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Published on: May 9, 2013
Mediation Analysis of Acute Carotid Stenting in Tandem Lesions: Effect on Functional Outcome in a Multicenter
Aaron Rodriguez Calienes1, Milagros Galecio-Castillo1, Nils H Petersen1
1From the Departments of Neurology (A.R.C., M.G.-C., M.F., D.Q.-O., Y.L., J.V.-S., M.D., S.O.-G.), Neurosurgery (S.O.-G.), and Radiology (S.O.-G.), University of Iowa Hospitals and Clinics, Iowa City; Neuroscience, Clinical Effectiveness, and Public Health Research Group (A.R.C.), Universidad Cientifica del Sur, Lima, Peru; Department of Neurology (N.H.P.), Yale University School of Medicine, New Haven, CT; Department of Neurology (M.R.), Hospital Vall d'Hebron, Barcelona, Spain; Department of Neurology (A.E.H.), Valley Baptist Medical Center/University of Texas Rio Grande Valley, Harlingen, TX; Department of Neurology (M.A.J.), ProMedica Toledo Hospital, OH; Department of Neurology (A.A.D.), University of New Mexico Health Science Center, Albuquerque; Department of Neurology (M.G.A.), University of Kansas Medical Center, Kansas City; Department of Neurosurgery (J.T.F.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology and Brain Repair (W.R.G., M.M.), University of South Florida, Tampa; Department of Neurology (A.M.M., D.R.Y.), University of Miami Miller School of Medicine, FL; Cooper Neurological Institute (J.E.S., T.G.J.), Cooper University Hospital, Camden, NJ; Department of Neurology (T.N.N.), Boston Medical Center, MA; Department of Neurology (S.S.), UT Health McGovern Medical School, Houston; Texas Stroke Institute (A.J.Y.), Dallas-Fort Worth, TX; Department of Neurology (G.L.), Saint Louis University, MO; Asia Pacific Comprehensive Stroke Institute (N.J.), Pomona Valley Hospital Medical Center, CA.
Insights
Acute carotid artery stenting (CAS) improves stroke outcomes in tandem lesions (TLs) by enhancing reperfusion. Successful reperfusion partially mediates this effect, explaining 25% of the benefit in patients undergoing endovascular therapy.
Area of Science:
- Neuroendovascular therapy
- Cerebrovascular disease
- Stroke treatment outcomes
Background:
- Acute carotid artery stenting (CAS) shows promise for improving functional outcomes in acute stroke patients with tandem lesions (TLs) treated with endovascular therapy (EVT).
- The precise pathophysiologic mechanism linking CAS to better outcomes, specifically the role of reperfusion, remains unclear compared to non-CAS strategies.
Purpose of the Study:
- To investigate whether successful reperfusion mediates the relationship between acute CAS and functional outcomes in patients with TLs undergoing EVT.
- To quantify the degree to which reperfusion explains the benefit of CAS on functional outcomes in this patient population.
Main Methods:
- Retrospective cohort study involving 570 patients with anterior circulation TLs who underwent EVT across 16 stroke centers.
- Mediation analysis was performed to assess the causal pathway where successful reperfusion (modified Thrombolysis in Cerebral Infarction scale ≥2B) links acute CAS to 90-day modified Rankin Scale scores.
Main Results:
- The CAS group (n=354) demonstrated significantly higher rates of successful reperfusion (91.2% vs 85.1%) and favorable functional outcomes (52% vs 29%) compared to the non-CAS group (n=216).
- Successful reperfusion was a strong predictor of favorable functional outcomes (adjusted common odds ratio [acOR] 4.88).
- Successful reperfusion partially mediated the CAS-outcome relationship, explaining 25% of the treatment effect, with CAS remaining independently associated with better outcomes (acOR 1.89).
Conclusions:
- In patients with TLs undergoing EVT, acute CAS is associated with improved functional outcomes, partly mediated by enhanced rates of successful reperfusion.
- The findings highlight successful reperfusion as a key mechanism contributing to the benefits of CAS in treating acute stroke with TLs.
Background And Objectives:
Current evidence suggests that acute carotid artery stenting (CAS) for cervical lesions is associated with better functional outcomes in patients with acute stroke with tandem lesions (TLs) treated with endovascular therapy (EVT). However, the underlying causal pathophysiologic mechanism of this relationship compared with a non-CAS strategy remains unclear. We aimed to determine whether, and to what degree, reperfusion mediates the relationship between acute CAS and functional outcome in patients with TLs.
Methods:
This subanalysis stems from a multicenter retrospective cohort study across 16 stroke centers from January 2015 to December 2020. Patients with anterior circulation TLs who underwent EVT were included. Successful reperfusion was defined as a modified Thrombolysis in Cerebral Infarction scale ≥2B by the local team at each participating center. Mediation analysis was conducted to examine the potential causal pathway in which the relationship between acute CAS and functional outcome (90-day modified Rankin Scale) is mediated by successful reperfusion.
Results:
A total of 570 patients were included, with a median age (interquartile range) of 68 (59-76), among whom 180 (31.6%) were female. Among these patients, 354 (62.1%) underwent acute CAS and 244 (47.4%) had a favorable functional outcome. The remaining 216 (37.9%) patients were in the non-CAS group. The CAS group had significantly higher rates of successful reperfusion (91.2% vs 85.1%; p = 0.025) and favorable functional outcomes (52% vs 29%; p = 0.003) compared with the non-CAS group. Successful reperfusion was a strong predictor of functional outcome (adjusted common odds ratio [acOR] 4.88; 95% CI 2.91-8.17; p < 0.001). Successful reperfusion partially mediated the relationship between acute CAS and functional outcome, as acute CAS remained significantly associated with functional outcome after adjustment for successful reperfusion (acOR 1.89; 95% CI 1.27-2.83; p = 0.002). Successful reperfusion explained 25% (95% CI 3%-67%) of the relationship between acute CAS and functional outcome.
Discussion:
In patients with TL undergoing EVT, successful reperfusion predicted favorable functional outcomes when CAS was performed compared with non-CAS. A considerable proportion (25%) of the treatment effect of acute CAS on functional outcome was found to be mediated by improvement of successful reperfusion rates.
