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Tailored clopidogrel dosing improves post-PCI prognosis of CYP 2C19 carriers
8 September 2010
MedWire News: Clopidogrel-induced high on-treatment platelet reactivity (HTPR), which is a predictor of poor patient prognosis after percutaneous coronary intervention (PCI), may be overcome in patients with the cytochrome (CYP) 2C19 2* polymorphism by tailoring pre-intervention clopidogrel loading doses (LDs) according to platelet reactivity, a study reports.
“Previous research strongly suggests that variable and insufficient active metabolite generation is the main explanation for clopidogrel response variability and HTPR,” comment Laurent Bonello, from Hopital Universitaire Nord in Marseille, France, and team.
“The present study is the first to demonstrate that, despite having reduced clopidogrel metabolism, most carriers of the loss-of-function CYP 2C19 polymorphism can reach optimal platelet reactivity inhibition (PRI) using a strategy of tailored LD according to PRI monitoring,” they explain.
The researchers recruited 411 patients undergoing PCI for non-ST elevation acute coronary syndrome. All patients were assessed for the CYP 2C19 polymorphism using polymerase chain reaction.
Platelet reactivity was measured by vasodilator-stimulated phosphoprotein (VASP) index, with HTPR defined as a VASP index of ≥50%.
Writing in the Journal of the American College of Cardiology, Bonello and team report that 134 (35.3%) patients had one or more copies of the CYP 2C19 allele. These patients also had a higher mean VASP index than non-carriers, at 61.7% versus 49.2% (p<0.001).
In addition, 76.9% (n=103) of CYP 2C19 carriers and 55.6% (n=154) of non-carriers met the definition of HTPR (p<0.0001).
The team found that for 88% of all CYP 2C19 carriers with HTPR, the administration of three additional LDs of 600 mg clopidogrel was needed to bring their initially elevated VASP levels to below 50%. The other 12.0%, however, never achieved a VASP of <50% despite receiving a total clopidogrel dose of 2400 mg over 4 days.
The researchers say: “We have previously demonstrated that tailoring clopidogrel LD according to PRI monitoring to achieve a VASP index <50% results in a reduction in the rate of major adverse cardiovascular events and stent thrombosis without increased bleeding in patients undergoing PCI.
“Thus, improving PRI in 2C19 2* carriers, as found in the present study using this therapeutic strategy, may be of clinical benefit,” they add.
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