Why Ticagrelor (Brilinta) Cannot Be Used Without Aspirin (ASA)
Ticagrelor must be used with low-dose aspirin (typically 81 mg daily) because the combination therapy was specifically designed and tested this way, and using ticagrelor alone may reduce its effectiveness in preventing cardiovascular events and mortality. 1
Mechanism and Evidence Base
Ticagrelor works differently than other P2Y12 inhibitors in several important ways:
- It is a direct-acting, reversibly binding P2Y12 receptor antagonist
- Its efficacy is dependent on the synergistic effect with aspirin
- The clinical trials that established its benefit specifically used the combination therapy
Clinical Trial Evidence
The 2012 ACCF/AHA guidelines explicitly state: "The recommended maintenance dose of ASA to be used with ticagrelor is 81 mg daily" 1. This recommendation is based on the PLATO trial, which demonstrated ticagrelor's superiority over clopidogrel only when combined with low-dose aspirin.
Aspirin Dose Considerations
A critical point to understand is that the dose of aspirin matters significantly when used with ticagrelor:
- Low-dose aspirin (75-100 mg): Optimal efficacy with ticagrelor
- High-dose aspirin (>100 mg): May actually reduce ticagrelor's effectiveness
This dose-dependent interaction was identified in a geographic subanalysis of the PLATO trial, where North American patients taking higher aspirin doses showed reduced benefit from ticagrelor 2. The proposed mechanism involves the balance between platelet inhibition and prostacyclin effects.
Clinical Implications
Dual Antiplatelet Therapy Requirements
Current guidelines from multiple organizations consistently recommend:
- Ticagrelor plus aspirin for acute coronary syndromes (ACS)
- Continuation of both medications for 12 months in most cases
- Low-dose aspirin (81 mg) as the preferred dose when combined with ticagrelor
The 2021 ESC guidelines for NSTE-ACS state: "In patients with NSTE-ACS treated with coronary stent implantation, DAPT with a P2Y12 receptor inhibitor on top of aspirin is recommended for 12 months unless there are contraindications" 1.
Physiological Rationale
The requirement for combined therapy stems from the complementary mechanisms of action:
- Aspirin: Irreversibly inhibits COX-1, blocking thromboxane A2 production
- Ticagrelor: Reversibly blocks ADP-mediated platelet activation via P2Y12 receptors
This dual pathway inhibition provides more comprehensive platelet inhibition than either agent alone.
Special Considerations
Bleeding Risk
While dual therapy is more effective, it does increase bleeding risk compared to single antiplatelet therapy. The 2021 cohort study by JAMA Network Open found that ASA plus ticagrelor was associated with a significantly increased risk for major bleeding during the first 12 months (adjusted HR 1.90; 95% CI 1.16-3.13) 3.
Potential Future Directions
Some recent research has explored ticagrelor monotherapy after a short period of DAPT:
- The GLOBAL LEADERS trial tested ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months
- Results showed this approach was not superior to standard DAPT followed by aspirin monotherapy 4
Clinical Decision Algorithm
For ACS patients requiring antiplatelet therapy:
- Use ticagrelor 180 mg loading dose with aspirin 325 mg loading dose
- Continue with ticagrelor 90 mg twice daily plus aspirin 81 mg daily
For maintenance therapy:
- Always pair ticagrelor with low-dose aspirin (81 mg)
- Avoid high-dose aspirin (>100 mg) when using ticagrelor
- Continue dual therapy for recommended duration (typically 12 months post-ACS)
If bleeding concerns arise:
- Consider alternative P2Y12 inhibitors with lower bleeding risk
- Do not discontinue aspirin while continuing ticagrelor
In conclusion, ticagrelor without aspirin is not recommended because the drug was specifically developed and tested as part of dual antiplatelet therapy, and its proven mortality benefit is dependent on this combination.