In a typical patient with ST‑segment‑elevation myocardial infarction undergoing primary percutaneous coronary intervention, which P2Y12 inhibitor—ticagrelor or clopidogrel—is preferred?

Ticagrelor is Superior to Clopidogrel for STEMI Patients Undergoing Primary PCI

For typical STEMI patients undergoing primary percutaneous coronary intervention, ticagrelor (180 mg loading dose, then 90 mg twice daily) is the preferred P2Y12 inhibitor over clopidogrel because it reduces major adverse cardiovascular events, stent thrombosis, and all-cause mortality. 1, 2

Guideline-Based Recommendation

• The 2018 ESC/EACTS guidelines assign a Class I recommendation for ticagrelor over clopidogrel in STEMI patients undergoing primary PCI. 1
• Clopidogrel should only be used when potent P2Y12 receptor inhibitors (ticagrelor or prasugrel) are contraindicated or unavailable. 1
• The 2025 ACC/AHA/SCAI guidelines similarly recommend ticagrelor as first-line therapy with a Class I, Level B-R recommendation for STEMI patients undergoing primary PCI. 2, 3

Evidence of Clinical Superiority

• Ticagrelor reduces MACE by 25% compared to clopidogrel in STEMI patients (standardized relative risk 0.75,95% CI 0.64-0.83). 4
• Ticagrelor provides an 18% reduction in all-cause mortality compared to clopidogrel in STEMI patients undergoing primary PCI. 3
• Ticagrelor significantly reduces stent thrombosis compared to clopidogrel. 3, 5
• Ticagrelor reduces microvascular injury in STEMI patients, as demonstrated by lower index of microcirculatory resistance (22.2±18.0 vs. 34.4±18.8 U, p=0.005). 6
• Real-world registry data confirm that ticagrelor is associated with lower bleeding risk than clopidogrel (standardized relative risk 0.77,95% CI 0.59-0.93). 4

Practical Dosing Algorithm for STEMI with Primary PCI

• Administer ticagrelor 180 mg loading dose immediately upon STEMI diagnosis, before coronary angiography. 1, 2
• Continue ticagrelor 90 mg twice daily for 12 months. 1, 2
• Combine with aspirin 75-100 mg daily (never exceed 100 mg, as higher doses blunt ticagrelor's efficacy). 2, 3
• Prescribe a proton pump inhibitor to all patients on dual antiplatelet therapy (Class I recommendation). 2

When to Use Clopidogrel Instead

• Clopidogrel (600 mg loading, then 75 mg daily) is reserved for patients with:
  • History of intracranial hemorrhage 2
  • Active bleeding or very high bleeding risk 2
  • Requirement for oral anticoagulation (triple therapy), where clopidogrel has substantially lower bleeding risk 2
  • Ticagrelor intolerance (e.g., dyspnea, which occurs in 13.8% of ticagrelor patients vs. 7.8% with clopidogrel) 7

Prasugrel as an Alternative

• Prasugrel (60 mg loading, then 10 mg daily) is an acceptable alternative to ticagrelor for STEMI patients undergoing primary PCI. 1, 2
• Absolute contraindication: Prior stroke or TIA (Class III Harm recommendation). 2, 3
• Relative contraindications: Age ≥75 years or body weight <60 kg (higher bleeding risk). 2
• Ticagrelor has a marginal advantage over prasugrel in reducing MACE (standardized relative risk 1.12 for prasugrel vs. ticagrelor, 95% CI 1.00-1.24). 4

Critical Distinction: STEMI Managed with Fibrinolytic Therapy

• For STEMI patients receiving fibrinolytic therapy (not primary PCI), clopidogrel is the only P2Y12 inhibitor with proven safety and efficacy (Class I, Level A recommendation). 1, 3
• Ticagrelor and prasugrel have not been adequately studied in the fibrinolytic setting and should not be used. 3
• Clopidogrel dosing with fibrinolysis: 300 mg loading if age ≤75 years; 75 mg initial dose if >75 years, followed by 75 mg daily. 1, 3

Bleeding Risk Mitigation

• Use radial artery access for PCI when performed by an experienced radial operator. 2
• Maintain aspirin at 75-100 mg daily; higher doses increase bleeding without improving efficacy. 2
• Prescribe a proton pump inhibitor to all patients (Class I recommendation to reduce gastrointestinal bleeding). 2

Critical Pitfalls to Avoid

• Never discontinue dual antiplatelet therapy within the first 30 days after stent placement—this dramatically increases risk of stent thrombosis, myocardial infarction, and death. 2
• Never use clopidogrel as first-line therapy when ticagrelor is available and not contraindicated—this represents suboptimal care for STEMI patients. 2
• Never use prasugrel in patients with prior stroke or TIA (absolute contraindication). 2, 3
• Never exceed aspirin 100 mg daily when using ticagrelor—higher doses blunt ticagrelor's antiplatelet effect. 2, 3
• Never substitute ticagrelor or prasugrel for clopidogrel in STEMI patients receiving fibrinolytic therapy—only clopidogrel has proven safety in this setting. 1, 3

Management of Ticagrelor-Related Dyspnea

• If dyspnea develops (occurs in 13.8% of patients), first rule out acute coronary events, heart failure, and bleeding with ECG, troponin, and hemoglobin. 7
• Switch to clopidogrel 75 mg daily without loading dose if dyspnea is confirmed to be ticagrelor-related. 7
• Dyspnea typically resolves within days of ticagrelor discontinuation. 7
• Never discontinue all P2Y12 inhibitor therapy—this dramatically increases thrombotic risk. 7