Should thienopyridines (e.g. clopidogrel) be given with aspirin and heparin in a patient with Non-ST-Elevation Myocardial Infarction (NSTEMI)?

Thienopyridines in NSTEMI Management

Thienopyridines (such as clopidogrel) should be administered in addition to aspirin and heparin in patients with NSTEMI as part of standard care to reduce mortality and recurrent ischemic events. 1

Evidence-Based Recommendations for Antiplatelet Therapy in NSTEMI

First-Line Therapy

• Aspirin: Should be administered as soon as possible after presentation (162-325 mg loading dose, non-enteric coated, chewed or crushed) and continued indefinitely (81 mg daily maintenance) 1, 2
• Thienopyridine (Clopidogrel): Should be added to aspirin and heparin in NSTEMI patients 1, 3
  • Loading dose: 300-600 mg (600 mg preferred for planned invasive strategy)
  • Maintenance dose: 75 mg daily
  • Duration: At least 1 month and up to 9 months 1

Treatment Strategy Considerations

1. For patients with planned non-interventional approach:

   • Clopidogrel + aspirin + heparin (UFH or LMWH) is recommended (Class I) 1
   • Should be started as soon as possible on admission 1

2. For patients with planned invasive strategy:

   • A GP IIb/IIIa inhibitor + aspirin + heparin is recommended (Class I) 1
   • If patient is already receiving aspirin, clopidogrel, and heparin, adding a GP IIb/IIIa inhibitor is reasonable (Class IIa) 1

Clinical Benefits and Considerations

• The CURE trial demonstrated that adding clopidogrel to aspirin in NSTEMI patients reduced the composite endpoint of cardiovascular death, MI, or stroke from 11.5% to 9.3% (RR 0.80; P<0.001) 1
• Significant reduction specifically in myocardial infarction (6.7% vs 5.2%, RR 0.77, P<0.001) 1
• Benefits observed across all subgroups of patients 1

Important Precautions

• Bleeding risk: Clopidogrel increases the risk of major bleeding (2.7% vs 3.7%, P=0.003) 1
• CABG considerations: If elective CABG is planned, clopidogrel should be withheld for 5-7 days prior to surgery 1
• Special populations: For patients ≥75 years, the ideal loading dose has not been clearly established and may range from 75-600 mg 1
• CYP2C19 poor metabolizers: Consider alternative P2Y12 inhibitors in patients identified as CYP2C19 poor metabolizers 3

Alternative Antiplatelet Options

• Prasugrel: May be administered after angiography in patients with NSTEMI presenting with stenoses amenable to PCI 1

  • Not recommended in patients ≥75 years, history of stroke/TIA, or weight <60 kg 2
  • Not recommended with fibrinolysis 1

• Ticagrelor: May be an option instead of clopidogrel in NSTEMI patients managed with early invasive strategy 1

  • When using ticagrelor, aspirin dose must not exceed 100 mg daily 2, 4

Common Pitfalls to Avoid

1. Delaying antiplatelet therapy: Initiate promptly after diagnosis
2. Inadequate loading doses: Use appropriate loading doses based on planned strategy
3. Failure to consider bleeding risk: Assess bleeding risk before choosing antiplatelet regimen
4. Not discontinuing clopidogrel before CABG: Withhold for 5-7 days if elective CABG is planned
5. Continuing NSAIDs: All NSAIDs except aspirin should be discontinued due to increased risks 2

By following these evidence-based recommendations, clinicians can optimize outcomes for NSTEMI patients through appropriate use of thienopyridines in combination with aspirin and heparin.