What are the potential interactions between Brilinta (ticagrelor) and proton pump inhibitors (PPIs) in a patient taking Brilinta?

Brilinta and PPI Interaction

Brilinta (ticagrelor) can be safely used with PPIs without the drug-drug interaction concerns that exist with clopidogrel, as ticagrelor does not require CYP2C19 metabolism for activation.

Key Mechanistic Difference

Unlike clopidogrel, ticagrelor is not a prodrug and does not require hepatic CYP2C19 metabolism to become active 1. Ticagrelor is an active drug that directly and reversibly inhibits the P2Y12 platelet receptor 2. This fundamental pharmacologic difference eliminates the theoretical basis for a clinically significant interaction between ticagrelor and PPIs that has been a concern with clopidogrel 1.

Clinical Evidence for Ticagrelor-PPI Combination

• Recent prospective data demonstrates that combining ticagrelor with PPIs (pantoprazole or omeprazole) does not increase ischemic events while significantly reducing gastrointestinal bleeding compared to ticagrelor alone 3

• No differences were observed in:

  • Platelet aggregation measures (thrombelastography parameters) 3
  • Platelet activation markers (P-selectin, glycoprotein IIb/IIIa) 3
  • Stent thrombosis rates 3
  • Major adverse cardiovascular events 3

• PPIs combined with ticagrelor significantly reduced GI bleeding events without compromising antiplatelet efficacy 3

When to Use PPIs with Brilinta

PPIs are recommended for patients on ticagrelor who have:

• History of upper GI bleeding (strongest indication) 1
• Multiple GI bleeding risk factors including:
  • Advanced age 1
  • Concurrent anticoagulant use 1
  • Concurrent steroid or NSAID use 1
  • Helicobacter pylori infection 1

For patients without these risk factors, routine PPI use is not recommended as the absolute benefit is minimal 1

PPI Selection

Any PPI can be used with ticagrelor without concern for the CYP2C19-mediated interactions seen with clopidogrel 1. The choice can be based on:

• Patient-specific factors (cost, formulary availability)
• GI indication severity (PPIs superior to H2RAs for acid suppression) 1

Important Caveats

• The guideline evidence provided focuses on clopidogrel-PPI interactions [1-1], which are not applicable to ticagrelor due to different metabolic pathways 1, 2

• While one observational study suggested PPIs alone may increase stroke risk 4, this finding was modest (HR 1.36) and a causal relationship was not established 4. This should not deter appropriate PPI use in high-risk patients where GI bleeding prevention benefits clearly outweigh theoretical cerebrovascular concerns 1

• Meta-analyses of dual antiplatelet therapy with PPIs show no increased cardiovascular risk and significant GI bleeding reduction 5, supporting the safety of this combination

Practical Algorithm

1. Assess GI bleeding risk in all patients starting ticagrelor
2. Add PPI if: Prior GI bleeding OR ≥2 risk factors (age >65, anticoagulants, steroids, NSAIDs, H. pylori)
3. Consider H2RA for lower-risk patients who need some GI protection 1
4. Do not routinely prescribe PPI for patients without risk factors 1