What are the latest guideline recommendations for ticagrelor dosing and duration of dual antiplatelet therapy in adult acute coronary syndrome (ST‑segment‑elevation or non‑ST‑segment‑elevation) patients undergoing percutaneous coronary intervention, including adjustments for high bleeding risk?

Ticagrelor in Acute Coronary Syndrome: Latest Guidelines

Ticagrelor (180 mg loading dose, then 90 mg twice daily) plus aspirin 75-100 mg daily is the first-line dual antiplatelet therapy for all adult patients with acute coronary syndrome undergoing percutaneous coronary intervention, regardless of whether they present with ST-elevation or non-ST-elevation ACS. 1, 2

Optimal Dosing Regimen

• Loading dose: Administer ticagrelor 180 mg as soon as ACS is diagnosed, before any invasive procedures 2, 3
• Maintenance dose: Continue ticagrelor 90 mg twice daily for 12 months 1, 2, 4
• Aspirin dose: Combine with low-dose aspirin 75-100 mg daily (not higher doses) 2, 3, 4

The 2025 ACC/AHA/SCAI guidelines explicitly recommend ticagrelor or prasugrel in preference to clopidogrel for all ACS patients undergoing PCI, representing a Class I recommendation. 1 This preference is based on superior reduction in cardiovascular death, myocardial infarction, and stroke compared to clopidogrel. 3

Standard Duration of Therapy

The default duration is 12 months for all ACS patients who are not at high bleeding risk, regardless of:

• ACS type (STEMI vs. NSTEMI) 2, 4
• Stent type (drug-eluting vs. bare-metal) 2
• Completeness of revascularization 2
• Management strategy (PCI, medical therapy alone, or CABG) 2, 4

Duration Modifications for High Bleeding Risk

• Shortened duration (6 months): May be reasonable in patients with high bleeding risk (e.g., PRECISE-DAPT score ≥25) 2, 3
• Extended duration (>12 months): After completing 12 months of ticagrelor 90 mg twice daily without bleeding complications, transition to ticagrelor 60 mg twice daily may be considered in high ischemic risk patients (age ≥50 years plus diabetes, prior MI, multivessel disease, or chronic kidney disease) 2

Mandatory Bleeding Risk Mitigation Strategies

Every patient on ticagrelor-based dual antiplatelet therapy must receive the following interventions:

1. Proton pump inhibitor: Class I recommendation for all patients to reduce gastrointestinal bleeding 1, 2, 3, 4
2. Radial artery access: Preferred over femoral access when PCI is performed by an experienced radial operator 1, 2, 3
3. Low-dose aspirin: Maintain at 75-100 mg daily, not higher doses 2, 3, 4

Transition to Ticagrelor Monotherapy

In patients who have tolerated dual antiplatelet therapy with ticagrelor without bleeding complications, transition to ticagrelor monotherapy (discontinue aspirin) is recommended ≥1 month after PCI. 1 This represents a novel 2025 guideline recommendation that reduces bleeding risk while maintaining ischemic protection. 1

Special Clinical Scenarios

Switching from Clopidogrel to Ticagrelor

• For ACS patients previously on clopidogrel, administer ticagrelor 180 mg loading dose immediately upon hospital admission 2, 3
• Do not wait for clopidogrel washout—give the loading dose regardless of timing and dose of prior clopidogrel 2, 3

Patients Requiring Oral Anticoagulation

• Discontinue aspirin 1-4 weeks after PCI 1, 2
• Continue P2Y12 inhibitor, but switch to clopidogrel (not ticagrelor) due to significantly lower bleeding risk with triple therapy 3, 4

Post-CABG Management

• Resume ticagrelor after CABG to complete 12 months of dual antiplatelet therapy 2, 4
• Continue aspirin perioperatively if bleeding risk allows 2

Upstream Treatment (Pre-Catheterization)

• In patients with non-ST-elevation ACS scheduled for invasive strategy with angiography delayed >24 hours, upstream treatment with ticagrelor may be considered to reduce major adverse cardiovascular events 1

Contraindications and When to Use Alternatives

Use clopidogrel instead of ticagrelor in:

• Patients with prior intracranial hemorrhage 2, 3
• Patients requiring oral anticoagulation (triple therapy) 3, 4
• Patients with ongoing active bleeding 2
• Patients with high bleeding risk who cannot tolerate potent P2Y12 inhibition 3

Use prasugrel instead of ticagrelor in:

• P2Y12 inhibitor-naïve patients with known coronary anatomy proceeding to PCI, unless age ≥75 years, weight <60 kg, or prior stroke/TIA 2, 3

Note that prasugrel is absolutely contraindicated in patients with prior stroke or TIA, whereas ticagrelor can be safely used in this population. 2, 3, 4

Critical Pitfalls to Avoid

1. Never discontinue dual antiplatelet therapy prematurely, especially within the first month after stent placement—this dramatically increases risk of stent thrombosis, myocardial infarction, and death 2, 3, 4

2. Never fail to prescribe a proton pump inhibitor with dual antiplatelet therapy—this simple intervention significantly reduces gastrointestinal bleeding and is a Class I recommendation 1, 2, 3, 4

3. Never use clopidogrel as first-line therapy when ticagrelor is available and not contraindicated—this represents suboptimal care for ACS patients 2, 3, 4

4. Never delay ticagrelor administration—give the loading dose as soon as ACS is diagnosed, before invasive procedures 2, 3

5. Never use high-dose aspirin (>100 mg) with ticagrelor—maintain aspirin at 75-100 mg daily to minimize bleeding risk 2, 3, 4

Timing of Optimal Platelet Inhibition

• Optimal platelet inhibition (VASP <50%) is achieved within 2 hours of ticagrelor loading dose 5
• Maximal platelet inhibition occurs within 4 hours 5
• This rapid onset supports early administration in ACS patients 5