A Randomized Controlled Trial of Platelet Activity Before and After Cessation of Clopidogrel Therapy in Patients With Stable Cardiovascular Disease

ObjectivesThe aim of this randomized placebo-controlled trial was to determine if withdrawing clopidogrel therapy leads to increased platelet activity compared with pre-treatment values in patients with stable coronary artery or peripheral arterial disease.BackgroundReports of increased cardiovascular events after planned cessation of clopidogrel therapy have raised concerns over the possible existence of a rebound in platelet activity.MethodsIn all, 171 patients receiving established aspirin therapy were randomly assigned to placebo or clopidogrel (75 mg daily) for 28 days. Blood samples were taken at pre-treatment baseline, on treatment just before discontinuation of study drug, and on days 7, 14, and 28 after discontinuation. The primary outcome measure was adenosine diphosphate (ADP)-stimulated platelet fibrinogen binding. Six secondary outcomes were assessed: ADP-stimulated platelet P-selectin, unstimulated platelet fibrinogen binding, and light transmission aggregometry with ADP 5 and 10 μmol/l recorded at maximum and at 6 min.ResultsThe ADP-stimulated platelet fibrinogen binding, P-selectin expression, and platelet aggregation were lower on treatment with clopidogrel compared with baseline (p < 0.0001), but returned to baseline levels by 7 days after discontinuation. Mixed model analyses excluding the on-treatment timepoint showed no overall differences between the clopidogrel and placebo groups (p > 0.05). Furthermore, there was no evidence of an interaction between platelet inhibition over time and treatment allocation.ConclusionsThis trial found no evidence for rebound of platelet activity to above baseline after stopping clopidogrel in patients with stable coronary artery disease or peripheral arterial disease. (Is Cessation of Clopidogrel Therapy Associated With Rebound of Platelet Activity in Stable Vascular Disease Patients?; ISRCTN77887299/77887299