF) suggest an influence of sex on cardiovascular death and stroke, however, results are conflicting.1,2 Discrepant findings could reflect sex-based differences in access to care, but no studies have explored sex-based differences in treatment and outcomes among countries with differing income levels and gender parity. Such data are needed to understand if sex-based care gaps exist and are associated with differences in outcomes. This knowledge could lead to country and sex-specific treatment recommendations. This study explores how sex differences in AF treatment and outcomes vary between countries based on their economic status and degree of gender parity in the Global RE-LY AF Registry. METHODS Study population and data collection From the prospective RE-LY registry [n = 15 400 patients presenting to an emergency department (ED) with AF in 47 countries between 2007 and 2011],3,4 we excluded patients without AF as primary listed reason for ED presentation (n = 8561), or missing outcomes or CHADS2 score (n = 213), resulting in a sample of 6626 patients. We defined rhythm control as treatment with cardioversion, AF ablation, or the use of any anti-arrhythmic drug. Outcomes were obtained at one-year follow-up and included repeated hospitalization for AF, heart failure (HF) hospitalization, stroke or transient ischaemic attack (TIA), and death.3 Statistical analysis Selected baseline variables are presented as means ± standard deviation, median [interquartile range (IQR)] or proportion. Sex-based differences in treatments and outcomes are presented as crude proportions, with odds ratios (OR) for female sex compared to male sex and P-values derived from multi-level logistic regression with a random effect on country, adjusted for CHADS2 score, which was the recommended risk stratification tool at the time of study initiation.4 To explore the influence on outcome risks by gender-based disparities or economic factors, we stratified on the World Economic Forum (WEF) Global Gender Gap score for 2011, which estimates country-level overall gender parity with a 0­100 score annually. We used World Bank classifications of income for 2011 to group countries as 'low and lower-middle', 'upper-middle', and 'high' income countries. Interaction parameters were assessed in CHADS2-adjusted logistic regression models. All statistical analyses were performed using Stata v 17.0 for Mac (StataCorp, College Station, TX, USA). The study conforms to the Declaration of Helsinki and received ethical approval at all sites. All subjects gave written informed consent. RESULTS: Overall, females were older (65.5 ± 14.4 vs. 61.5 ± 14.2 years, P < .0001), had a higher median CHADS2 score [1 (IQR 1) vs. 1 (IQR 2), P < .0001], and more permanent AF (21.5% vs. 18.9%, P = .008). The ED visit resulted in hospitalization in 56.1% of females and 53.6% of males (P = .09).

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Humanos , Feminino , Fibrilação Atrial , Serviço Hospitalar de Emergência , Identidade de Gênero , Sexo , Razão de Chances , Interpretação Estatística de Dados , Acidente Vascular Cerebral , Transversalidade de Gênero

RESUMO

ABSTRACT: Aims Data on patient characteristics, prevalence, and outcomes of atrial fibrillation (AF) patients without traditional risk factors, often labelled 'lone AF', are sparse. METHODS AND RESULTS: The RE-LY AF registry included 15 400 individuals who presented to emergency departments with AF in 47 countries. This analysis focused on patients without traditional risk factors, including age ≥60 years, hypertension, coronary artery disease, heart failure, left ventricular hypertrophy, congenital heart disease, pulmonary disease, valve heart disease, hyperthyroidism, and prior cardiac surgery. Patients without traditional risk factors were compared with age- and region-matched controls with traditional risk factors (1:3 fashion). In 796 (5%) patients, no traditional risk factors were present. However, 98% (779/796) had less-established or borderline risk factors, including borderline hypertension (130-140/80-90 mmHg; 47%), chronic kidney disease (eGFR < 60 mL/min; 57%), obesity (body mass index > 30; 19%), diabetes (5%), excessive alcohol intake (>14 units/week; 4%), and smoking (25%). Compared with patients with traditional risk factors (n = 2388), patients without traditional risk factors were more often men (74% vs. 59%, P < 0.001) had paroxysmal AF (55% vs. 37%, P < 0.001) and less AF persistence after 1 year (21% vs. 49%, P < 0.001). Furthermore, 1-year stroke occurrence rate (0.6% vs. 2.0%, P = 0.013) and heart failure hospitalizations (0.9% vs. 12.5%, P < 0.001) were lower. However, risk of AF-related re-hospitalization was similar (18% vs. 21%, P = 0.09). CONCLUSION: Almost all patients without traditionally defined AF risk factors have less-established or borderline risk factors. These patients have a favourable 1-year prognosis, but risk of AF-related re-hospitalization remains high. Greater emphasis should be placed on recognition and management of less-established or borderline risk factors.

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Fibrilação Atrial , Transtorno da Personalidade Borderline , Fatores de Risco

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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.

Assuntos

Fibrilação Atrial/tratamento farmacológico , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Medição de Risco/métodos , Acidente Vascular Cerebral/prevenção & controle , Varfarina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/epidemiologia , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Saúde Global , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Taxa de Sobrevida/tendências , Resultado do Tratamento

RESUMO

OBJECTIVE: To assess stroke/systemic embolism, major bleeding and other outcomes, and treatment effect of apixaban versus warfarin, in patients with atrial fibrillation (AF) and different types of valvular heart disease (VHD), using data from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial. METHODS: There were 14 793 patients with known VHD status, categorised as having moderate or severe mitral regurgitation (MR) (n=3382), aortic regurgitation (AR) (n=842) or aortic stenosis (AS) (n=324); patients with moderate or severe mitral stenosis were excluded from the trial. Baseline characteristics, efficacy and safety outcomes were compared between each type and no significant VHD. Treatment effect was assessed using an adjusted model. Results Patients with MR or AR had similar rates of stroke/systemic embolism and bleeding compared with patients without MR or AR, respectively. Patients with AS had significantly higher event rates (presented as rate per 100 patient-years of follow-up) of stroke/ systemic embolism (3.47 vs 1.36; adjusted HR (adjHR) 2.21, 95% CI 1.35 to 3.63), death (8.30 vs 3.53; adjHR 1.92, 95% CI 1.41 to 2.61), major bleeding (5.31 vs 2.53; adjHR 1.80, 95% CI 1.19 to 2.75) and intracranial bleeding (1.29 vs 0.51; adjHR 2.54, 95% CI 1.08 to 5.96) than patients without AS. The superiority of apixaban over warfarin on stroke/systemic embolism was similar in patients with versus without MR (HR 0.69, 95% CI 0.46 to 1.04 vs HR 0.79, 95% CI 0.63 to 1.00; interaction P value 0.52), with versus without AR (HR 0.57, 95% CI 0.27 to 1.20 vs HR 0.78, 95% CI 0.63 to 0.96; interaction P value 0.52), and with versus without AS (HR 0.44, 95% CI 0.17 to 1.13 vs HR 0.79, 95% CI 0.64 to 0.97; interaction P value 0.19). For each of the primary and secondary efficacy and safety outcomes, there was no evidence of a different effect of apixaban over warfarin in patients with any VHD subcategory. CONCLUSIONS: In anticoagulated patients with AF, AS is associated with a higher risk of stroke/systemic embolism, bleeding and death. The efficacy and safety benefits of apixaban compared with warfarin were consistent, regardless of presence of MR, AR or AS.

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Valva Aórtica , Fibrilação Atrial , Doenças das Valvas Cardíacas , Anticoagulantes

RESUMO

METHOD AND RESULTS:Thrombo-embolic events were defined as stroke (ischaemic or unknown cause) or systemic embolism (SE). Clinical outcomes were estimated using the Kaplan­Meier method. All-cause mortality and International Society on Thrombosis and Haemostasis (ISTH) major bleeding after events were analysed using a Cox proportional hazards model with time-dependent covariates. Of 18 201 patients in ARISTOTLE, 365 experienced a thrombo-embolic event [337 strokes (ischaemic or unknown cause), 28 SE]; 46 (12.6%) of which were fatal. In the 30 days before and after a thrombo-embolic event, 11% and 37% of patients, respectively, were not taking an oral anticoagulant. During follow-up (median 1.8 years), 22 patients (7.1%/year) had a recurrent stroke, 97 (30.1%/year) died, and 10 (6.7%/year) had major bleeding. Compared with patients without a thrombo-embolic event, the short- and long-term adjusted hazards of death in patients with a thrombo-embolic event were high [30 days: HR 3.5, 95% CI 2.5­4.8; both P< 0.001]. The adjusted hazards of major bleeding were also high short-term (HR 10.37, 95% CI 3.87­27.78; P< 0.001) but not long-term (HR 1.7, 95% CI: 0.77­3.88; P= 0.18). CONCLUSIONS: Thrombo-embolic events were rare but associated with high short- and long-term morbidity and mortality. Substantial numbers of patients are not receiving oral anticoagulant therapy before and, despite this risk, after a first thrombo-embolic event.

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Fibrilação Atrial , Trombose , Modelos de Riscos Proporcionais , Fibrinolíticos , Anticoagulantes

RESUMO

OBJECTIVE: Acute coronary syndrome (ACS) trials typically use a composite primary outcome (myocardial infarction [MI], stroke, or cardiovascular death), but differential patient characteristics, timing, and consequences associated with individual component end points as first events have not been well studied. We compared patient characteristics and prognostic significance associated with first cardiovascular events in the post-ACS setting for initially stabilized patients. METHODS: We combined patient-level data from 4 trials of post-ACS antithrombotic therapies (PLATO, APPRAISE-2, TRACER, and TRILOGY ACS) to characterize the timing of and characteristics associated with first cardiovascular events (MI, stroke, or cardiovascular death). Landmark analysis at 7 days after index ACS presentation was used to focus on spontaneous, postdischarge events that were not confounded by in-hospital procedural complications. Using a competing risk framework, we tested for differential associations between prespecified covariates and the occurrence of nonfatal stroke vs MI as the first event, and we examined subsequent events after the first nonfatal event. RESULTS: Among 46,694 patients with a median follow-up of 358 (25th, 75th percentiles 262, 486) days, a first ischemic event occurred in 4,307 patients (9.2%) as follows: MI in 5.8% (n = 2,690), stroke in 1.0% (n = 477), and cardiovascular death in 2.4% (n = 1,140). Older age, prior stroke/transient ischemic attack, prior atrial fibrillation, and higher diastolic blood pressure were associated with a significantly greater risk of stroke vs MI, whereas prior percutaneous coronary intervention was associated with a greater risk of MI vs stroke. Second events occurred in 32% of those with a first nonfatal stroke at a median of 13 (3, 59) days after the first event and in 32% of those with a first nonfatal MI at a median of 35 (5, 137) days after the first event. The most common second event was a recurrent MI among those with MI as the first event and cardiovascular death among those with stroke as the first event. CONCLUSIONS: Approximately 9% of patients experienced a first cardiovascular event in the post-ACS setting during a median follow-up of 1 year. Although the profile and prognostic implications of stroke vs MI as the first nonfatal event differ substantially, approximately one-third of these patients experienced a second event, typically soon after the first event. These findings have implications for improving post-ACS care and influencing the design of future cardiovascular trials.

Assuntos

Síndrome Coronariana Aguda/complicações , Infarto do Miocárdio/etiologia , Acidente Vascular Cerebral/etiologia , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Recidiva , Acidente Vascular Cerebral/mortalidade , Fatores de Tempo

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

RESUMO

BACKGROUND: Underlying mechanisms behind the hypothesized relationship between periodontal disease (PD) and coronary heart disease (CHD) have been insufficiently explored. We evaluated associations between self-reported tooth loss- a marker of PD- and prognostic biomarkers in 15,456 (97%) patients with stable CHD in the global STABILITY trial. METHODS AND RESULTS: Base line blood samples were obtained and patients reported their number of teeth according to the following tooth loss levels: "26-32 (All)" [lowest level], "20-25", "15-19", "1-14", and "No Teeth" [highest level]. Linear and Cox regression models assessed associations between tooth loss levels and biomarker levels, and the relationship between tooth loss levels and outcomes, respectively. After multivariable adjustment, the relative biomarker increase between the highest and the lowest tooth loss level was: high-sensitivity C-reactive protein 1.21 (95% confidence interval, 1.14-1.29), interleukin 6 1.14 (1.10-1.18), lipoprotein-associated phospholipase A2 activity 1.05 (1.03-1.06), growth differentiation factor 15 1.11 (1.08-1.14), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) 1.18 (1.11-1.25)...

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Biomarcadores , Doenças Periodontais , Fatores de Risco , Perda de Dente

RESUMO

Background: Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor prevents ischaemic events after coronary stenting, but increases bleeding. Guidelines support weighting bleeding risk before the selection of treatment duration, but no standardised tool exists for this purpose. Methods: A total of 14 963 patients treated with DAPT after coronary stenting—largely consisting of aspirin and clopidogrel and without indication to oral anticoagulation—were pooled at a single-patient level from eight multicentre randomised clinical trials with independent adjudication of events. Using Cox proportional hazards regression, we identified predictors of out-of-hospital Thrombosis in Myocardial Infarction (TIMI) major or minor bleeding stratified by trial, and developed a numerical bleeding risk score. The predictive performance of the novel score was assessed in the derivation cohort and validated in patients treated with percutaneous coronary intervention from the PLATelet inhibition and patient Outcomes (PLATO) trial (n=8595) and BernPCI registry (n=6172). The novel score was assessed within patients randomised to different DAPT durations (n=10 081) to identify the effect on bleeding and ischaemia of a long (12–24 months) or short (3–6 months) treatment in relation to baseline bleeding risk...

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Conduta do Tratamento Medicamentoso , Coração , Pacientes , Stents Farmacológicos , Terapêutica

RESUMO

BACKGROUND: Antithrombotic therapy plays an important role in the treatment of non-ST-segment elevation acute coronary syndromes (NSTE ACS) but is associated with bleeding risk. Advanced age may modify the relationship between efficacy and safety. METHODS: Efficacy and safety of vorapaxar (a protease-activated receptor 1 antagonist) was analyzed across ages as a continuous and a categorical variable in the 12,944 patients with NSTE ACS enrolled in the TRACER trial. To evaluate the effect of age, Cox regression models were developed to estimate hazard ratios (HRs) with the adjustment of other baseline characteristics and randomized treatment for the primary efficacy composite of cardiovascular death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization, and the primary safety composite of moderate or severe Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) bleeding. RESULTS: The median age of the population was 64years (25th, 75th percentiles = 58, 71). Also, 1,791 patients (13.8%) were ≤54years of age, 4,968 (38.4%) were between 55 and 64 years, 3,979 (30.7%) were between 65 and 74 years, and 2,206 (17.1%) were 75years or older. Older patients had higher rates of hypertension, renal insufficiency, and previous stroke and worse Killip class. The oldest age group (≥75years) had substantially higher 2-year rates of the composite ischemic end point and moderate or severe GUSTO bleeding compared with the youngest age group (≤54years). The relationships between treatment assignment (vorapaxar vs placebo) and efficacy outcomes did not vary by age. For the primary efficacy end point, the HRs (95% CIs) comparing vorapaxar and placebo in the 4 age groups were as follows: 1.12 (0.88-1.43), 0.88 (0.76-1.02), 0.89 (0.76-1.04), and 0.88 (0.74-1.06), respectively (P value for interaction = .435). Similar to what was observed for efficacy outcomes, we did not observe any interaction between vorapaxar and age on bleeding outcomes. For the composite of moderate or severe bleeding according to the GUSTO classification, the HRs (95% CIs) comparing vorapaxar and placebo in the 4 age groups were 1.73 (0.89-3.34), 1.39 (1.04-1.86), 1.10 (0.85-1.42), and 1.73 (1.29-2.33), respectively (P value for interaction = .574). CONCLUSION: Older patients had a greater risk for ischemic and bleeding events; however, the efficacy and safety of vorapaxar in NSTE ACS were not significantly influenced by age.

Assuntos

Síndrome Coronariana Aguda/tratamento farmacológico , Lactonas/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Piridinas/uso terapêutico , Fatores Etários , Idoso , Doenças Cardiovasculares/mortalidade , Método Duplo-Cego , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Revascularização Miocárdica , Readmissão do Paciente , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Acidente Vascular Cerebral/epidemiologia , Resultado do Tratamento

RESUMO

Methods: Efficacy and safety of vorapaxar (a protease-activated receptor 1 antagonist) was analyzed across ages as a continuous and a categorical variable in the 12,944 patients with NSTE ACS enrolled in the TRACER trial. To evaluate the effect of age, Cox regression models were developed to estimate hazard ratios (HRs) with the adjustment of other baseline characteristics and randomized treatment for the primary efficacy composite of cardiovascular death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization, and the primary safety composite of moderate or severe Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) bleeding. ResultsThe median age of the population was 64 years (25th, 75th percentiles = 58, 71). Also, 1,791 patients (13.8%) were ≤54 years of age, 4,968 (38.4%) were between 55 and 64 years, 3,979 (30.7%) were between 65 and 74 years, and 2,206 (17.1%) were 75 years or older. Older patients had higher rates of hypertension, renal insufficiency, and previous stroke and worse Killip class. The oldest age group (≥75 years) had substantially higher 2-year rates of the composite ischemic end point and moderate or severe GUSTO bleeding compared with the youngest age group (≤54 years). The relationships between treatment assignment (vorapaxar vs placebo) and efficacy outcomes did not vary by age. For the primary efficacy end point, the HRs (95% CIs) comparing vorapaxar and placebo in the 4 age groups were as follows: 1.12 (0.88-1.43), 0.88 (0.76-1.02), 0.89 (0.76-1.04), and 0.88 (0.74-1.06), respectively (P value for interaction = .435)...

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Síndrome Coronariana Aguda , Terapêutica

RESUMO

Background-—We evaluated lipoprotein-associated phospholipase A2 (Lp-PLA2) activity in patients with stable coronary heart disease before and during treatment with darapladib, a selective Lp-PLA2 inhibitor, in relation to outcomes and the effects ofdarapladib in the STABILITY trial. Methods and Results-—Plasma Lp-PLA2 activity was determined at baseline (n=14 500); at 1 month (n=13 709); serially (n=100)at 3, 6, and 18 months; and at the end of treatment. Adjusted Cox regression models evaluated associations between Lp-PLA2activity levels and outcomes. At baseline, the median Lp-PLA2 level was 172.4 lmol/min per liter (interquartile range 143.1–204.2lmol/min per liter). Comparing the highest and lowest Lp-PLA2 quartile groups, the hazard ratios were 1.50 (95% CI 1.23–1.82) forthe primary composite end point (cardiovascular death, myocardial infarction, or stroke), 1.95 (95% CI 1.29–2.93) forhospitalization for heart failure, 1.42 (1.07–1.89) for cardiovascular death, and 1.37 (1.03–1.81) for myocardial infarction afteradjustment for baseline characteristics, standard laboratory variables, and other prognostic biomarkers. Treatment with darapladibled to a 65% persistent reduction in median Lp-PLA2 activity. There were no associations between on-treatment Lp-PLA2 activityor changes of Lp-PLA2 activity and outcomes, and there were no significant interactions between baseline and on-treatment LpPLA2 activity or changes in Lp-PLA2 activity levels and the effects of darapladib on outcomes...

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Colecistite , Doenças das Artérias Carótidas , Infarto do Miocárdio , Lipase Lipoproteica

RESUMO

Background Atrial fi brillation is an important cause of morbidity and mortality worldwide, but scant data are availablefor long-term outcomes in individuals outside North America or Europe, especially in primary care settings. Methods We did a cohort study using a prospective registry of patients in 47 countries who presented to a hospital emergency department with atrial fi brillation or atrial fl utter as a primary or secondary diagnosis. 15 400 individuals were enrolled to determine the occurrence of death and strokes (the primary outcomes) in this cohort over eight geographical regions (North America, western Europe, and Australia; South America; eastern Europe; the Middle Eastand Mediterrane an crescent; sub-Saharan Africa; India; China; and southeast Asia) 1 year after attending the emergency department. Patients from North America, western Europe, and Australia were used as the reference population, and compared with patients from the other seven regions...

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Acidente Vascular Cerebral , Fibrilação Atrial

RESUMO

BACKGROUND: Amiodarone is an effective medication in preventing atrial fibrillation (AF), but it interferes with the metabolism of warfarin. OBJECTIVES: This study sought to examine the association of major thrombotic clinical events and bleeding with the use of amiodarone in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. METHODS: Baseline characteristics of patients who received amiodarone at randomization were compared with those who did not receive amiodarone. The interaction between randomized treatment and amiodarone was tested using a Cox model, with main effects for randomized treatment and amiodarone and their interaction. Matching on the basis of a propensity score was used to compare patients who received and who did not receive amiodarone at the time of randomization. RESULTS: In ARISTOTLE, 2,051 (11.4%) patients received amiodarone at randomization. Patients on warfarin and amiodarone had time in the therapeutic range that was lower than patients not on amiodarone (56.5% vs. 63.0%; p < 0.0001). More amiodarone-treated patients had a stroke or a systemic embolism (1.58%/year vs. 1.19%/year; adjusted hazard ratio [HR]: 1.47, 95% confidence interval [CI]: 1.03 to 2.10; p = 0.0322). Overall mortality and major bleeding rates were elevated, but were not significantly different in amiodarone-treated patients and patients not on amiodarone. When comparing apixaban with warfarin, patients who received amiodarone had a stroke or a systemic embolism rate of 1.24%/year versus 1.85%/year (HR: 0.68, 95% CI: 0.40 to 1.15), death of 4.15%/year versus 5.65%/year (HR: 0.74, 95% CI: 0.55 to 0.98), and major bleeding of 1.86%/year versus 3.06%/year (HR: 0.61, 95% CI: 0.39 to 0.96). In patients who did not receive amiodarone, the stroke or systemic embolism rate was 1.29%/year versus 1.57%/year (HR: 0.82, 95% CI: 0.68 to 1.00), death was 3.43%/year versus 3.68%/year (HR: 0.93, 95% CI: 0.83 to 1.05), and major bleeding was 2.18%/year versus 3.03%/year (HR: 0.72, 95% CI: 0.62 to 0.84). The interaction p values for amiodarone use by apixaban treatment effects were not significant. CONCLUSIONS: Amiodarone use was associated with significantly increased stroke and systemic embolism risk and a lower time in the therapeutic range when used with warfarin. Apixaban consistently reduced the rate of stroke and systemic embolism, death, and major bleeding compared with warfarin in amiodarone-treated patients and patients who were not on amiodarone.

Assuntos

Amiodarona/administração & dosagem , Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Idoso , Antiarrítmicos/administração & dosagem , Fibrilação Atrial/fisiopatologia , Brasil/epidemiologia , Causas de Morte/tendências , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Eletrocardiografia , Europa (Continente)/epidemiologia , Inibidores do Fator Xa/administração & dosagem , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Taxa de Sobrevida/tendências , Tromboembolia/complicações , Tromboembolia/epidemiologia , Tromboembolia/prevenção & controle , Resultado do Tratamento , Estados Unidos/epidemiologia , Varfarina/administração & dosagem

RESUMO

Amiodarone is an effective medication in preventing atrial fibrillation (AF), but it interferes with the metabolism of warfarin.Objectives This study sought to examine the association of major thrombotic clinical events and bleeding with the use of amiodarone in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial.Methods Baseline characteristics of patients who received amiodarone at randomization were compared with those who did not receive amiodarone. The interaction between randomized treatment and amiodarone was tested using a Cox model, with main effects for randomized treatment and amiodarone and their interaction. Matching on the basis of a propensity score was used to compare patients who received and who did not receive amiodarone at the time of randomization.Results In ARISTOTLE, 2,051 (11.4%) patients received amiodarone at randomization. Patients on warfarin and amiodarone had time in the therapeutic range that was lower than patients not on amiodarone (56.5% vs. 63.0%; p < 0.0001). More amiodarone-treated patients had a stroke or a systemic embolism (1.58%/year vs. 1.19%/year; adjusted hazard ratio [HR]: 1.47, 95% confidence interval [CI]: 1.03 to 2.10; p = 0.0322). Overall mortality and major bleeding rates were elevated, but were not significantly different in amiodarone-treated patients and patients not on amiodarone. When comparing apixaban with warfarin, patients who received amiodarone had a stroke or a systemic embolism rate of 1.24%/year versus 1.85%/year (HR: 0.68, 95% CI: 0.40 to 1.15), death of 4.15%/year versus 5.65%/year (HR: 0.74, 95% CI: 0.55 to 0.98)...

Assuntos

Acidente Vascular Cerebral , Amiodarona , Fibrilação Atrial

RESUMO

BACKGROUND: A substantial portion of patients with atrial fibrillation (AF) also have coronary artery disease (CAD) and are at risk for coronary events. Warfarin is known to reduce these events, but increase the risk of bleeding. We assessed the effects of apixaban compared with warfarin in AF patients with and without prior CAD. METHODS AND RESULTS: In ARISTOTLE, 18,201 patients with AF were randomized to apixaban or warfarin. History of CAD was defined as documented CAD, prior myocardial infarction, and/or history of coronary revascularization. We analyzed baseline characteristics and clinical outcomes of patients with and without prior CAD and compared outcomes by randomized treatment using Cox models. A total of 6639 (36.5%) patients had prior CAD. These patients were more often male, more likely to have prior stroke, diabetes, and hypertension, and more often received aspirin at baseline (42.2% vs. 24.5%). The effects of apixaban were similar among patients with and without prior CAD on reducing stroke or systemic embolism and death from any cause (hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.71-1.27, P for interaction=0.12; HR 0.96, 95% CI 0.81-1.13, P for interaction=0.28). Rates of myocardial infarction were numerically lower with apixaban than warfarin among patients with and without prior CAD. The effect of apixaban on reducing major bleeding and intracranial hemorrhage was consistent in patients with and without CAD. CONCLUSIONS: In patients with AF, apixaban more often prevented stroke or systemic embolism and death and caused less bleeding than warfarin, regardless of the presence of prior CAD. Given the common occurrence of AF and CAD and the higher rates of cardiovascular events and death, our results indicate that apixaban may be a better treatment option than warfarin for these high-risk patients.

Assuntos

Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/mortalidade , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/mortalidade , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Varfarina/administração & dosagem , Adulto , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Embolia/mortalidade , Embolia/prevenção & controle , Feminino , Fibrinolíticos/administração & dosagem , Fibrinolíticos/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Fatores de Risco , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/prevenção & controle , Resultado do Tratamento , Varfarina/efeitos adversos

RESUMO

Dabigatran reduces ischemic stroke in comparison with warfarin; however, given the lack of antidote, thereis concern that it might increase bleeding when surgery or invasive procedures are required.Methods and Results—The current analysis was undertaken to compare the periprocedural bleeding risk of patients in theRandomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial treated with dabigatran and warfarin.Bleeding rates were evaluated from 7 days before until 30 days after invasive procedures, considering only the firstprocedure for each patient. A total of 4591 patients underwent at least 1 invasive procedure: 24.7% of patients receiveddabigatran 110 mg, 25.4% received dabigatran 150 mg, and 25.9% received warfarin, P 0.34. Procedures included:pacemaker/defibrillator insertion (10.3%), dental procedures (10.0%), diagnostic procedures (10.0%), cataract removal(9.3%), colonoscopy (8.6%), and joint replacement (6.2%). Among patients assigned to either dabigatran dose, the lastdose of study drug was given 49 (35– 85) hours before the procedure on comparison with 114 (87–144) hours in patientsreceiving warfarin, P 0.001. There was no significant difference in the rates of periprocedural major bleeding betweenpatients receiving dabigatran 110 mg (3.8%) or dabigatran 150 mg (5.1%) or warfarin (4.6%); dabigatran 110 mg versuswarfarin: relative risk, 0.83; 95% CI, 0.59 to 1.17; P 0.28; dabigatran 150 mg versus warfarin: relative risk, 1.09; 95%CI, 0.80 to 1.49; P 0.58. Among patients having urgent surgery, major bleeding occurred in 17.8% with dabigatran 110mg, 17.7% with dabigatran 150 mg, and 21.6% with warfarin: dabigatran 110 mg; relative risk, 0.82; 95% CI, 0.48 to1.41; P 0.47; dabigatran 150 mg: relative risk, 0.82; 95% CI, 0.50 to 1.35; P 0.44.Conclusions—Dabigatran and warfarin were associated with similar rates of periprocedural bleeding, including patientshaving urgent surgery. Dabigatran facilitated a shorter interruption...

Assuntos

Acidente Vascular Cerebral , Anticoagulantes , Fibrilação Atrial

RESUMO

To discuss and share knowledge around advances in the care of patients with thrombotic disorders, the Third International Symposium of Thrombosis and Anticoagulation was held in São Paulo, Brazil, from October 14-16, 2010. This scientific program was developed by clinicians for clinicians, and was promoted by four major clinical research institutes: the Brazilian Clinical Research Institute, the Duke Clinical Research Institute of the Duke University School of Medicine, the Canadian VIGOUR Centre, and the Uppsala Clinical Research Center. Comprising 3 days of academic presentations and open discussion, the symposium had as its primary goal to educate, motivate, and inspire internists, cardiologists, hematologists, and other physicians by convening national and international visionaries, thought-leaders, and dedicated clinician-scientists. This paper summarizes the symposium proceedings.

Assuntos

Anticoagulantes/uso terapêutico , Congressos como Assunto , Trombose/tratamento farmacológico , Trombose/metabolismo , Brasil , Humanos

RESUMO

Background: A recent randomized, controlled trial, the Fifth Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS 5) trial, reported that major bleeding was 2-fold less frequent with fondaparinux than with enoxaparin in acute coronary syndromes (ACS). Renal dysfunction increases the risk for major bleeding. Objective: To compare the efficacy and safety of fondaparinux and enoxaparin over the spectrum of renal dysfunction observed in the OASIS 5 trial. Design: Subgroup analysis of a randomized, controlled trial. Setting: Patients presenting to the hospital with non–ST-segment elevation ACS. Patients: 19 979 of the 20 078 patients in the OASIS 5 trial in whom creatinine was measured at baseline. Measurements: Death, myocardial infarction, refractory ischemia, and major bleeding were evaluated separately and as a composite end point at 9, 30, and 180 days. Glomerular filtration rate (GFR) was calculated by using the Modification of Diet in Renal Disease formula. Results: The absolute differences in favor of fondaparinux (efficacy and safety) were most marked in patients with a GFR less than 58 mL/min per 1.73 m2; the largest differences occurred in major bleeding events. At 9 days, death, myocardial infarction, or refractory ischemia occurred in 6.7% of patients receiving fondaparinux and 7.4% of those receiving enoxaparin (hazard ratio, 0.90 [95% CI, 0.73 to 1.11]); major bleeding occurred in 2.8% and 6.4%, respectively (hazard ratio, 0.42 [CI, 0.32 to 0.56]). Statistically significant differences in major bleeding persisted at 30 and 180 days. The rates of the composite end point were lower with fondaparinux than with enoxaparin in all quartiles of GFR, but the differences were statistically significant only among patients with a GFR less than 58 mL/min per 1.73 m2. Limitations: Subgroup analyses warrant caution; the study was powered to detect noninferiority at 9 days. Fondaparinux is not approved for use in patients with ACS in the United States. Conclusions: The benefits of fondaparinux over enoxaparin when administered for non–ST-segment elevation ACS are most marked among patients with renal dysfunction and are largely explained by lower rates of major bleeding with fondaparinux.

Assuntos

Doença das Coronárias , Enoxaparina , Rim