Variability in initial response to standard clopidogrel therapy, delayed conversion to clopidogrel hyper-response, and associated thromboembolic and hemorrhagic complications in patients undergoing endovascular treatment of unruptured cerebral aneurysms.

Background and purpose Variability in response to clopidogrel therapy is increasingly being recognized as an important factor in thromboembolic and hemorrhagic complications encountered after neurointerventional procedures. This study aims to determine the variability in response to clopidogrel therapy and associated complications in patients undergoing endovascular treatment of unruptured cerebral aneurysms. Methods We recorded baseline patient characteristics, co-administered medications, P2Y12 reaction units (PRU) values with VerifyNow, clopidogrel dosing, and thromboembolic and hemorrhagic complications in patients undergoing endovascular treatment of unruptured cerebral aneurysms at our institution during a 19 month period. Results 100 patients were included in the study, 76 women and 24 men, mean age 57.3years. 15 patients exhibited an initial clopidogrel hypo-response (PRU >240) and 21 patients an initial clopidogrel hyper-response (PRU <60). 36 patients had a follow-up VerifyNow test performed without changes to the standard 75mg daily clopidogrel dose, which demonstrated that 59% of patients who had initially been within the target 60-240 PRU range exhibited a delayed conversion to clopidogrel hyper-response. In our cohort, a clopidogrel hypo-response was associated with a significantly increased risk of thromboembolic complications in patients undergoing cerebral aneurysm treatment with stent assistance or the pipeline embolization device (60%, p=0.003), while a clopidogrel hyper-response was associated with a significantly increased risk of major hemorrhagic complications in all patients undergoing endovascular treatment of cerebral aneurysms (11%, p=0.016). Conclusions We found wide and dynamic variability in response to clopidogrel therapy in patients undergoing endovascular treatment of unruptured cerebral aneurysms, which was significantly associated with thromboembolic and major hemorrhagic complications in our cohort.