Vitamin K antagonists: relative strengths and weaknesses vs. direct oral anticoagulants for stroke prevention in patients with atrial fibrillation

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Vitamin K antagonists (VKAs) have been the mainstay of anticoagulation therapy for more than 50 years. VKAs are mainly used for the prevention of stroke in patients with atrial fibrillation (AF) and the treatment and secondary prevention of venous thromboembolism. In the past 5 years, four new agents—the direct factor Xa inhibitors apixaban, edoxaban and rivaroxaban and the direct thrombin inhibitor dabigatran [collectively known as direct oral anticoagulants (DOACs) or non-VKA oral anticoagulants]—have been approved for these and other indications. Despite these new treatment options, the VKA warfarin currently remains the most frequently prescribed oral anticoagulant. The availability of DOACs provides an alternative management option for patients with AF, especially when the treating physician is hesitant to prescribe a VKA owing to associated limitations, such as food and drug interactions, and concerns about bleeding complications. Currently available real-world evidence shows that DOACs have similar or improved effectiveness and safety outcomes compared with warfarin. Treatment decisions on which DOAC is best suited for which patient to maximize safety and effectiveness should take into account not only clinically relevant patient characteristics but also patient preference. This article reviews and highlights real and perceived implications of VKAs for the prevention of stroke in patients with non-valvular AF, with specific reference to their strengths and weaknesses compared with DOACs.

Electronic supplementary material

The online version of this article (doi:10.1007/s11239-016-1446-0) contains supplementary material, which is available to authorized users.

Related collections

Most cited references 79

Record: found
Abstract: found
Article: not found

Stroke and bleeding in atrial fibrillation with chronic kidney disease.

Jonas Olesen, Gregory Lip, Anne-Lise Kamper … (2012)

Both atrial fibrillation and chronic kidney disease increase the risk of stroke and systemic thromboembolism. However, these risks, and the effects of antithrombotic treatment, have not been thoroughly investigated in patients with both conditions. Using Danish national registries, we identified all patients discharged from the hospital with a diagnosis of nonvalvular atrial fibrillation between 1997 and 2008. The risk of stroke or systemic thromboembolism and bleeding associated with non-end-stage chronic kidney disease and with end-stage chronic kidney disease (i.e., disease requiring renal-replacement therapy) was estimated with the use of time-dependent Cox regression analyses. In addition, the effects of treatment with warfarin, aspirin, or both in patients with chronic kidney disease were compared with the effects in patients with no renal disease. Of 132,372 patients included in the analysis, 3587 (2.7%) had non-end-stage chronic kidney disease and 901 (0.7%) required renal-replacement therapy at the time of inclusion. As compared with patients who did not have renal disease, patients with non-end-stage chronic kidney disease had an increased risk of stroke or systemic thromboembolism (hazard ratio, 1.49; 95% confidence interval [CI], 1.38 to 1.59; P<0.001), as did those requiring renal-replacement therapy (hazard ratio, 1.83; 95% CI, 1.57 to 2.14; P<0.001); this risk was significantly decreased for both groups of patients with warfarin but not with aspirin. The risk of bleeding was also increased among patients who had non-end-stage chronic kidney disease or required renal-replacement therapy and was further increased with warfarin, aspirin, or both. Chronic kidney disease was associated with an increased risk of stroke or systemic thromboembolism and bleeding among patients with atrial fibrillation. Warfarin treatment was associated with a decreased risk of stroke or systemic thromboembolism among patients with chronic kidney disease, whereas warfarin and aspirin were associated with an increased risk of bleeding. (Funded by the Lundbeck Foundation.).

0 comments Cited 250 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy).

Paul Reilly, Thorsten Lehr, Sebastian Haertter … (2014)

The goal of this study was to analyze the impact of dabigatran plasma concentrations, patient demographics, and aspirin (ASA) use on frequencies of ischemic strokes/systemic emboli and major bleeds in atrial fibrillation patients. The efficacy and safety of dabigatran etexilate were demonstrated in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial, but a therapeutic concentration range has not been defined. In a pre-specified analysis of RE-LY, plasma concentrations of dabigatran were determined in patients treated with dabigatran etexilate 110 mg twice daily (bid) or 150 mg bid and correlated with the clinical outcomes of ischemic stroke/systemic embolism and major bleeding using univariate and multivariate logistic regression and Cox regression models. Patient demographics and ASA use were assessed descriptively and as covariates. Plasma concentrations were obtained from 9,183 patients, with 112 ischemic strokes/systemic emboli (1.3%) and 323 major bleeds (3.8%) recorded. Dabigatran levels were dependent on renal function, age, weight, and female sex, but not ethnicity, geographic region, ASA use, or clopidogrel use. A multiple logistic regression model (c-statistic 0.657, 95% confidence interval [CI]: 0.61 to 0.71) showed that the risk of ischemic events was inversely related to trough dabigatran concentrations (p = 0.045), with age and previous stroke (both p < 0.0001) as significant covariates. Multiple logistic regression (c-statistic 0.715, 95% CI: 0.69 to 0.74) showed major bleeding risk increased with dabigatran exposure (p < 0.0001), age (p < 0.0001), ASA use (p < 0.0003), and diabetes (p = 0.018) as significant covariates. Ischemic stroke and bleeding outcomes were correlated with dabigatran plasma concentrations. Age was the most important covariate. Individual benefit-risk might be improved by tailoring dabigatran dose after considering selected patient characteristics. (Randomized Evaluation of Long Term Anticoagulant Therapy [RE-LY] With Dabigatran Etexilate; NCT00262600). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

0 comments Cited 197 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis.

O Benavente, R McBride, L. Pearce … (1999)

To characterize the efficacy and safety of anticoagulants and antiplatelet agents for prevention of stroke in patients with atrial fibrillation. Randomized trials identified by using the search strategy developed by the Cochrane Collaboration Stroke Review Group. All published randomized trials testing antithrombotic agents to prevent stroke in patients with atrial fibrillation. Data on interventions, number of participants, duration of exposure and occurrence of all stroke (ischemic and hemorrhagic), major extracranial bleeding, and death were extracted independently by two investigators. Sixteen trials included a total of 9874 participants (mean follow-up, 1.7 years). Adjusted-dose warfarin (six trials, 2900 participants) reduced stroke by 62% (95% CI, 48% to 72%); absolute risk reductions were 2.7% per year for primary prevention and 8.4% per year for secondary prevention. Major extracranial bleeding was increased by warfarin therapy (absolute risk increase, 0.3% per year). Aspirin (six trials, 3119 participants) reduced stroke by 22% (CI, 2% to 38%); absolute risk reductions were 1.5% per year for primary prevention and 2.5% per year for secondary prevention. Adjusted-dose warfarin (five trials, 2837 participants) was more efficacious than aspirin (relative risk reduction, 36% [CI, 14% to 52%]). Other randomized comparisons yielded inconclusive results. Adjusted-dose warfarin and aspirin reduce stroke in patients with atrial fibrillation, and warfarin is substantially more efficacious than aspirin. The benefit of antithrombotic therapy was not offset by the occurrence of major hemorrhage among participants in randomized trials. Judicious use of antithrombotic therapy, tailored according to the inherent risk for stroke, importantly reduces stroke in patients with atrial fibrillation.

0 comments Cited 157 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Andreas Zirlik: +49-761-270-34415 , andreas.zirlik@universitaets-herzzentrum.de

Journal

Journal ID (nlm-ta): J Thromb Thrombolysis

Journal ID (iso-abbrev): J. Thromb. Thrombolysis

Title: Journal of Thrombosis and Thrombolysis

Publisher: Springer US (New York )

ISSN (Print): 0929-5305

ISSN (Electronic): 1573-742X

Publication date (Electronic): 28 November 2016

Publication date PMC-release: 28 November 2016

Publication date (Print): 2017

Volume: 43

Issue: 3

Pages: 365-379

Affiliations

Department of Cardiology and Angiology I, University Heart Centre Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany

Article

Publisher ID: 1446

DOI: 10.1007/s11239-016-1446-0

PMC ID: 5337242

PubMed ID: 27896543

SO-VID: 8844a2d9-bbfa-4da4-a069-ff5189af3f0a

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

History

Custom metadata

ScienceOpen disciplines: Hematology

Keywords: anticoagulants,antithrombins,atrial fibrillation,factor xa inhibitors,stroke

Data availability:

ScienceOpen disciplines: Hematology

Keywords: anticoagulants, antithrombins, atrial fibrillation, factor xa inhibitors, stroke

Vitamin K antagonists: relative strengths and weaknesses vs. direct oral anticoagulants for stroke prevention in patients with atrial fibrillation

Read this article at

Abstract

Electronic supplementary material

Related collections

Stroke MRI

Most cited references 79

Stroke and bleeding in atrial fibrillation with chronic kidney disease.

The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy).

Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis.

Author and article information

Contributors

Journal

Affiliations

Article

History

Categories

Custom metadata

Comments

Comment on this article

Similar content 260

Cited by 39

Most referenced authors 2,251