Randomized trial comparing 600- with 300-mg loading dose of clopidogrel in patients with non-ST elevation acute coronary syndrome undergoing percutaneous coronary intervention: results of the Platelet Responsiveness to Aspirin and Clopidogrel and Troponin Increment after Coronary intervention in Acute coronary Lesions (PRACTICAL) Trial.
BACKGROUND
There is uncertainty about the benefit of a higher loading dose (LD) of clopidogrel in patients with non-ST elevation acute coronary syndrome (NSTEACS) undergoing early percutaneous coronary intervention (PCI).


METHODS
We compared the effects of a 600- versus a 300-mg LD of clopidogrel on inhibition of platelet aggregation, myonecrosis, and clinical outcomes in patients with NSTEACS undergoing an early invasive management strategy. Patients with NSTEACS (n = 256, mean age 63 years, 81.6% elevated troponin) without thienopyridine for at least 7 days were randomized to receive 600- or 300-mg LD of clopidogrel. Percutaneous coronary intervention was performed in 140 patients, with glycoprotein IIb/IIIa inhibitor use in 68.6%. Adenosine diphosphate (ADP)-induced platelet aggregation was measured by optical platelet aggregometry immediately before coronary angiography.


RESULTS
Post-PCI myonecrosis was defined as a next-day troponin I greater than 5 times the upper limit of reference range and greater than baseline levels. Clopidogrel 600-mg LD compared with 300-mg LD was associated with significantly reduced ADP-induced platelet aggregation (49.7% vs 55.7% with ADP 20 micromol/L) but did not reduce post-PCI myonecrosis or adverse clinical outcomes to 6 months. There was no association between preprocedural platelet aggregation and outcome.


CONCLUSIONS
These data confirm a modest incremental antiplatelet effect of a 600-mg clopidogrel LD compared with 300-mg LD but provide no support for a clinical benefit in patients with NSTEACS managed with an early invasive strategy including a high rate (69%) of glycoprotein IIb/IIIa inhibitor use during PCI.
Yong
Gerald
G
Royal Perth Hospital, Perth, Western Australia, Australia.
Rankin
Jamie
J
Ferguson
Louise
L
Thom
Jim
J
French
John
J
Brieger
David
D
Chew
Derek P
DP
Dick
Ron
R
Eccleston
David
D
Hockings
Bernard
B
Walters
Darren
D
Whelan
Alan
A
Eikelboom
John W
JW
D054058:Acute Coronary Syndrome / Q000097:blood / Q000628:therapy*; D015906:Angioplasty, Balloon, Coronary; D001241:Aspirin / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D000077144:Clopidogrel; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014336:Troponin / Q000097:blood
D010975:Platelet Aggregation Inhibitors; D014336:Troponin; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin