Predictors of Clopidogrel Hyper-Responsiveness in Neuro-Interventional Procedures

Abstract

Background: Hyper-responsiveness to clopidogrel abnormally inhibits platelet aggregation and increases hemorrhagic complications. The present study investigated clinical factors related to clopidogrel hyper-responsiveness in neuro-interventional procedures.

Methods: Two hundred twenty-four patients receiving clopidogrel for coil embolization to treat unruptured cerebral aneurysm or carotid artery stenting to treat carotid artery stenosis at the internal carotid artery origin were retrospectively reviewed for their P2Y12 reactivity unit (PRU) values and clinical characteristics. Hyper-responsiveness to clopidogrel was defined as a PRU of <95.

Results: The mean PRU was 218.2 ± 77.8. Hyper-responsiveness to clopidogrel was observed in 12 patients (5.4%). Hyper-responsiveness was observed in younger patients, patients with a lower concentration of hemoglobin A1c, and patients with a higher low-density lipoprotein cholesterol (LDL-C) concentration compared with non-hyper-responsive patients (P = 0.01, P < 0.01, P < 0.01, respectively). On analysis of concomitant drugs, the patients in the hyper-responsive group were less frequently administered calcium channel blockers (CCBs) compared with the non-hyper-responsive group (P = 0.01). No significant differences in the usage of proton pump inhibitors or statins were observed. A LDL-C concentration of >120 mg/dL and no usage of CCBs were significant independent predictors of hyper-responsiveness to clopidogrel with a multivariate analysis (OR; 6.16, 95% CI, 1.57-26.64, P = 0.01, OR; 0.09, 95% CI, 0.01-0.82, P = 0.03, respectively).

Conclusion: The present study shows that a higher LDL-C concentration and no usage of CCBs are independent predictors of clopidogrel hyper-responsiveness. These results are useful to predict perioperative hemorrhagic complications. Considering dose reduction of clopidogrel or alternative drugs in high risk cases is necessary to prevent perioperative hemorrhagic complications.

Keywords: Antiplatelet therapy; Calcium channel blockers; Clopidogrel hyper-responsiveness; Low-density lipoprotein cholesterol; Neuro-interventional procedure.