Rationale and design of the Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation (ARTESiA) trial.

BACKGROUND: Device-detected subclinical atrial fibrillation (AF) refers to infrequent, short-lasting, asymptomatic AF that is detected only with long-term continuous monitoring. Subclinical AF is common and associated with an increased risk of stroke; however, the risk of stroke with subclinical AF is lower than for clinical AF, and very few patients with subclinical AF alone have been included in large AF anticoagulation trials. The net benefit of anticoagulation in patients with subclinical AF is unknown. DESIGN: ARTESiA is a prospective, multicenter, double-blind, randomized controlled trial, recruiting patients with subclinical AF detected by an implanted pacemaker, defibrillator, or cardiac monitor, and who have additional risk factors for stroke. Patients with clinical AF documented by surface electrocardiogram will be excluded from the study. Participants will be randomized to receive either apixaban (according to standard AF dosing) or aspirin 81mg daily. The primary outcome is the composite of stroke, transient ischemic attack with diffusion-weighted magnetic resonance imaging evidence of cerebral infarction, and systemic embolism. Approximately 4,000 patients will be enrolled from around 230 clinical sites, with an anticipated mean follow-up of 36months until 248 adjudicated primary outcome events have occurred. SUMMARY: ARTESiA will determine whether oral anticoagulation therapy with apixaban compared with aspirin reduces the risk of stroke or systemic embolism in patients with subclinical AF and additional risk factors

Development of an international standard set of outcome measures for patients with atrial fibrillation: a report of the International Consortium for Health Outcomes Measurement (ICHOM) atrial fibrillation working group.

AIMS: As health systems around the world increasingly look to measure and improve the value of care that they provide to patients, being able to measure the outcomes that matter most to patients is vital. To support the shift towards value-based health care in atrial fibrillation (AF), the International Consortium for Health Outcomes Measurement (ICHOM) assembled an international Working Group (WG) of 30 volunteers, including health professionals and patient representatives to develop a standardized minimum set of outcomes for benchmarking care delivery in clinical settings. METHODS AND RESULTS: Using an online-modified Delphi process, outcomes important to patients and health professionals were selected and categorized into (i) long-term consequences of disease outcomes, (ii) complications of treatment outcomes, and (iii) patient-reported outcomes. The WG identified demographic and clinical variables for use as case-mix risk adjusters. These included baseline demographics, comorbidities, cognitive function, date of diagnosis, disease duration, medications prescribed and AF procedures, as well as smoking, body mass index (BMI), alcohol intake, and physical activity. Where appropriate, and for ease of implementation, standardization of outcomes and case-mix variables was achieved using ICD codes. The standard set underwent an open review process in which over 80% of patients surveyed agreed with the outcomes captured by the standard set. CONCLUSION: Implementation of these consensus recommendations could help institutions to monitor, compare and improve the quality and delivery of chronic AF care. Their consistent definition and collection, using ICD codes where applicable, could also broaden the implementation of more patient-centric clinical outcomes research in AF

Heart Rhythm Monitoring Strategies for Cryptogenic Stroke: 2015 Diagnostics and Monitoring Stroke Focus Group Report.

No abstract available

Postoperative phlegmasia caerulea dolens: a case report and consideration of potential iatrogenic factors

While the haemorrhagic consequences of anti-coagulants are well and frequently described in the surgical literature, the paradoxical prothrombotic tendencies of these drugs tend to be under-recognised due, perhaps, to their clinical infrequency. However, when these effects pertain, their consequences can be devastating. Here, we present a postoperative oncology patient who suffered a massive recrudescence of his lower limb venous thrombosis immediately after discontinuation of his heparin infusion, despite seemingly being adequately anticoagulated by warfarin therapy (INR > 2.0). We intend this case to graphically illustrate the theoretical considerations that must govern the perioperative use of these drugs in high-risk patients

Edoxaban: an update on the new oral direct factor Xa inhibitor.

Edoxaban is a once-daily oral anticoagulant that rapidly and selectively inhibits factor Xa in a concentration-dependent manner. This review describes the extensive clinical development program of edoxaban, including phase III studies in patients with non-valvular atrial fibrillation (NVAF) and symptomatic venous thromboembolism (VTE). The ENGAGE AF-TIMI 48 study (N = 21,105; mean CHADS2 score 2.8) compared edoxaban 60 mg once daily (high-dose regimen) and edoxaban 30 mg once daily (low-dose regimen) with dose-adjusted warfarin [international normalized ratio (INR) 2.0-3.0] and found that both regimens were non-inferior to warfarin in the prevention of stroke and systemic embolism in patients with NVAF. Both edoxaban regimens also provided significant reductions in the risk of hemorrhagic stroke, cardiovascular mortality, major bleeding and intracranial bleeding. The Hokusai-VTE study (N = 8,292) in patients with symptomatic VTE had a flexible treatment duration of 3-12 months and found that following initial heparin, edoxaban 60 mg once daily was non-inferior to dose-adjusted warfarin (INR 2.0-3.0) for the prevention of recurrent VTE, and also had a significantly lower risk of bleeding events. Both studies randomized patients at moderate-to-high risk of thromboembolic events and were further designed to simulate routine clinical practice as much as possible, with edoxaban dose reduction (halving dose) at randomisation or during the study if required, a frequently monitored and well-controlled warfarin group, a well-monitored transition period at study end and a flexible treatment duration in Hokusai-VTE. Given the phase III results obtained, once-daily edoxaban may soon be a key addition to the range of antithrombotic treatment options

Clinimetrics in rehabilitation medicine: current issues in developing and applying measurement instruments 1

Clinimetrics in rehabilitation medicine, i.e. the field of developing, evaluating and applying measurement instruments, has undergone considerable progress. Despite this progress, however, several issues remain. These include: (i) selection of an instrument out of the wide range available; (ii) using an instrument in a variety of diagnostic groups; (iii) using an instrument in individual patients, as opposed to a group of patients; and (iv) the use of instruments in clinical practice. This paper reviews these issues, as well as current attempts at resolving them. Illustrative examples are given. It is concluded that solutions seem to be available, but considerable research effort is required to make these a reality. Clinimetrics in rehabilitation medicine remains a field with challenging opportunities for researc

Anemia is associated with bleeding and mortality, but not stroke, in patients with atrial fibrillation: Insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial

Background Patients with atrial fibrillation (AF) are prone to cardiovascular events and anticoagulation-related bleeding complications. We hypothesized that patients with anemia are at increased risk for these outcomes. Methods We performed a post hoc analysis of the ARISTOTLE trial, which included N 18,000 patients with AF randomized to warfarin (target international normalized ratio, 2.0-3.0) or apixaban 5 mg twice daily. Multivariable Cox regression analysis was used to determine if anemia (defined as hemoglobin b 13.0 in men and b 12.0 g/dL in women) was associated with future stroke, major bleeding, or mortality. Results Anemia was present at baseline in 12.6% of the ARISTOTLE population. Patients with anemia were older, had higher mean CHADS 2 and HAS-BLED scores, and were more likely to have experienced previous bleeding events. Anemia was associated with major bleeding (adjusted hazard ratio [HR], 1.92; 95% CI, 1.62-2.28; P b .0001) and all-cause mortality (adjusted HR, 1.68; 95% CI, 1.46-1.93; P b .0001) but not stroke or systemic embolism (adjusted HR, 0.92; 95% CI, 0.70- 1.21). The benefits of apixaban compared with warfarin on the rates of stroke, mortality, and bleeding events were consistent in patients with and without anemia. Conclusions Chronic anemia is associated with a higher incidence of bleeding complications and mortality, but not of stroke, in anticoagulated patients with AF. Apixaban is an attractive anticoagulant for stroke prevention in patients with AF with or without anemia. (Am Heart J 2017;185:140-9.