Can holding Eliquis (apixaban) for 24 hours increase the risk of stroke in an older adult patient with atrial fibrillation and a history of cardiovascular disease who is compliant with therapy?

Risk of Stroke from Holding Apixaban for 24 Hours in Compliant Atrial Fibrillation Patients

Holding apixaban for 24 hours in an otherwise compliant atrial fibrillation patient carries a measurable but relatively low acute stroke risk, though the FDA explicitly warns that stopping apixaban increases stroke risk and should only be done when medically necessary. 1

Understanding the Acute Thrombotic Risk

• The FDA drug label for apixaban clearly states: "If you stop taking apixaban, you may have increased risk of forming a clot in your blood. Do not stop taking apixaban tablets without talking to the doctor who prescribes it for you. Stopping apixaban increases your risk of having a stroke." 1

• The baseline annual stroke risk in atrial fibrillation patients varies from 1-12% per year depending on CHA₂DS₂-VASc score, which translates to approximately 0.003-0.03% risk per day in an anticoagulated patient. 2

• However, the immediate post-discontinuation period may carry heightened risk due to potential rebound hypercoagulability, similar to the increased thrombotic risk observed during transitions from atrial fibrillation to sinus rhythm. 2

Critical Context: Why Apixaban is Being Held

• For elective procedures, the FDA recommends that "apixaban tablets may need to be stopped, if possible, prior to surgery or a medical or dental procedure," and emphasizes that physicians should determine appropriate timing and consider bridging anticoagulation. 1

• The American College of Cardiology guidelines note that patients with prior stroke or TIA have a stroke recurrence rate of 10-12% per year despite aspirin, making even brief interruptions particularly concerning in this high-risk subgroup. 2

• In patients with cardiovascular disease and age ≥75 years (which increases CHA₂DS₂-VASc score), approximately 23.5% of ischemic strokes are attributable to atrial fibrillation, underscoring the importance of continuous anticoagulation. 3

Pharmacokinetic Considerations

• Apixaban has a half-life of approximately 12 hours, meaning that at 24 hours post-dose, approximately 25% of anticoagulant effect remains. 1

• The risk is not binary—there is a gradual decline in anticoagulant protection over the 24-hour period rather than an immediate loss of protection. 1

Quantifying the Risk in High-Risk Patients

• For a patient with prior stroke/TIA and atrial fibrillation (annual stroke risk ~10-12% without anticoagulation), a 24-hour interruption theoretically increases daily stroke risk from ~0.01% to potentially 0.03-0.04% during that period. 2

• Recent evidence from the ARTESiA trial subgroup analysis showed that in patients with subclinical atrial fibrillation and prior stroke/TIA, the absolute risk difference between apixaban and aspirin was 7% over 3.5 years, demonstrating the substantial protective effect of continuous anticoagulation in this population. 4

• The absolute increase in stroke risk from a single 24-hour interruption is likely in the range of 0.01-0.05%, but this risk is cumulative with each interruption and substantially higher in patients with prior stroke/TIA or multiple risk factors. 2, 4

Critical Management Principles

• The FDA explicitly states: "If you have to stop taking apixaban tablets, your doctor may prescribe another medicine to help prevent a blood clot from forming." This indicates that even brief interruptions should be managed with alternative anticoagulation strategies when possible. 1

• The European Heart Rhythm Association emphasizes that anticoagulation interruption should only occur when absolutely necessary, and reinitiation should be as prompt as possible after addressing the reason for interruption. 5

• For patients with CHA₂DS₂-VASc ≥4 or prior stroke/TIA, even brief interruptions carry disproportionate risk and warrant consideration of bridging anticoagulation or minimizing the interruption window. 2, 4

Common Pitfalls to Avoid

• Never discontinue apixaban without a clear medical indication—the FDA label emphasizes this is not a decision to be made casually. 1

• Do not assume that because a patient is "otherwise compliant" that a single 24-hour interruption is harmless—the risk is real, though relatively small in absolute terms. 1, 4

• In patients with prior stroke/TIA, the absolute risk reduction from apixaban is 7% over 3.5 years compared to aspirin, meaning these patients derive exceptional benefit from continuous anticoagulation and are at highest risk from interruptions. 4

• Avoid holding anticoagulation for low-risk procedures where bleeding risk is minimal—many dental and minor dermatologic procedures can be performed safely without interrupting anticoagulation. 3