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

Indications for Dual Antiplatelet Therapy

Dual antiplatelet therapy (DAPT) is indicated for all patients with acute coronary syndrome (ACS)—including STEMI, NSTEMI, and unstable angina—for at least 12 months, combining aspirin with a P2Y12 inhibitor (preferably ticagrelor or prasugrel over clopidogrel). 1

Primary Indications

DAPT is mandatory in the following clinical scenarios:

• All ACS patients regardless of management strategy: This includes patients with STEMI, NSTEMI, and unstable angina, whether managed with percutaneous coronary intervention (PCI), medical therapy alone, or coronary artery bypass grafting 1, 2, 3

• Patients undergoing PCI with stent placement: DAPT is essential for all patients receiving either bare-metal stents or drug-eluting stents to prevent stent thrombosis 1, 4

• FDA-approved indications: Prasugrel is specifically indicated for ACS patients managed with PCI, including both unstable angina/NSTEMI and STEMI 5. Clopidogrel is indicated for non-ST-elevation ACS and STEMI 6

Optimal P2Y12 Inhibitor Selection

The choice of P2Y12 inhibitor follows a clear hierarchy:

• First-line: Ticagrelor (180 mg loading dose, then 90 mg twice daily) is preferred for all ACS patients regardless of treatment strategy, including those already on clopidogrel (which should be discontinued) 2, 4, 3

• Alternative first-line: Prasugrel (60 mg loading dose, then 10 mg daily) is recommended for P2Y12 inhibitor-naïve patients with ACS undergoing PCI, unless contraindications exist 2, 3

• Second-line: Clopidogrel (600 mg loading dose, then 75 mg daily) should only be used when ticagrelor or prasugrel are contraindicated, such as in patients with prior intracranial bleeding, those requiring long-term anticoagulation, or those at very high bleeding risk 2, 4

Critical contraindication: Prasugrel must not be used in patients with prior stroke or transient ischemic attack due to increased risk of cerebrovascular events; ticagrelor is the preferred potent P2Y12 inhibitor in this population 2, 5

Standard Duration: 12 Months

• Default duration is 12 months for all ACS patients who are not at high bleeding risk, regardless of ACS type, stent type, or completeness of revascularization 1, 4, 3

• Upstream therapy consideration: In patients with NSTE-ACS scheduled for invasive strategy with angiography delayed >24 hours, upstream treatment with clopidogrel or ticagrelor may be considered to reduce major adverse cardiovascular events 1, 4

Bleeding Risk Mitigation Strategies

Several evidence-based approaches reduce bleeding complications without compromising efficacy:

• Proton pump inhibitor (PPI) co-prescription: Recommended for all patients on DAPT to reduce gastrointestinal bleeding risk 1, 2, 4, 3

• Low-dose aspirin: Maintain aspirin at 75-100 mg daily (specifically 81 mg when using ticagrelor) rather than higher doses 2, 3

• Radial artery access: Use radial over femoral access for coronary angiography and PCI when performed by an experienced radial operator 2, 3

De-escalation Strategies After Initial Period

For patients who have tolerated DAPT without bleeding complications, several de-escalation options exist:

• Ticagrelor monotherapy: In patients who have tolerated DAPT with ticagrelor, transition to ticagrelor monotherapy (discontinue aspirin) is recommended ≥1 month after PCI 1, 4

• Triple therapy patients: For patients requiring long-term anticoagulation, discontinue aspirin 1-4 weeks after PCI and continue P2Y12 inhibitor, preferably clopidogrel rather than ticagrelor 1, 4

• High bleeding risk patients: Consider shorter DAPT duration (3-6 months) in patients with PRECISE-DAPT score ≥25 or meeting ARC-HBR criteria 3

Perioperative Management

• Continue aspirin perioperatively if bleeding risk allows 2, 3

• Never discontinue DAPT within the first month after stent placement for elective non-cardiac surgery—this dramatically increases risk of stent thrombosis, MI, and death 2, 4

• Resume DAPT as soon as possible post-operatively 2, 3

Critical Pitfalls to Avoid

• Do not use clopidogrel as first-line therapy when ticagrelor or prasugrel are available and not contraindicated—this represents suboptimal care for ACS patients 1, 2, 4

• Do not discontinue DAPT prematurely, especially within the first month after stent placement, as this dramatically increases thrombotic risk 4, 3

• Do not fail to prescribe a PPI with DAPT—this simple intervention significantly reduces gastrointestinal bleeding 1, 4

• Do not administer prasugrel to patients with prior stroke or TIA—this is contraindicated and increases cerebrovascular event risk 2, 5