Efficacy and safety of perioperative dual antiplatelet therapy with ticagrelor versus clopidogrel in carotid artery stenting

Abstract

Background: Clopidogrel resistance is associated with increased periprocedural neurologic events after carotid artery stenting (CAS). Ticagrelor offers an improved resistance profile; however, its bleeding risk has not been assessed with CAS. Therefore, we examined the efficacy and safety of perioperative dual antiplatelet therapy with aspirin/ticagrelor vs aspirin/clopidogrel in patients undergoing transfemoral carotid artery stenting (tfCAS) or transcarotid artery revascularization (TCAR).

Methods: We identified all patients who underwent tfCAS or TCAR in the Vascular Quality Initiative registry from January 2016 to March 2021. We stratified patients by procedure and assessed outcomes using 1:3 propensity score-matched cohorts of patients who received perioperative aspirin/ticagrelor vs aspirin/clopidogrel. The primary efficacy outcome was a composite endpoint of in-hospital stroke/death, and the primary safety outcome was access-related bleeding. As a secondary analysis, we assessed these outcomes after stratifying each cohort by intraoperative protamine use.

Results: Among 17,731 tfCAS patients, 593 (3.3%) received aspirin/ticagrelor and 11,404 (64%) received aspirin/clopidogrel. For the 2065 matched patients, no significant differences were found in the composite endpoint of stroke/death (aspirin/ticagrelor, 4.1%; vs aspirin/clopidogrel, 2.6%; relative risk [RR],1.5; 95% confidence interval [CI], 0.88-2.7) or in the individual endpoints of stroke (2.9% vs 1.8%; RR, 1.6; 95% CI, 0.87-3.0) or death (1.7% vs 1.1%; RR, 1.6; 95% CI, 0.71-3.5). However, aspirin/ticagrelor was associated with a higher risk of bleeding (5.8% vs 2.8%; RR, 2.0; 95% CI, 1.2-3.2). In a subgroup analysis of 297 tfCAS patients (14%) who received intraoperative protamine, no differences remained in stroke/death (1.5% vs 3.9%; RR, 0.38; 95% CI, 0.05-3.0), and there was no longer a difference in bleeding (3.0% vs 2.6%; RR, 1.1; 95% CI, 0.24-5.5). Among 17,946 TCAR patients, 453 (2.5%) received aspirin/ticagrelor and 13,696 (76%) received aspirin/clopidogrel. For the 1618 matched patients, no differences were found in stroke/death (0.7% vs 1.4%; RR, 0.53; 95% CI, 0.16-1.8), stroke (0.2% vs 1.2%; RR, 0.20; 95% CI, 0.03-1.5), death (0.5% vs 0.2%; RR, 3.0; 95% CI, 0.42-21), or bleeding (1.2% vs 1.6%; RR, 0.75; 95% CI, 0.28-2.0). For the 1429 TCAR patients (88%) who received protamine, no differences were found in stroke/death (0.8% vs 1.2%; RR, 0.68; 95% CI, 0.20-2.4) or bleeding (0.6% vs 1.4%; RR, 0.39; 95% CI, 0.09-1.7).

Conclusions: Compared with aspirin/clopidogrel, aspirin/ticagrelor was associated with a potentially lower risk of stroke/death and bleeding complications after CAS in cases in which protamine was used but a higher risk of these outcomes in the absence of protamine. Given our limited sample size, our analysis should be repeated when more patients are available for study. However, our findings suggest that aspirin/ticagrelor could be a reasonable alternative to aspirin/clopidogrel for both tfCAS and TCAR when protamine is used.

Keywords: Carotid artery stenting; Clopidogrel; Dual antiplatelet therapy; TCAR; Ticagrelor; tfCAS.