At the time of carotid endarterectomy (CEA), surgeons should consider single antiplatelet therapy (SAPT) rather than dual antiplatelet therapy (DAPT). This is the conclusion of a new meta-analysis—reportedly the largest conducted on the topic to date—published in the European Journal of Vascular and Endovascular Surgery (EJVES).
“At the time of CEA in symptomatic or asymptomatic patients with carotid stenosis, perioperative DAPT has no effect on the occurrence of the ischaemic CEA complications versus perioperative aspirin SAPT,” authors Jerry C Ku (University of Toronto, Toronto, Canada) and Shervin Taslimi (Kingston General Hospital, Kingston, USA) et al write. “However,” they note, “DAPT does result in an increase of haemorrhagic CEA complications.” These are the key findings behind the investigators’ recommendation of SAPT over DAPT at the time of CEA, although Ku, Taslimi and colleagues acknowledge that the overall quality of the available evidence is poor.
In the introduction to their study, the authors highlight a lack of granularity in the available guidelines on this topic. “Consensus medical management guidelines recommend aspirin monotherapy for asymptomatic atherosclerotic carotid artery disease and DAPT with aspirin and the addition of clopidogrel or dipyridamole for symptomatic carotid artery disease,” they write. However, they stress that “it remains unclear whether the second antiplatelet agent should be withheld preoperatively and resumed after surgery to reduce bleeding risk or continued throughout the perioperative period to reduce the ischaemic complication risk in patients with symptomatic carotid stenosis.”
This ambiguity is reflected in surgeons’ practice. “Surveys of surgeons who perform CEA have shown significant variations in perioperative antiplatelet prescribing patterns,” the authors communicate. “Although the vast majority would not stop aspirin prior to CEA, 43% and 55% of surgeons would stop clopidogrel prior to CEA for asymptomatic and symptomatic patients, respectively.”
The authors state that their objective was to conduct a systematic review and meta-analysis of the perioperative outcomes of CEA on DAPT versus aspirin monotherapy in order to determine optimal perioperative management with these antiplatelet agents. What sets their study apart in the literature, according to Ku, Taslimi et al, is the addition of newly published articles, the subgroup analysis for symptomatic carotid stenosis, which had yet to be explored previously, and the use of improved statistical methodology over previous meta-analyses of SAPT versus DAPT for CEA.
The investigators note that they searched the Web of Science, PubMed, and Embase databases from inception to July 2021. The main outcomes included ischaemic complications (stroke, transient ischaemic attack [TIA], and transcranial Doppler [TCD]- measured micro-emboli), haemorrhagic complications (haemorrhagic stroke, neck haematoma, and reoperation for bleeding), and composite outcomes.
Writing in EJVES, Ku, Taslimi and colleagues communicate that a total of 47,411 patients were included in 11 studies, with 14,345 (30.2%) receiving DAPT and 33,066 (69.7%) receiving aspirin only. They report that there was no significant difference in the rates of perioperative stroke (odds ratio [OR], 0.87; 95% confidence interval [CI], 0.72–1.05) and TIA (OR, 0.78; 95% CI, 0.52–1.17) despite a significant reduction in TCD-measured micro-emboli (OR, 0.19; 95% CI, 0.1–0.35) in the DAPT compared with the aspirin monotherapy group.
In addition, the authors relay that subgroup analysis did not reveal any significant difference in ischaemic stroke risk between patients with asymptomatic and symptomatic carotid artery stenosis, and that DAPT was associated with an increased risk of neck haematoma (OR, 2.79; 95% CI, 1.87–4.18) and reoperation for bleeding (OR, 1.98; 95% CI, 1.77–2.23) versus aspirin. Finally, they highlight that haemorrhagic stroke was an under-reported outcome in the literature.
Despite the present analysis representing what the authors claim to be the largest conducted on the topic to date, Ku, Taslimi et al also acknowledge some limitations of the study. For example, they write that this review was limited by the studies available in the literature, as is the case in meta-analyses. “Most were retrospective reviews and other observational trials, with only two RCTs [randomised controlled trials],” they elaborate, adding that additional subgroup analyses could not be performed as a result of the heterogeneity in reporting.”
Another limitation the authors highlight relates to the drawbacks of the information available within the literature. “Reporting of ischaemic stroke outcomes for asymptomatic versus symptomatic carotid artery stenosis was lacking in many studies,” they note, stating that this limited the number of studies available for this subgroup analysis. In addition, they state that information on the timing of CEA in symptomatic patients and ischaemic events that occurred while waiting for surgery was also lacking. The reporting of haemorrhagic stroke was also limited in the literature.
“The risks of performing CEA on DAPT outweigh the benefits, even in patients with symptomatic carotid stenosis,” Ku, Taslimi and colleagues conclude. They note, however, that the overall quality of studies was low, and suggest that “improved reporting of CEA outcomes in the literature is necessary”.