Evaluation of Clopidogrel Resistance and Its Role in Predicting Stent Thrombosis in Transcarotid Artery Revascularization

Abstract

While up to 70% of patients have resistance to clopidogrel (Plavix) in the coronary literature, resistance testing is not routinely performed despite its common use as an antiplatelet for prevention of stent thrombosis in transcarotid arterial revascularization (TCAR) procedures. The extent to which resistance exists in patients undergoing TCAR has not been well-described. We sought to compare the modalities for clopidogrel resistance testing and determine the prevalence of resistance and its effect on stent outcomes. Patients undergoing TCAR at our institution between 2018 and 2022 were retrospectively identified. Clopidogrel-resisting test results were recorded. Patient characteristics, perioperative details, and outcomes are described. A total of 85 patients underwent TCAR, 52 (61%) for symptomatic disease. Sixty-five patients (77%) were on dual antiplatelet therapy (DAPT) for at least 7 days prior to TCAR. 7 (8%) patients not on DAPT were on anticoagulation prior to surgery and most (6) received a loading dose of a second antiplatelet the day of their procedure. Nine patients (10.6%) developed stent thrombosis during the follow-up period. Patients not taking DAPT for at least 7 days prior to surgery were more likely to develop stent thrombosis (30% vs 4.6%; P < .001). Clopidogrel resistance testing was performed in 35 (41%) patients, with 25 patients undergoing thromboelastogram with platelet mapping, 5 undergoing VerifyNow P2Y12 inhibitor testing, and 5 undergoing testing with both modalities. Clopidogrel resistance was noted in 24 patients (69%) using all testing results. In patients that underwent both testing modalities, agreement was poor (Cohen's Kappa −0.05) (Table I). Among patients with clopidogrel resistance, 17 (72%) did not thrombose and 5 (20%) patients did thrombose. Comparatively, 1 (9.1%) patient without resistance thrombosed (P = .161). Of the five patients with thrombosed stents that underwent testing, four were clopidogrel resistant (80%) (Table II). VerifyNow correctly predicted resistance and nonresistance more accurately than thromboelastogram (7 of 9 correct, 78% vs 11 of 29 correct, 38%; P = .001). VerifyNow had a sensitivity of 60% and specificity of 100% for stent thrombosis. Our experience demonstrates that clopidogrel resistance rates are high in the TCAR patient population, with higher thrombosis rates in those that test positive for resistance. VerifyNow more reliably predicts clopidogrel resistance than thromboelastography. In addition to determining clopidogrel susceptibility, patients may also obtain benefit by initiating DAPT at least 7 days prior to surgery.Table IComparison of platelet mapping methodsThromboelastogram value (% ADP inhibition)VerifyNow value (P2y12 reaction units)Clopidogrel resistance present?Congruence in testing results?Patient 125.6182YesNoPatient 235.6172YesNoPatient 350.6187YesNoPatient 474.5163NoNoPatient 545.39YesYesAdenosine diphosphate (ADP) inhibition ≤ 50% confers platelet resistance by thromboelastography. Platelet reactivity unit (PRU) >194 confers platelet resistance by VerifyNow testing. Open table in a new tab Table IIDescription of testing among nine patients with thrombosed stentsTEG value (% ADP inhibition)Verify Now value (P2y12 reaction units)Clopidogrel resistance present?Testing result correctly predicts thrombosis?Stent 1N/AN/AN/AN/AStent 2N/AN/AN/AN/AStent 3-213YesYesStent 4-253YesYesStent 5-413YesYesStent 622.4-YesYesStent 774.5163NoNoStent 845.39Yes- TEGNo- VerifyNowYes- TEGNo- VerifyNowStent 9N/AN/AN/AN/AAdenosine diphosphate (ADP) inhibition ≤50% confers platelet resistance by thromboelastography. PRU >194 confers platelet resistance by VerifyNow testing. Open table in a new tab