Dual Antiplatelet Therapy in NSTEMI: Aspirin and Clopidogrel
Yes, patients with NSTEMI should receive both aspirin and clopidogrel together as dual antiplatelet therapy (DAPT), initiated as soon as possible after presentation and continued for at least 12 months. This combination is a Class I, Level A recommendation from the ACC/AHA guidelines and is explicitly indicated in the FDA label for clopidogrel 1, 2, 3.
Immediate Administration Protocol
Both medications should be started simultaneously upon NSTEMI diagnosis:
- Aspirin: Administer 162-325 mg of non-enteric-coated, chewable aspirin immediately, followed by 75-100 mg daily maintenance dose 1, 2, 4
- Clopidogrel: Give a 300-600 mg loading dose (600 mg preferred for faster platelet inhibition), followed by 75 mg daily 1, 2, 4
The FDA label explicitly states that "clopidogrel tablets should be administered in conjunction with aspirin" for patients with non-ST-elevation ACS 3. This is not optional—it is the standard of care.
Evidence Supporting Combination Therapy
The recommendation for dual antiplatelet therapy is based on robust clinical trial evidence:
- The CURE trial demonstrated that adding clopidogrel to aspirin in NSTEMI patients significantly reduced the combined endpoint of death, non-fatal MI, and stroke compared to aspirin alone 1
- Real-world registry data from 4,290 NSTEMI patients showed that aspirin plus clopidogrel reduced one-year mortality (15.6% vs 28.1%) and major adverse cardiac events compared to aspirin alone, with an adjusted odds ratio of 0.69 (95% CI: 0.64-0.74) 5
- The ACC/AHA guidelines upgraded clopidogrel to a Class I recommendation specifically because of its proven benefit when added to aspirin 1
Management Strategy Considerations
The timing and approach differ slightly based on your planned strategy:
For Early Invasive Strategy (catheterization planned):
- Start both aspirin and clopidogrel immediately upon presentation 1, 2
- The 600 mg clopidogrel loading dose provides more rapid and reliable platelet inhibition than 300 mg 1, 2, 4
- GP IIb/IIIa inhibitors may be added as a third agent at the time of PCI if needed 1
For Conservative Strategy (no immediate catheterization):
- Start both aspirin and clopidogrel as soon as the NSTEMI diagnosis is established 1, 2
- Continue DAPT for at least 1 month (Level A evidence) and ideally up to 12 months (Level B evidence) 1
Duration of Therapy
Continue dual antiplatelet therapy for at least 12 months unless bleeding risk outweighs benefit 1, 2, 6. The ACC/AHA guidelines provide Level A evidence for at least 1 month of therapy and Level B evidence for extending to 9-12 months 1.
Critical Pitfalls to Avoid
Do not withhold clopidogrel due to concerns about future CABG unless surgery is imminent within 5-7 days 1. The guidelines explicitly state that the benefit of preventing ischemic events during the waiting period outweighs the bleeding risk in most cases 1.
If CABG becomes necessary, discontinue clopidogrel 5-7 days before elective surgery 1. However, this should not prevent you from starting it initially, as most NSTEMI patients will not require urgent CABG 1.
Monitor for bleeding complications, as the combination increases bleeding risk compared to aspirin alone (5.4% vs 3.3% in-hospital major bleeding) 5. However, this risk is acceptable given the substantial reduction in ischemic events 5, 7.
Special Considerations
Patients with aspirin hypersensitivity or major GI intolerance should receive clopidogrel alone as a Class I recommendation 1. In these cases, clopidogrel serves as the sole antiplatelet agent rather than being withheld entirely 1.
Consider adding proton-pump inhibitors to reduce GI bleeding risk when using DAPT, though avoid omeprazole or esomeprazole as they significantly reduce clopidogrel's antiplatelet activity through CYP2C19 inhibition 1, 3.
Be aware of CYP2C19 poor metabolizers who form less active metabolite and have reduced platelet inhibition with clopidogrel 3. Consider alternative P2Y12 inhibitors (ticagrelor or prasugrel) in these patients if identified 2, 3.