article16

PLATO

"Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes". The New England Journal of Medicine. 2009. 361:1045-1057. PubMed•Full text•PDF

1 Clinical Question
2 Bottom Line
3 Major Points
4 Guidelines
5 Design
6 Population
6.1 Inclusion Criteria
6.2 Exclusion Criteria
6.3 Baseline Characteristics
7 Interventions
8 Outcomes
8.1 Primary Outcome
8.2 Secondary Outcomes
8.3 Subgroup Analysis
9 Criticisms
10 Funding
11 Further Reading

Clinical Question

In patients admitted with an acute coronary syndrome, does ticagrelor reduce the risk of cardiovascular events compared to clopidogrel?

Bottom Line

In patients with an acute coronary syndrome, ticagrelor was superior to clopidogrel in reducing the risk of death from vascular causes, myocardial infarction, or stroke, without an increased risk of overall major bleeding but with an increase in non–procedure-related bleeding.

Major Points

Guidelines

As of 2009, guidelines had not been published that reflect the results of this trial.

Design

Multicenter, randomized, double-blind, double-dummy trial
N=18,624
Ticagrelor (n=9,333)
Clopidogrel (n=9,291)
Mean follow-up: 12 months

Population

Inclusion Criteria: Hospitalized patients within 24 hours of onset of acute coronary syndromes with or without ST-segment elevation
Exclusion Criteria: Contraindications to clopidogrel, fibrinolytic therapy within 24 hours before randomization, need for oral anticoagulation, increased risk of bradycardia, strong cytochrome P-450 3A inhibitor or inducer therapy
Baseline Characteristics: Well balanced across both groups

Interventions

Ticagrelor – 180 mg loading dose, followed by 90 mg twice daily
Clopidogrel – 300-600 mg loading dose if not previously received, followed by 75 mg daily

Outcomes

Primary Outcome: Death from vascular causes, myocardial infarction, or stroke at 12 months
9.8% with ticagrelor vs. 11.7% with clopidogrel (hazard ratio, 0.84; 95% CI, 0.77 to 0.92; P<0.001)

Secondary Outcomes
Death from any cause: 4.5% with ticagrelor vs. 5.9% with clopidogrel (P<0.001)
No significant difference in the rates of major bleeding between groups

Subgroup Analysis
Benefit of ticagrelor appeared to be attenuated in patients under median weight, those not taking lipid-lowering drugs at randomization, and those enrolled in North America

Criticisms

Ticagrelor was associated with a higher rate of major bleeding not related to coronary-artery bypass grafting and more instances of fatal intracranial bleeding.

Funding

Supported by AstraZeneca.