Key result
Immediate CEA shows no benefit over deferred surgery for 10-year stroke-free days.
Why the study?
Conventional analyses fail to adequately address competing risks and event timing in preventive surgeries like CEA, limiting risk-benefit assessment.
Does immediate CEA improve stroke-free days and life years compared to deferred CEA in patients with asymptomatic carotid stenosis when evaluated using competing risk analysis?
Does immediate CEA improve stroke-free days and life years compared to deferred CEA in patients with asymptomatic carotid stenosis when evaluated using competing risk analysis?
Using competing risk analysis and restricted mean survival time instead of traditional Kaplan-Meier estimates may alter study conclusions by showing no significant difference in stroke-free days for immediate versus deferred CEA.
No benefit of immediate over deferred CEA on stroke-free days; leaves optimal timing open in asymptomatic stenosis.
OBJECTIVE: Preventive surgeries, such as carotid endarterectomy (CEA), involve immediate procedural risks for every patient, yet only survivors experience benefit. Conventional analyses such as Kaplan-Meier estimates and Cox models fail to adequately address competing risks and the timing of events, limiting their ability to assess the risk-benefit trade off. This study aimed to evaluate alternative methodologies, specifically competing risk analysis and restricted mean survival time (RMST), using a landmark CEA trial as an example. METHODS: Methodological re-evaluation was performed on reconstructed individual patient data from the ACST-1 trial, a randomised clinical trial of 3 120 patients comparing immediate vs. deferred CEA for asymptomatic carotid stenosis. Data were derived from published Kaplan-Meier curves and supplemental materials, with mortality modelled from a comparable study. Key parameters for the reconstructed data fell within 1% of the original data. The Aalen-Johansen estimator and RMST were used to quantify stroke free days and life years gained or lost. RESULTS: Accounting for competing risks reduced Kaplan-Meier based ten year stroke risk estimates by 20% and lowered the estimated risk reduction for immediate CEA from 6.1% to 5.6%. Alternative analysis strategies did not indicate a difference in stroke free days between the two arms at 10 years: difference, 40 stroke free days (95% confidence interval [CI] -52 - 129 days; p = .375). Across mortality scenarios, the overall balance between prevented stroke related deaths and procedural deaths resulted in a small net disadvantage for immediate CEA ranging from 1 (95% CI -21 - 39; p = .53) to 16 (95% CI -39 - 4; p = .12) life days lost over 10 years. CONCLUSION: Competing risk analysis and RMST overcome the limitations of traditional analyses, enabling comprehensive evaluation of the surgical trade off in preventive surgery and potentially altering study conclusions based on traditional approaches. By providing more tangible outcome measures, this framework facilitates intertrial comparisons and medical decision making.
No takes yet. Share an insight, caveat, or question.
Biemond et al. (2026) studied asymptomatic carotid stenosis (n=3,120). Immediate carotid endarterectomy (CEA) vs. Deferred CEA was evaluated on Stroke-free days at 10 years (MD 40, 95% CI -52 - 129, p=0.375). Immediate carotid endarterectomy did not significantly increase stroke-free days at 10 years compared to deferred surgery (difference 40 days; 95% CI -52 to 129; p=0.375) using competing risk analysis.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: