JOURNAL CLUB PRESENTATION - Reanalysis of the Final Results of the European Carotid Surgery Trial.pptx

Reanalysis of final results of ECST Trial Journal club

1. Reanalysis of the Final Results of the European Carotid Surgery Trial Presenter: KIRENGO T. MBChB, MBA, MSc, MRCS(ed) VASC SURG JOURNAL CLUB

2. ARTICLE PRESENTED: Title: Reanalysis of the Final Results of the European Carotid Surgery Trial Location of study: Authors: P. M. Rothwell, PhD, FRCP, S. A.  Gutnikov , MD, PhD, C. P.  Warlow , MD, FRCP, and for the European Carotid Surgery Trialists’ Year of Publication: 23 Jan, 2003 Ethics: Conflict of interest: Journal Publication: AHA Journal Stroke

3. LEVEL OF EVIDENCE

4. JOURNAL INTRO AHA Journal Stroke Monthly reviewed multispeciality journal 1970 - Current Location: USA Impact factor (2022): 10.170 (2 year), 9.39 (5 year) Manuscript Acceptance Rate: 9%

5. STUDY BACKGROUND European Carotid Surgery Trial (ECST, 1998) & North American Symptomatic Carotid Endarterectomy Trial (NASCET, 1998) showed that endarterectomy reduced stroke risk NASCET reported benefit in patients with ≥50% stenosis However, ECST reported that surgery was beneficial only in patients with ≥80% stenosis The 2 studies were similar but differed in: Method of measurement of degree of carotid stenosis Definition of outcome events Differences in results caused confusion

6. OBJECTIVES OF STUDY Properly compare results from ECST & NASCET Remeasuring original ECST angiograms with NASCET Method Redefine ECST outcomes similar to NASCET

7. STUDY PICO QUESTION Population: Patients with symptomatic carotid artery stenosis Intervention: Carotid endarterectomy. Comparison: Best medical therapy (non-surgical management) Outcome: Reduction in the risk of stroke or death following intervention

8. STUDY DESIGN Reanalysis of RCT data Patients recruited after assessment by neurologist or stroke physician Inclusion: stenosis of symptomatic carotid (w/ i 6 mo ) + recent carotid distribution TIA, non-disabling stroke, retinal infarction *NASCET included only patients with >30% stenosis Imaging: Selective catheter angiography Randomization (via a central telephone randomization service): immediate carotid endarterectomy + best medical treatment (BMT) vs. BMT alone

9. ECST VS NASCET Numerator = point of max stenosis Denominator = ECST: Estimated normal diameter (A, dotted lines) NASCET: Distal ICA (B) 3018 ECST prerandomization angiogram remeasured by 1 observer Intraobserver agreement with NASCET principal neuroradiologist

10. STUDY DESIGN Stenosis could not be calculated in patients with narrowed poststenotic ICA, *arbitrarily defined as 95% stenosis in Original NASCET Near occlusion: evidence of red flow to distal ICA & narrowing of poststenotic ICA Severe stenosis defined as: >70% stenosis (by ECST method) + ICA:CCA ration <0.4 in men & <0.45 in women Analysis groups: <30%, 30% to 49%, 50% to 69%, 70% to 99% without near occlusion, and near occlusion Primary outcome: any 1 st stroke or surgical death Analysis: Intention to treat, Kaplan-Meier event-free survival curves, comparisons tested by χ2  test or Student’s  t  test

11. STUDY FINDINGS 3008 patients (99.7%) included, 10 excluded ECST method of carotid measures produced higher values ie . NASCET 50-70% stenosis = ECST 65-82% stenosis Near occlusion (NASCET criteria) present in 125 cases vs Severe stenosis with narrowing of ICA (ECST criteria) present in 108 cases. Overlap in 102 cases Surgery was harmful in patients with <30% stenosis, with an increased risk of any stroke or surgical death (log rank=7.2, P=0.007)  No effect of surgery on any outcome in patients with 30% to 49% stenosis (log rank=0.3, P=0.6) Some evidence of benefit from surgery in patients with 50% to 69% (log rank=3.9, P=0.05). 70% to 99% stenosis without near occlusion, there was a highly significant reduction in the surgery group in risks of all outcomes (log rank=17.5, P=<0.0001)

12. STUDY FINDINGS: Kaplan-Meier curves Effect of surgery on survival free of any stroke or surgical death

13. STUDY DISCUSSION Results resolve the differences between ECST & NASCET No significant differences between the studies on reanalysis of ECST Original ECST reported surgery effective only in 80-99% stenosis >> reanalysis shows: High efficacy at 70-99% present up to 10 yr f/u Modest efficacy at 50-69% ECST had a low patient crossover (<1%) from medical to surgical rx ; NASCET had approx. 50% crossover Surgery has no benefit in near occlusion (NASCET) or severe stenosis (ECST) Measurement of carotid stenosis should be accurate to inform Rx

14. STUDY LIMITATIONS Arterial angiography not conventional means of carotid measurement Common imaging is non-invasive USS Retrospective nature of analysis/ review – inherits previous study limitations Single reviewer of reanalyzed angiograms Challenging to determine near occlusions/ severe stenosis with narrowing ECST definition of narrow ICA (below 2 SD population mean ICA:CCA ration) is arbitrary, therefore false-positive near occlusion

15. STUDY CONCLUSION ECST & NASCET results similar after remeasurement and reanalysis Surgical benefit in: 50-69% and 70-99% stenosis No Surgical benefit in: Near occlusion/ severe stenosis with narrowing of ICA

16. CRITICAL APPRAISAL ISSUES WITH THE STUDY WAS THE OBJECTIVE CLEAR & DID THE STUDY ADDRESS IT? BIAS? CONCLUSION MAKE SENSE? APPLICABILITY OF STUDY TO OUR SETTING

17. RECOMMENDATIONS: Current improvements in BMT Conventional/ pragmatic imaging techniques for carotid disease Standardization of protocols for consistent/ comparable measurements in future studies Standardized definition of near occlusion

18. THANK YOU ANY QUESTIONS Created by Kirengo T.