Does sex modify the effect of endovascular treatment for ischemic stroke? A subgroup analysis of seven randomized trials

Background and Purpose: Previous studies have reported less favorable outcome and less effect of endovascular treatment (EVT) after ischemic stroke in women than in men. Our aim was to study the influence of sex on outcome and on the effect of EVT for ischemic stroke in recent randomized trials on EVT. Methods: We used data from 7 randomized controlled trials on EVT within the HERMES collaboration. The primary outcome was 90-day functional outcome (modified Rankin Scale). We compared baseline characteristics and outcomes between men and women. With ordinal logistic regression, we evaluated the association between EVT and 90-day functional outcome for men and women separately, adjusted for potential confounders. We tested for interaction between sex and EVT. Results: We included 1762 patients in the analyses, of whom 833 (47%) were women. Women were older (median, 70 versus 66 years; P<0.001), were smoking less often (30% versus 44%; P<0.001), and had higher collateral grades (grade 3: 46% versus 35%; P<0.001) than men. Functional independence (modified Rankin Scale score, 0–2) at 90 days was reached by 318 women (39%) and 364 men (39%). The effect of EVT on the ordinal modified Rankin Scale was similar in women (adjusted common odds ratio [acOR], 2.13; 95% CI, 1.47–3.07) and men (acOR, 2.16; 95% CI, 1.59–2.96), with a P for interaction of 0.926. Conclusions: Sex does not influence clinical outcome after EVT and does not modify treatment effect of EVT. Therefore, sex should not be a consideration in the selection of patients for EVT

Glucose modifies the effect of endovascular thrombectomy in patients with acute stroke: a pooled-data meta-analysis

Background and Purpose: Hyperglycemia is a negative prognostic factor following acute ischemic stroke but is not known whether glucose is associated with the effects of endovascular thrombectomy in patients with large vessel stroke. In a pooled-data meta-analysis, we analyzed whether serum glucose is a treatment modifier of the efficacy of endovascular thrombectomy in acute stroke. Methods: Seven randomized trials compared endovascular thrombectomy with standard care between 2010 and 2017 (HERMES Collaboration). 1764 patients with large vessel stroke were allocated to endovascular thrombectomy (n=871) or standard care (n=893). Measurements included blood glucose on admission and functional outcome [modified Rankin Scale (mRS) range: 0-6; lower scores indicating less disability] at 3 months. The primary analysis evaluated whether glucose modified the effect of EVT over standard care on functional outcome, using ordinal logistic regression to test the interaction between treatment and glucose level. Results: Median (IQR) serum glucose on admission was 120 (104-140) mg/dl [6.6mmol/l (5.7-7.7) mmol/l]. Endovascular thrombectomy (EVT) was better than standard care in the overall pooled-data analysis [common odds ratio (acOR), 2.00 (95% CI 1.69–2.38); however, lower glucose levels were associated with greater effects of EVT over standard care. The interaction was nonlinear such that significant interactions were found in subgroups of patients split at glucose < or > 90mg/dl (5.0mmol/l) [(p=0.019 for interaction, acOR 3.81 (95% CI 1.73–8.41) for patients < 90 mg/dl vs 1.83 (95% CI 1.53–2.19) for patients > 90 mg/dl], and glucose < or > 100mg/dl (5.5mmol/l) [(p=0.004 for interaction, acOR 3.17 (95% CI 2.04–4.93) vs acOR 1.72 (95% CI 1.42–2.08)], but not between subgroups above these levels of glucose. Conclusions: Endovascular thrombectomy improved stroke outcomes compared to standard treatment regardless of glucose levels but the treatment effects were larger at lower glucose levels, with significant interaction effects persisting up to 90 to 100mg/dl (5.0-5.5mmol/l). Whether tight control of glucose improves the efficacy of endovascular thrombectomy following large vessel stroke warrants appropriate testing

Value of infarct location in the prediction of functional outcome in patients with an anterior large vessel occlusion: results from the HERMES study

Purpose: Follow-up infarct volume (FIV) is moderately associated with functional outcome. We hypothesized that accounting for infarct location would strengthen the association of FIV with functional outcome. Methods: We included 252 patients from the HERMES collaboration with follow-up diffusion weighted imaging. Patients received endovascular treatment combined with best medical management (n = 52%) versus best medical management alone (n = 48%). FIV was quantified in low, moderate and high modified Rankin Scale (mRS)-relevant regions. We used binary logistic regression to study the relation between the total, high, moderate or low mRS-relevant FIVs and favorable outcome (mRS < 2) after 90 days. The strength of association was evaluated using the c-statistic. Results: Small lesions only occupied high mRS-relevant brain regions. Lesions additionally occupied lower mRS-relevant brain regions if FIV expanded. Higher FIV was associated with a higher risk of unfavorable outcome, as were volumes of tissue with low, moderate and high mRS relevance. In multivariable modeling, only the volume of high mRS-relevant infarct was significantly associated with favorable outcome. The c-statistic was highest (0.76) for the models that included high mRS-relevant FIV or the combination of high, moderate and low mRS-relevant FIV but was not significantly different from the model that included only total FIV (0.75). Conclusion: This study confirms the association of FIV and unfavorable functional outcome but showed no strengthened association if lesion location was taken into account

Stroke laterality did not modify outcomes in the HERMES meta-analysis of individual patient data of seven trials

Background and Purpose: There is contradictory evidence on the impact of the stroke side (hemisphere) on outcomes. We investigated any effect modification by laterality on stroke patients’ outcomes in recent endovascular trials. Methods: Individual patient-level data were combined in this meta-analysis of all patients included in randomized trials comparing endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischemic patients with stroke (HERMES [Highly Effective Reperfusion Using Multiple Endovascular Devices] Collaboration). We stratified the 90-day functional outcome assessed by ordinal analysis of the modified Rankin Scale according to the stroke side of patients treated with endovascular therapy versus standard care, adjusted for important prognostic variables. Results: The meta-analysis included 1737 patients (871 right hemispheric strokes and 866 left hemispheric) from 7 trials. Baseline median National Institutes of Health Stroke Scale scores were significantly higher in left (20) versus right (16) hemispheric strokes (P<0.001). Other clinical and radiological baseline characteristics were similar. The beneficial response to endovascular therapy assessed by 90-day modified Rankin Scale shift was not modified by the side of the stroke. There were no significant differences between right and left hemispheric stroke in the 90-day functional outcome (modified Rankin Scale score ≤2; 40.7% [95% CI, 37.4%–44.1%] versus 37.6% [95% CI, 37.4%–44.1%]; P=0.19), median final infarct volumes (45 versus 39.5 mL, P=0.51), nor 90-day mortality (15.1% vs 16.8%, P=0.31). Conclusions: Stroke side was not a prognostic factor and did not modify the treatment effect among patients treated in the endovascular or control groups in recent endovascular thrombectomy trials

Value of infarct location in the prediction of functional outcome in patients with an anterior large vessel occlusion: results from the HERMES study

Purpose: Follow-up infarct volume (FIV) is moderately associated with functional outcome. We hypothesized that accounting for infarct location would strengthen the association of FIV with functional outcome. Methods: We included 252 patients from the HERMES collaboration with follow-up diffusion weighted imaging. Patients received endovascular treatment combined with best medical management (n = 52%) versus best medical management alone (n = 48%). FIV was quantified in low, moderate and high modified Rankin Scale (mRS)-relevant regions. We used binary logistic regression to study the relation between the total, high, moderate or low mRS-relevant FIVs and favorable outcome (mRS < 2) after 90 days. The strength of association was evaluated using the c-statistic. Results: Small lesions only occupied high mRS-relevant brain regions. Lesions additionally occupied lower mRS-relevant brain regions if FIV expanded. Higher FIV was associated with a higher risk of unfavorable outcome, as were volumes of tissue with low, moderate and high mRS relevance. In multivariable modeling, only the volume of high mRS-relevant infarct was significantly associated with favorable outcome. The c-statistic was highest (0.76) for the models that included high mRS-relevant FIV or the combination of high, moderate and low mRS-relevant FIV but was not significantly different from the model that included only total FIV (0.75). Conclusion: This study confirms the association of FIV and unfavorable functional outcome but showed no strengthened association if lesion location was taken into account