Bleeding Risk: Plavix (Clopidogrel) vs Brillinta (Ticagrelor)
Clopidogrel has a lower bleeding risk profile than ticagrelor, particularly for non-CABG major bleeding and gastrointestinal bleeding, though overall major bleeding rates are similar between the two agents. 1
Overall Bleeding Risk Comparison
The landmark PLATO trial demonstrated no significant difference in overall major bleeding between ticagrelor and clopidogrel (11.6% vs 11.2%; HR: 1.04; 95% CI: 0.95 to 1.13). 1 This finding has been consistently replicated across multiple real-world studies. 2, 3
However, the devil is in the details:
- Ticagrelor significantly increases non-CABG major bleeding compared to clopidogrel (4.5% vs 3.8%, P<0.03), representing an 18% relative increase in bleeding risk. 4, 1
- Ticagrelor causes more non-procedure-related major bleeding (3.1% vs 2.3%; P=0.05). 4
- Fatal intracranial bleeding is higher with ticagrelor (0.1% vs 0.01%, P=0.02). 4
Clinical Decision Algorithm for Agent Selection
Choose Clopidogrel When:
- History of gastrointestinal bleeding (strongest indication) - clopidogrel is strongly preferred over ticagrelor in this population 1
- Age ≥75 years with multiple bleeding risk factors 4
- Body weight <60 kg 4
- Prior stroke or TIA (absolute contraindication to prasugrel; clopidogrel preferred over ticagrelor) 4, 1
- Concurrent oral anticoagulation required - clopidogrel is the P2Y12 inhibitor of choice due to lower bleeding risk 4
- High bleeding risk score (PRECISE-DAPT ≥25) 4
Choose Ticagrelor When:
- Standard ACS patient without high bleeding risk - ticagrelor is preferred per current guidelines 4, 5
- Chronic kidney disease with eGFR <60 mL/min - ticagrelor demonstrates superior efficacy without increased bleeding risk in this population 1
- High ischemic/thrombotic risk with low bleeding risk 4
Critical Nuances in the Evidence
The 2025 ACC/AHA guidelines recommend ticagrelor or prasugrel in preference to clopidogrel for ACS patients undergoing PCI 4, but this recommendation must be balanced against individual bleeding risk. The European Society of Cardiology similarly recommends ticagrelor over clopidogrel unless bleeding risk outweighs ischemic benefit. 4
The mortality benefit of ticagrelor (4.5% vs 5.9%; HR: 0.78) must be weighed against the increased non-CABG bleeding risk in individual patients. 1 Recent real-world data from Sweden found no superiority of ticagrelor over clopidogrel in unselected PCI patients, with higher in-hospital bleeding rates (aOR 2.88; 95% CI 1.53-5.44; P=0.001). 6
Bleeding Risk Mitigation Strategies (Mandatory for Both Agents)
- Prescribe a proton pump inhibitor (PPI) with DAPT in all patients - this is a Class I recommendation 4, 5, 1
- Maintain aspirin dose at 75-100 mg daily (not higher doses) when combined with either P2Y12 inhibitor 4, 5
- Use radial artery access over femoral access for PCI when performed by an experienced radial operator 4, 5
Common Pitfalls to Avoid
- Never fail to prescribe a PPI with DAPT - this simple intervention significantly reduces gastrointestinal bleeding and can partially mitigate the increased GI bleeding risk with ticagrelor 5, 1
- Never use ticagrelor in patients with prior intracranial hemorrhage - this is an absolute contraindication 4
- Never ignore bleeding risk assessment - patients with multiple Academic Research Consortium high bleeding risk criteria should preferentially receive clopidogrel 4
- Never assume "more potent is always better" - in high bleeding risk patients, clopidogrel may provide a better net clinical benefit despite lower platelet inhibition 3, 6