What is the recommended dual antiplatelet therapy (DAPT) regimen for patients with non-ST elevation myocardial infarction (NSTEMI)?

Dual Antiplatelet Therapy for Non-ST Elevation Myocardial Infarction

All NSTEMI patients should receive aspirin (75-100 mg daily) plus a P2Y12 inhibitor for 12 months, with ticagrelor (180 mg loading dose, then 90 mg twice daily) as the preferred P2Y12 inhibitor, or prasugrel (60 mg loading, then 10 mg daily) for those undergoing PCI who are P2Y12-naïve, unless contraindications exist. 1

Initial Antiplatelet Regimen

Aspirin Administration

• Administer aspirin immediately upon presentation with a loading dose of 150-300 mg oral (or 75-250 mg IV), followed by a maintenance dose of 75-100 mg daily indefinitely 1
• This lower maintenance dose (75-100 mg) is specifically recommended when used in combination with a P2Y12 inhibitor to minimize bleeding risk 1

P2Y12 Inhibitor Selection

For patients proceeding to PCI:

• First choice: Ticagrelor 180 mg loading dose, then 90 mg twice daily, regardless of whether the patient was pre-treated with clopidogrel 1, 2
• Second choice: Prasugrel 60 mg loading dose, then 10 mg daily for P2Y12-naïve patients proceeding to PCI 1
• The ESC guidelines give prasugrel a Class IIa recommendation (should be considered) in preference to ticagrelor specifically for NSTE-ACS patients who proceed to PCI 1

For patients managed conservatively (non-invasive strategy):

• Ticagrelor (180 mg loading, 90 mg twice daily) or clopidogrel (300-600 mg loading, 75 mg daily) should be added to aspirin as soon as possible after admission 1

Clopidogrel as third-line option:

• Use clopidogrel (300-600 mg loading dose, then 75 mg daily) only when prasugrel or ticagrelor are unavailable, cannot be tolerated, or are contraindicated 1

Critical Contraindications to Avoid

Prasugrel Must NOT Be Used If:

• History of prior stroke or TIA (Class III: Harm recommendation) - prasugrel increases stroke risk including intracranial hemorrhage in these patients 3, 4
• Active pathological bleeding 3
• Age ≥75 years (generally not recommended except in high-risk situations like diabetes or prior MI) 3

Dose Adjustments for Prasugrel:

• Reduce maintenance dose to 5 mg daily for patients weighing <60 kg due to increased bleeding risk, though this dose has not been prospectively studied 1, 3

Duration of Therapy

Standard duration is 12 months for all NSTEMI patients regardless of management strategy (PCI, medical therapy alone, or CABG) 1

Shortened Duration (High Bleeding Risk):

• Consider 6 months of DAPT in patients with high bleeding risk (PRECISE-DAPT score ≥25 or meeting ARC-HBR criteria) 1
• Very high bleeding risk patients (recent bleeding in past month or non-deferrable planned surgery) may require even shorter duration 1

Extended Duration (Beyond 12 Months):

• Class IIa recommendation for extending DAPT beyond 12 months in patients at high ischemic risk WITHOUT increased bleeding risk 1
• Class IIb recommendation for moderately increased ischemic risk patients without bleeding risk 1
• Extended DAPT reduces stent thrombosis and major adverse cardiovascular events but increases bleeding risk 5, 6

Bleeding Risk Mitigation Strategies

Mandatory interventions to reduce bleeding:

• Prescribe a proton pump inhibitor (PPI) with DAPT to reduce gastrointestinal bleeding risk 1, 2
• Use radial over femoral access for coronary angiography and PCI when performed by an expert radial operator 1, 2
• Maintain aspirin at 75-100 mg daily (not higher doses) when combined with P2Y12 inhibitors 1, 2

Timing of P2Y12 Inhibitor Administration

The ESC guidelines recommend AGAINST routine pre-treatment with P2Y12 inhibitors in patients where coronary anatomy is not yet known and early invasive management is planned (Class III recommendation) 1

Acceptable timing strategies:

• Administer P2Y12 inhibitor after coronary anatomy is established in UA/NSTEMI patients 1
• Pre-treatment may be considered only in patients NOT planned for early invasive strategy and who do not have high bleeding risk (Class IIb) 1

Common Pitfalls to Avoid

1. Do not use prasugrel in patients with prior stroke/TIA - this is an absolute contraindication with demonstrated harm 3, 4
2. Do not discontinue DAPT prematurely, especially within the first month after stent placement, as this dramatically increases thrombotic risk 2
3. Do not omit PPI co-prescription - this simple intervention significantly reduces gastrointestinal bleeding 1, 2
4. Do not use clopidogrel as first-line therapy when ticagrelor or prasugrel are available and not contraindicated 1, 2
5. Do not use high-dose aspirin (>100 mg) during DAPT maintenance phase - this increases bleeding without additional benefit 1
6. Do not pre-treat with P2Y12 inhibitors before knowing coronary anatomy if early invasive strategy is planned 1

Special Populations

Patients requiring oral anticoagulation:

• Discontinue aspirin 1-4 weeks after PCI and continue with P2Y12 inhibitor (preferably clopidogrel rather than ticagrelor due to lower bleeding risk) 2

Elderly patients (≥75 years):

• Prasugrel is generally not recommended due to increased fatal and intracranial bleeding risk, except in high-risk situations (diabetes or prior MI) 3
• Ticagrelor or clopidogrel are preferred alternatives 1

Patients with high bleeding risk:

• Consider clopidogrel over more potent P2Y12 inhibitors 2
• Consider shortened DAPT duration (6 months or less) 1
• Mandatory PPI co-prescription 1