"Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes". The New England Journal of Medicine. 2009. 361:1045-1057. PubMed•Full
Links to original sources: Wiki Journal Post Full Journal Article
Contents 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
In patients admitted with an acute coronary syndrome, does ticagrelor reduce the risk of cardiovascular events compared to clopidogrel?
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.
Dual antiplatelet therapy with aspirin and clopidogrel is recommended for patients with an acute coronary syndrome. Ticagrelor, a new reversible direct-acting oral P2Y12 receptor antagonist, provides more consistent P2Y12 inhibition than clopidogrel. The PLATO trial compared ticagrelor with clopidogrel in 18,624 patients with acute coronary syndromes and found that ticagrelor reduced the risk of vascular death, myocardial infarction, or stroke, without an increased risk of overall major bleeding.
As of 2009, guidelines had not been published that reflect the results of this trial.
Multicenter, randomized, double-blind, double-dummy trial N=18,624 Ticagrelor (n=9,333) Clopidogrel (n=9,291) Mean follow-up: 12 months
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
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
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)
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
Ticagrelor was associated with a higher rate of major bleeding not related to coronary-artery bypass grafting and more instances of fatal intracranial bleeding.
Supported by AstraZeneca.
Full text article available at NEJM.org