Observations on clot properties in atrial fibrillation: Relation to renal function and choice of anticoagulant.

INTRODUCTION: Atrial fibrillation (AF) is associated with increased risk of stroke and thromboembolism. Patients with AF have a higher incidence of renal impairment, which may influence the risks of systemic thromboembolism or bleeding. We determined how different oral anticoagulants affect plasma clot properties and whether progressive renal dysfunction affects plasma clot properties in patients on warfarin. MATERIALS AND METHODS: We studied 257 patients with AF receiving oral anticoagulants. Furthermore, we recruited 192 separate patients with AF on warfarin and divided them in 4 groups based on estimated glomerular filtration rate (eGFR). Platelet poor plasma was prepared and clot formation and fibrinolysis was monitored kinetically up to 1 h. RESULTS: Rate of clot formation was significantly slower with dabigatran and rivaroxaban. Time between 50% clotting and 50% lysis was prolonged in patients receiving warfarin compared to NOACs. Time to 50% lysis from maximum absorbance was significantly shorter in patients receiving rivaroxaban. Time between 50% clotting and 50% lysis became significantly prolonged with worsening eGFR. Time to 50% lysis from maximum absorbance was prolonged as renal function worsened. CONCLUSIONS: Compared to warfarin, NOACs differently modulate coagulation and fibrinolysis under ex vivo conditions. Worsening renal function in AF patients on warfarin prolongs fibrinolysis, potentially increasing the risk of thrombosis.

Ingested bread clip as an unexpected diagnostic tool.

We describe a case where a bread clip has in fact became lodged adjacent to a portion of small bowel affected by a deposit of previously undiagnosed metastatic serous carcinoma of likely ovarian origin.

Atrial Fibrillation and Thromboembolism in Patients With Chronic Kidney Disease.

A bidirectional relationship exists between atrial fibrillation (AF) and chronic renal disease. Patients with AF have a higher incidence of renal dysfunction, and the latter predisposes to incident AF. The coexistence of both conditions results in a higher risk for thromboembolic-related adverse events but a paradoxical increased hemorrhagic risk. Oral anticoagulants (both vitamin K antagonists [VKAs] and non-VKA oral anticoagulants [NOACs]) have been demonstrated to be effective in mild to moderate renal dysfunction. Patients with severe renal impairment were excluded from the non-VKA oral anticoagulant trials, so limited data are available. In end-stage renal failure, the net clinical benefit of VKAs in dialysis-dependent patients remains uncertain, although some evidence suggests that such patients may do well with high-quality anticoagulation control. Risk stratification and careful follow-up of such patients are necessary to ensure a net clinical benefit from thromboprophylaxis.

Apixaban versus edoxaban for stroke prevention in nonvalvular atrial fibrillation.

Oral anticoagulation therapy is the mainstay of stroke prevention in nonvalvular atrial fibrillation patients. Vitamin K antagonists (such as warfarin) have been effective conventional oral anticoagulants for several decades. However, due to their limitations in clinical use, several nonvitamin K antagonist oral anticoagulants (NOACs, including dabigatran, rivaroxaban, apixaban and edoxaban) have been developed. Nonetheless, no head to head trials have been performed to directly compare these NOACs in patient cohorts. In this review article, two direct factor Xa inhibitors, apixaban and edoxaban, are briefly described with focus on their pharmacokinetic and pharmacodynamic profiles, plus drug interactions. Moreover, both efficacy and safety will be discussed based on the available data from the large Phase III clinical trials and indirect comparison studies.

Pharmacodynamic profile and drug interactions with non-vitamin K antagonist oral anticoagulants: implications for patients with atrial fibrillation.

INTRODUCTION: Non-vitamin K antagonist oral anticoagulants (NOACs) have been developed to prevent ischemic stroke and systemic thromboembolism in patients with nonvalvular atrial fibrillation. Owing to their predictable pharmacological profiles, they can be given in fixed doses without the need for routine coagulation monitoring. However, their distinctive pharmacological properties also raise issues about potential drug interactions. AREAS COVERED: A literature search was conducted to extract published studies on the pharmacodynamics and drug interactions involving NOACs. Available data from US FDA and European Medicine Agency were also included. As these agents are substrates of permeability glycoprotein (P-gp) efflux transporter and/or CYP3A4 enzymes, articles focusing on the co-administration of NOACs and drugs affecting these pathways are discussed. Concomitant use of NOACs with antiplatelet agents may potentially increase bleeding risk. EXPERT OPINION: Measurement of anticoagulant effects is desired to evaluate the risk of thromboembolism or bleeding for patients with NOACs. Prescribers should be vigilant against combination prescription of NOACs with strong inhibitors (such as ketoconazole) or inducers of P-gp and/or CYP3A4 (such as rifampicin). Potential benefit of concurrent use of these agents with antiplatelet drugs should be cautiously balanced against latent risk in specific clinical situations.

New advances in the treatment of atrial fibrillation: focus on stroke prevention.

INTRODUCTION: Atrial fibrillation (AF) is the most common arrhythmia and brings about significant mortality and morbidity as a result of heart failure and ischemic stroke. Besides vitamin K antagonists (VKA), several new pharmacological agents (nonvitamin K antagonist oral anticoagulants [NOACs]) and procedures have since been developed to improve stroke prevention efforts in AF. AREAS COVERED: This paper will discuss the antiplatelet agents, VKA and NOACs, and their efficacy and safety for stroke prevention in AF. Focus will be placed on the NOACs, their limitations and special considerations. A short assessment of other nonpharmacological antithrombotic procedures will also be made. An extensive PubMed search was used to identify suitable papers. EXPERT OPINION: Despite the advent of NOACs, the VKAs will remain as an important oral anticoagulant due to its versatility. However, convenience and limited food or drug interactions will make NOACs attractive options. The choice between various NOACs will depend on several important factors as illustrated below. Over time, the role for antiplatelet agents will gradually diminish. Left atrial appendage occlusion devices have shown promising results and may have the potential to change the way clinicians manage thromboembolism risks related to AF.

Which drug should we use for stroke prevention in atrial fibrillation?

PURPOSE OF REVIEW: Oral anticoagulation (OAC) remains the mainstay for prevention of ischaemic stroke in atrial fibrillation. This article reviews the latest evidence and development of new oral anticoagulants for the prevention of ischaemic stroke, as well as bleeding risk assessment, mitigation and management. RECENT FINDINGS: Decision-making for stroke prevention has evolved towards the initial identification of 'low-risk' patients who do not need any antithrombotic therapy. Subsequent to this step, patients with at least 1 stroke risk factor can be offered effective stroke prevention, which is OAC. There is increased morbidity and mortality amongst warfarin users, if time in therapeutic range is poor. New oral anticoagulants (such as dabigatran, rivaroxaban, apixaban and edoxaban) offer relative efficacy, safety and convenience compared to warfarin, in relation to stroke prevention in atrial fibrillation. Bleeding risk can be assessed by HAS-BLED score, whereas the new SAMe-TT2R2 score can predict the patient's suitability for vitamin K antagonists. SUMMARY: The landscape for stroke prevention in atrial fibrillation has greatly changed. It is no longer a question of 'if we treat' but more of 'how to treat', as the presence of one or more stroke risk factors in atrial fibrillation confers a risk of fatal and devastating strokes. OAC use, whether as well controlled vitamin K antagonists or nonvitamin K antagonists oral anticoagulant, will reduce the burden of stroke in atrial fibrillation.

Management of Atrial Fibrillation in Patients With Kidney Disease.

The increasing burden of Chronic Kidney Disease (CKD) is highly relevant to cardiologists, as cardiovascular mortality is 10-30 times higher amongst people with End-stage Renal Disease (ESRD), comparing with general population. One of the commonest associations is the increased frequency of atrial fibrillation (AF) amongst those experiencing CKD. Overall, we know that AF is the most common cardiac arrhythmia. AF leads to a substantial risk of mortality and morbidity, from stroke and thromboembolism, heart failure, reduced cognitive function and impaired quality of life. However, most clinical trials in AF (for example, for stroke prevention in AF with anticoagulation therapy) have largely excluded patients with significant renal impairment. In this review article, we will focus on stroke prevention in AF, and the clinical impact of CKD and its implications for management.