Original title: A randomised controlled trial of platelet activity before and after cessation of clopidogrel therapy in patients with stable cardiovascular disease. Reference: Ford I et al. J Am Coll Cardiol. 2013;E-pub ahead of print.
Some previous studies have suggested an excess of cardiovascular events after discontinuation of clopidogrel, and this could be due to a rebound effect on platelet activity caused by drug discontinuation. Still, none of this works performed a measuring of the baseline platelet activity, so rebound theory was never confirmed.
This study randomized 171 patients with stable coronary or peripheral disease who were receiving aspirin to clopidogrel or placebo for 30 days. Blood samples were taken at the time of starting treatment, immediately before of holdup and at 7, 14 and 28 days after the suspension. The baseline characteristics of both groups were well balanced. The platelet reactivity measured by platelet adhesion to fibrinogen stimulated by ADP decreased in the clopidogrel group during treatment and then gradually returned to baseline with the suspension. Platelet reactivity was unchanged in the placebo group. The mean reactivity measured in the clopidogrel group was 73.9 % at baseline and 30.9 % of the length of the treatment. After suspension, it was increasing gradually , resulting 69.2 % after 7 days , 75.6 % at 14 days and 77.3% at 28 days (p <0.0001 for all differences). Other secondary measurements were also conducted, including the expression of P- selective ADP induced platelet, in which we observed the same progressive pattern with the exception of the binding to non-stimulated fibrinogen.
Conclusion:
This study found no evidence of a rebound effect of platelet activity above baseline after discontinuation of clopidogrel in patients with ischemic heart disease or stable peripheral vascular disease.
Editorial Comment
While the rebound effect in laboratory measurements seems to be discarded, from the clinical point of view, it could cause events due to the loss of drug protection rather than exaggerated platelet activity.
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