Authors
Wiviott SD, Braunwald E, McCabe CH, et al.
Title
Prasugrel versus Clopidogrel in Patients with Acute Coronary Syndromes
References
N Engl J Med 2007;357:2001-2015.
Background
The combination of clopidogrel with aspirin is beneficial in acute coronary syndromes and percutaneous coronary intervention. Many patients continue to experience recurrent atherothrombotic events possibly due to the limitations of clopidogrel. Prasugrel inhibits platelet aggregation more rapidly, more consistently and is a more potent antiplatelet agent than clopidogrel.
Purpose
To determine whether prasugrel is superior to clopidogrel in preventing death from cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke in patients with acute coronary syndromes undergoing percutaneous coronary intervention (PCI).
Design
  • Multicenter, randomised, double blind study
  • 13,608 patients with acute coronary syndrome with scheduled PCI
  • 10,074 patients with moderate to high risk unstable angina or non-ST-elevation myocardial infarction.
  • 3,534 patients with ST-elevation myocardial infarction

Note: coronary anatomy had to be known to be suitable for PCI before randomization in all patients with non-ST acute coronary syndromes or in those enrolled after medical treatment for ST-elevation myocardial infarction.
Exclusion Criteria
None.
Follow-Up
14.5 months (mean duration)
Treatment Regimen
  • Clopidogrel 300 mg x 1 dose, then 75 mg once daily versus Prasugrel 60 mg po x 1 dose, then 10 mg once daily.
  • Aspirin 75-162 mg/day was required.
Results
Prasugrel was superior to clopidogrel in decreasing the primary composite endpoint of cardiovascular death/nonfatal MI/nonfatal stroke, driven by a decreased rate of MI. Total mortality was not significantly different.

Major bleeding was increased in the prasugrel group, including lifethreatening bleeding.

Patients with a history of cerebrovascular event had a strong trend toward a greater rate of TIMI major bleeding (p=0.06), including intracranial hemorrhage with prasugrel compared to clopidogrel (2.3% vs 0%; p=0.02) without a net clinical benefit. Among the elderly (≥ 75 years) and patients with a body weight less than 60 kg there was neither a net benefit nor net harm.
Summary
Compared to clopidogrel, prasugrel significantly reduces the rates of ischemic events, including stent thrombosis in patients with acute coronary syndromes with scheduled PCI. Major bleeding (including fatal bleeding) was increased with prasugrel. Overall mortality was not different between the groups.
Implications
None.
Related Figures
[1, 2, 3, 4]