What are the indications for dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome (ACS), including those with ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI)?

Indications for Dual Antiplatelet Therapy in Acute Coronary Syndrome

Dual antiplatelet therapy (DAPT) is mandatory for ALL patients with acute coronary syndrome—including STEMI, NSTEMI, and unstable angina—regardless of management strategy (PCI, medical therapy alone, or CABG), and should be continued for 12 months unless excessive bleeding risk exists. 1, 2, 3

Primary Indications

DAPT is indicated for:

• All patients with ST-elevation myocardial infarction (STEMI) whether managed with primary PCI, delayed PCI, or fibrinolytic therapy 2, 4, 5
• All patients with non-ST-elevation myocardial infarction (NSTEMI) 2, 4, 5
• All patients with unstable angina 1, 4, 5
• All patients undergoing percutaneous coronary intervention with stent placement for any indication 1, 2

The indication exists independent of whether patients receive invasive or conservative management—DAPT is required even for medically managed ACS patients who do not undergo PCI 6, 1.

Optimal DAPT Regimen

First-Line Therapy

Aspirin 75-100 mg daily PLUS ticagrelor (180 mg loading dose, then 90 mg twice daily) is the first-line regimen for all ACS patients, regardless of initial treatment strategy. 1, 2, 3

• Ticagrelor is preferred over clopidogrel because it reduces cardiovascular death, myocardial infarction, and stroke 1
• This applies even to patients previously treated with clopidogrel—switch to ticagrelor immediately with the 180 mg loading dose without waiting for clopidogrel washout 6, 1

Alternative P2Y12 Inhibitors

Prasugrel (60 mg loading dose, then 10 mg daily) plus aspirin is an alternative for P2Y12 inhibitor-naïve patients with NSTE-ACS or STEMI undergoing PCI, unless contraindications exist 1, 3, 4

Clopidogrel (600 mg loading dose, then 75 mg daily) plus aspirin should only be used when ticagrelor or prasugrel are contraindicated 1, 5

• Use clopidogrel for patients with prior intracranial hemorrhage 1
• Use clopidogrel (NOT prasugrel) for patients with prior ischemic stroke or TIA 1
• Use clopidogrel for patients requiring oral anticoagulation 1

Critical Contraindications

Never administer prasugrel to patients with prior stroke or TIA—this is an absolute contraindication due to increased cerebrovascular bleeding risk 6, 1, 2, 4

• Prasugrel is also not recommended for patients ≥75 years or weighing <60 kg 6
• Prasugrel should not be used in medically managed ACS patients (those not undergoing PCI) 6

Standard Duration: 12 Months

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, or completeness of revascularization. 6, 1, 2, 3

Duration Modifications Based on Bleeding Risk

• High bleeding risk (PRECISE-DAPT score ≥25): Consider shortened duration of 6 months 6, 1, 2
• Low bleeding risk with high ischemic risk: Extended DAPT beyond 12 months may be considered, though this increases bleeding risk 6

Special Scenarios

• ACS patients treated with fibrinolytic therapy: Continue P2Y12 inhibitor for minimum 14 days, ideally 12 months 2
• ACS patients undergoing CABG: Resume P2Y12 inhibitor after surgery to complete 12 months of DAPT 2

Bleeding Risk Mitigation Strategies (Class I Recommendations)

These measures are mandatory for all patients on DAPT:

• Prescribe a proton pump inhibitor (PPI) with DAPT in ALL patients to reduce gastrointestinal bleeding risk 6, 1, 2, 3
  • Pantoprazole or rabeprazole are preferred over omeprazole/esomeprazole due to lower drug-drug interaction potential with clopidogrel 6
• Maintain aspirin dose at 75-100 mg daily (not higher doses) when combined with a P2Y12 inhibitor 6, 1, 2, 3
• Use radial artery access over femoral access for PCI when performed by an experienced radial operator 6, 1, 2, 3

Perioperative Management

• Continue aspirin perioperatively if bleeding risk allows 6, 2, 3
• Never discontinue DAPT within the first month after stent placement for elective non-cardiac surgery—the thrombotic risk is highest during this period 6, 2, 3
• Resume antiplatelet therapy as soon as possible post-operatively 6, 2

Critical Pitfalls to Avoid

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, 2, 3

2. Never discontinue DAPT prematurely, especially within the first month after stent placement—this dramatically increases risk of stent thrombosis, myocardial infarction, and death 6, 1, 2, 3

3. Never fail to prescribe a PPI with DAPT—this simple intervention significantly reduces gastrointestinal bleeding 1, 2, 3

4. Never administer prasugrel to patients with prior stroke/TIA or to those not undergoing PCI 6, 1, 2, 4

5. Never fail to switch from clopidogrel to ticagrelor in ACS patients when indicated—give the ticagrelor loading dose immediately without waiting for clopidogrel washout 6, 1