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The optimal warfarin dose for patients beginning therapy

Warfarin is commonly prescribed to prevent blot clots in patients with medical conditions such as atrial fibrillation, heart valve replacement or previous blood clots. Warfarin is an effective treatment which has been used for many years but needs to be closely monitored, especially at the beginning of treatment, as there is a wide variation in response to dose. Monitoring of the response to dose is done using an International Normalized Ratio (INR) and it is important that patients remain within a narrow range (typically 2 to 3 INR) due to the need to balance the goal of preventing blood clots with the risk of causing excessive bleeding.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2012

Management of warfarin in patients desiring tattoo placement: a review of recommendations for cutaneous procedures

Bibliographic details: Causey HE, Hodulik KL.  Management of warfarin in patients desiring tattoo placement: a review of recommendations for cutaneous procedures. Journal of Pharmacy Technology 2013; 29(6): 250-254

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2013

Recommendations for Optimal Warfarin Management for Prevention of Thromboembolic Events in Patients with Atrial Fibrillation [Internet]

The objective of this report is to provide recommendations for the optimal management of warfarin for the prevention of thromboembolic events in patients with atrial fibrillation (AF). Three specific questions were asked to CADTH COMPUS Expert Review Committee (CERC) members:

CADTH Optimal Use Report - Canadian Agency for Drugs and Technologies in Health.

Version: November 2011
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Optimal Warfarin Management for the Prevention of Thromboembolic Events in Patients with Atrial Fibrillation: Review of Canadian Economic Studies [Internet]

The objective was to review the published literature for Canadian studies that provided information on the following question: What are the costs associated with specialized anticoagulation services?

CADTH Optimal Use Report - Canadian Agency for Drugs and Technologies in Health.

Version: November 2011
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Optimal Warfarin Management for the Prevention of Thromboembolic Events in Patients with Atrial Fibrillation: A Systematic Review of the Clinical Evidence [Internet]

Warfarin is an oral anticoagulant in the drug class of vitamin K antagonists. It is often used for stroke prevention in patients with atrial fibrillation (AF) at high risk for stroke who have no contraindications. Warfarin and related anticoagulants have consistently been shown to reduce the risk of stroke in patients with AF by more than 60% compared with no treatment, and by 30% to 40% compared with low-dose aspirin. Long-term anticoagulation with vitamin K antagonists is typically required for prevention and treatment of thromboembolism in patients with AF and other high-risk groups, such as patients with mechanical heart valves, venous thromboembolism, pulmonary embolism, or peripheral vascular disease. However, warfarin use has some disadvantages, including numerous food and drug interactions, the need for frequent laboratory monitoring, and the risk of bleeding complications.

CADTH Optimal Use Report - Canadian Agency for Drugs and Technologies in Health.

Version: November 2011
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Warfarin initiation nomograms of 5 mg and 10 mg for venous thromboembolism

Venous thromboembolism is the presence of a blood clot that blocks a blood vessel within the venous system; it includes deep vein thrombosis (DVT) and pulmonary embolism (PE), which can be fatal. Venous thromboembolism occurs in 40% to 60% of patients after major orthopedic surgery.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2016

Warfarin Management in Patients with Atrial Fibrillation — Current Practice Study [Internet]

The objective of this current practice study was to explore the views and experiences of health care professionals and patients with atrial fibrillation regarding the use of warfarin and management of warfarin therapy for the prevention of thromboembolic events.

CADTH Optimal Use Report - Canadian Agency for Drugs and Technologies in Health.

Version: March 2012
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Comparative Effectiveness of Warfarin and Newer Oral Anticoagulants for the Long-Term Prevention and Treatment of Arterial and Venous Thromboembolism [Internet]

The Veterans Health Administration (VHA) System serves a largely older, male population with a high prevalence of chronic atrial fibrillation (AF) and venous thromboembolism (VTE). Many veterans with chronic AF have risk profiles for stroke that, according to current clinical guidelines, place them in a risk group where chronic anticoagulation is recommended. Adjusted-dose warfarin has been the preferred approach to chronic anticoagulation in the VHA, and in many VHA settings, specialized therapeutic drug-monitoring services provide high-quality warfarin treatment. However, the advent of newer anticoagulants with the promise of simplified long-term anticoagulation requires reconsideration of current treatment practices. The purpose of this systematic review was to study the comparative effectiveness of warfarin and the newer oral anticoagulants used for the long-term prevention and treatment of arterial and venous thromboembolism. An evaluation of newer oral anticoagulants for VTE prophylaxis in the perioperative period will be the subject of a later report.

Evidence-Based Synthesis Program - Department of Veterans Affairs (US).

Version: April 2012
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Safety, Effectiveness, and Cost-Effectiveness of New Oral Anticoagulants Compared with Warfarin in Preventing Stroke and Other Cardiovascular Events in Patients with Atrial Fibrillation [Internet]

Approximately 250,000 Canadians are affected by atrial fibrillation (AF). Stroke is a complication of AF, and Canadians with AF are five times more likely to have a stroke and are twice as likely to die than individuals without AF. AF and stroke are more common among the elderly.

CADTH Therapeutic Review - Canadian Agency for Drugs and Technologies in Health.

Version: April 9, 2012
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Outcomes of pharmacogenetics-guided dosing of warfarin: a systematic review and meta-analysis

Bibliographic details: Tang Q, Zou H, Guo C, Liu Z.  Outcomes of pharmacogenetics-guided dosing of warfarin: a systematic review and meta-analysis. International Journal of Cardiology 2014; 175(3): 587-59125005340

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

Oral anticoagulants for primary prevention, treatment and secondary prevention of venous thromboembolic disease, and for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis and cost-effectiveness analysis

The study found that the use of novel oral anticoagulants has advantages over warfarin in patients with atrial fibrillation, but there was no strong evidence that they should replace warfarin or low-molecular-weight heparin in the primary prevention, treatment or secondary prevention of venous thromboembolic disease.

Health Technology Assessment - NIHR Journals Library.

Version: March 2017
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Antithrombotic Agents for the Prevention of Stroke and Systemic Embolism in Patients With Atrial Fibrillation [Internet]

Atrial fibrillation (AF) is a common cardiac arrhythmia associated with increased morbidity and mortality. Patients with AF are at increased risk of systemic embolism (SE) and stroke, which can cause death, disability, and impaired quality of life. Antithrombotic therapies, such as oral anticoagulant and antiplatelet drugs, can reduce the risk for stroke and systemic thromboembolism and are recommended for most AF patients with risk factors for stroke. Antithrombotic therapies are also associated with a risk of bleeding, and their efficacy for stroke prevention should always be balanced against a patient’s risk of hemorrhage.

CADTH Therapeutic Review - Canadian Agency for Drugs and Technologies in Health.

Version: March 2013
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The addition of vitamin K to improve anticoagulation stability for patients starting or already on warfarin

People with irregularity in heart activity, mechanical heart valves, and clotting disorders are at increased risk of developing blood clots, which could lead to stroke or death. Taking warfarin significantly reduces this risk. However, taking too much warfarin can lead to excessive bleeding, while taking too little reduces its benefit. To monitor this, patients taking warfarin must have regular blood tests to check if their dose of warfarin is stable enough to find the correct balance. There is some evidence that adding a small dose of vitamin K to the warfarin improves this balance. In this review, our primary outcomes were to assess if the addition of low‐dose vitamin K to warfarin had an effect on the time taken to the first INR in range; the mean within the therapeutic range; or any adverse events, such as thromboembolic events, haemorrhage, or mortality. We found two studies that met our inclusion criteria. Neither study reported the time taken to the first INR in range. One study was only available in an abbreviated format, so we were unable to interpret the results fully. Nonetheless, it was suggested that the addition of vitamin K had no benefit. A second six‐month study gave a small dose of vitamin K (150 mcg daily) or placebo to participants taking warfarin with existing poor INR control. This study reported the mean time in therapeutic range as a percentage and found that in the group of participants deemed to have poor INR control, the addition of 150 mcg oral vitamin K significantly improved their anticoagulation control. However, the study was relatively small. Neither study reported any adverse events, such as thromboembolism, haemorrhage, or death. We conclude that further larger, higher quality studies are needed to conclude whether adding vitamin K to warfarin for patients starting or already on warfarin improves their anticoagulation control.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2014

Meta-analysis of efficacy and safety of genotype-guided pharmacogenetic dosing of warfarin

Bibliographic details: Xu H, Xie X, Wang B, Chen Y, Meng T, Ma S, Wang F.  Meta-analysis of efficacy and safety of genotype-guided pharmacogenetic dosing of warfarin. International Journal of Cardiology 2014; 177(2): 654-65725449474

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

[Safety and efficacy of pharmacogenomics-guided warfarin dosing algorithms: a systematic review]

Bibliographic details: Zhao N, Zhang YT, Cheng G, Zou MJ, Hu X.  [Safety and efficacy of pharmacogenomics-guided warfarin dosing algorithms: a systematic review]. Chinese Journal of New Drugs 2012; 21(15): 1722-1728

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2012

Venous Thromboembolism: Reducing the Risk of Venous Thromboembolism (Deep Vein Thrombosis and Pulmonary Embolism) in Patients Admitted to Hospital

Venous thromboembolism (VTE) is a term used to include the formation of a blood clot (a thrombus) in a vein which may dislodge from its site of origin to travel in the blood, a phenomenon called embolism. A thrombus most commonly occurs in the deep veins of the legs; this is called deep vein thrombosis. A dislodged thrombus that travels to the lungs is known as a pulmonary embolism.

NICE Clinical Guidelines - National Clinical Guideline Centre – Acute and Chronic Conditions (UK).

Version: 2010
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A meta-analysis on the efficacy of dabigatran versus warfarin among patients with atrial fibrillation

Bibliographic details: Morilla MA, Tumulak CD, Gulay CB, Dioquino CP, Morales DD.  A meta-analysis on the efficacy of dabigatran versus warfarin among patients with atrial fibrillation. Philippine Journal of Internal Medicine 2012; 50(4): 1-4 Available from: http://www.pcp.org.ph/index.php/pjim/429-phil-journal-of-internal-medicine-vol50-no4

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2012

A meta-analysis to determine the effect of pre-injury warfarin on mortality in trauma patients

Bibliographic details: Batchelor JS, Ahmed S.  A meta-analysis to determine the effect of pre-injury warfarin on mortality in trauma patients. Trauma 2014; 16(2): 108-113 Available from: http://tra.sagepub.com/content/16/2/108

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

Therapy-related complication incidences of warfarin with different anticoagulation intensity in Chinese after mechanical heart valve replacement: a systematic review

Bibliographic details: Zhang JH, Guan CF, Chen ZJ, Tian HL, Cao H.  Therapy-related complication incidences of warfarin with different anticoagulation intensity in Chinese after mechanical heart valve replacement: a systematic review. Chinese Journal of Evidence-Based Medicine 2014; 14(11): 1361-1366 Available from: http://www.cjebm.org.cn/en/oa/darticle.aspx?type=view&id=20141114

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

Safety, effectiveness, and cost-effectiveness of new oral anticoagulants compared with warfarin in preventing stroke and other cardiovascular events in patients with arterial fibrillation

Bibliographic details: Wells G, Coyle D, Cameron C, Steiner S, Coyle K, Kelly S, Tang A, Healey J, Hsieh SC, van Berkom J.  Safety, effectiveness, and cost-effectiveness of new oral anticoagulants compared with warfarin in preventing stroke and other cardiovascular events in patients with arterial fibrillation. Canada: Canadian Agency for Drugs and Technologies in Health (CADTH). Therapeutic review. 2012 Available from: http://cadth.ca/media/pdf/NOAC_Therapeutic_Review_final_report.pdf

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2012

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