Does Sex Modify the Effect of Endovascular Treatment for Ischemic Stroke?

A Subgroup Analysis of 7 Randomized Trials

Vicky Chalos, MD; Inger R. de Ridder, MD, PhD; Hester F. Lingsma, PhD; Scott Brown, PhD; Robert J. van Oostenbrugge, MD, PhD; Mayank Goyal, MD, PhD; Bruce C.V. Campbell, PhD; Keith W. Muir, MD; Francis Guillemin, MD, PhD; Serge Bracard, MD; Philip White, MD; Antoni Davalos, MD; Tudor G. Jovin, MD; Michael D. Hill, MD; Peter J. Mitchell, MD; Andrew M. Demchuk, MD; Jeffrey L. Saver, MD; Wim H. van Zwam, MD, PhD; Diederik W.J. Dippel, MD, PhD; on behalf of the HERMES Collaborators


Stroke. 2019;50(9):2413-2419. 

In This Article


Study Population and Design

We pooled the data from 1764 participants in the 7 RCTs on EVT within the HERMES collaboration (MR CLEAN,[12] ESCAPE [Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times],[5] EXTEND-IA [Extending the Time for Thrombolysis in Emergency Neurological Deficits - Intra-Arterial],[13] SWIFT PRIME [Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment],[6] REVASCAT [Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke due to Anterior Circulation Large Vessel Occlusion Presenting Within 8 Hours of Symptom Onset],[14] THRACE [Mechanical Thrombectomy After Intravenous Alteplase Versus Alteplase Alone After Stroke],[10] and PISTE [Pragmatic Ischaemic Stroke Thrombectomy Evaluation][11]). These RCTs compared EVT (intervention), primarily performed with stent retrievers, with standard care (control) in patients with an ischemic stroke caused by a large vessel occlusion in the anterior circulation. All participants provided informed consent according to each trial protocol, and each RCT was approved by the local ethics committee. The HERMES protocol and main outcomes have been reported previously.[7,15] HERMES data are available via the VISTA-Endovascular repository.

Outcome Measures

The primary outcome was functional outcome, measured with the modified Rankin Scale (mRS) score, at 90 days. Secondary outcomes were excellent 90-day functional outcome (mRS, 0–1), 90-day functional independence (mRS, 0–2), extent of neurological deficits measured with the National Institutes of Health Stroke Scale (NIHSS) at 24 hours after randomization, successful reperfusion after EVT (modified Thrombolysis in Cerebral Infarction score ≥2B), and follow-up infarct volume (FIV) on noncontrast CT or magnetic resonance imaging at 12 hours to 2 weeks. Safety outcomes were 90-day mortality and symptomatic intracranial hemorrhage, defined according to each trial protocol.[15]

Statistical Analyses

Patients with missing data on sex were excluded from the analyses. We compared baseline characteristics and outcomes between men and women using descriptive statistics. With generalized linear mixed models, with trial as a random effect, we evaluated the association between EVT and primary and secondary outcomes. FIV was log transformed (log+1) because of its skewed distribution, to best satisfy the linear model. We tested for interaction between sex and treatment allocation using multiplicative interaction terms in the regression model. Regression analyses were adjusted for age, baseline NIHSS, time from onset to randomization, diabetes mellitus, prior stroke, occlusion location, intravenous tPA (tissue-type plasminogen activator) administration, and collateral grade. Missing data in these covariates were imputed with simple imputation, with the exception of collateral grade (≥10% missing data), which was imputed with single imputation with regression based on relevant covariates, trial, and mRS. Unadjusted and adjusted common odds ratios and adjusted betas are reported with 95% CIs, and all P are 2-sided. Statistical analyses were performed with SAS software, version 9.4, and R, version 3.3.