O-021 Induced Hyper-Response to Clopidogrel after Elective Endovascular Intracranial Aneurysm Treatment

Introduction A variable response to clopidogrel among patients undergoing neurointerventional procedures has been observed. To minimise thromboembolic and haemorrhagic complications, patients premedicated with clopidogrel in anticipation of elective endovascular intracranial aneurysm treatment at our institution are asked to start clopidogrel 75 mg daily, 17 days prior to their procedure date, with pre-procedure P2Y12 inhibition testing using the VerifyNow assay performed at 10 and 17 days, as well as post-procedure testing for patients treated with stents or flow-diverters. The protocol allows for a single dose adjustment after the first test in order to achieve pre-procedure P2Y12 reaction units (PRU) in a target range without rescheduling. The goal of the present study is to determine the efficacy of this protocol in reaching an in-range pre-procedure PRU and to determine the rate of delayed clopidogrel hyper-response post-procedure. Methods All patients who were started on clopidogrel using the above 17 day, 2 test protocol in anticipation of elective endovascular treatment of an intracranial aneurysm at our institution from April 30, 2013 to March 6, 2014 were included. Patient age, sex, procedural variables and PRU values were recorded. Hyper-response to clopidogrel was defined as PRU less than 60; hypo-response was defined as PRU greater than 240. Results Forty patients met the inclusion criteria, mean age 55 (range 35 to 79), 33 women, 7 men. Of these patients, 29 (72.5%) had a PRU value between 60 and 240 at 10 days, and 27 of the 29 (93.1%) stayed within range at 17 days. Of the 11 patients (27.5%) who were initially out of range and had a dose adjustment per the tables below, 10 (90.9%) reached an in-range PRU at day 17, for a total of 37 patients (92.5%) with an in-range pre-procedure PRU. A post-procedure PRU was performed in 28 of the 37 patients (75.7%, mean 14 days post-procedure). Among these, 14 (50%) showed a delayed hyper-response to clopidogrel, and there was 1 delayed hypo-responder (3.6%), leaving 13 patients (46.4%) who remained in-range post-procedure. There were no major peri-procedural thromboembolic or haemorrhagic neurological complications in patients following this protocol. Conclusion The protocol described to reach a pre-procedure PRU within a target range limited the rate of rescheduled procedures to 7.5%. Nevertheless, half of the patients who were in-range pre-procedure exhibited a hyper-response to clopidogrel in post-procedure VerifyNow testing. This apparently induced hyper-response to clopidogrel may be related to a post-procedural change in hepatic clopidogrel metabolism. Abstract O-021 Table 1 Clopidogrel dosing schedule Step 0 150 mg daily Step 1 75 mg daily Step 2 75 mg every other day Step 3 75 mg every 3 days Step 4 75 mg q Mon Fri Step 5 Clopidogrel oral suspension 2.5 mg/mL, titrate to target PRU Abstract O-021 Table 2 PRU-based dosing adjustment protocol PRU >240 Increase dosing schedule by 1 step PRU 40–59 Decrease dosing schedule by 1 step PRU 10–39 Decrease dosing schedule by 2 steps PRU <10 Decrease dosing schedule by 3 steps Disclosures Y. Kadkhodayan: 2; C; Covidien. J. Delgado Almandoz: 2; C; Covidien, MicroVention, Penumbra. J. Scholz: None. J. Fease: None. A. Blem: None. K. Tran: None. B. Crandall: 2; C; Covidien.