CASE STUDY: Reducing Stroke Risk in Atrial Fibrillation (AF)

PAULA, 76
Paula is a 76-year-old female with a history of atrial fibrillation (AF) (currently on low-dose digoxin), hypertension, and type 2 diabetes. She experienced an exacerbated episode of osteoarthritis several days ago for which she is taking OTC ibuprofen 400 mg TID. She has been on a vitamin K antagonist (VKA) for the last 6 months with variable INR readings (1.2-4.5) that required frequent dose adjustments despite her compliance with treatment and diet.
Learning objectives
- Identify complexities of anticoagulation management
- Describe considerations for long-term anticoagulation
What do you think are possible causes of the variable INR readings in this patient?
YOU CHOSE:
WHAT YOUR COLLEAGUES THINK: | |
---|---|
24% | Variations in sensitivity due to genetic differences in metabolism |
18% | Potential interactions with food and drugs |
12% | Variation in the formulation of different vitamin K antagonists |
47% | All of the above |
Response results do not constitute an endorsement of any particular response by Daiichi Sankyo |
Causes of INR Variability
Vitamin K antagonists (VKA) are very effective to reduce the risk for stroke, thromboembolic events, and all-cause mortality in patients with atrial fibrillation (AF).1,2 However, important clinical considerations include the need for frequent monitoring of the international normalized ratio (INR) and need for dose adjustment to maintain the INR within a narrow therapeutic window (2 to 3 for most indications in caucasian patients, and 1.5 to 2.5 for some Asian patients).2,3
Values above or below a target INR range may lead to excessive bleeding or thromboembolism, respectively. Even with frequent monitoring and dose adjustment, it can be difficult to maintain the INR in the desired range.1 This challenge is highlighted by the wide (up to 10-fold) interindividual variation in the dose of VKAs required to achieve optimal therapeutic anticoagulation response.3
Much of the variability in VKA response is due to factors such as:
- Drug-drug and drug-food interactions
- Alcohol consumption
- Liver dysfunction
- Dietary intake of vitamin K.1
In addition, pharmacokinetics of VKAs can vary considerably from patient to patient. Genetic variations in metabolic enzyme activity can result in significant variations in response to VKAs.4
Variability in formulations of VKAs also contributes to suboptimal control.5 Such factors often lead to suboptimal anticoagulation, and may lead to discontinuation of this valuable treatment.2
In your opinion, what is the most significant clinical consideration to optimal management of therapy for stroke prevention for this patient?
YOU CHOSE:
WHAT YOUR COLLEAGUES THINK: | |
---|---|
56% | Balancing anticoagulation with bleeding risk |
17% | Difficulty choosing the appropriate antihypertensive medication |
6% | Concerns about digoxin toxicity |
22% | Difficulty selecting the appropriate antiarrhythmic therapy |
Response results do not constitute an endorsement of any particular response by Daiichi Sankyo |
Balancing Risk Assessment
Even though there is strong evidence from clinical trials to support the use of OACs to decrease the risk for thromboembolic events, this therapy is often underutilized.2 A major reason, particularly among elderly patients, is the perceived risk for increased bleeding, especially in patients with variable pharmacology.1,2
Bleeding risk is, of course, an important consideration. However, use of balanced risk assessment strategies that consider a patient’s risk for both thromboembolism and bleeding may help identify candidates appropriate for treatment with OACs.
This is especially important among the elderly, like the patient in this case, who may not be given OACs due to concerns about adverse events, but who may benefit from this therapy more than younger patients because of the increased risk of stroke and mortality.1
What is your strategy at this time for long-term anticoagulation treatment in this patient?
YOU CHOSE:
WHAT YOUR COLLEAGUES THINK: | |
---|---|
17% | Monitor INR more frequently and continue to adjust VKA dosing accordingly |
17% | Discontinue anticoagulants because of lack of net benefit for anticoagulation (prevention of stroke vs increased risk of bleeding) |
33% | Consider an alternative anticoagulant |
33% | Admit patient to the hospital to start heparin and bridge to another anticoagulant |
Response results do not constitute an endorsement of any particular response by Daiichi Sankyo |
Managing Anticoagulation
The American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) recommends that healthcare professionals who manage oral anticoagulation therapy develop a systematic and coordinated plan of care that includes:
- Patient education
- Systematic INR testing
- Tracking
- Follow-up
- Effective communication with the patient about results and dose adjustments [Grade 1B]6
Considerations in choosing oral anticoagulants (OACs) may include2:
- Predictable pharmacology
- Oral dosing
- Need for frequent anticoagulation monitoring
- Clinically relevant drug-food interactions
- Potential for drug-drug interactions
Novel oral anticoagulants (NOACs), with established efficacy and safety profiles, have been added to the armamentarium of agents for prevention of stroke and thromboembolism in patients with AF. Clinicians now have options beyond VKAs for use in the prevention and treatment of thromboembolic disorders.2
Finished. Thank You!
Thank you for completing this patient case study. If you would like to see more case studies, please visit the other rooms in the Coagulation Center.
- Lassen MR, Laux V. Emergence of new oral antithrombotics: critical appraisal of their clinical potential. Vasc Health Risk Manag. 2008; 4(6):1373–86.
- Lane DA, Lip GYH. Maintaining therapeutic anticoagulation: the importance of keeping "within range." Chest. 2007;131:1277-79.
- Takahashi H, Echizen H. Pharmacogenetics of CYP2C and interindividual variability in anticoagulant response to warfarin. Pharmacogenom J. 2003;3:202-214.
- Moyer TP, O'Kane DJ, Baudhuin LM, et al. Warfarin sensitivity genotyping: a review of the literature and summary of patient experience. Mayo Clin Proc. 2009;84(12):1079-1094.
- Jaffer A, Bragg L. Practical tips for warfarin dosing and monitoring. Cleve Clin J Med. 2003;70(4):361-371.
- Ansell J, Hirsh J, Hylek E, et al. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest. 2008;133(6 Suppl):160S-198S.
Important: This information is not medical advice. The information presented in this case study is for educational purposes only.

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The Coagulation Center is an educational resource for healthcare professionals. Guided by a global editorial board of experts, the Coagulation Center offers a range of clinical perspectives on balancing the benefit and risk of anticoagulation in a rapidly changing landscape. Within the Coagulation Center you will find roundtable discussions on anticoagulation management, materials for patient management including patient case studies, tools to help evaluate bleeding risk and stroke risk, and downloadable resources for your practice.