Platelet inhibition with cangrelor in patients undergoing PCI.
BACKGROUND
Cangrelor, a nonthienopyridine adenosine triphosphate analogue, is an intravenous blocker of the adenosine diphosphate receptor P2Y(12). This agent might have a role in the treatment of patients who require rapid, predictable, and profound but reversible platelet inhibition.


METHODS
We performed a large-scale international trial comparing cangrelor with 600 mg of oral clopidogrel administered before percutaneous coronary intervention (PCI) in patients with acute coronary syndromes. The primary efficacy end point was a composite of death from any cause, myocardial infarction, or ischemia-driven revascularization at 48 hours.


RESULTS
We enrolled 8877 patients, and 8716 underwent PCI. At 48 hours, cangrelor was not superior to clopidogrel with respect to the primary composite end point, which occurred in 7.5% of patients in the cangrelor group and 7.1% of patients in the clopidogrel group (odds ratio, 1.05; 95% confidence interval [CI], 0.88 to 1.24; P=0.59). Likewise, cangrelor was not superior at 30 days. The rate of major bleeding (according to Acute Catheterization and Urgent Intervention Triage Strategy criteria) was higher with cangrelor, a difference that approached statistical significance (3.6% vs. 2.9%; odds ratio, 1.26; 95% CI, 0.99 to 1.60; P=0.06), but this was not the case with major bleeding (according to the Thrombolysis in Myocardial Infarction criteria) or severe or life-threatening bleeding (according to Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria). A secondary exploratory end point of death from any cause, Q-wave myocardial infarction, or ischemia-driven revascularization showed a trend toward a reduction with cangrelor, but it was not significant (0.6% vs. 0.9%; odds ratio, 0.67; 95% CI, 0.39 to 1.14; P=0.14).


CONCLUSIONS
Cangrelor, when administered intravenously 30 minutes before PCI and continued for 2 hours after PCI, was not superior to an oral loading dose of 600 mg of clopidogrel, administered 30 minutes before PCI, in reducing the composite end point of death from any cause, myocardial infarction, or ischemia-driven revascularization at 48 hours. (ClinicalTrials.gov number, NCT00305162.)
Harrington
Robert A
RA
Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27705, USA. robert.harrington@duke.edu
Stone
Gregg W
GW
McNulty
Steven
S
White
Harvey D
HD
Lincoff
A Michael
AM
Gibson
C Michael
CM
Pollack
Charles V
CV
Montalescot
Gilles
G
Mahaffey
Kenneth W
KW
Kleiman
Neal S
NS
Goodman
Shaun G
SG
Amine
Maged
M
Angiolillo
Dominick J
DJ
Becker
Richard C
RC
Chew
Derek P
DP
French
William J
WJ
Leisch
Franz
F
Parikh
Keyur H
KH
Skerjanec
Simona
S
Bhatt
Deepak L
DL
D054058:Acute Coronary Syndrome / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D000249:Adenosine Monophosphate / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000284:Administration, Oral; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D000077144:Clopidogrel; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D019233:Retreatment; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D017211:Treatment Failure
D010975:Platelet Aggregation Inhibitors; D000249:Adenosine Monophosphate; C117446:cangrelor; D000077144:Clopidogrel; D013988:Ticlopidine