What is the preferred dual antiplatelet therapy for a patient presenting with non‑ST‑elevation myocardial infarction (NSTEMI)?

Preferred Dual Antiplatelet Therapy for NSTEMI

For patients presenting with NSTEMI, ticagrelor (180 mg loading dose, then 90 mg twice daily) plus aspirin (81 mg daily) is the preferred dual antiplatelet therapy regimen, with a Class IIa recommendation from ACC/AHA guidelines. 1, 2

First-Line P2Y12 Inhibitor Selection

Ticagrelor should be used in preference to clopidogrel for patients with NSTEMI regardless of whether they undergo an early invasive strategy or ischemia-guided approach. 1, 2 This recommendation is based on superior reduction in cardiovascular death, myocardial infarction, and stroke compared to clopidogrel. 2

Loading and Maintenance Dosing

• Ticagrelor: 180 mg loading dose, followed by 90 mg twice daily 1, 2
• Aspirin: 81 mg daily (not higher doses) when combined with ticagrelor 1, 2
• Initiate immediately upon NSTEMI diagnosis, before any invasive procedures 2

Alternative P2Y12 Inhibitors

Prasugrel

Prasugrel (60 mg loading, 10 mg daily) is an acceptable alternative for P2Y12 inhibitor-naïve patients undergoing PCI, but only after coronary anatomy is defined. 1, 2

Critical contraindications for prasugrel:

• Prior stroke or TIA (Class III: Harm) 1, 2
• Age ≥75 years (increased bleeding risk) 1, 2
• Weight <60 kg (consider 5 mg maintenance dose) 1, 2

Clopidogrel

Clopidogrel (600 mg loading, 75 mg daily) should only be used when ticagrelor or prasugrel are contraindicated, unavailable, or not tolerated. 1, 2 This represents suboptimal therapy for NSTEMI patients. 2

Specific indications for clopidogrel:

• Prior intracranial hemorrhage 2
• Need for concurrent oral anticoagulation 2
• Severe renal impairment (CrCl <30 mL/min) 2

Duration of Therapy

Continue DAPT for 12 months in all NSTEMI patients, regardless of management strategy (PCI, medical therapy, or CABG) or stent type. 1, 2 This is a Class I recommendation. 1

Shortened duration (6 months) may be considered only in patients with high bleeding risk (PRECISE-DAPT score ≥25), but 12 months remains the default. 2

Mandatory Bleeding Risk Mitigation

Every NSTEMI patient on DAPT must receive:

• Proton pump inhibitor (Class I recommendation) to reduce gastrointestinal bleeding 3, 2
• Low-dose aspirin (75-100 mg daily, not higher doses) 3, 2
• Radial artery access if cardiac catheterization is performed (when operator is experienced) 2

Anticoagulation in Addition to DAPT

All NSTEMI patients require anticoagulation in addition to DAPT, irrespective of treatment strategy (Class I). 1 Options include:

• Enoxaparin: 1 mg/kg SC every 12 hours (reduce to once daily if CrCl <30 mL/min) 1
• Bivalirudin: 0.10 mg/kg loading, then 0.25 mg/kg/hour (early invasive strategy only) 1
• Fondaparinux: 2.5 mg SC daily (contraindicated if CrCl <30 mL/min) 1
• Unfractionated heparin: 60 IU/kg loading (max 4000 IU), then 12 IU/kg/hour (max 1000 IU/h) 1

Special Populations

Patients Previously on Clopidogrel

Switch immediately to ticagrelor by administering the 180 mg loading dose without waiting for clopidogrel washout. 2 Do not continue clopidogrel when ticagrelor is indicated. 2

Patients Requiring Oral Anticoagulation (Triple Therapy)

Discontinue aspirin 1-4 weeks after PCI and continue clopidogrel (not ticagrelor or prasugrel) plus anticoagulation to minimize bleeding risk. 2 Clopidogrel is strongly preferred over ticagrelor in this setting due to significantly lower bleeding risk. 2

Severe Renal Impairment (CrCl <30 mL/min)

Use clopidogrel as the P2Y12 inhibitor because ticagrelor and prasugrel lack robust safety data in this population. 2 Adjust anticoagulant dosing: enoxaparin to once daily, avoid fondaparinux entirely, and reduce bivalirudin infusion to 1 mg/kg/hour. 2

Critical Pitfalls to Avoid

Never discontinue DAPT within the first month after stent placement – this dramatically increases risk of stent thrombosis, myocardial infarction, and death (hazard ratio ~161). 2

Never use prasugrel in patients with prior stroke/TIA – this is an absolute contraindication due to increased cerebrovascular bleeding risk. 1, 2

Never omit proton pump inhibitor – this simple intervention significantly reduces gastrointestinal bleeding and is a Class I recommendation. 3, 2

Never use clopidogrel as first-line therapy when ticagrelor is available and not contraindicated – this represents suboptimal care. 2

Never use high-dose aspirin (>100 mg) with DAPT – maintain 75-100 mg daily to minimize bleeding without losing efficacy. 3, 2