A single-centre, randomised study on platelet reactivity after abrupt or gradual discontinuation of long-term clopidogrel therapy in patients after percutaneous coronary intervention.

Abstract

Clinical studies have suggested increased risk of thrombotic events after planned cessation of clopidogrel therapy, due to increased platelet reactivity (platelet rebound); however, in many studies platelet function was not assessed before introducing clopidogrel. Patients who are scheduled to stop clopidogrel therapy, do it abruptly, so a gradual drug cessation might provide a beneficial treatment strategy. To determine whether a clopidogrel discontinuation results in platelet rebound hyperaggregability with increased activity compared to pre-treatment values and to assess whether abrupt or tapering clopidogrel cessation may affect platelet reactivity. Patients with stable coronary artery disease (n = 49), on chronic acetylsalicylic acid treatment, who underwent coronary angiography, and were scheduled for elective percutaneous coronary intervention with stent implantation were en-rolled. Patients were randomised to either a tapering clopidogrel discontinuation during a two-week period (tapering group, n = 25) or abrupt drug cessation (abrupt group, n = 24). After 12 months of dual antiplatelet therapy with clopidogrel and acetylsalicylic acid, we performed three follow-up visits with blood sampling. Platelet aggregation was assessed using a mul-tiple electrode aggregometer at inclusion, at cessation day, and seven and 14 days after complete clopidogrel discontinuation. The primary endpoint was the level of adenosine-diphosphate (ADP)-induced platelet aggregation. We also analysed platelet function in the ASPI test and platelet count as secondary endpoints. In 36 patients included in the main analysis, we found significant differences between the two study groups in the levels of ADP-induced platelet aggregation at days seven and 14 after cessation of clopidogrel (p = 0.004 and p = 0.04, respectively). In the abrupt group, platelet aggregation returned to the values similar to baseline at day seven. There were no significant differences between baseline, seven, and 14 days after drug cessation (p = 0.92 and p = 0.37, respectively). However, in the tapering group, ADP values at seven and 14 days after drug cessation were significantly decreased, comparing to baseline (p < 0.0001 and p = 0.009, respectively). For the ASPI test and platelet count we did not find significant differ-ences between the groups. All values returned to levels similar to the baseline. During the follow-up there were no serious cardiovascular events or bleedings. Tapering vs. abrupt discontinuation of clopidogrel treatment results in significantly lower platelet aggregation values after 14 days from complete drug cessation. We found no evidence of a platelet rebound effect.