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1.
Thromb Haemost ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33634446

RESUMO

BACKGROUND: Lack of data on balancing bleeding and thrombosis risk causes uncertainty about restarting anticoagulants after major bleeding. Anticoagulant reversal trials offer prospectively gathered data after major bleeding with well-documented safety events and restarting behavior. OBJECTIVES: To examine the relationship of restarting anticoagulation with thrombosis, rebleeding and death. PATIENTS/METHODS: This is a post hoc analysis of a prospective factor Xa inhibitor reversal study at 63 centers in North America and Europe. We compared outcomes of restarted patients with those not restarted using landmark and time-dependent Cox Proportional Hazards models. Outcomes included thrombotic and bleeding events and death and a composite of all three. RESULTS: Of 352 patients enrolled, oral anticoagulation was restarted in 100 (28%) during 30-day follow-up. Thirty-four (9.7%) had thrombotic events, 15 (4.3%) had bleeding events (after day 3) and 49 (14%) died. In the landmark analysis comparing patients restarted within 14 days to those not, restarting was associated with decreased thrombotic events (hazard ratio [HR]=0.112; 95% CI, 0.001 to 0.944; P=0.043) and increased rebleeding (HR=8.39; 95% CI, 1.13 to 62.29; P=0.037). The time-dependent Cox model showed evidence for a reduction in a composite (thrombotic events, bleeding and death) attempting to capture net benefit (HR=0.384; 95% CI, 0.161 to 0.915; P=0.031). CONCLUSIONS: This analysis provides modest evidence that restarting anticoagulation in factor Xa inhibitor-associated major bleeding patients is correlated with reduced risk of thrombotic events and increased risk of re-bleeding. There is low-level evidence of net benefit for re-starting. A randomized trial of re-starting would be appropriate.

2.
JAMA Cardiol ; 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33625468

RESUMO

Importance: Atrial fibrillation (AF) is a major cause of preventable strokes. Screening asymptomatic individuals for AF may increase anticoagulant use for stroke prevention. Objective: To evaluate 2 home-based AF screening interventions. Design, Setting, and Participants: This multicenter randomized clinical trial recruited individuals from primary care practices aged 75 years or older with hypertension and without known AF. From April 5, 2015, to March 26, 2019, 856 participants were enrolled from 48 practices. Interventions: The control group received standard care (routine clinical follow-up plus a pulse check and heart auscultation at baseline and 6 months). The screening group received a 2-week continuous electrocardiographic (cECG) patch monitor to wear at baseline and at 3 months, in addition to standard care. The screening group also received automated home blood pressure (BP) machines with oscillometric AF screening capability to use twice-daily during the cECG monitoring periods. Main Outcomes and Measures: With intention-to-screen analysis, the primary outcome was AF detected by cECG monitoring or clinically within 6 months. Secondary outcomes included anticoagulant use, device adherence, and AF detection by BP monitors. Results: Of the 856 participants, 487 were women (56.9%); mean (SD) age was 80.0 (4.0) years. Median cECG wear time was 27.4 of 28 days (interquartile range [IQR], 18.4-28.0 days). In the primary analysis, AF was detected in 23 of 434 participants (5.3%) in the screening group vs 2 of 422 (0.5%) in the control group (relative risk, 11.2; 95% CI, 2.7-47.1; P = .001; absolute difference, 4.8%; 95% CI, 2.6%-7.0%; P < .001; number needed to screen, 21). Of those with cECG-detected AF, median total time spent in AF was 6.3 hours (IQR, 4.2-14.0 hours; range 1.3 hours-28 days), and median duration of the longest AF episode was 5.7 hours (IQR, 2.9-12.9 hours). Anticoagulation was initiated in 15 of 20 patients (75.0%) with cECG-detected AF. By 6 months, anticoagulant therapy had been prescribed for 18 of 434 participants (4.1%) in the screening group vs 4 of 422 (0.9%) in the control group (relative risk, 4.4; 95% CI, 1.5-12.8; P = .007; absolute difference, 3.2%; 95% CI, 1.1%-5.3%; P = .003). Twice-daily AF screening using the home BP monitor had a sensitivity of 35.0% (95% CI, 15.4%-59.2%), specificity of 81.0% (95% CI, 76.7%-84.8%), positive predictive value of 8.9% (95% CI, 4.9%-15.5%), and negative predictive value of 95.9% (95% CI, 94.5%-97.0%). Adverse skin reactions requiring premature discontinuation of cECG monitoring occurred in 5 of 434 participants (1.2%). Conclusions and Relevance: In this randomized clinical trial, among older community-dwelling individuals with hypertension, AF screening with a wearable cECG monitor was well tolerated, increased AF detection 10-fold, and prompted initiation of anticoagulant therapy in most cases. Compared with continuous ECG, intermittent oscillometric screening with a BP monitor was an inferior strategy for detecting paroxysmal AF. Large trials with hard clinical outcomes are now needed to evaluate the potential benefits and harms of AF screening. Trial Registration: ClinicalTrials.gov Identifier: NCT02392754.

3.
Cardiovasc Res ; 2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33386845

RESUMO

AIMS: Patients with atrial fibrillation (AF) and rheumatic heart disease (RHD), especially mitral stenosis, are assumed to be at high risk of stroke, irrespective of other factors. We aimed to re-evaluate stroke risk factors in a contemporary cohort of AF patients. METHODS AND RESULTS: We analyzed data of 15,400 AF patients presenting to an emergency department and who were enrolled in the global RE-LY AF registry, representing 47 countries from all inhabited continents. Follow-up occurred at 1 year after enrollment. A total of 1,788 (11.6%) patients had RHD. These patients were younger (51.4 ± 15.7 vs. 67.8 ± 13.6 years), more likely to be female (66.2% vs. 44.7%) and had a lower mean CHA2DS2-VASc score (2.1 ± 1.7 vs. 3.7 ± 2.2) as compared to patients without RHD (all p < 0.001). Significant mitral stenosis (average mean transmitral gradient 11.5 ± 6.5 mmHg) was the predominant valve lesion in those with RHD (59.6%). Patients with RHD had a higher baseline rate of anticoagulation use (60.4% vs. 45.2%, p < 0.001). Unadjusted stroke rates at 1 year were 2.8% and 4.1% for patients with and without RHD, respectively. The performance of the CHA2DS2-VASc score was modest in both groups (stroke at 1 year, c-statistics 0.69, 95% confidence interval [CI] 0.60-0.78 and 0.63, 95% CI 0.61-0.66, respectively). In the overall cohort, advanced age, female sex, prior stroke, tobacco use and non-use of anticoagulation were predictors for stroke (all p < 0.05). Mitral stenosis was not associated with stroke risk (adjusted odds ratio 1.07, 95% CI 0.67-1.72, p = 0.764). CONCLUSIONS: The performance of the CHA2DS2-VASc score was modest in AF patients both with and without RHD. In this cohort, moderate-to-severe mitral stenosis was not an independent risk factor for stroke. TRANSLATIONAL PERSPECTIVE: Based on studies conducted several decades ago, the presence of moderate-to-severe mitral stenosis has been associated with a very high risk of stroke in patients with AF. Our results, based on a large, global sample of contemporary patients with AF that contained a significant proportion of individuals with RHD, challenge the assumption that mitral stenosis is a major, independent risk factor for stroke. The performance of the widely used CHA2DS2-VASc score was modest in both patients with and without RHD. At least one ongoing randomized trial is evaluating the optimal antithrombotic strategy in patients with AF and RHD.

4.
Can J Cardiol ; 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33271225

RESUMO

BACKGROUND: Atrial fibrillation (AF) is often detected during hospitalization for surgery or medical illness and is often assumed to be due to the acute condition. METHODS: ASSERT enrolled patients >65 years old without AF. Pacemakers or implantable cardioverter defibrillators recorded device-detected AF. We identified participants who were hospitalized and compared the prevalence of AF before and after hospitalization. RESULTS: Among 2580 participants, 436 (16.9%) had a surgical or medical hospitalization. In the 30 days following a first hospitalization, 43 participants (9.9%, 95% confidence interval [CI] 7.2%-13.1%) had >6 minutes of device-detected AF; 20 (4.6%, 95% CI 2.8%-7.0%) had >6 hours. More participants had AF >6 minutes in the 30 days following hospitalization, as compared to the period 30-60 days before hospitalization (9.9% versus 4.4%, P < 0.001). Similar results were observed for episodes >6 hours (4.6% versus 2.3%, P = 0.03). Roughly half of participants with device-detected AF in the 30 days following hospitalization had ≥1 episodes of the same duration in the 6 months prior (50% [95% CI 31.3%-68.7%] for >6 minutes; 68.8% [95% CI 41.3%-89.0%] for >6 hours). Those with AF in the 30 days following hospitalization were more likely to have had AF in the past (adjusted OR 7.2 95%CI 3.2-15.8 for episodes >6 minutes; adjusted OR 32.6, 95%CI 10.3-103.4 for >6 hours). CONCLUSIONS: The prevalence of device-detected AF increases around the time of hospitalization for non-cardiac surgery or medical illness. About half of patients with AF around the time of hospitalization previously had similar episodes.

5.
J Am Heart Assoc ; : e018984, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33292046

RESUMO

Background To explore the pathophysiological features of ischemic stroke in patients with atrial fibrillation (AF), we evaluated the association between 268 plasma proteins and subsequent ischemic stroke in 2 large AF cohorts receiving oral anticoagulation. Methods and Results A case-cohort sample of patients with AF from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial, including 282 cases with ischemic stroke or systemic embolism and a random sample of 4124 without these events, during 1.9 years of follow-up was used for identification. Validation was provided by a similar case-cohort sample of patients with AF from the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial, including 149 cases with ischemic stroke/systemic embolism and a random sample of 1062 without these events. In plasma obtained before randomization, 268 unique biomarkers were measured with OLINK proximity extension assay panels (CVD II, CVD III, and Inflammation) and conventional immunoassays. The association between biomarkers and outcomes was evaluated by random survival forest and adjusted Cox regression. According to random survival forest or Cox regression analyses, the biomarkers most strongly and consistently associated with ischemic stroke/systemic embolism were matrix metalloproteinase-9, NT-proBNP (N-terminal pro-B-type natriuretic peptide), osteopontin, sortilin, soluble suppression of tumorigenesis 2, and trefoil factor-3. The corresponding hazard ratios (95% CIs) for an interquartile difference were as follows: 1.18 (1.00-1.38), 1.55 (1.28-1.88), 1.28 (1.07-1.53), 1.19 (1.02-1.39), 1.23 (1.05-1.45), and 1.19 (0.97-1.45), respectively. Conclusions In patients with AF, of 268 unique biomarkers, the 6 biomarkers most strongly associated with subsequent ischemic stroke/systemic embolism represent fibrosis/remodeling (matrix metalloproteinase-9 and soluble suppression of tumorigenesis 2), cardiac dysfunction (NT-proBNP), vascular calcification (osteopontin), metabolism (sortilin), and mucosal integrity/ischemia (trefoil factor-3). Registration URL: https://www.clinicaltrials.gov. Unique Identifiers: NCT00412984 and NCT00262600.

6.
Am Heart J ; 2020 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-33296688

RESUMO

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) are the preferred class of medications for prevention of stroke and systemic embolism in patients with atrial fibrillation unless contraindications exist. Five large, international, randomized, controlled trials of NOACs versus either warfarin or aspirin have been completed to date. DESIGN: COMBINE AF incorporates de-identified individual patient data from 77,282 patients with atrial fibrillation at risk for stroke randomized to NOAC, warfarin, or aspirin from 5 pivotal randomized controlled trials. All patients randomized in the constituent trials are included. Variables common to ≥3 of the constituent trials are included in the master database. Individual trial data sets from the 4 coordinating centers were combined at the Duke Clinical Research Institute. The final database will be securely shared with the 4 academic coordinating centers. The combined master database will be used to perform statistical analyses aimed at better understanding underlying risk factors and outcomes in patients with atrial fibrillation treated with oral anticoagulants, with a special focus on patient subgroups and uncommon outcomes. The initial analysis from COMBINE AF will be a network meta-analysis investigating the relative efficacy and safety of pooled higher-dose NOACs versus pooled lower-dose NOACs versus warfarin with respect to multiple time-to-event efficacy and safety outcomes. COMBINE AF is registered with PROSPERO (CRD42020178771). CONCLUSIONS: In conclusion, COMBINE AF provides a rich and robust database consisting of individual patient data and will offer opportunities to investigate oral anticoagulants across many patient subgroups. Data sharing and collaboration across academic institutions and investigators will serve as overarching themes.

8.
JAMA Neurol ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33074284

RESUMO

Importance: The reported associations of cerebral microbleeds with recurrent stroke and intracerebral hemorrhage have raised concerns regarding antithrombotic treatment in patients with a history of stroke and microbleeds on magnetic resonance imaging. Objective: To characterize microbleeds in embolic strokes of undetermined source (ESUS) and report interactions between microbleeds and the effects of random assignment to anticoagulant vs antiplatelet therapy. Design, Setting, and Participants: Subgroup analyses of the New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs Aspirin to Prevent Embolism in ESUS (NAVIGATE ESUS) international, double-blind, randomized, event-driven phase 3 clinical trial. Participants were enrolled between December 2014 and September 2017 and followed up for a median of 11 months. The study setting included 459 stroke recruitment centers in 31 countries. Patients aged 50 years or older who had neuroimaging-confirmed ESUS between 7 days and 6 months before screening were eligible. Of these 7213 NAVIGATE ESUS participants, 3699 (51%) had information on cerebral microbleeds reported on their baseline clinical magnetic resonance imaging and were eligible for these analyses. Patients with a prior history of symptomatic intracerebral hemorrhage were excluded from the NAVIGATE ESUS trial. Interventions: Rivaroxaban, 15 mg, compared with aspirin, 100 mg, daily. Main Outcomes and Measures: The primary outcome was recurrent stroke. Secondary outcomes were ischemic stroke, intracerebral hemorrhage, and all-cause mortality. Results: Microbleeds were present in 395 of 3699 participants (11%). Of patients with cerebral microbleeds, mean (SD) age was 69.5 (9.4) years, 241 were men (61%), and 201 were White (51%). Advancing age (odds ratio [OR] per year, 1.03; 95% CI, 1.01-1.04), East Asian race/ethnicity (OR, 1.57; 95% CI, 1.04-2.37), hypertension (OR, 2.20; 95% CI, 1.54-3.15), multiterritorial infarcts (OR, 1.95; 95% CI, 1.42-2.67), chronic infarcts (OR, 1.78; 95% CI, 1.42-2.23), and occult intracerebral hemorrhage (OR, 5.23; 95% CI, 2.76-9.90) were independently associated with microbleeds. The presence of microbleeds was associated with a 1.5-fold increased risk of recurrent stroke (hazard ratio [HR], 1.5; 95% CI, 1.0-2.3), a 4-fold risk of intracerebral hemorrhage (HR, 4.2; 95% CI, 1.3-13.9), a 2-fold risk of all-cause mortality (HR, 2.1; 95% CI, 1.1-4.3), and strictly lobar microbleeds with an approximately 2.5-fold risk of ischemic stroke (HR, 2.3; 95% CI, 1.3-4.3). There were no interactions between microbleeds and treatment assignments for recurrent stroke, ischemic stroke, or all-cause mortality. The HR of intracerebral hemorrhage on rivaroxaban was similar between persons with microbleeds (HR, 3.1; 95% CI, 0.3-30.0) and persons without microbleeds (HR, 3.0; 95% CI, 0.6-14.7; interaction P > .99). Conclusions and Relevance: Microbleeds mark an increased risk of recurrent stroke, ischemic stroke, intracerebral hemorrhage, and mortality in ESUS but do not appear to influence effects of rivaroxaban on clinical outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02313909.

9.
Thromb Haemost ; 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33011964

RESUMO

BACKGROUND: AVERROES, a randomized controlled trial in high-risk patients with atrial fibrillation, unsuitable for vitamin K antagonist therapy, demonstrated efficacy and safety of apixaban compared with aspirin. At the conclusion of the double-blind phase, an open-label extension was initiated to allow study participants to receive apixaban until it became locally available. This study reports outcomes of patients on apixaban during the open-label extension. METHODS: Rates of stroke or systemic embolism, hemorrhagic stroke, major bleeding, and other outcomes during the open-label extension are reported. RESULTS: Of the 5,599 participants enrolled in AVERROES, 3,275 (58.5%) received apixaban during the open-label extension. Median (interquartile range) follow-up in the open-label extension was 3.0 (2.5-3.5) years. The rate of stroke or systemic embolism during the open-label extension was 1.0% per year, and the annual rates of hemorrhagic stroke and major bleeding were 0.3 and 1.2%, respectively. After adjustment for imbalances in patient variables, event rates in patients on apixaban during the open-label extension were similar to those of patients receiving apixaban during AVERROES. Additional analyses in all patients who received apixaban, at any time from the start of AVERROES to the end of the open-label extension, were performed. This cohort (n = 4,414) showed annual event rates of 1.1% for stroke or systemic embolism, 0.3% for hemorrhagic stroke, and 1.2% for major bleeding. CONCLUSION: During the open-label extension, annual rates of stroke or systemic embolism, hemorrhagic stroke, and major bleeding remained as low as those observed during apixaban treatment in AVERROES. These data support the long-term efficacy and safety of apixaban in patients with atrial fibrillation.

10.
CJC Open ; 2(5): 354-359, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32995720

RESUMO

Background: The number of implantable cardioverter defibrillator (ICD) infections is increasing due to an increased number of ICD implants, higher-risk patients, and more frequent replacement procedures, which carry a higher risk of infection. Reducing the morbidity, mortality, and cost of ICD-related infections requires an understanding of the current rate of this complication and its predictors. Methods: The Shock Implant Evaluation Trial (SIMPLE) trial randomized 2500 ICD recipients to defibrillation testing or not. Over an average of 3.1 years, patients were seen every 6 months and examined for evidence of ICD infection, which was defined as requiring device removal and/or intravenous antibiotics. Results: Within 24 months, 21 patients (0.8%) developed infection. Fourteen patients (67%) with infection presented within 30 days, 20 patients by 12 months, and only 1 patient beyond 12 months. Univariate analysis demonstrated that patients with primary electrical disorders (3 patients, P = 0.009) and those with a secondary prevention indication (13 patients, P = 0.0009) were more likely to develop infection. Among the 2.2% of patients who developed an ICD wound hematoma, 10.4% developed an infection. Among the 8.3% of patients requiring an ICD reintervention, 1.9% developed an infection. Conclusions: This cohort of ICD recipients at high-volume centres have a low risk of device-related infection. However; strategies to reduce wound hematoma and the need for ICD reintervention could further reduce the rate of infection.

11.
Stroke ; 51(10): 2901-2909, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32951537

RESUMO

BACKGROUND AND PURPOSE: Covert brain infarcts are associated with cognitive decline. It is not known whether therapies that prevent symptomatic stroke prevent covert infarcts. COMPASS compared rivaroxaban with and without aspirin with aspirin for the prevention of stroke, myocardial infarction, and vascular death in participants with stable vascular disease and was terminated early because of benefits of rivaroxaban 2.5 mg twice daily plus aspirin over aspirin. We obtained serial magnetic resonance imagings and cognitive tests in a consenting subgroup of COMPASS patients to examine treatment effects on infarcts, cerebral microbleeds, and white matter hyperintensities. METHODS: Baseline and follow-up magnetic resonance imagings were completed in 1445 participants with a mean (SD) interval of 2.0 (0.7) years. Whole-brain T1, T2 fluid-attenuated inversion recovery, T2* sequences were centrally interpreted by blinded, trained readers. Participants had serial measurements of cognition and function. The primary end point was the proportion of participants with incident covert infarcts. Secondary end points were the composite of clinical stroke and covert brain infarcts, cerebral microbleeds, and white matter hyperintensities. RESULTS: At baseline, 493 (34.1%) participants had infarcts. Incident covert infarcts occurred in 55 (3.8%) participants. In the overall trial rivaroxaban plus aspirin reduced ischemic stroke by 49% (0.7% versus 1.4%; hazard ratio [95% CI], 0.51 [0.38-0.68]). In the magnetic resonance imaging substudy the effects of rivaroxaban+aspirin versus aspirin were: covert infarcts: 2.7% versus 3.5% (odds ratio [95% CI], 0.77 [0.37-1.60]); Covert infarcts or ischemic stroke: 2.9% versus 5.3% (odds ratio [95% CI], 0.53 [0.27-1.03]). Incident microbleeds occurred in 6.6% of participants and 65.7% of participants had an increase in white matter hyperintensities volume with no effect of treatment for either end point. There was no effect on cognitive tests. CONCLUSIONS: Covert infarcts were not significantly reduced by treatment with rivaroxaban and aspirin but estimates for the combination of ischemic stroke and covert infarcts were consistent with the effect on ischemic stroke in the overall trial. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01776424.


Assuntos
Aspirina/uso terapêutico , Infarto Encefálico/prevenção & controle , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/prevenção & controle , Inibidores do Fator Xa/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Idoso , Infarto Encefálico/complicações , Infarto Encefálico/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Quimioterapia Combinada , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Resultado do Tratamento
12.
Curr Cardiol Rep ; 22(11): 144, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32910288

RESUMO

PURPOSE OF REVIEW: A novel permanent carotid filter device for percutaneous implantation was developed for the purpose of stroke prevention. In this review, we cover rationale, existing preclinical and clinical data, and potential future directions for research using such a device. RECENT FINDINGS: The Vine™ filter was assessed for safety in sheep and in 2 observational human studies, the completed CAPTURE 1 (n = 25) and the ongoing CAPTURE 2 (planned n = 100). CAPTURE 1 has shown high procedural and long-term implant safety. A control group was not available for comparison. A mechanical filter for permanent stroke prevention can be implanted bilaterally in the common carotid artery safely and efficiently. A randomized trial is planned for 2021 (n = 3500, INTERCEPT) to demonstrate superiority of a filter + anticoagulation strategy over anticoagulation alone in patients at high risk for ischemic stroke.

13.
Cardiovasc Res ; 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32777820

RESUMO

AIMS: To compare the prevalence of electrocardiogram (ECG)-documented atrial fibrillation (or flutter) (AF) across eight regions of the world, and to examine anti-thrombotic use and clinical outcomes. METHODS AND RESULTS: Baseline ECGs were collected in 153,152 middle-aged participants (ages 35 to 70 years) to document AF in two community-based studies, spanning 20 countries. Medication use and clinical outcome data (mean follow up of 7.4 years) were available in one cohort. Cross sectional analyses were performed to document the prevalence of AF and medication use, and associations between AF and clinical events were examined prospectively. Mean age of participants was 52.1 years, and 57.7% were female. Age and sex-standardized prevalence of AF varied 12-fold between regions; with the highest in North America, Europe, China and Southeast Asia (270-360 cases per 100,000 persons); and lowest in the Middle East, Africa, and South Asia (30-60 cases per 100,000 persons)(p < 0.001). Compared with low-income countries (LICs), AF prevalence was 7-fold higher in middle-income countries (MICs) and 11-fold higher in high-income countries (HICs)(p < 0.001). Differences in AF prevalence remained significant after adjusting for traditional AF risk factors. In LICs/MICs, 24% of participants with AF and a CHADS2 score ≥1 received anti-thrombotic therapy, compared with 85% in HICs. AF was associated with an increased risk of stroke (hazard ratio [HR: 2.29; 95% confidence interval [CI] 1.49-3.52) and death (HR: 2.97; 95% CI 2.25-3.93); with similar rates in different country income levels. CONCLUSIONS: Large variations in AF prevalence occur in different regions and country income settings, but this is only partially explained by traditional AF risk factors. Anti-thrombotic therapy is infrequently used in poorer countries despite the high risk of stroke associated with AF. TRANSLATIONAL PERSPECTIVE: We examined atrial fibrillation (AF) prevalence in 153,152 middle-aged participants spanning 20 countries. Age and sex-standardized prevalence of AF varied by as much as 12-fold between regions; highest in North America, Europe, China and Southeast Asia (270-360 cases per 100,000 persons); and lowest in the Middle East, Africa, and South Asia (30-60 cases per 100,000 persons)(p < 0.001); and by as much as 11-fold between groups of countries at different income levels (p < 0.001). Global variations were poorly explained by traditional AF risk factors. Future studies are needed to understand the predominant determinants driving the variation in AF burden across different regions of the world.

14.
Eur. j. prev. cardiol ; 27(3): 1-12, Ago. 2020. gráfico, tabela
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1050001

RESUMO

Abstract Aims: Secondary prevention in patients with coronary artery disease and peripheral artery disease involves antithrombotic therapy and optimal control of cardiovascular risk factors. In the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) study, adding low-dose rivaroxaban on top of aspirin lowered cardiovascular events, but there is limited data about risk factor control in secondary prevention. We studied the association between risk factor status and outcomes, and the impact of risk factor status on the treatment effect of rivaroxaban, in a large contemporary population of patients with coronary artery disease or peripheral artery disease. Methods and results: We reported ischemic events (cardiovascular death, stroke, or myocardial infarction) in participants from the randomized, double-blind COMPASS study by individual risk factor (blood pressure, smoking status, cholesterol level, presence of diabetes, body mass index, and level of physical activity), and by number of risk factors. We compared rates and hazard ratios of patients treated with rivaroxaban plus aspirin vs aspirin alone within each risk factor category and tested for interaction between risk factor status and antithrombotic regimen. Complete baseline risk factor status was available in 27,117 (99%) patients. Status and number of risk factors were both associated with increased risk of ischemic events. Rates of ischemic events (hazard ratio 2.2; 95% confidence interval 1.8­2.6) and cardiovascular death (hazard ratio 2.0; 1.5­2.7) were more than twofold higher in patients with 4­6 compared with 0­1 risk factors (p<0.0001 for both). Rivaroxaban reduced event rates independently of the number of risk factors (p interaction 0.93), with the largest absolute benefit in patients with the highest number of risk factors. Conclusion: More favorable risk factor status and low-dose rivaroxaban were independently associated with lower risk of cardiovascular events. (AU)


Assuntos
Doença da Artéria Coronariana , Prevenção Secundária
15.
JAMA Neurol ; 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32628266

RESUMO

Importance: The concept of embolic stroke of undetermined source (ESUS) unifies a subgroup of cryptogenic strokes based on neuroimaging, a defined minimum set of diagnostic tests, and exclusion of certain causes. Despite an annual stroke recurrence rate of 5%, little is known about the etiology underlying recurrent stroke after ESUS. Objective: To identify the stroke subtype of recurrent ischemic strokes after ESUS, to explore the interaction with treatment assignment in each category, and to examine the consistency of cerebral location of qualifying ESUS and recurrent ischemic stroke. Design, Setting, and Participants: The NAVIGATE-ESUS trial was a randomized clinical trial conducted from December 23, 2014, to October 5, 2017. The trial compared the efficacy and safety of rivaroxaban and aspirin in patients with recent ESUS (n = 7213). Ischemic stroke was validated in 309 of the 7213 patients by adjudicators blinded to treatment assignment and classified by local investigators into the categories ESUS or non-ESUS (ie, cardioembolic, atherosclerotic, lacunar, other determined cause, or insufficient testing). Five patients with recurrent strokes that could not be defined as ischemic or hemorrhagic in absence of neuroimaging or autopsy were excluded. Data for this secondary post hoc analysis were analyzed from March to June 2019. Interventions: Patients were randomly assigned to receive rivaroxaban, 15 mg/d, or aspirin, 100 mg/d. Main Outcomes and Measures: Association of recurrent ESUS with stroke characteristics. Results: A total of 309 patients (205 men [66%]; mean [SD] age, 68 [10] years) had ischemic stroke identified during the median follow-up of 11 (interquartile range [IQR], 12) months (annualized rate, 4.6%). Diagnostic testing was insufficient for etiological classification in 39 patients (13%). Of 270 classifiable ischemic strokes, 156 (58%) were ESUS and 114 (42%) were non-ESUS (37 [32%] cardioembolic, 26 [23%] atherosclerotic, 35 [31%] lacunar, and 16 [14%] other determined cause). Atrial fibrillation was found in 27 patients (9%) with recurrent ischemic stroke and was associated with higher morbidity (median change in modified Rankin scale score 2 [IQR, 3] vs 0 (IQR, 1]) and mortality (15% vs 1%) than other causes. Risk of recurrence did not differ significantly by subtype between treatment groups. For both the qualifying and recurrent strokes, location of infarct was more often in the left (46% and 54%, respectively) than right hemisphere (40% and 37%, respectively) or brainstem or cerebellum (14% and 9%, respectively). Conclusions and Relevance: In this secondary analysis of randomized clinical trial data, most recurrent strokes after ESUS were embolic and of undetermined source. Recurrences associated with atrial fibrillation were a minority but were more often disabling and fatal. More extensive investigation to identify the embolic source is important toward an effective antithrombotic strategy. Trial Registration: ClinicalTrials.gov Identifier: NCT02313909.

17.
J Stroke Cerebrovasc Dis ; 29(8): 104936, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32689594

RESUMO

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


Assuntos
Aspirina/administração & dosagem , Inibidores do Fator Xa/administração & dosagem , Fibrinolíticos/administração & dosagem , Arteriosclerose Intracraniana/tratamento farmacológico , Embolia Intracraniana/prevenção & controle , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/administração & dosagem , Rivaroxabana/administração & dosagem , Acidente Vascular Cerebral/prevenção & controle , Idoso , Aspirina/efeitos adversos , Método Duplo-Cego , Inibidores do Fator Xa/efeitos adversos , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/epidemiologia , Embolia Intracraniana/diagnóstico por imagem , Embolia Intracraniana/epidemiologia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/epidemiologia , Inibidores da Agregação de Plaquetas/efeitos adversos , Prevalência , Recidiva , Medição de Risco , Fatores de Risco , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo , Resultado do Tratamento
18.
J Thromb Haemost ; 18(9): 2287-2295, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32510737

RESUMO

BACKGROUND: The inflammatory biomarker interleukin-6 (IL-6) is associated with mortality in atrial fibrillation (AF). OBJECTIVE: To investigate if repeated IL-6 measurements improve the prognostication for stroke or systemic embolism, major bleeding, and mortality in anticoagulated patients with AF. METHODS: IL-6 levels by ELISA were measured at study entry and at 2 months in 4830 patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial with 1.8 years median follow-up. In the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial, IL-6 was measured at study entry, 3, 6, and 12 months in 2559 patients with 2.0 years median follow-up. Associations between a second IL-6 measurement and outcomes, adjusted for baseline IL-6, clinical variables, and other cardiovascular biomarkers, were analyzed by Cox regression. RESULTS: Median IL-6 levels were 2.0 ng/L (interquartile range [IQR] 1.30-3.20) and 2.10 ng/L (IQR 1.40-3.40) at the two time-points in ARISTOTLE, and, in RE-LY, 2.5 ng/L (IQR 1.6-4.3), 2.5 ng/L (IQR 1.6-4.2), 2.4 ng/L (IQR 1.6, 3.9), and 2.4 ng/L (IQR 1.5, 3.9), respectively. IL-6 was associated with mortality; hazard ratios per 50% higher IL-6 at 2 or 3 months, respectively, were 1.32 (95% confidence interval, 1.23-1.41; P < .0001) in ARISTOTLE, and 1.11 (1.01-1.22, P = .0290) in RE-LY; with improved C index from 0.74 to 0.76 in ARISTOTLE, but not in the smaller RE-LY cohort. There were no consistent associations with second IL-6 and stroke or systemic embolism, or major bleeding. CONCLUSIONS: Persistent systemic inflammatory activity, assessed by repeated IL-6 measurements, is associated with mortality independent of established clinical risk factors and other strong cardiovascular biomarkers in anticoagulated patients with AF.

19.
Stroke ; 51(7): 2139-2147, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32517582

RESUMO

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


Assuntos
Hemorragia Cerebral/induzido quimicamente , Inibidores do Fator Xa/efeitos adversos , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Método Duplo-Cego , Extremo Oriente , Feminino , Taxa de Filtração Glomerular , Hemorragia/induzido quimicamente , Humanos , Embolia Intracraniana/complicações , Masculino , Pessoa de Meia-Idade , Fatores de Risco
20.
Am Heart J ; 225: 69-77, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32474206

RESUMO

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


Assuntos
Fibrilação Atrial/tratamento farmacológico , Embolia/prevenção & controle , Inibidores do Fator Xa/uso terapêutico , Cardiopatia Reumática/tratamento farmacológico , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Vitamina K/antagonistas & inibidores , Adulto , Idoso , Fibrilação Atrial/complicações , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Cardiopatia Reumática/complicações , Rivaroxabana/efeitos adversos
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