Dual antiplatelet therapy reduces stroke but increases bleeding at the time of carotid endarterectomy

Abstract

Objective Controversy persists regarding the perioperative management of clopidogrel among patients undergoing carotid endarterectomy (CEA). This study examined the effect of preoperative dual antiplatelet therapy (aspirin and clopidogrel) on in-hospital CEA outcomes. Methods Patients undergoing CEA in the Vascular Quality Initiative were analyzed (2003–2014). Patients on clopidogrel and aspirin (dual therapy) were compared with patients taking aspirin alone preoperatively. Study outcomes included reoperation for bleeding and thrombotic complications defined as transient ischemic attack (TIA), stroke, or myocardial infarction. Secondary outcomes were in-hospital death and composite stroke/death. Univariate and multivariable analyses assessed differences in demographics and operative factors. Propensity score-matched cohorts were derived to control for subgroup heterogeneity. Results Of 28,683 CEAs, 21,624 patients (75%) were on aspirin and 7059 (25%) were on dual therapy. Patients on dual therapy were more likely to have multiple comorbidities, including coronary artery disease (P < .001), congestive heart failure (P < .001), and diabetes (P < .001). Patients on dual therapy were also more likely to have a drain placed (P < .001) and receive protamine during CEA (P < .001). Multivariable analysis showed that dual therapy was independently associated with increased reoperation for bleeding (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.20–2.42; P = .003) but was protective against TIA or stroke (OR, 0.61; 95% CI, 0.43–0.87; P = .007), stroke (OR, 0.63; 95% CI, 0.41–0.97; P = .03), and stroke/death (OR, 0.66; 95% CI, 0.44–0.98; P = .04). Propensity score matching yielded two groups of 4548 patients and showed that patients on dual therapy were more likely to require reoperation for bleeding (1.3% vs 0.7%; P = .004) but less likely to suffer TIA or stroke (0.9% vs 1.6%; P = .002), stroke (0.6% vs 1.0%; P = .04), or stroke/death (0.7% vs 1.2%; P = .03). Within the propensity score-matched groups, patients on dual therapy had increased rates of reoperation for bleeding regardless of carotid symptom status. However, asymptomatic patients on dual therapy demonstrated reduced rates of TIA or stroke (0.6% vs 1.5%; P < .001), stroke (0.4% vs 0.9%; P = .01), and composite stroke/death (0.5% vs 1.0%; P = .02). Among propensity score-matched patients with symptomatic carotid disease, these differences were not statistically significant. Conclusions Preoperative dual antiplatelet therapy was associated with a 40% risk reduction for neurologic events but also incurred a significant increased risk of reoperation for bleeding after CEA. Given its observed overall neurologic protective effect, continued dual antiplatelet therapy throughout the perioperative period is justified. Initiating dual therapy in all patients undergoing CEA may lead to decreased neurologic complication rates.

Editor's Choice – Very Urgent Carotid Endarterectomy is Associated with an Increased Procedural Risk: The Carotid Alarm Study

“…Given the relatively low proportion of patients with dual antiplatelet treatment in the present study, it may be speculated that some of the ipsilateral strokes could have been avoided with a more aggressive pre-operative medical therapy. 13 The finding that CEA carried out within 48 hours confers an increased 30 day risk of stroke and/or mortality emphasizes the need for a randomised trial, to determine whether the increased risk of recurrent events will outweigh the increased risk of complications observed during very early surgical intervention. If the same risk of complication as in the Carotid Alarm Study is assumed, a randomised study will have to incorporate > 700 patients in each arm to reach a power of 80% (Appendix S1; see Supplementary Material).…”

Effect of aspirin in vascular surgery in patients from a randomized clinical trial (POISE-2)

“…Patients scheduled for carotid endarterectomy (CEA) were excluded from POISE‐2 as perioperative aspirin treatment in these patients showed evidence of benefit in an RCT. This was further validated in a large observational cohort study of over 28 000 patients undergoing CEA, where the risk of thrombotic complications exceeded the risk of bleeding associated with CEA. Based on these data it would be advisable to continue aspirin therapy in patients undergoing CEA.…”

Perioperative clopidogrel is associated with increased bleeding and blood transfusion at the time of lower extremity bypass

“…In our previous work, reoperation for bleeding was nearly twice as high in propensity-matched CEA patients taking aspirin and clopidogrel compared with those taking aspirin alone (1.3% vs 0.7%; P = .004). 19 However, a lower associated rate of thrombotic complications led to an overall protective effect of dual antiplatelet therapy in patients undergoing CEA. In the current study, LEB patients also had higher rates of bleeding complications, but this occurred without any offsetting benefit.…”