What are the alternative antiplatelet therapies for a patient with a confirmed ticagrelor (Brilinta) allergy?

Alternative Antiplatelet Therapies for Ticagrelor Allergy

For patients with confirmed ticagrelor allergy, clopidogrel 75 mg daily is the recommended alternative P2Y12 inhibitor, with prasugrel as a second option in specific clinical scenarios. 1

Primary Alternative: Clopidogrel

Clopidogrel 75 mg daily (with appropriate loading dose) should be used as the first-line alternative in patients with ticagrelor allergy across all acute coronary syndrome presentations. 1

Loading Dose Strategy

• 600 mg loading dose for patients with unstable angina/NSTEMI or those undergoing PCI 1
• 300 mg loading dose for STEMI patients receiving fibrinolysis (75 mg if age ≥75 years) 1
• Continue maintenance dose of 75 mg daily indefinitely 1

Evidence Base

• Clopidogrel is specifically recommended for patients who cannot receive ticagrelor, including those with hypersensitivity reactions 1
• It has established efficacy in reducing cardiovascular events when combined with aspirin in ACS patients 1
• The drug has a well-characterized safety profile with decades of clinical use 2

Secondary Alternative: Prasugrel

Prasugrel 60 mg loading dose followed by 10 mg daily may be considered in P2Y12 inhibitor-naïve patients undergoing PCI, but only after careful exclusion of contraindications. 1

Critical Contraindications to Prasugrel

• Absolute contraindications: Active pathological bleeding, history of TIA or stroke 1
• Relative contraindication: Age ≥75 years (generally not recommended due to increased fatal and intracranial bleeding risk, except in high-risk situations like diabetes or prior MI) 1
• Dose adjustment required: Body weight <60 kg (consider 5 mg maintenance dose, though not prospectively studied) 1

Timing Considerations

• Prasugrel should not be given upstream before coronary anatomy is known in NSTEMI patients 1
• It is recommended only at the time of PCI or after angiography demonstrates anatomy amenable to PCI 1
• Discontinue at least 7 days before any planned surgery 1

Clinical Decision Algorithm

For Aspirin-Tolerant Patients

1. First choice: Clopidogrel 75 mg daily + aspirin 81 mg daily 1
2. Second choice (PCI patients only): Prasugrel 10 mg daily + aspirin 81 mg daily (if no contraindications) 1

For Aspirin-Allergic Patients

Use clopidogrel or ticagrelor alone (indefinitely) as monotherapy, or attempt aspirin desensitization. 1

• Since ticagrelor is contraindicated due to allergy in this scenario, clopidogrel 75 mg daily as monotherapy is the appropriate choice 1
• Note that dual P2Y12 receptor inhibitor therapy (e.g., clopidogrel + prasugrel) is not recommended and has no supporting data 1

Duration of Therapy

Post-Stent Patients

• Drug-eluting stents (DES): At least 12 months of dual antiplatelet therapy 1
• Bare-metal stents (BMS): Up to 12 months of dual antiplatelet therapy 1
• Earlier discontinuation may be considered if bleeding risk outweighs anticipated benefits 1

Medically Managed Patients (No Stent)

• Continue dual antiplatelet therapy for up to 12 months 1
• Aspirin should be continued indefinitely 1

Important Pharmacologic Differences

Clopidogrel Limitations

• Requires metabolic activation via CYP2C19, leading to delayed onset of action and variable response 3, 4
• Genetic polymorphisms in CYP2C19 can reduce effectiveness 3
• Irreversible P2Y12 receptor binding means prolonged recovery of platelet function 3, 4
• Concomitant use with strong CYP2C19 inhibitors (omeprazole, esomeprazole) should be avoided 2

Prasugrel Advantages Over Clopidogrel

• More rapid and consistent platelet inhibition 4
• Less affected by genetic polymorphisms 4
• However, associated with increased bleeding risk, including fatal bleeding 1, 4

Critical Drug Interactions

With Clopidogrel

• Avoid: Omeprazole and esomeprazole (significantly reduce antiplatelet activity) 2
• Use caution: Other proton pump inhibitors have less effect but should still be monitored 2
• Avoid: Strong CYP2C19 inducers like rifampin (may increase bleeding risk) 2
• Monitor: Repaglinide (clopidogrel increases exposure 3.9-5.1 fold; avoid concomitant use if possible) 2
• Increased bleeding risk: NSAIDs, warfarin, SSRIs, SNRIs, other antiplatelet agents 2

Opioid Considerations

• Opioid agonists delay and reduce absorption of clopidogrel due to slowed gastric emptying 2
• Consider parenteral antiplatelet agents in ACS patients requiring morphine or other opioids 2

Agents NOT Recommended

Dipyridamole is not recommended as an antiplatelet agent in post-ACS patients because it has not been shown to be effective (Class III: No Benefit). 1

Bleeding Management Considerations

• After PCI, use 81 mg daily aspirin in preference to higher maintenance doses to reduce bleeding risk 1
• Proton pump inhibitor therapy should be added to dual antiplatelet therapy to reduce gastrointestinal bleeding 1
• Use radial over femoral access for coronary procedures when performed by experienced operators 1

Common Pitfalls to Avoid

• Do not use two P2Y12 inhibitors concurrently (e.g., clopidogrel + prasugrel) in aspirin-allergic patients—no data supports this approach 1
• Do not give prasugrel upstream in NSTEMI before knowing coronary anatomy 1
• Do not use prasugrel in patients with prior stroke/TIA or age ≥75 years (except high-risk situations) 1
• Do not combine clopidogrel with omeprazole or esomeprazole—this significantly reduces antiplatelet efficacy 2
• Do not switch between anticoagulants (e.g., enoxaparin to UFH) as this increases bleeding risk 1