PLATO

Ticagrelor vs clopidogrel in acute coronary syndrome
In ACS, ticagrelor reduced cardiovascular death, MI or stroke compared with clopidogrel without significantly increasing overall major bleeding. Non-CABG bleeding and dyspnea were more common

Study design

  • Multicenter randomized double-blind trial
  • N = 18,624
  • ACS with or without ST elevation
  • Ticagrelor vs clopidogrel
  • Follow-up to 12 months
  • Primary outcome: cardiovascular death, MI or stroke

Population

Included
  • ACS within 24 hours of symptom onset
  • STEMI, NSTEMI or unstable angina
  • Planned invasive or medical management
  • Eligible for DAPT
Key exclusions
  • Need for oral anticoagulation
  • Recent fibrinolysis
  • High bleeding risk
  • Contraindication to study drugs
  • Clinically significant bradycardia without pacemaker
ACS STEMI + NSTE-ACS N = 18,624 DAPT 12 months

Interventions

Ticagrelor
  • 180 mg loading dose
  • 90 mg BID maintenance
  • Aspirin background therapy
Clopidogrel
  • 300–600 mg loading dose
  • 75 mg daily maintenance
  • Aspirin background therapy

Primary outcome

Cardiovascular death, MI or stroke at 12 months
9.8% ticagrelor vs 11.7% clopidogrel
HR 0.84, 95% CI 0.77–0.92, P < 0.001

Ticagrelor vs clopidogrel

Cardiovascular death, MI or stroke at 12 months

15% 10% 5% 0%
9.8%
Ticagrelor
11.7%
Clopidogrel
9.8% vs 11.7%  |  HR 0.84  |  95% CI 0.77–0.92  |  P < 0.001

Ticagrelor reduced the primary ischemic endpoint

Secondary outcomes

MI

5.8% vs 6.9%
P = 0.005

Cardiovascular death

4.0% vs 5.1%
P = 0.001

All-cause mortality

4.5% vs 5.9%
P < 0.001

Stroke

1.5% vs 1.3%
P = 0.22

Death, MI or stroke

10.2% vs 12.3%
P < 0.001

Definite stent thrombosis

1.3% vs 1.9%
P = 0.009

Safety

Overall major bleeding

11.6% vs 11.2%
No significant difference

Non-CABG major bleeding

4.5% vs 3.8%
Increased with ticagrelor

Dyspnea

13.8% vs 7.8%
More common with ticagrelor

Ventricular pauses

More common early with ticagrelor
Usually asymptomatic

Tradeoff: Better ischemic protection with ticagrelor, but more spontaneous bleeding and dyspnea

Clinical interpretation

  • Ticagrelor was superior to clopidogrel for ischemic outcomes in ACS
  • Benefit included lower MI, cardiovascular death and all-cause mortality
  • Overall major bleeding was similar, but non-CABG bleeding increased
  • Dyspnea is common and can limit therapy
  • Clopidogrel remains useful when bleeding risk, tolerance, adherence or cost favor it
Think: ACS → ticagrelor generally provides stronger ischemic protection than clopidogrel when bleeding risk and tolerance are acceptable

Limitations

  • Compared ticagrelor with clopidogrel rather than prasugrel
  • Predates some contemporary PCI and antithrombotic practice
  • Patients requiring oral anticoagulation were excluded
  • North American subgroup showed less apparent benefit
PLATO established ticagrelor as a potent P2Y12 option in ACS, but drug choice still depends on bleeding risk, PCI strategy, need for anticoagulation, tolerance and adherence
Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes. N Engl J Med. 2009;361:1045–1057. doi:10.1056/NEJMoa0904327. NEJM