Let’s Review Direct Oral Anticoagulant (DOACs)

If you’ve ever worked an ED at 3 AM during a holiday weekend, you know what’s coming: a patient visiting from out of town presents with a radiology report that is positive for a DVT. With no hematology or cardiology consults available, no access to the patient’s records, and the clock ticking, you’re left to manage the situation.

Should you prescribe a direct oral anticoagulant (DOAC)? What if the patient has renal disease or obesity? Is a “half dose” an option for an uncomplicated, first-time DVT? These are the questions we face in real-time. Let’s break down the unique challenges and evidence behind initiating DOAC therapy.

Renal Disease

Concerns:

• Increased risk of adverse events because of decreased renal clearance, leading to a higher risk of bleeding.
• Potential to worsen renal function.
• The expense of DOAC therapy 

The Evidence:

• Outcomes Associated With Apixaban Use in Patients With End-Stage Kidney Disease and Atrial Fibrillation in the United States 

• Direct Oral Anticoagulant Use: A Practical Guide to Common Clinical Challenges.

Findings:

• • • No difference in the incidence of stroke/thromboembolism between Apixaban and Warfarin.
  • Apixaban was found to have a lower risk of major bleeding compared to Warfarin. 
  • Standard dose Apixaban (5mg BID)  
    - Has the most data.
    - Was found to have a lower risk of stroke/systemic embolism and death compared to reduced dose Apixaban (2.5mg BID) or Warfarin. 
    
    • • Data show no difference—perhaps safer—compared to Warfarin.

Verdict: Renal disease—DOACs Are Ok!

Obesity

Concerns:

• • DOACs are not as effective in the prevention and treatment of venous thromboembolism in patients with severe obesity (BMI > 40 kg/m2 or weight >120 kg).

The Evidence:

• Use of direct oral anticoagulants in patients with obesity for treatment and prevention of venous thromboembolism: Updated communication from the ISTH SSC Subcommittee on Control of Anticoagulation.

Findings:

• Available data suggest that rivaroxaban and apixaban can be adequate for the treatment of VTE in patients with obesity regardless of body weight and BMI.
• Further studies are needed to investigate therapeutic ranges for individual DOACs.

Verdict: Obesity—Sort of Ok!

• Use weight, NOT BMI
  - Atrial fibrillation
  - Ok if < 150kg
• Venous Thrombosis
  - “Guidelines”: no limit 
  - Acute < 150 kg
  - Chronic < 200 kg

Bariatric Patients

Concerns:

• Decreased bio-availability in the post-operative patient due to the physical decrease in absorptive surfaces and or decreased caloric intake.

The Evidence:

• Use of direct oral anticoagulants in patients with obesity for treatment and prevention of venous thromboembolism: Updated communication from the ISTH SSC Subcommittee on Control of Anticoagulation. 

Findings:

• DOACs may be appropriate to prescribe 6-12 months after bariatric surgery. 
• Expected Impact of bariatric surgery procedures on absorption of DOACs:

- Apixaban: primarily absorbed in the upper GI tract
     - Gastric Banding - unlikely to affect absorption

     - Partial/Sleeve Gastrectomy - unlikely to affect absorption 

• Dabigatran: absorbed in the lower stomach and proximal small intestine

• Edoxaban: absorbed in the proximal small intestine

• Rivaroxaban: primarily absorbed in the stomach

Verdict:  Bariatric Patients—It Depends  

• Early/Acute setting after bariatric surgery—consider other agents
• The acute alterations in the GI tract may lead to malabsorption.
• Consider parenteral anticoagulation (Low molecular weight heparin).
• Can switch to DOAC in stable post-acute bariatric patients (6-12 months post-op).

Half Dosing

Concerns:

• Underdosed for concern for increased bleeding risk.
• Underdosed populations most commonly: older patients, women, and patients with multiple comorbidities. 

The Evidence:

• Association Between Inappropriately Dosed Anticoagulation Therapy With Stroke Severity and Outcomes in Patients With Atrial Fibrillation.
• Benefits and Harms of Standard Versus Reduced‐Dose Direct Oral Anticoagulant Therapy for Older Adults With Multiple Morbidities and Atrial Fibrillation. 

Findings:

• Most data is for apixaban 2.5 mg bid and rivaroxaban 10mg daily 6 months or more after DVT/PE.
• Higher rate of bleeding with minimal difference in the effectiveness of standard versus reduced-dose DOAC treatment in a nationwide study of nursing home residents with nonvalvular atrial fibrillation. 
• 2023 article supported the use of reduced-dose DOACs for older adults with multiple comorbidities. 

Bottom Line:  Half-Dosing - Maybe

• Inappropriate dose reduction of DOAC is associated with more strokes and no difference in bleeding.
• Dose reduction for AFIB only if the patient meets the criteria.