O-007 Initial Institutional Experience Using a Target P2Y12 Reaction Units Range to Tailor the Clopidogrel Dose Administered to Patients with Cerebral Aneurysms Treated with the Pipeline Embolization Device and Stents
Authors: Delgado Almandoz J , Kadkhodayan Y , Scholz J , Fease J , Blem A , Tran K , Crandall B 
Published: July 2014

Background and purpose

Variability in response to the P2Y12 receptor antagonists administered to patients with cerebral aneurysms treated with the Pipeline Embolization device (PED) or stents may play an important role in post-operative thromboembolic and haemorrhagic complications. We present our initial institutional experience using a target P2Y12 reaction units (PRU) range to tailor the clopidogrel dose administered.

Methods

We retrospectively reviewed all patients who underwent endovascular treatment of cerebral aneurysms with the PED or stent-assistance at our institution from November 15th, 2011 until December 31st, 2013. Patient characteristics, P2Y12 receptor antagonist administered, thromboembolic and haemorrhagic complications, and clinical outcomes using the modified Rankin Scale (mRS) were recorded. The target PRU range was 60–240.

Results

Sixty-six patients were included, 49 females (74%) and 17 males (26%), mean age 57.5 years (25–82 years). Forty-six patients were treated with the PED (70%), 19 with a stent (29%) and 1 with a PED and a stent (1%). Eight patients were switched to prasugrel due to an initial clopidogrel hypo-response (12.1%). Forty patients underwent at least 1 adjustment to the clopidogrel dose due to either a hypo-response (PRU > 240) or hyper-response (PRU < 60) to the standard 75mg daily clopidogrel dose (61%), occurring on average 23 days after initiation of clopidogrel therapy. Among these, the first adjustment was made on average 8.5 days before the procedure in 13 patients (32.5%), on the day of the procedure in 6 patients (15%), and on average 23.7 days after the procedure in 21 patients (52.5%). After the first dose adjustment, the target 60–240 PRU range was reached in 71% of hypo-responders and 46% of hyper-responders. Table 1 illustrates the PRU change after the first clopidogrel dose adjustment. Table 2 illustrates the PRU change after subsequent clopidogrel dose adjustments. Table 3 illustrates the final P2Y12 receptor antagonist administered and associated thromboembolic and haemorrhagic complications leading to a permanent disabling neurological deficit (mRS ≥ 3).

Conclusion

Overall, 73% of patients with cerebral aneurysms treated with the PED or stents required at least 1 adjustment to the clopidogrel dose or a switch to an alternate P2Y12 receptor antagonist to remain within the target 60–240 PRU range.

Abstract O-007 Table 1

Change in PRU values after first clopidogrel dose adjustment

Clopidogrel dose adjustment (DA)Number of patientsMean Pre-DA PRUMean Post-DA PRUMean PRU ChangePatients within target 60–240 PRU range after DAHypo-Responders, 75 mg daily to 150mg daily7264182–8271%Hyper-Responders332169+4846%75 mg daily to 75 mg every-other-day:173061+3135%75 mg daily to 75 mg every-third-day:131371+5854%75 mg daily to 75 mg every-Monday-and-Friday:35104+9967%Abstract O-007 Table 2

Change in PRU values after subsequent clopidogrel dose adjustments

Clopidogrel dose adjustment (DA)Number of patientsMean days after clopidogrel initiationMean days after procedureMean PRU pre-DAMean PRU post-DAMean PRU changePatients within target 60–240 PRU range after DASecond DA:2440252992+6371%150mg daily to 75mg daily (n = 1) or 75mg every-other-day (n = 1)243106+63100%75 mg every-other-day to 75 mg every-third-day (n = 9) or 75 mg every-Monday-and-Friday (n = 3)123372+3958%75 mg every-third-day to 75 mg every-Monday-and-Friday (n = 3), 75mg every-fifth-day (n = 4) or 75mg once-a-week (n = 1)824119+9588%75 mg every-Monday-and-Friday to 75 mg once-a-week (n = 1) or 7.5 mg daily suspension (n = 1)2787+8050%Third DA7473133115+8257%75 mg every-third-day to 75 mg every-fourth-day (n = 3) or 75 mg every-Monday-and-Friday (n = 3)637105+6850%75 mg every-Monday-and-Friday to 75 mg once-a-week19178+169100%Fourth DA, 75 mg every-fourth-day to 75 mg every-fifth-day1392942155+113100%Abstract O-007 Table 3

Finalreceptor antagonist and major thromboembolic and haemorrhagic complications

P2Y12 receptor antagonist dosingNumber of patients (%)Major thromboembolic complications (mRS ≥ 3)PRU at time of complication (% with PRU >240)Major haemorrhagic complications (mRS ≥ 3)PRU at time of complication (% with PRU < 60)Clopidogrel, 150 mg daily5 (8%)1 (20%)292 (100%)1 (20%)10 (100%)Clopidogrel, 75 mg daily20 (30%)0n/a0n/aClopidogrel, 75 mg every-other-day (n = 4) or 75 mg every-third-day (n = 7)11 (17%)0n/a0n/aClopidogrel, 75 mg every-fourth-day2 (3%)0n/a1 (50%)58 (100%)Clopidogrel, 75 mg every-Monday-and-Friday10 (15%)0n/a0n/aClopidogrel, 75 mg every-fifth-day (n = 5) or 75 mg once-a-week (n = 3)8 (12%)0n/a0n/aClopidogrel suspension, 7.5 mg daily:1 (1.5%)0n/a0n/aPrasugrel, 5 mg daily (n = 5) or 10mg daily (n = 3)8 (12%)0n/a2 (25%)0, 185 (50%)Ticagrelor, 90 mg twice-a-day1 (1.5%)0n/a0n/a

Disclosures

J. Delgado Almandoz: 2; C; Covidien/ev3, Microvention/Terumo, Penumbra Inc. Y. Kadkhodayan: 2; C; Covidien/ev3. J. Scholz: None. J. Fease: None. A. Blem: None. K. Tran: None. B. Crandall: 2; C; Covidien/ev3.