Clopidogrel, in combination with aspirin, is a commonly used anti-platelet agents after PCI (percutaneous coronary intervention) in CHD patients. In one study, about 70% of the inter-individual variability in platelet response to clopidogrel is due to hereditary factors. A polymorphism in the CYP2C19 has been shown to be significantly associated with poor platelet response to clopidogrel. Even more important, poor platelet responsiveness to clopidogrel in patients with PCI has been shown to be associated with increased MACE (major adverse cardiac events).
While focus has been generally on inter-individual variation, it is possible that there is a significant intra-individual variability. This difference can't be explained by stable factors such as genetics or gender but is likely to be due to factors that vary over a short period of time. These include inflammatory state.
In recently published study, Armero et al examined patients on two different occasions after they had clopidogrel 600 mg loading dose. Platelet reactivity was measured using VASP (vasodilator-stimulated phosphoprotein). Interestingly, they found that there was a poor intra-individual correlation between the two occasions (kappa 0.33). In 65% of patients, platelet inhibition increased on the second evaluation while in 35% of the patients, platelet inhibition decreased.
The implications of this finding are worthy of notice. This mean that there are some rapidly varying factors that can alter platelet responsiveness to clopidogrel. On potential candidate is inflammation, although this was not measured and tested as such in this study. Investigators did measure leukocyte count and fibrinogen (and there was no difference) but both are rather crude measures of low-grade inflammation. Other possibilities include poor glycemic control in diabetics; in fact, investigators did find a relationship between the presence of diabetes and poor clopidogrel responsiveness.
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