What dual antiplatelet therapy (aspirin plus a P2Y12‑receptor inhibitor) and duration is recommended after acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) with stent placement?

Dual Antiplatelet Therapy After Acute Coronary Syndrome and Percutaneous Coronary Intervention

For all patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI) with stent placement, the recommended dual antiplatelet therapy (DAPT) is aspirin 75–100 mg daily plus ticagrelor (180 mg loading dose, then 90 mg twice daily) for 12 months, unless contraindications exist. 1

Optimal DAPT Regimen

First-Line P2Y12 Inhibitor: Ticagrelor

• Ticagrelor is the preferred P2Y12 inhibitor over clopidogrel for all ACS patients undergoing PCI because it reduces major adverse cardiovascular events, stent thrombosis, and all-cause mortality. 2, 1
• Loading dose: Administer 180 mg orally immediately after ACS diagnosis and before any invasive procedure. 1
• Maintenance dose: Continue 90 mg twice daily for 12 months. 1
• Aspirin dosing: Maintain aspirin at 75–100 mg daily; doses exceeding 100 mg diminish ticagrelor's antiplatelet efficacy (FDA black-box warning). 1
• Ticagrelor provides an absolute risk reduction of 1.4% in 12-month all-cause mortality versus clopidogrel (4.5% vs 5.9%; P < 0.001). 1

Second-Line P2Y12 Inhibitor: Prasugrel

• Prasugrel (60 mg loading dose, then 10 mg daily) is an acceptable alternative for P2Y12-inhibitor naïve patients whose coronary anatomy is already defined before PCI. 1
• Absolute contraindication: Prasugrel must never be used in patients with prior stroke or transient ischemic attack (TIA), regardless of how remote the event was—this is a Class III (Harm) recommendation. 2, 1
• Relative contraindications: Age ≥75 years or body weight <60 kg due to higher bleeding risk. 1
• Critical timing requirement: Prasugrel should not be administered before coronary anatomy is known (Class III recommendation). 1

Third-Line P2Y12 Inhibitor: Clopidogrel

• Clopidogrel (600 mg loading dose, then 75 mg daily) should be reserved only when ticagrelor and prasugrel are unavailable, not tolerated, or contraindicated. 1
• Clopidogrel is preferred when oral anticoagulation is required (triple therapy) because it has substantially lower bleeding risk than ticagrelor or prasugrel. 1
• Clopidogrel is the default choice for patients with prior intracranial hemorrhage or active bleeding. 1

Standard Duration of DAPT

• The default DAPT duration is 12 months for all ACS patients who are not at high bleeding risk, regardless of ACS type (STEMI, NSTEMI, unstable angina), stent type (drug-eluting or bare-metal), or completeness of revascularization. 2, 1
• For stable coronary artery disease (SCAD) patients undergoing PCI, DAPT is recommended for 6 months irrespective of stent type. 2
• In ACS patients with high bleeding risk (PRECISE-DAPT score ≥25), a shortened DAPT duration of 6 months may be reasonable. 2, 1

Bleeding Risk Mitigation Strategies (Class I Recommendations)

• Prescribe a proton pump inhibitor (PPI) with DAPT in all patients to reduce gastrointestinal bleeding risk—this is a Class I recommendation. 1
• Pantoprazole 40 mg daily is preferred because it has the lowest propensity for CYP2C19 inhibition and does not attenuate clopidogrel's antiplatelet activity. 1
• Use radial artery access over femoral access for PCI when performed by an experienced radial operator to reduce bleeding and vascular complications. 2, 1
• Maintain aspirin dose at 75–100 mg daily (not higher doses) when combined with a P2Y12 inhibitor. 2, 1

Special Clinical Scenarios

ACS Patients Requiring CABG

• In ACS patients treated with DAPT who undergo coronary artery bypass grafting (CABG), P2Y12 inhibitor therapy should be resumed after CABG to complete 12 months of DAPT therapy. 2, 1
• Ticagrelor and clopidogrel should be discontinued at least 5 days before elective CABG. 2
• Prasugrel should be discontinued at least 7 days before elective CABG. 2

Patients Requiring Oral Anticoagulation (Triple Therapy)

• Discontinue aspirin 1–4 weeks after PCI and switch the P2Y12 inhibitor from ticagrelor/prasugrel to clopidogrel, because clopidogrel carries substantially lower bleeding risk in triple-therapy settings. 1

Patients with Prior Stroke or TIA

• Ticagrelor is the preferred P2Y12 inhibitor for ACS patients with prior ischemic stroke or TIA. 1
• Prasugrel is absolutely contraindicated in any patient with prior stroke or TIA, with no temporal exemption—this applies to events occurring 5,10, or 20 years ago. 1
• Clopidogrel is the default alternative when ticagrelor is unavailable or not tolerated. 1

Transition to P2Y12 Inhibitor Monotherapy

• In selected patients who have tolerated DAPT without bleeding complications, discontinuation of aspirin after 1–3 months with continued P2Y12 inhibitor monotherapy is reasonable to reduce bleeding risk. 2
• This strategy reduces bleeding while preserving ischemic protection. 2

Critical Pitfalls to Avoid

• Never discontinue DAPT within the first month after stent placement—early discontinuation dramatically increases the risk of stent thrombosis, myocardial infarction, and death. 1
• Approximately 80% of stent-thrombosis events occur within the first 30 days after PCI. 1
• Never fail to prescribe a PPI with DAPT—this simple intervention significantly reduces gastrointestinal bleeding. 1
• Never use clopidogrel as first-line therapy when ticagrelor or prasugrel are available and not contraindicated—this represents suboptimal care for ACS patients. 1
• Never administer prasugrel to patients with prior stroke or TIA—this is contraindicated due to increased cerebrovascular bleeding risk. 2, 1
• Never use aspirin doses >100 mg daily with ticagrelor—higher doses blunt ticagrelor's benefit. 1
• Never administer prasugrel before coronary anatomy is known. 1

Algorithm for P2Y12 Inhibitor Selection in ACS

Step 1: Assess for absolute contraindications

• Prior stroke/TIA → Use ticagrelor (NOT prasugrel)
• Prior intracranial hemorrhage → Use clopidogrel (NOT ticagrelor or prasugrel)
• Active bleeding → Use clopidogrel

Step 2: If no absolute contraindications exist

• First choice: Ticagrelor 180 mg loading, then 90 mg twice daily 1
• Second choice (if coronary anatomy known before PCI): Prasugrel 60 mg loading, then 10 mg daily 1
• Third choice (if ticagrelor/prasugrel unavailable or not tolerated): Clopidogrel 600 mg loading, then 75 mg daily 1

Step 3: Add aspirin 75–100 mg daily to the selected P2Y12 inhibitor 1

Step 4: Prescribe PPI (pantoprazole 40 mg daily preferred) 1

Step 5: Continue DAPT for 12 months unless high bleeding risk develops 1