Usual On-therapy Ranges of Drug Concentrations in Patients with Atrial Fibrillation Treated with Direct Oral Anticoagulants: A Systematic Review and Meta-analysis.

Background:  Although most patients with atrial fibrillation (AF) receiving a direct oral anticoagulant (DOAC) do not require drug concentration measurements, there are situations where such information could be useful. Existing guidance documents provide usual on-therapy ranges for drug concentrations, but these have important limitations.

Methods:  This is a systematic review and meta-analysis of studies reporting trough and peak levels of DOAC regimens approved for stroke prevention in AF.

Anticoagulation Stewardship to Bridge the Implementation Gap in Perioperative Anticoagulation Management.

Lack of alignment of care protocols among providers in health care is a driver of increased costs and suboptimal patient outcomes. Perioperative anticoagulation management is a good example of a complex area where protocol creation is a clinical challenge that demands input from multiple experts. Questions regarding the need for anticoagulation interruptions are frequent.

Building Your Peripheral Artery Disease Toolkit: Medical Management of Peripheral Artery Disease in 2022.

Peripheral artery disease (PAD) is associated with substantial morbidity, including a high risk of cardiovascular and limb events and death. A growing body of evidence has demonstrated the benefits of antithrombotic therapy, lipid lowering, blood pressure control, diabetes management, smoking cessation, and exercise programs on improving symptoms and reducing these complications. Guidelines make specific recommendations on how to use these strategies to prevent adverse cardiovascular and limb outcomes in patients with PAD.

Can a Single Measurement of Apixaban Levels Identify Patients at Risk of Overexposure? A Prospective Cohort Study.

 Patients with atrial fibrillation (AF) are frequently treated with apixaban 2.5-mg twice daily (BID) off-label, presumably to reduce the bleeding risk. However, this approach has the potential to increase the risk of ischemic stroke.

Plasma Rivaroxaban Level to Identify Patients at Risk of Drug Overexposure: Is a Single Measurement of Drug Level Reliable?

 Dose adjustment based on laboratory monitoring is not routinely recommended for patients treated with rivaroxaban but because an association has been reported between high drug level and bleeding, it would be of interest to know if measuring drug level once could identify patients at risk of bleeding who might benefit from a dose reduction.  This study was aimed to investigate the reliability of a single measurement of rivaroxaban level to identify clinic patients with persistently high levels, defined as levels that remained in the upper quintile of drug-level distribution.  In this prospective cohort study of 100 patients with atrial fibrillation or venous thromboembolism, peak and trough rivaroxaban levels were measured using the STA-Liquid Anti-Xa assay at baseline and after 2 months.

Apixaban for Stroke Prevention in Atrial Fibrillation: Why are Event Rates Higher in Clinical Practice than in Randomized Trials?-A Systematic Review.

Background:  Recent reports suggest an important contribution from frequent off-label use of apixaban 2.5 mg twice daily to the higher rates of thromboembolic events observed in observational studies (OSs) relative to in randomized controlled trials (RCTs), and consequently, advocate against such use in all patients.

Objectives:  To examine factors contributing to the higher thromboembolic event rates, we estimated the prevalence of off-label use in contemporary practice, and compared patient characteristics and rates of stroke/systemic embolism, major bleeding, and mortality by apixaban dose and by study design in a systematic review and meta-analysis.

Mortality benefit in the COMPASS trial: is it related to superior statistical power or better efficacy and safety?

Until recently, attempts to improve the benefit of aspirin by adding another antithrombotic agent have not resulted in a mortality reduction in patients with chronic symptomatic atherosclerosis. In this population, COMPASS is the only one among six trials to show a significant mortality reduction, thereby providing evidence of a clear net clinical benefit with the combination of low-dose rivaroxaban plus aspirin. In this systematic review, we sought to determine whether the mortality benefit of the combination arm in COMPASS is best explained by greater statistical power or by a more favorable efficacy-safety profile than the other regimens evaluated in patients with chronic symptomatic atherosclerosis.

Rivaroxaban and Aspirin in Peripheral Vascular Disease: a Review of Implementation Strategies and Management of Common Clinical Scenarios.

Purpose Of Review: Peripheral artery disease (PAD) affects an estimated 200 million people worldwide and is associated with significant cardiovascular morbidity and mortality. Cardiovascular risk is further increased among individuals with polyvascular disease, where either cerebrovascular or coronary artery disease is present in addition to PAD. In this review, we present common clinical scenarios encountered when managing patients with PAD and provide an evidence-based approach to prescribing optimal antithrombotics in this population.

Low-dose rivaroxaban plus aspirin for the prevention of cardiovascular events: an evaluation of COMPASS.

The cardiovascular outcomes for people using anticoagulation strategies (NCT01776424) trial randomized 27,395 patients with stable coronary artery disease or peripheral artery disease (PAD) to receive rivaroxaban 5 mg twice-daily alone, the combination of rivaroxaban 2.5 mg twice-daily and aspirin 100 mg daily, or aspirin 100 mg daily alone. The combination arm resulted in a 24% reduction in the primary end point of cardiovascular death, stroke or myocardial infarction, and an 18% reduction in mortality.

In Vitro Reversal of the Anti-Aggregant Effect of Ticagrelor Using Untreated Platelets.

Background:  Ticagrelor is an anti-platelet agent that is indicated for prevention of thrombosis after acute coronary syndrome or intra-coronary artery stent implantation, but it increases the risk of bleeding. Platelet transfusion has the potential to treat or prevent bleeding in patients taking ticagrelor, but the optimal quantity of platelets and timing of administration have not been fully defined.

Methods And Results:  Ten healthy subjects took ticagrelor in combination with acetylsalicylic acid for 5 days, and had blood collected prior to treatment and at 2, 10, 24, 48, 72 and 96 hours after the last doses.

Impact of cost on use of non-vitamin K antagonists in atrial fibrillation patients in Ontario, Canada.

Canadian guidelines recommend non vitamin K antagonists (NOACs) in preference to vitamin K antagonists (VKAs) for stroke prevention in patients with atrial fibrillation (AF), but NOACs are more expensive than VKAs. Canada has a universal healthcare system that covers the cost of NOACs for select patient groups. Ability to pay for NOACs may influence their use.

The Massive Online Needs Assessment (MONA) to inform the development of an emergency haematology educational blog series.

Background: Online educational resources are criticized as being teacher-centred, failing to address learner's needs. Needs assessments are an important precursor to inform curriculum development, but these are often overlooked or skipped by developers of online educational resources due to cumbersome measurement tools. Novel methods are required to identify perceived and unperceived learning needs to allow targeted development of learner-centred curricula.

NOACs only for those who cannot tolerate a VKA: where is the evidence?

The 2016 European Society of Cardiology Guidelines recommend non-vitamin K antagonist oral anticoagulants (NOACs) in preference to vitamin K antagonists (VKA) for stroke prevention in atrial fibrillation. A recent report from the Belgian Healthcare Knowledge Centre (KCE) raised concerns about the results of the phase 3 randomised trials that led to the approval of the NOACs for this indication and concluded that NOACs should only be used for patients who fail or cannot undergo treatment with a vitamin K antagonist because they cannot achieve stable INR values. Evidence from community-based studies suggests that NOACs are often not optimally used; however, our critical review of the randomised trial data provides no support for the concerns raised by the Belgian KCE about the trials.

Apixaban-Calibrated Anti-FXa Activity in Relation to Outcome Events and Clinical Characteristics in Patients with Atrial Fibrillation: Results from the AVERROES Trial.

 In patients with nonvalvular atrial fibrillation (AF), apixaban is given in doses of 5 or 2.5 mg twice daily, according to clinical characteristics. The usual on-treatment range of apixaban drug levels, as determined by apixaban-calibrated anti-factor Xa (anti-Xa) activity, has previously been measured in small cohorts; however, the association between anti-Xa activity and clinical outcomes and the predictors of variability in anti-Xa activity have not been well studied in the AF population.

Clinical implications of reversal agents for direct oral anticoagulants.

Direct oral anticoagulants (DOACs) are effective in preventing and treating venous thromboembolism, and preventing stroke in atrial fibrillation. Until recently, there has been no specific reversal agent for DOACs. Now, a specific antidote for the direct thrombin inhibitor, dabigatran has been approved for use, and antidotes for factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) are being developed.

Quantification of Cell-Free DNA in Red Blood Cell Units in Different Whole Blood Processing Methods.

. Whole blood donations in Canada are processed by either the red cell filtration (RCF) or whole blood filtration (WBF) methods, where leukoreduction is potentially delayed in WBF. Fresh WBF red blood cells (RBCs) have been associated with increased in-hospital mortality after transfusion.

Comparison of the Proinflammatory and Procoagulant Properties of Nuclear, Mitochondrial, and Bacterial DNA.

Purpose: Cell-free DNA (CFDNA) is elevated in sepsis and correlates with mortality. This DNA may come from nuclear, mitochondrial, or bacterial sources. Cell-free DNA from all three sources may play a pathogenic role in sepsis via activation of coagulation through the contact pathway, whereas CpG motifs on bacterial and mitochondrial DNA may additionally stimulate inflammatory responses via Toll-like receptor 9.

Rituximab maintenance for relapsed refractory thrombotic thrombocytopenic purpura.

Background: Rituximab, an anti-CD20 chimeric monoclonal antibody, has been used successfully to treat patients with relapsed or refractory thrombotic thrombocytopenic purpura (TTP); however, the optimal dose and frequency and the role of rituximab maintenance remain uncertain.

Study Design And Methods: We describe a 45-year-old woman with chronic relapsing immune thrombocytopenia who responded to rituximab retreatment administered in four doses over the course of 12 months. Previously, she had received four doses of rituximab and sustained a remission for 19 months.

Management of bleeding complications in the anticoagulated patient.

As new anticoagulants become available, and the number of anticoagulated patients continues to rise, it is necessary to know how to deal with associated bleeding complications. In this review, reversal strategies for traditional anticoagulants (warfarin and heparin) as well as newer anticoagulants are described. Prothrombin complex concentrates (PPCs) can be used to reverse vitamin K antagonists (VKA), and plasma may be used where they are not available.