Stent thrombosis associated with non-response to clopidogrel despite co-administration of aspirin and ibrutinib

Managing atherosclerotic cardiovascular disease in individuals with chronic lymphocytic leukaemia (CLL) is complicated by the uncertain antiplatelet effect exerted by Bruton’s tyrosine kinase inhibitors. Concerns over increased bleeding risk with concurrent ibrutinib and dual antiplatelet therapy (DAPT) are balanced with the need to provide robust antiplatelet cover following percutaneous coronary intervention (PCI) and reduce the risk of stent-related complications.

We describe a case of an 83-year-old patient with a background of stable CLL on ibrutinib. He was appropriately established on DAPT (clopidogrel and aspirin) prior to elective PCI. Post-procedure, the patient re-presented after six days with subacute stent thrombosis (SST). Platelet function tests demonstrated clopidogrel non-responder status, with high platelet reactivity to multiple agonists. He was switched to ticagrelor with excellent antiplatelet response and underwent repeat PCI.

This case is the first description of SST in a patient on concurrent DAPT and ibrutinib. It highlights the need for appropriately robust P2Y₁₂ inhibition despite bleeding concerns and ex vivo studies demonstrating some antiplatelet effect by ibrutinib. This case also highlights the role for platelet function testing to tailor antithrombotic regimens in complex and high-risk PCI patients.