What is the risk of gastrointestinal (GI) bleeding with Brilinta (ticagrelor)?

Risk of GI Bleeding with Brilinta (Ticagrelor)

Ticagrelor (Brilinta) increases the risk of gastrointestinal bleeding, particularly when used in combination with aspirin as dual antiplatelet therapy, with a 2-3 fold increased risk compared to aspirin alone. 1

Bleeding Risk Profile

• Ticagrelor, like other antiplatelet agents, does not directly cause ulcers or erosions of the digestive tract but promotes bleeding at sites of preexisting lesions through its antiplatelet effects 1
• The absolute risk increase for GI bleeding with dual antiplatelet therapy (ticagrelor plus aspirin) compared to aspirin alone is approximately 0.6% to 2.0% 1
• Case fatality rates for GI bleeding associated with dual antiplatelet therapy are relatively low (0% to 0.3%), but GI bleeding remains a significant predictor of death with a relative risk of 2.5 1

Risk Factors for GI Bleeding with Ticagrelor

Several factors increase the risk of GI bleeding in patients taking ticagrelor:

• History of bleeding or other complications of peptic ulcer disease (strongest risk factor) 1
• Advanced age (significantly increases absolute risk) 1
• Concurrent use of:
  • Anticoagulants 1
  • Steroids 1
  • NSAIDs 1
• Helicobacter pylori infection 1
• Multiple comorbid conditions 2
• Impaired renal function 3

The relative risk of GI bleeding increases with the number of adverse risk factors present in an individual patient 1.

Comparative Risk with Other Antiplatelet Agents

• In head-to-head randomized trials, clopidogrel has shown lower risk of GI bleeding compared to aspirin, although the absolute difference is small 1
• Recent evidence suggests no significant difference in GI bleeding risk among clopidogrel-, ticagrelor-, or prasugrel-based dual antiplatelet therapy when used with appropriate preventive measures 4
• Case reports have documented major GI bleeding with ticagrelor, highlighting the potential for serious bleeding complications 5

Prevention Strategies

For patients requiring ticagrelor who are at increased risk of GI bleeding:

• Proton pump inhibitors (PPIs) are recommended to reduce GI bleeding risk in high-risk patients 1
• PPIs are more effective than histamine H2 receptor antagonists (H2RAs) in preventing upper GI bleeding in patients on antiplatelet therapy 1
• In a cohort of patients on dual antiplatelet therapy, PPI use led to a greater reduction in upper GI bleeding (odds ratio: 0.04) compared to H2RA use (odds ratio: 0.43) 1
• Routine use of either a PPI or an H2RA is not recommended for patients at lower risk of upper GI bleeding 1

Clinical Decision-Making Algorithm

1. Assess patient's baseline GI bleeding risk:

   • History of peptic ulcer disease or GI bleeding
   • Age ≥60 years
   • Concurrent medications (anticoagulants, NSAIDs, steroids)
   • Presence of H. pylori infection
   • Number of comorbidities

2. For high-risk patients (history of GI bleeding or multiple risk factors):

   • Add PPI prophylaxis 1
   • Consider testing for and treating H. pylori infection 1
   • Avoid concomitant use of NSAIDs when possible 1

3. For patients requiring endoscopic procedures:

   • Consider timing of procedures relative to ticagrelor initiation 1
   • For high-risk endoscopic procedures, consider temporarily discontinuing ticagrelor if clinically appropriate 1

4. Monitor all patients on ticagrelor for signs of GI bleeding:

   • Educate patients about recognizing bleeding symptoms 1
   • Perform periodic monitoring of hemoglobin levels, particularly in those with impaired renal function 3

Caveats and Pitfalls

• Clinical decisions regarding concomitant use of PPIs and ticagrelor must balance overall risks and benefits, considering both cardiovascular and GI complications 1
• Patients with a history of GI bleeding are at particularly high risk for recurrent bleeding on antiplatelet therapy 6
• When dual antiplatelet therapy is required, the risk-benefit ratio should be carefully assessed, especially in older patients with multiple comorbidities 2
• Avoid assuming that ticagrelor is safer than other antiplatelet agents regarding GI bleeding risk; recent evidence suggests similar bleeding profiles when appropriate preventive measures are used 4