What is the recommended dual antiplatelet therapy (DAPT) regimen for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) with stent placement?

Dual Antiplatelet Therapy for ACS with PCI and Stent Placement

For patients with acute coronary syndrome undergoing PCI with stent placement, initiate aspirin (75-100 mg daily) plus either ticagrelor (180 mg loading dose, then 90 mg twice daily) or prasugrel (60 mg loading dose, then 10 mg daily) for at least 12 months, with ticagrelor or prasugrel strongly preferred over clopidogrel. 1

P2Y12 Inhibitor Selection

First-line therapy is ticagrelor or prasugrel, not clopidogrel. 1, 2

• Ticagrelor is the preferred first-line P2Y12 inhibitor for all ACS patients regardless of initial treatment strategy, including those pre-treated with clopidogrel (which should be discontinued when ticagrelor is started) 2
• Prasugrel is an alternative for P2Y12 inhibitor-naïve patients with NSTE-ACS or STEMI undergoing PCI, unless contraindications exist 2, 3
• Clopidogrel (600 mg loading dose, 75 mg daily) should only be used when ticagrelor or prasugrel are contraindicated, such as in patients with prior intracranial bleeding or those requiring oral anticoagulation 2

Critical Contraindications

• Prasugrel is absolutely contraindicated in patients with prior stroke or TIA due to increased risk of intracranial hemorrhage (6.5% stroke rate vs 1.2% with clopidogrel in patients with prior stroke/TIA) 3
• Ticagrelor can be safely used in patients with prior stroke or TIA 2
• Prasugrel should not be used in patients ≥75 years old except in high-risk situations (diabetes or prior MI) 3

Dosing Adjustments

• For patients <60 kg on prasugrel: Consider reducing maintenance dose to 5 mg daily due to increased bleeding risk 3
• Aspirin dose: Maintain 75-100 mg daily when used with DAPT to minimize bleeding risk 1, 2

Standard Duration: 12 Months

The default DAPT duration is 12 months for all ACS patients who are not at high bleeding risk. 1

This 12-month recommendation applies regardless of:

• Type of ACS (STEMI vs NSTE-ACS) 1
• Type of stent used 1
• Whether complete revascularization was achieved 1

Bleeding Risk Mitigation Strategies

Several evidence-based approaches reduce bleeding without compromising ischemic protection:

Mandatory Interventions

• Prescribe a proton pump inhibitor (PPI) with DAPT in all patients to reduce gastrointestinal bleeding 1, 2
• Use radial artery access over femoral access for PCI when performed by an experienced radial operator 1, 2

De-escalation Options After Initial Period

For patients who have tolerated DAPT with ticagrelor, transition to ticagrelor monotherapy (discontinue aspirin) ≥1 month after PCI 1

This strategy reduces bleeding while maintaining ischemic protection and represents a major shift from traditional 12-month DAPT 1.

For patients requiring long-term anticoagulation, discontinue aspirin 1-4 weeks after PCI and continue P2Y12 inhibitor (preferably clopidogrel, not ticagrelor) 1, 2

Special Clinical Scenarios

Upstream Treatment in NSTE-ACS

For patients with NSTE-ACS scheduled for invasive strategy with angiography >24 hours away, upstream treatment with clopidogrel or ticagrelor may be considered to reduce MACE 1

However, in NSTEMI patients, no clear benefit was observed when prasugrel loading dose was administered prior to diagnostic angiography compared to at time of PCI, and bleeding risk increased with early administration 3

Timing of Prasugrel Loading Dose

• In UA/NSTEMI: Do not administer until coronary anatomy is established 3
• In STEMI presenting >12 hours after symptom onset: Wait until coronary anatomy is established 3
• In STEMI presenting within 12 hours: May administer at time of diagnosis, though most receive it at time of PCI 3

High Bleeding Risk Patients

For patients at high bleeding risk (PRECISE-DAPT score ≥25), consider shorter DAPT duration (6 months) 2

Critical Pitfalls to Avoid

• Never use prasugrel in patients with prior stroke or TIA - this is an absolute contraindication with demonstrated harm 3
• Do not discontinue DAPT prematurely, especially within the first month after stent placement, as this dramatically increases risk of stent thrombosis, MI, and death 1, 2
• Do not fail to prescribe a PPI with DAPT - this is a simple intervention that significantly reduces GI bleeding 1, 2
• Do not use clopidogrel as first-line therapy when ticagrelor or prasugrel are available and not contraindicated 1
• Do not forget to switch from clopidogrel to ticagrelor in ACS patients when indicated (give 180 mg loading dose regardless of prior clopidogrel timing/dose) 2

Perioperative Management

• Continue aspirin perioperatively if bleeding risk allows 2
• Do not discontinue DAPT within the first month for elective non-cardiac surgery 2
• When P2Y12 inhibitor must be stopped: clopidogrel 5-7 days, prasugrel 7-10 days, ticagrelor 3-5 days before surgery 4
• Resume antiplatelet therapy as soon as possible post-operatively 2