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Evevident
Original paper
2001NEJMCardiology

CURE

Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation

RCTACS

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Overview

In NSTE-ACS, adding clopidogrel to aspirin reduced CV death, MI, or stroke but increased bleeding.

Clinical takeaway

CURE established dual antiplatelet therapy as standard care after NSTE-ACS, balancing ischemic benefit against bleeding risk.

Key result

CV death, nonfatal MI, or stroke: 9.3% with clopidogrel plus aspirin vs 11.4% with aspirin alone; RR 0.80.

Practice impact

DAPT became routine ACS therapy unless bleeding risk or procedural context argues otherwise.

Evidence

Study design

Randomized, double-blind, placebo-controlled trial.

Enrollment

12,562

Follow-up

3 to 12 months (mean 9 months).

Geography

Multinational

Clinical question

Does clopidogrel added to aspirin improve outcomes in NSTE-ACS?

Population

  • Patients with acute coronary syndromes without ST-segment elevation.

Intervention

Clopidogrel plus aspirin.

Comparator

Placebo plus aspirin.

Primary outcome

Composite of CV death, nonfatal MI, or stroke.

Clopidogrel plus aspirin reduced cardiovascular death, nonfatal MI, or stroke compared with aspirin alone.

Relative risk / 0.8 / CI 95% CI 0.72-0.90 / p=<0.001

Key results

  • CV death, nonfatal MI, or stroke: 9.3% with clopidogrel plus aspirin vs 11.4% with aspirin alone; RR 0.80; 95% CI 0.72-0.90; p<0.001.
  • The first primary outcome plus refractory ischemia: 16.5% vs 18.8%; RR 0.86; 95% CI 0.79-0.94; p<0.001.
  • Major bleeding increased with clopidogrel: 3.7% vs 2.7%; RR 1.38; p=0.001.

Harms

  • Major bleeding increased with clopidogrel: 3.7% vs 2.7%; RR 1.38; p=0.001.

Clinical Use

When to cite

  • When explaining the ischemic benefit and bleeding tradeoff of adding clopidogrel to aspirin in NSTE-ACS.

Practice impact

  • DAPT became routine ACS therapy unless bleeding risk or procedural context argues otherwise.

Applicability

  • Most applicable to patients with acute coronary syndromes without ST-segment elevation.

Limitations

  • Conducted before contemporary early-invasive strategies and potent P2Y12 inhibitors.
  • The bleeding tradeoff is clinically important and rises with dose of aspirin and around surgery.
  • Used clopidogrel; later trials tested more potent agents.

Common misinterpretations

  • The benefit accrues over months of dual therapy, not from a single loading dose; ischemic and bleeding risks must be weighed together.
  • More potent P2Y12 inhibitors (ticagrelor in PLATO, prasugrel in TRITON-TIMI 38) later outperformed clopidogrel in many ACS patients.

Related evidence

PLATO - Later Trial

Citation

Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345(7):494-502. doi:10.1056/NEJMoa010746

The antiplatelet agent clopidogrel has beneficial effects in patients with acute coronary syndromes without ST-segment elevation. However, the risk of major bleeding is increased among patients treated with clopidogrel.