Editor's Choice - Risk of Stroke before Revascularisation in Patients with Symptomatic Carotid Stenosis: A Pooled Analysis of Randomised Controlled Trials

Urs Fisch; Stefanie von Felten; Andrea Wiencierz; Olav Jansen; George Howard; Jeroen Hendrikse; Alison Halliday; Gustav Fraedrich; Hans-Henning Eckstein; David Calvet; Richard Bulbulia; Jean-Pierre Becquemin; Ale Algra; Peter Rothwell; Peter Ringleb; Jean-Louis Mas; Martin M Brown; Thomas G Brott; Leo H Bonati; Carotid Stenosis Trialists’ Collaboration

doi:10.1016/j.ejvs.2021.02.024

Editor's Choice - Risk of Stroke before Revascularisation in Patients with Symptomatic Carotid Stenosis: A Pooled Analysis of Randomised Controlled Trials

Eur J Vasc Endovasc Surg. 2021 Jun;61(6):881-887. doi: 10.1016/j.ejvs.2021.02.024. Epub 2021 Apr 5.

Authors

Urs Fisch¹, Stefanie von Felten², Andrea Wiencierz³, Olav Jansen⁴, George Howard⁵, Jeroen Hendrikse⁶, Alison Halliday⁷, Gustav Fraedrich⁸, Hans-Henning Eckstein⁹, David Calvet¹⁰, Richard Bulbulia¹¹, Jean-Pierre Becquemin¹², Ale Algra¹³, Peter Rothwell¹⁴, Peter Ringleb¹⁵, Jean-Louis Mas¹⁰, Martin M Brown¹⁶, Thomas G Brott¹⁷, Leo H Bonati¹⁸; Carotid Stenosis Trialists’ Collaboration

Affiliations

¹ Department of Neurology and Stroke Centre, Department of Clinical Research, University Hospital, University of Basel, Basel, Switzerland.
² Clinical Trial Unit, Department of Clinical Research, University of Basel, Basel, Switzerland; Department of Biostatistics, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.
³ Clinical Trial Unit, Department of Clinical Research, University of Basel, Basel, Switzerland.
⁴ Clinic for Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
⁵ Department of Biostatistics, UAB School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
⁶ Department of Radiology, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands.
⁷ Nuffield Department of Surgery University of Oxford, Oxford, UK.
⁸ Department of Vascular Surgery, Medical University of Innsbruck, Innsbruck, Austria.
⁹ Department for Vascular and Endovascular Surgery-Vascular Centre, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.
¹⁰ Department of Neurology, Hôpital Sainte-Anne, Université Paris-Descartes, DHU Neurovasc Sorbonne Paris Cité, INSERM U894, Paris, France.
¹¹ Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, UK.
¹² Vascular Institute of Paris East, Hôspital Paul D Egine, Champigny-sur-Marne, France.
¹³ Department of Neurology and Neurosurgery, UMC Utrecht Brain Centre, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands; Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands.
¹⁴ Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital and University of Oxford, Oxford, UK.
¹⁵ Department of Neurology, University of Heidelberg Medical School, Heidelberg, Germany.
¹⁶ Stroke Research Centre, Department of Brain Repair and Rehabilitation, UCL Queen Square Institute of Neurology, University College London, London, UK.
¹⁷ Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
¹⁸ Department of Neurology and Stroke Centre, Department of Clinical Research, University Hospital, University of Basel, Basel, Switzerland; Stroke Research Centre, Department of Brain Repair and Rehabilitation, UCL Queen Square Institute of Neurology, University College London, London, UK. Electronic address: [email protected].

PMID: 33827781
DOI: 10.1016/j.ejvs.2021.02.024

Abstract

Objective: Current guidelines recommending rapid revascularisation of symptomatic carotid stenosis are largely based on data from clinical trials performed at a time when best medical therapy was potentially less effective than today. The risk of stroke and its predictors among patients with symptomatic carotid stenosis awaiting revascularisation in recent randomised controlled trials (RCTs) and in medical arms of earlier RCTs was assessed.

Methods: The pooled data of individual patients with symptomatic carotid stenosis randomised to stenting (CAS) or endarterectomy (CEA) in four recent RCTs, and of patients randomised to medical therapy in three earlier RCTs comparing CEA vs. medical therapy, were compared. The primary outcome event was any stroke occurring between randomisation and treatment by CAS or CEA, or within 120 days after randomisation.

Results: A total of 4 754 patients from recent trials and 1 227 from earlier trials were included. In recent trials, patients were randomised a median of 18 (IQR 7, 50) days after the qualifying event (QE). Twenty-three suffered a stroke while waiting for revascularisation (cumulative 120 day risk 1.97%, 95% confidence interval [CI] 0.75 - 3.17). Shorter time from QE until randomisation increased stroke risk after randomisation (χ² = 6.58, p = .011). Sixty-one patients had a stroke within 120 days of randomisation in the medical arms of earlier trials (cumulative risk 5%, 95% CI 3.8 - 6.2). Stroke risk was lower in recent than earlier trials when adjusted for time between QE and randomisation, age, severity of QE, and degree of carotid stenosis (HR 0.47, 95% CI 0.25 - 0.88, p = .019).

Conclusion: Patients with symptomatic carotid stenosis enrolled in recent large RCTs had a lower risk of stroke after randomisation than historical controls. The added benefit of carotid revascularisation to modern medical care needs to be revisited in future studies. Until then, adhering to current recommendations for early revascularisation of patients with symptomatic carotid stenosis considered to require invasive treatment is advisable.

Keywords: Endarterectomy; Ischaemic stroke; Medical treatment; Revascularisation; Stenosis; Stent.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carotid Stenosis* / complications
Carotid Stenosis* / diagnosis
Carotid Stenosis* / physiopathology
Carotid Stenosis* / therapy
Cerebral Revascularization / trends
Endarterectomy, Carotid* / methods
Endarterectomy, Carotid* / statistics & numerical data
Humans
Ischemic Stroke* / diagnosis
Ischemic Stroke* / etiology
Medication Therapy Management / statistics & numerical data*
Percutaneous Coronary Intervention* / instrumentation
Percutaneous Coronary Intervention* / methods
Percutaneous Coronary Intervention* / statistics & numerical data
Risk Assessment
Stents
Waiting Lists