Skip to content
Evevident
Original paper
2009NEJMCardiology

PLATO

Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes

RCTAcute Coronary Syndrome

On this page

Overview

Ticagrelor beat clopidogrel for cardiovascular events in ACS, including lower cardiovascular and all-cause mortality.

Clinical takeaway

PLATO showed that ticagrelor reduced cardiovascular death, MI, or stroke compared with clopidogrel in patients with acute coronary syndromes, with lower cardiovascular and all-cause mortality and no increase in overall major bleeding.

Key result

Primary composite: 9.8% vs 11.7%, HR 0.84 (95% CI 0.77-0.92), p<0.001.

Practice impact

Established ticagrelor as a preferred P2Y12 inhibitor in many ACS patients.

Evidence

Study design

Randomized, double-blind, active-controlled trial

Enrollment

18,624

Follow-up

12 months

Geography

Multinational

Clinical question

In patients with acute coronary syndromes, with or without ST-elevation, is ticagrelor superior to clopidogrel for preventing cardiovascular death, MI, or stroke?

Population

  • Acute coronary syndrome, including STEMI managed invasively and NSTE-ACS
  • Managed with or without planned invasive strategy

Intervention

Ticagrelor 180 mg load, then 90 mg twice daily

Comparator

Clopidogrel 300-600 mg load, then 75 mg daily

Primary outcome

Composite of cardiovascular death, myocardial infarction, or stroke at 12 months

Ticagrelor reduced cardiovascular death, MI, or stroke compared with clopidogrel.

HR / 0.84 / CI 0.77-0.92 / p=<0.001

Key results

  • Primary composite: 9.8% vs 11.7%, HR 0.84 (95% CI 0.77-0.92), p<0.001
  • Cardiovascular death: 4.0% vs 5.1%
  • All-cause mortality reduced
  • No increase in overall major bleeding, but more non-CABG-related major bleeding

Harms

  • No increase in overall major bleeding.
  • More non-CABG-related major bleeding with ticagrelor.
  • More dyspnea and ventricular pauses with ticagrelor.

Clinical Use

When to cite

  • When explaining ticagrelor preference over clopidogrel in ACS
  • When asked why aspirin maintenance dose should stay low with ticagrelor

Practice impact

  • Established ticagrelor as a preferred P2Y12 inhibitor in ACS
  • Shaped dual antiplatelet therapy guidelines
  • Highlighted reversible, non-prodrug P2Y12 inhibition

Applicability

  • Most applicable to ACS patients where ticagrelor is not contraindicated
  • Useful when comparing oral P2Y12 inhibitor options after ACS

Limitations

  • More dyspnea and ventricular pauses with ticagrelor
  • Twice-daily dosing affects adherence
  • Regional variation in results, notably North America, linked to higher aspirin dose

Common misinterpretations

  • Do not pair ticagrelor with high-dose maintenance aspirin; PLATO's benefit was attenuated with maintenance aspirin doses above 100 mg daily.

Related evidence

CURE - Earlier Trial

Citation

Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045-1057. doi:10.1056/NEJMoa0904327