Archives of Neurology Carotid Artery Stenting vs Carotid Endarterectomy: Meta-analysis and Diversity-Adjusted Trial Sequential Analysis of Randomized Trials Sripal Bangalore, MD, MHA; Sunil Kumar, MD; Jorn Wetterslev, MD, PhD; Anthony A. Bavry, MD, MPH; Christian Gluud, MD, DMSci; Donald E. Cutlip, MD; Deepak L. Bhatt, MD, MPH Background: The role of carotid artery stenting (CAS) when compared with carotid endarterectomy (CEA) is controversial, with recent trials showing an increased risk of harm with CAS. Objective: To evaluate the periprocedural and intermediate to long-term benefits and harms of CAS compared with CEA. Data Sources and Study Selection: PubMed, EMBASE, and Cochrane Central Register of Controlled Trials searches for randomized clinical trials until June 2010 of CAS compared with CEA for carotid artery disease. Periprocedural (≤30-day) outcomes (death, myocardial infarction [MI], or stroke; death or any stroke; any stroke; and MI) and intermediate to long-term outcomes (outcomes as in the Stenting and Angioplasty With Protection in Patients at High Risk for Endarterectomy [SAPPHIRE] trial: composite of periprocedural death, MI, or stroke plus ipsilateral stroke or death thereafter; periprocedural death or stroke plus ipsilateral stroke thereafter; death or any stroke; and any stroke) were evaluated. Data Extraction: Two of us independently extracted data in duplicate. Baseline characteristics, inclusion and exclusion criteria, use of an embolic protection device, US vs non-US study, and the earlier-mentioned outcomes of interest were extracted from each trial. Data Synthesis: We identified 13 randomized clinical trials randomizing 7477 participants. Carotid artery stenting was associated with an increased risk of periprocedural outcomes of death, MI, or stroke (odds ratio = 1.31; 95% confidence interval, 1.08-1.59), 65% and 67% increases in death or stroke and any stroke, respectively, but with 55% and 85% reductions in the risk of MI and cranial nerve injury, respectively, when compared with CEA. The trial sequential monitoring boundary was crossed by the cumulative z curve, suggesting firm evidence for at least a 20% relative risk increase of periprocedural death or stroke and any stroke and at least a 15% reduction in MI with CAS compared with CEA. Similarly, CAS was associated with 19%, 38%, 24%, and 48% increases in the intermediate to long-term outcomes of SAPPHIRE-like outcome, periprocedural death or stroke and ipsilateral stroke thereafter, death or any stroke, and any stroke, respectively. The trial sequential monitoring boundary was crossed by the cumulative z curve, suggesting firm evidence for at least a 20% relative risk increase of any stroke. Conclusions: In this largest and most comprehensive meta-analysis to date using outcomes that are standard in contemporary studies, CAS was associated with an increased risk of both periprocedural and intermediate to long-term outcomes, but with a reduction in periprocedural MI and cranial nerve injury. Strategies are urgently needed to identify patients who are best served by CAS vs CEA. Published online October 11, 2010.