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Altered profile of circulating microparticles in nonvalvular atrial fibrillation.

ABSTRACT: BACKGROUND:Nonvalvular atrial fibrillation (AF) is the most common cardiac arrhythmia, and it is associated with the prothrombotic state. Circulating microparticles (cMPs) are membrane vesicles that are shed from many cell types in response to cell activation and cell apoptosis. Several studies reported that cMPs may play a role in the hypercoagulable state that can be observed in patients with AF. The aim of this study was to determine the levels of total cMPs and characterize their cellular origins in AF patients. METHODS:Atotal of 66 AF patients and 33 healthy controls were enrolled. This study investigated total cMP levels and their cellular origin in AF patients using polychromatic flow cytometry. RESULTS:AF patients had significantly higher levels of total cMPs (median 36.38, interquartile range [IQR] 21.16-68.50 × 105 counts/mL vs median 15.21, IQR 9.91-30.86 × 105 counts/mL; P = 0.004), platelet-derived MPs (PMPs) (median 10.61, IQR 6.55-18.04 × 105 counts/mL vs median 7.83, IQR 4.44-10.26 × 10/mL; P = 0.009), and endothelial-derived MPs (EMPs CD31+ CD41-) (median 2.94, IQR 1.78-0.60 × 105 counts/mL vs median 1.16, IQR 0.71-2.30 × 105 counts/mL; P = 0.001) than healthy controls after adjusting for potential confounders. Phosphatidylserine positive MP (PS + MP) levels were similar compared between AF patients and healthy controls. CONCLUSION:The results of this study revealed a marked increase in total cMP levels, and evidence of elevated endothelial damage and platelet activation, as demonstrated by increased PMP and EMP levels, in AF patients. Additional study is needed to further elucidate the role of cMPs (PMPs and EMPs) in the pathophysiology of and the complications associated with AF.

SUBMITTER: Siwaponanan P

PROVIDER: S-EPMC6712324 | biostudies-other | 2019 Apr

REPOSITORIES: biostudies-other

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Project description:Three target-specific oral anticoagulants (TSOACs)-dabigatran, rivaroxaban, and apixaban-have been approved by the FDA to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation; however, no agents are currently approved to reverse the anticoagulant effects of these TSOACs in cases of active bleeding. This review discusses the benefits and risks of these TSOACs from a clinician's perspective, with a focus on the interruption of treatment for either elective or emergent surgery, monitoring, and reversal of anticoagulation. Available coagulation assays are not ideal for monitoring the effects of TSOACs and do not provide reliable quantitative measurement of their anticoagulant effects. When necessary, activated partial thromboplastin time (aPTT) may provide qualitative information on dabigatran, and prothrombin time (PT) may provide qualitative assessment of the presence of the factor Xa inhibitors, rivaroxaban and apixaban. Current recommendations for reversal of TSOACs are based largely on limited and sometimes conflicting data from in vitro or in vivo animal models, and clinical experience with these recommendations is also limited. Methods that have been investigated for effectiveness for reversal of the pharmacodynamic effects of the TSOACs include dialysis, activated charcoal, prothrombin complex concentrate (PCC), and recombinant activated factor VII. It is important to note that even within a class of anticoagulant drugs, compounds respond differently to reversal agents; therefore, recommendations for one agent should not be extrapolated to another, even if they are from the same therapeutic class. New antidotes are being explored, including a mouse monoclonal antibody to dabigatran; andexanet alfa, a potential universal factor Xa inhibitor reversal agent; and a synthetic small molecule (PER977) that may be effective for the reversal of factor Xa inhibitors and direct thrombin inhibitors. Given the short half-lives of TSOACs, watchful waiting, rather than reversal, may be the best approach in some circumstances.

Project description:OBJECTIVES:Older adult patients are underrepresented in clinical trials comparing non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin. This subgroup analysis of the ARISTOPHANES study used multiple data sources to compare the risk of stroke/systemic embolism (SE) and major bleeding (MB) among very old patients with nonvalvular atrial fibrillation (NVAF) prescribed NOACs or warfarin. DESIGN:Retrospective observational study. SETTING:The Centers for Medicare & Medicaid Services and three US commercial claims databases. PARTICIPANTS:A total of 88 582 very old (aged ≥80 y) NVAF patients newly initiating apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, to September 30, 2015. MEASUREMENTS:In each database, six 1:1 propensity score matched (PSM) cohorts were created for each drug comparison. Patient cohorts were pooled from all four databases after PSM. Cox proportional hazards models were used to estimate hazard ratios (HRs) of stroke/SE and MB. RESULTS:The patients in the six matched cohorts had a mean follow-up time of 7 to 9 months. Compared with warfarin, apixaban (HR = .58; 95% confidence interval [CI] = .49-.69), dabigatran (HR = .77; 95% CI = .60-.99), and rivaroxaban (HR = .74; 95% CI = .65-.85) were associated with lower risks of stroke/SE. For MB, apixaban (HR = .60; 95% CI = .54-.67) was associated with a lower risk; dabigatran (HR = .92; 95% CI = .78-1.07) was associated with a similar risk, and rivaroxaban (HR = 1.16; 95% CI = 1.07-1.24) was associated with a higher risk compared with warfarin. Apixaban was associated with a lower risk of stroke/SE and MB compared with dabigatran (stroke/SE: HR = .65; 95% CI = .47-.89; MB: HR = .60; 95% CI = .49-.73) and rivaroxaban (stroke/SE: HR = .72; 95% CI = .59-.86; MB: HR = .50; 95% CI = .45-.55). Dabigatran was associated with a lower risk of MB (HR = .77; 95% CI = .67-.90) compared with rivaroxaban. CONCLUSION:Among very old NVAF patients, NOACs were associated with lower rates of stroke/SE and varying rates of MB compared with warfarin. J Am Geriatr Soc 67:1662-1671, 2019.

Project description:Background and Purpose- This ARISTOPHANES study (Anticoagulants for Reduction in Stroke: Observational Pooled Analysis on Health Outcomes and Experience of Patients) used multiple data sources to compare stroke/systemic embolism (SE) and major bleeding (MB) among a large number of nonvalvular atrial fibrillation patients on non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin. Methods- A retrospective observational study of nonvalvular atrial fibrillation patients initiating apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, to September 30, 2015, was conducted pooling Centers for Medicare and Medicaid Services Medicare data and 4 US commercial claims databases. After 1:1 NOAC-warfarin and NOAC-NOAC propensity score matching in each database, the resulting patient records were pooled. Cox models were used to evaluate the risk of stroke/SE and MB across matched cohorts. Results- A total of 285?292 patients were included in the 6 matched cohorts: 57?929 apixaban-warfarin, 26?838 dabigatran-warfarin, 83?007 rivaroxaban-warfarin, 27?096 apixaban-dabigatran, 62?619 apixaban-rivaroxaban, and 27?538 dabigatran-rivaroxaban patient pairs. Apixaban (hazard ratio [HR], 0.61; 95% CI, 0.54-0.69), dabigatran (HR, 0.80; 95% CI, 0.68-0.94), and rivaroxaban (HR, 0.75; 95% CI, 0.69-0.82) were associated with lower rates of stroke/SE compared with warfarin. Apixaban (HR, 0.58; 95% CI, 0.54-0.62) and dabigatran (HR, 0.73; 95% CI, 0.66-0.81) had lower rates of MB, and rivaroxaban (HR, 1.07; 95% CI, 1.02-1.13) had a higher rate of MB compared with warfarin. Differences exist in rates of stroke/SE and MB across NOACs. Conclusions- In this largest observational study to date on NOACs and warfarin, the NOACs had lower rates of stroke/SE and variable comparative rates of MB versus warfarin. The findings from this study may help inform the discussion on benefit and risk in the shared decision-making process for stroke prevention between healthcare providers and nonvalvular atrial fibrillation patients. Clinical Trial Registration- URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT03087487.

Project description:INTRODUCTION: Oral anticoagulants (OAs) are significantly more effective than Aspirin in the prevention of cerebrovascular accidents among patients with atrial fibrillation (AF). Several studies, however, showed OAs to be widely underused in these patients. OBJECTIVE: To assess the appropriateness of antithrombotic therapy in an Italian population of AF patients. METHODS: Two hundred and fifty-five consecutive patients affected by nonvalvular AF participated in the study. Data were collected on demographic characteristics, risk factors for stroke, current prophylactic therapy, and perceived or actual risk factors for bleeding. INR levels were measured. Patients were stratified by their risk for stroke (214 at high risk, 21 moderate, 20 low), and their prophylactic therapy was analysed in light of international antithrombotic therapy recommendations. After therapy adjustment, 203 of our patients were followed-up for the occurrence of cerebrovascular events for an average of 27 months. RESULTS: Upon admission, 35% (n=75) of patients in the high-risk category were either taking no antithrombotic prophylaxis or were being treated with Aspirin. In addition, 38 of 139 patients receiving OAs had an INR<2. Thus, a total of 113 (52.8%) high-risk subjects were not receiving adequate antithrombotic therapy. Of high-risk patients not treated with OAs, 46.7% reported no perceived or actual risk factors for bleeding. The annual incidence of cerebrovascular accidents was 3.8% among 163 high-risk patients assigned to OA treatment, and 4.5% among 39 patients given Aspirin treatment. Relative to expected annual incidence rates, cerebrovascular risk in anticoagulated patients was reduced by about 70%. CONCLUSIONS: Underuse of OAs is still common in Italy, and much of it cannot be explained by the concern for haemorrhage. Support and training in the complex task of anticoagulation management may help to extend this efficacious prophylactic therapy to all patients who may benefit from it.

Project description:BackgroundBridging anticoagulation is commonly prescribed to patients with atrial fibrillation who are initiating warfarin or require interruption of anticoagulation. Current guidelines recommend bridging for patients at high risk of stroke. Among patients with atrial fibrillation and one or more risk factors for ischemic stroke, the recently published BRIDGE trial found forgoing bridging during interruption to be, on average, noninferior to bridging with respect to ischemic complications, with significantly fewer hemorrhagic complications.ObjectiveWe sought to examine the benefits and harms of bridging anticoagulation across the spectrum of ischemic and hemorrhagic stroke risk and thereby enable more nuanced, risk-stratified decision-making when bridging is considered during initiation or interruption of vitamin K antagonists.DesignA Monte Carlo simulation, using a combination of literature-derived estimates, registry data, and trial data.Main measuresNet clinical benefit, weighting for ischemic strokes, intracranial hemorrhages, and extracranial major hemorrhages.Key resultsThe benefits and harms of bridging anticoagulation vary according to underlying patient risk profiles for both thromboembolic stroke and major intracranial bleeding. Patients at high risk of ischemic stroke and low risk of hemorrhage derive benefit from bridging during initiation or interruption of warfarin therapy. Patients at similarly high or low risk of both outcomes may receive benefit from bridging during initiation and bridging during interruption, but this was sensitive to underlying assumptions. The need for stratification along both axes of risk was robust to a wide range of parameters.ConclusionsBridging anticoagulation may provide benefit to patients at high risk of ischemic stroke and low risk of intracranial hemorrhage who are initiating or interrupting warfarin therapy, while patients at high or low risk of both complications may be harmed. The use of bridging anticoagulation in patients with non-valvular atrial fibrillation should be considered only after stratification by risk of ischemic and hemorrhagic complications.

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Altered profile of circulating microparticles in nonvalvular atrial fibrillation.

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