Is Proton Pump Inhibitor (PPI) recommended for patients taking Eliquis (apixaban)?

PPI Therapy for Patients Taking Eliquis (Apixaban)

Proton pump inhibitors (PPIs) are recommended for patients taking Eliquis (apixaban) who have risk factors for gastrointestinal bleeding, but are not routinely recommended for all patients on apixaban without bleeding risk factors.

Risk Assessment for PPI Co-Therapy

The decision to prescribe a PPI for patients on apixaban should be based on the patient's risk factors for gastrointestinal bleeding:

High-Risk Patients (PPI Recommended)

Patients with any of the following risk factors should receive PPI therapy 1:

• History of upper GI bleeding
• Taking multiple antithrombotics (dual antiplatelet therapy + anticoagulant)
• Age ≥65 years with additional risk factors
• Concomitant use of:
  • Aspirin or NSAIDs
  • Corticosteroids
  • Other antiplatelet agents
• History of peptic ulcer disease
• Helicobacter pylori infection
• Chronic alcohol use
• Dyspepsia or gastroesophageal reflux disease

Low-Risk Patients (PPI Not Routinely Recommended)

Patients without the above risk factors do not require routine PPI prophylaxis 1.

Evidence Supporting PPI Use with Anticoagulants

The European Society of Cardiology (ESC) guidelines specifically recommend PPI therapy for patients on anticoagulants with increased bleeding risk 1. According to the 2021 ESC guidelines, PPIs are recommended in patients on dual antiplatelet therapy (DAPT) who are at higher-than-average risk of gastrointestinal bleeds 1.

The American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines state that "proton pump inhibitors should be used in patients with a history of prior gastrointestinal bleeding who require DAPT" (Class I recommendation) 1. Additionally, "use of proton pump inhibitors is reasonable in patients with an increased risk of gastrointestinal bleeding who require DAPT" (Class IIa recommendation) 1.

Benefits of PPI Co-Therapy with Anticoagulants

Research shows that PPIs reduce the risk of upper GI bleeding in patients taking oral anticoagulants 2. A 2021 study demonstrated that among patients on oral anticoagulant and PPI co-therapy, NOACs (including apixaban) were associated with lower risk of upper GI bleeding compared to warfarin 2.

Potential Concerns with Long-Term PPI Use

When prescribing PPIs for patients on apixaban, consider these potential issues:

• Rebound acid hypersecretion upon discontinuation 1, 3
• Potential vitamin B12, iron, calcium, and magnesium deficiencies with long-term use 4
• Increased risk of Clostridium difficile infection 4
• Possible increased risk of osteoporotic fractures with prolonged use 4, 5

Implementation Recommendations

1. Assess bleeding risk in all patients starting apixaban
2. Prescribe standard-dose PPI (e.g., omeprazole 20mg daily, pantoprazole 40mg daily) for high-risk patients
3. Monitor for side effects of long-term PPI therapy in patients requiring extended treatment
4. Consider periodic reassessment of the need for continued PPI therapy in stable patients

Key Pitfalls to Avoid

• Overuse of PPIs in low-risk patients without bleeding risk factors
• Failure to prescribe PPIs in high-risk patients, particularly those with a history of GI bleeding or multiple risk factors
• Abrupt discontinuation of long-term PPI therapy, which can lead to rebound hyperacidity 1, 3
• Neglecting to monitor for potential nutrient deficiencies in patients on long-term PPI therapy

Remember that while PPIs are generally safe and effective for reducing GI bleeding risk in patients on anticoagulants, their use should be targeted to those patients most likely to benefit based on their individual risk profile.