Can a patient on Warfarin (coumarin) experience an embolic stroke with atrial fibrillation (fib)?

From the Guidelines

Yes, it is possible to have an embolic stroke while having atrial fibrillation (AFib) and taking warfarin. Warfarin significantly reduces the risk of stroke in AFib patients by about 60% 1, but it does not eliminate the risk entirely. Several factors can contribute to stroke occurrence despite warfarin therapy, including:

• Poor medication adherence
• Warfarin resistance
• Certain medical conditions like severe hypertension, diabetes, or previous stroke history
• Clots forming during periods of subtherapeutic anticoagulation or from sources other than the left atrial appendage

The effectiveness of warfarin depends on maintaining the INR (International Normalized Ratio) within the therapeutic range of 2.0-3.0 1. If the INR falls below this range, stroke protection decreases substantially. The CHADS2 score is a useful tool for stratifying stroke risk in AFib patients, with higher scores indicating a greater risk of stroke 1. Warfarin is generally recommended for AFib patients with a CHADS2 score of 2 or higher, as the benefits of anticoagulation outweigh the risks of bleeding in these patients. However, the decision to anticoagulate should be individualized based on patient preferences, bleeding risk, and access to high-quality anticoagulation monitoring. If you experience any stroke symptoms such as sudden weakness, facial drooping, speech difficulties, or severe headache while on warfarin, seek emergency medical attention immediately, as prompt treatment is crucial for limiting brain damage.

From the FDA Drug Label

The results for each endpoint separately, including an analysis of vascular death, are provided in the following table: TABLE 3 Event Warfarin Placebo RR % Risk Reduction (N=607) (N=607) (95% CI) (p- value) RR= Relative risk; Risk reduction = (I - RR); CI=Confidence interval; MI=Myocardial infarction; py = patient years Total Patient Years of Follow-up 2018 1944 Total Mortality 94 (4. 7/100 py) 123 (6.3/100 py) 0.76 (0.60,0.97) 24 (p=0.030) Vascular Death 82 (4.1/100 py) 105 (5.4/100 py) 0.78 (0.60,1.02) 22 (p=0.068) Recurrent MI 82 (4.1/100 py) 124 (6.4/100 py) 0.66 (0.51,0.85) 34 (p=0.001) Cerebrovascular Event 20 (1.0/100 py) 44 (2.3/100 py) 0.46 (0.28,0.75) 54 (p=0. 002)

Warfarin reduces the risk of systemic thromboembolism, including stroke.

• The risk reduction ranged from 60% to 86% in all except one trial.
• The incidence of major bleeding in these trials ranged from 0.6 to 2.7%.
• Warfarin is recommended for patients with atrial fibrillation at high risk of stroke. However, the FDA drug label does not directly answer if you can have an embolic stroke with a fib on warfarin, as it does not provide information on the incidence of embolic stroke in patients with atrial fibrillation taking warfarin. 2 2

From the Research

Embolic Stroke with Atrial Fibrillation on Warfarin

• Atrial fibrillation (AF) increases the risk of stroke, and warfarin is commonly used to prevent stroke in patients with AF 3.
• However, warfarin can cause hemorrhage, and the time in international normalized ratio (INR) therapeutic range (TTR) mediates stroke reduction and bleeding risk 4.
• Studies have shown that increased baseline stroke and bleeding risk is associated with poor INR control, despite similar rates of INR monitoring 4.
• The relationship between INR and outcomes in patients with AF on warfarin has been examined, and the results suggest that INR between 2 and 2.5 provides the best balance between ischemic stroke and intracranial hemorrhage (ICH) 5.
• Additionally, historic time in therapeutic range (TTR) has been found to be weakly associated with future TTR, and INRs collected through routine management are not sufficiently predictive to provide reassurance about future time in therapeutic range or to prevent subsequent outcomes 6.

Risk of Embolic Stroke on Warfarin

• The risk of embolic stroke in patients with AF on warfarin is still present, even with careful INR control 6.
• In fact, most bleeding events may not have been preventable despite careful INR control 6.
• The principal risk with AF is stroke or thrombotic embolism, which is increased 5-fold in some series, and AF accounts for ≥15% of all strokes in the United States 3.
• Patients with ischemic stroke and AF are significantly more likely to be chronically disabled, bedridden, and to require constant nursing care, particularly older patients (≥85 years) 3.

Prevention of Embolic Stroke

• Prevention of thromboembolic outcomes in patients with AF requires prophylactic anticoagulation therapy, and warfarin has been the "gold standard" for anticoagulation despite its well-known side effects and adherence challenges for patients 3.
• However, the recent approvals of several new, novel oral anticoagulation (NOAC) agents present physicians with a benefit/risk profile that represents an important advance over warfarin prophylaxis 3.
• The principal risk assessment scores for thromboembolic risk are CHADS2 and CHA2DS2-VASc, which can be used to assess the risk of stroke in patients with AF 3.