Prasugrel versus clopidogrel in patients with acute coronary syndromes.
BACKGROUND
Dual-antiplatelet therapy with aspirin and a thienopyridine is a cornerstone of treatment to prevent thrombotic complications of acute coronary syndromes and percutaneous coronary intervention.


METHODS
To compare prasugrel, a new thienopyridine, with clopidogrel, we randomly assigned 13,608 patients with moderate-to-high-risk acute coronary syndromes with scheduled percutaneous coronary intervention to receive prasugrel (a 60-mg loading dose and a 10-mg daily maintenance dose) or clopidogrel (a 300-mg loading dose and a 75-mg daily maintenance dose), for 6 to 15 months. The primary efficacy end point was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The key safety end point was major bleeding.


RESULTS
The primary efficacy end point occurred in 12.1% of patients receiving clopidogrel and 9.9% of patients receiving prasugrel (hazard ratio for prasugrel vs. clopidogrel, 0.81; 95% confidence interval [CI], 0.73 to 0.90; P<0.001). We also found significant reductions in the prasugrel group in the rates of myocardial infarction (9.7% for clopidogrel vs. 7.4% for prasugrel; P<0.001), urgent target-vessel revascularization (3.7% vs. 2.5%; P<0.001), and stent thrombosis (2.4% vs. 1.1%; P<0.001). Major bleeding was observed in 2.4% of patients receiving prasugrel and in 1.8% of patients receiving clopidogrel (hazard ratio, 1.32; 95% CI, 1.03 to 1.68; P=0.03). Also greater in the prasugrel group was the rate of life-threatening bleeding (1.4% vs. 0.9%; P=0.01), including nonfatal bleeding (1.1% vs. 0.9%; hazard ratio, 1.25; P=0.23) and fatal bleeding (0.4% vs. 0.1%; P=0.002).


CONCLUSIONS
In patients with acute coronary syndromes with scheduled percutaneous coronary intervention, prasugrel therapy was associated with significantly reduced rates of ischemic events, including stent thrombosis, but with an increased risk of major bleeding, including fatal bleeding. Overall mortality did not differ significantly between treatment groups. (ClinicalTrials.gov number, NCT00097591 [ClinicalTrials.gov].)
Wiviott
Stephen D
SD
Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Braunwald
Eugene
E
McCabe
Carolyn H
CH
Montalescot
Gilles
G
Ruzyllo
Witold
W
Gottlieb
Shmuel
S
Neumann
Franz-Joseph
FJ
Ardissino
Diego
D
De Servi
Stefano
S
Murphy
Sabina A
SA
Riesmeyer
Jeffrey
J
Weerakkody
Govinda
G
Gibson
C Michael
CM
Antman
Elliott M
EM
D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D001241:Aspirin / Q000627:therapeutic use; D000077144:Clopidogrel; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000517:prevention & control; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000068799:Prasugrel Hydrochloride; D011355:Prodrugs / Q000009:adverse effects / Q000627:therapeutic use; D058919:Purinergic P2 Receptor Antagonists; D020521:Stroke / Q000453:epidemiology; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D013927:Thrombosis / Q000517:prevention & control; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D011355:Prodrugs; D058919:Purinergic P2 Receptor Antagonists; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine; D001241:Aspirin