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
Received 6 June 2008; accepted 29 September 2008.
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 μmol/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.
aRoyal Perth Hospital, Perth, Western Australia, Australia
bLiverpool Hospital, Sydney, New South Wales, Australia
cConcord Hospital, Concord, New South Wales, Australia
dFlinders University, Bedford Park, South Australia, Australia
ABSTRACT