Carotid Artery Surgery to Reduce Long-Term Stroke Rates: Individual Patient Data Meta-Analysis of the Randomised Trials in Asymptomatic Patients

Background: Among patients with severe carotid artery stenosis but no recent symptoms from it, carotid surgery involves hazards, but then reduces long-term stroke rates. Triple-drug therapy (statin, anti-thrombotic, anti-hypertensive) also reduces long-term stroke rates in these asymptomatic patients. Past trials of carotid endarterectomy (CEA) can help assess the proportional reduction by carotid surgery in long-term stroke rates before and since triple-drug therapy became common. Methods: Intention-to-treat analyses used individual data from all 3 properly randomised trials among asymptomatic patients of immediate CEA vs deferral of any CEA until definitely indicated. Analyses of long-term stroke rates, censored at non-stroke death, used Kaplan-Meier life-tables and logrank methods. Findings: 2599 patients were allocated immediate CEA vs 2627 allocated deferral, with 89% vs 7% operated on within 1 year. Non-perioperative stroke rates were halved by allocation to immediate CEA (10-year stroke rate ratio [RR]=0.54, 95%CI 0.46-0.65, p<0.0001; 5.8% vs 11.7% by year 5); for fatal/disabling strokes, RR=0.55 (0.40-0.77, p<0.0001). Proportional reductions depended little on gender, or other patient characteristics. Ipsilateral and contralateral strokes were both reduced. In analyses restricted to strokes occurring on triple-drug therapy, absolute hazards and long-term stroke rates were lower than in the overall findings, but allocation to immediate CEA still halved long-term stroke rates (RR=0.56, 0.41-0.76; p=0.0002; 3.5% vs 7.0% by year 5). Of all CEAs undertaken, 3.1% involved perioperative stroke/death (71/3348; 40 dead/disabled, 31 not). Interpretation: Successful CEA halves long-term stroke rates. Net benefits will depend on surgical risks, long-term stroke rates without surgery, and life expectancy. Trial Registration: The trial is registered with the ISRCTN registry, ISRCTN21144362. Funding: MRC. Declaration of Interest: None to declare.