Pooled RCTs: In symptomatic carotid stenosis, endarterectomy had lower periprocedural risk than stenting

Question In patients with symptomatic carotid stenosis, does time from symptom onset to carotid artery stenting (CAS) or endarterectomy (CEA) affect risk for stroke or death? Methods Design Individual patient data meta-analysis of 4 randomized controlled trials (RCTs). Allocation {Concealed}*. Blinding Blinded (outcome adjudicators). Follow-up period 30 days posttreatment. Setting {Centers in Europe, Australia, New Zealand, Canada, and the USA}. * Patients 4754 patients (mean age 69 y, 70% men). 3 RCTs included patients with moderate-to-severe symptomatic carotid stenosis (50% stenosis based on North American Symptomatic Carotid Endarterectomy Trial criteria) who were candidates for CAS or CEA; 1 RCT included patients with transient ischemic attack, amaurosis fugax, or minor nondisabling ischemic stroke and carotid artery stenosis (50% stenosis on invasive angiography, 70% on ultrasonography, or 70% on computed tomographic or magnetic resonance angiography). Intervention CAS (n =2393) or CEA (n =2361). Subgroup analysis was performed by time of treatment (within 0 to 7 d vs >7 d of neurologic symptoms). Outcomes Primary composite outcome was any stroke or death. Secondary outcomes were any stroke and fatal or disabling stroke. Patient follow-up 87% (per-protocol analysis). Main results The main results are in the Table. 287 patients (14%) had CAS and 226 (11%) had CEA within 7 days of symptom onset. CAS increased procedural events compared with CEA, regardless of whether the procedure was conducted 7 or >7 days of symptom onset. However, the risk difference was marginally greater for procedures done within 7 days (P for interaction with time interval =0.06). Conclusion In patients with symptomatic carotid stenosis, carotid endarterectomy decreased 30-day periprocedural risk for stroke or death compared with carotid artery stenting irrespective of the time of the procedure from symptom onset. Carotid artery stenting (CAS) or endarterectomy (CEA) in patients with symptomatic carotid stenosis Outcomes Time from symptom onset to procedure Event rates At 30 d CAS CEA RRI (95% CI) NNH (CI) Any stroke or death 0 to 7 d 8.4% 1.3% 574% (107 to 2092) 14 (4 to 71) >7 d 7.1% 3.6% 100% (50 to 168) 28 (17 to 56) Any stroke 0 to 7 d 8.0% 1.3% 548% (99 to 2010) 14 (4 to 77) >7 d 6.8% 3.4% 99% (48 to 168) 30 (18 to 62) Fatal or disabling stroke 0 to 7 d 3.1% 0.4% 738% (9 to 6376) 31 (4 to 2512) >7 d 2.5% 1.4% 79% (12 to 187) 89 (38 to 584) Abbreviations defined in Glossary. RRI, NNH, and CI calculated from control event rates and relative risks in article. Analyses were adjusted for age at treatment, sex, and qualifying event. P for interaction was 0.06 for any stroke or death, 0.07 for any stroke, and 0.17 for fatal or disabling stroke. P for interaction <0.10 was considered statistically significant. Commentary Despite best medical therapy, the risk for stroke after transient ischemic attack or ischemic stroke is highest in the first week after symptom onset and when the cause is large artery atherosclerosis (1). For patients with symptomatic extracranial carotid stenosis, CAS or CEA is recommended within the first 7 days after symptom onset (2). Although CAS may seem safer than CEA, a systematic review of 47 studies reported similar risks for periprocedural stroke after CEA (3.3%, 95% CI 2.1 to 4.6) and CAS (4.8%, 95% CI 2.5 to 7.8) performed within 7 days (2). In contrast, in the pooled analysis by Rantner and colleagues of 4 RCTs of 513 patients treated within 7 days of symptom onset, the risk for periprocedural stroke or death was 8.4% vs 1.3% for CAS vs CEA, respectively. Because this was a post hoc analysis, the estimate of relative risk for CAS vs CEA may be confounded by an imbalance between treatment groups in such unmeasured predictors of perioperative risk as clinical stability and plaque severity and stability. The small number of outcome events also predisposes the analysis to random error. Nevertheless, the reported absolute rate of periprocedural stroke or death after CAS of 8.4% (CI 5.4 to 12.2) is unacceptable, particularly if potent medical therapies can reduce stroke as effectively as CAS and without as much harm (3). The current European Carotid Surgery Trial 2 is comparing modern optimal medical management plus immediate carotid revascularization (surgery or stenting) in patients with moderate or severe carotid stenosis (4). Given accumulated clinical experience and improved technologies for selecting and treating patients with CAS, periprocedural risks for CAS may be lower than reported in previous trials and acceptable. Estimates of risks and benefits of CAS vs CEA (in addition to, and compared with, best medical therapy) in the first week after onset of symptoms may now need to be based on ongoing or new studies (4).