Should we discontinue Xarelto (Rivaroxaban) 2.5 mg daily?

Should Xarelto (Rivaroxaban) 2.5 mg Daily Be Discontinued?

Do not discontinue rivaroxaban 2.5 mg daily without a compelling clinical reason, as premature discontinuation significantly increases the risk of thrombotic events including stroke, myocardial infarction, and death. 1

Critical Warning About Discontinuation

The FDA explicitly warns that premature discontinuation of Xarelto increases the risk of thrombotic events. 1 If rivaroxaban must be stopped for any reason other than pathological bleeding, coverage with another anticoagulant should be strongly considered. 1

Understanding the 2.5 mg Dose

The 2.5 mg daily dose is not the standard anticoagulation dose for atrial fibrillation or venous thromboembolism. This specific low-dose regimen is FDA-approved for two distinct indications:

• Coronary artery disease (CAD): Reduction of major cardiovascular events when combined with aspirin 1
• Peripheral artery disease (PAD): Reduction of major thrombotic vascular events, including after lower extremity revascularization, when combined with aspirin 1, 2

When Temporary Discontinuation Is Appropriate

For Elective Surgery or Procedures

Low hemorrhagic risk procedures:

• Stop rivaroxaban 1 day before (skip 1 dose) if creatinine clearance >30 mL/min 2
• Resume 24 hours postoperatively 2

High hemorrhagic risk procedures:

• Stop rivaroxaban 2 days before surgery (corresponding to approximately 4 half-lives) 2
• For procedures requiring complete hemostasis (neuraxial anesthesia, intracranial surgery): discontinue ≥48 hours before 2
• Resume at reduced dose (10 mg once daily) for 2-3 days postoperatively, then return to therapeutic dose 2

Critical caveat: The entire perioperative management group strongly recommends never performing spinal or epidural anesthesia in patients with possible residual rivaroxaban concentration. 2

Adjusting for Renal Function

Timing of preoperative interruption must account for creatinine clearance, as rivaroxaban has 33% renal elimination. 2 Longer interruption periods are required with impaired renal function, though specific protocols for the 2.5 mg dose in renal impairment are not well-established in guidelines. 2

When Permanent Discontinuation Should Be Considered

Absolute indications for stopping:

• Active pathological bleeding that cannot be controlled 1
• Severe hypersensitivity reaction 1
• Development of rivaroxaban-induced thrombocytopenia (rare but documented) 3

Relative indications requiring careful assessment:

• Major bleeding events (1.7 events per 100 patient-years in real-world data) 4
• Gastrointestinal bleeding, which occurs more frequently with rivaroxaban than warfarin 2
• Significant drug interactions with strong CYP3A4 and P-glycoprotein inhibitors or inducers 1

Critical Management Points

If discontinuation is necessary:

1. Never stop abruptly without bridging anticoagulation if the patient has high thrombotic risk 1
2. Recognize that therapeutic anticoagulation resumes within 3 hours of taking rivaroxaban, unlike warfarin which takes days 2
3. Be aware that stroke risk increases 2-7 days after discontinuation 2
4. Consider transitioning to alternative anticoagulation rather than complete cessation 1

Monitoring after discontinuation:

• No specific reversal agent is currently FDA-approved, though andexanet alfa is in development 2
• Prothrombin time may provide useful information about residual anticoagulant effect 2
• Four-factor prothrombin complex concentrate (50 IU/kg) may be considered for life-threatening bleeding 2

Real-World Safety Data

In the global XANTUS registry of 11,121 patients, rivaroxaban demonstrated low bleeding rates (1.7 per 100 patient-years) and stroke rates (1.0 per 100 patient-years) with 77.4% one-year treatment persistence. 4 In the Dutch subset, only 11.8% permanently discontinued treatment, suggesting good tolerability in routine practice. 5

The decision to discontinue should weigh the specific indication for the 2.5 mg dose (CAD or PAD risk reduction) against any bleeding complications or contraindications that have developed. For patients with CAD or PAD, stopping rivaroxaban 2.5 mg eliminates proven cardiovascular protection. 1