Rebound platelet hyperactivity after clopidogrel cessation unlikely
MedWire News: Results from the PACT study suggest that rebound platelet hyperactivity does not occur when clopidogrel therapy is discontinued.
Andrew Frelinger (Children's Hospital Boston, Massachusetts) and team imply that previous reports of an increased incidence of thrombotic events after clopidogrel termination may be due to the "recovery of platelet function to pre-treatment levels rather than a "rebound" phenomenon."
In the PACT (Platelet Activity After Clopidogrel Termination) study, the researchers measured the platelet reactivity levels of 15 healthy participants at baseline, during a 14 day treatment course of clopidogrel 75 mg or placebo, and again 1, 4, 8, 11, 15, and 45 days after completion of the treatment course.
Platelet reactivity was determined by several factors including adenosine diphosphate (ADP)-induced (0.5, 1.0, and 20.0 µmol/l) platelet surface activated glycoprotein (GP)IIb-IIIa complex and platelet surface P-selectin, light transmission aggregation with ADP 2.5, 5.0, and 20.0 µmol/l, and whole blood impedance aggregation with ADP 1.6 and 6.5 µmol.
The findings, published in the journal Circulation: Cardiovascular Interventions, showed that at the start of treatment, patients taking clopidogrel had a significant reduction in ADP-induced platelet surface activated GPIIb-IIIa compared with those taking placebo.
After treatment cessation, ADP-induced platelet surface activated GPIIb-IIIa levels gradually increased, reaching baseline levels by day 8 to 11. However, the platelet reactivity of clopidogrel patients never rose to a level greater than that of placebo patients.
The researchers highlight that the observed time frame for the restoration of original platelet activity is "consistent with the lifespan of platelets" as clopidogrel's action on platelets is irreversible and only eliminated when affected platelets are replaced by new platelets.
Frelinger and team say that the use of healthy participants rather than patients in this study prevents them from ruling out "a possible effect of cardiovascular risk factors such as smoking or diabetes, which have an impact on clopidogrel responsiveness, on platelet function after discontinuation of clopidogrel."
They conclude that large scale clinical trials are required for further evidence.
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By Lauretta Ihonor