Whether thrombectomy benefits differ according to sex remains debatable. We aimed to investigate whether there was a difference in stroke outcomes between men and women treated with thrombectomy.
We studied 173 patients with anterior circulation strokes. Failed recanalization was defined as thrombolysis in cerebral infarction grade 0-2a. Scores >2 on the modified Rankin Scale at 3 months were regarded as poor outcomes. To prove that failed recanalization mediated the association between sex differences and functional outcome, the four steps of the reasoning process adapted from Baron and Kenny’s causal-steps approach were tested. The adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated.
This study included 76 women and 97 men. Women were older and presented with atrial fibrillation more frequently than men. Female sex was independently associated with failed recanalization (aOR, 2.729; 95% CI, 1.334–5.582), which was an independent predictor of poor outcomes (aOR, 4.630; 95% CI, 1.882–11.389). Women were associated with poor outcomes in the analysis adjusted for confounders, except for failed recanalization (aOR, 2.285; 95% CI, 1.064–4.906). However, the association became insignificant in the additional analysis adjusted for failed recanalization (aOR, 1.670; 95% CI, 0.738–3.784). The indirect effect between female sex and poor outcomes via failed recanalization was statistically significant (aOR, 1.038; 95% CI, 1.010–1.127).
Our study showed that failed recanalization mediated the association between women and poor outcomes after thrombectomy. Nonetheless, this might be explained by chance given our limited study population.
Mechanical thrombectomy has recently been established as an essential treatment modality for emergent large vessel occlusion within 8–24 hours of symptom onset, as multiple randomized clinical trials (RCTs) have demonstrated its dramatic efficacy in the improvement of patient outcomes [
We retrospectively reviewed the medical records of 216 patients who were prospectively enrolled in the patient registry for endovascular thrombectomy at Soonchunhyang University Bucheon Hospital from January 2012 to November 2020. Among them, we excluded 20 patients with posterior circulation stroke, 16 patients without collateral score data (no computed tomography [CT] angiography performed), four patients without outcome data, and three patients who proved to have cancer-related strokes. Finally, 173 patients with anterior circulation stroke were included in this study.
For all the included patients, non-contrast-enhanced CT and CT angiography were performed before treatment. Using a 128-detector high-definition CT scanner (Discovery CT750 HD; GE Healthcare, Milwaukee, WI, USA), CT angiography images were obtained from the aortic arch to the vertex in series (section thickness, 0.625 mm; tube voltage, 100 kV; tube current, 200 mA) after a single bolus injection of 100 mL nonionic contrast agent into the antecubital vein. Candidates for intravenous thrombolysis (IVT) and thrombectomy were selected in accordance with previously published guidelines [
Catheter angiography for thrombectomy was performed via the femoral artery under local anesthesia. If necessary, conscious sedation was used at the discretion of the treating interventionists. An 8-Fr flow-gate balloon guide catheter was placed in the proximal internal carotid artery to approach the target artery. Thrombectomy was performed using a stent retriever (Solitaire, Medtronic, Dublin, Ireland or Trevo, Stryker, Kalamazoo, MI, USA) or an aspiration device (Penumbra system; Penumbra Inc., Alameda, CA, USA). Non-contrast-enhanced CT and magnetic resonance diffusion-weighted imaging (DWI) were performed immediately and 24 hours after the procedure, respectively. Additional CT or DWI was performed on the basis of the decision of the treating physician.
The following clinical information was obtained: age, sex, hypertension, diabetes mellitus, hyperlipidemia, history of prior stroke, ischemic heart disease, atrial fibrillation, current smoking habits, premorbid independence (pre-stroke modified Rankin Scale [mRS] ≤2), history of antithrombotic and statin medication use, initial blood pressure, blood glucose level, National Institutes of Health Stroke Scale (NIHSS) score, time interval from stroke onset to arrival at the emergency department and from arrival to groin puncture, thrombectomy procedure time, location of symptomatic occlusion, clot burden score [
The Alberta Stroke Program Early CT score (ASPECTS) was rated based on pretreatment CT angiography source images (CTA-SI). All images were adjusted to have maximum contrast between the normal and abnormal sides. Diminished contrast enhancement in each region of ASPECTS compared with the healthy hemisphere was considered abnormal [
Statistical analyses were performed using IBM SPSS version 21.0 (IBM Corp., Armonk, NY, USA) and R software, version 4.0.5 (The R Foundation for Statistical Computing, Vienna, Austria). Univariate group comparisons were performed using the independent two-sample
Among 173 patients, 76 were women and 97 were men. Compared to men, women were older and tended to have less premorbid independence and more frequent antiplatelet medication use. Women more frequently presented with atrial fibrillation and were more likely to have a cardioembolic or undetermined stroke than men. Men were more likely to be current smokers and tended to have higher pretreatment CTA-SI ASPECTS scores than women (
Women were associated with poor functional outcomes in the univariate analysis (
Similar to previous studies [
There are many reports in the literature regarding sex differences in thrombectomy outcomes. However, the results of these studies have been conflicting. Several results were obtained from clinical trials that tested thrombectomy. An analysis of 500 patients from an RCT of thrombectomy in the Netherlands (Multicenter Randomized Clinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands) showed a significant interaction between sex and thrombectomy treatment (
Meanwhile, most studies based on nonclinical trial data have suggested worse thrombectomy outcomes in women than in men, which is similar to our study. A study of 2,420 patients with large vessel occlusion from a Japanese multi-center registry showed a tendency for poor outcomes among women in both groups who underwent thrombectomy (aOR, 0.83; 95% CI, 0.63–1.09) and who did not undergo thrombectomy (aOR, 0.73; 95% CI, 0.52–1.04) [
To sum up the aforementioned studies, there appears to be a trend toward poor functional outcomes in women after thrombectomy under certain circumstances. However, most of the studies described no sex difference in recanalization outcome during thrombectomy [
On the other hand, sex-specific differences in intravascular coagulation and fibrinolysis could be responsible for the more frequent failure of recanalization in women. A study of South Asian stroke patients reported higher plasminogen activator inhibitor-I and factor VII levels in women [
Our study had several limitations. Above all, this was a single-center retrospective study with a small sample size, thus potentially producing a selection bias. Therefore, our results might be explained by chance and could not be generalized to other stroke populations. In addition, we could not analyze several factors affecting clinical outcomes, such as psycho-cognitive morbidities and social factors. For example, we had no information about the cohabitation of family members, although less family support may be associated with the time taken to arrive at the hospital and post-stroke functional recovery [
In contrast, our study has strengths in that it adds to real-world data on sex differences in stroke outcomes after thrombectomy. Clinical trial conditions are different from those of real-world clinical practice [
In our stroke patients treated with thrombectomy, female sex was associated with failed recanalization, which mediated the association of female sex with poor functional outcomes. However, this might be explained by chance given our limited study population.
This study was approved with a waiver of informed consent by the Institutional Review Board of Soonchunhyang University Bucheon Hospital (No. SCHBC 2021-04-018).
No potential conflict of interest relevant to this article.
Conceptualization: SJL. Data curation: SJL, TKL. Formal analysis: SJL, JEM. Investigation: SJL, TKL. Supervision: SJL. Visualization: SJL. Writing–original draft: SJL, JEM. Writing–review & editing: all authors.
Supplementary materials can be found via
Comparison of characteristics between patients with failed and successful recanalization
Mediation analysis: failed recanalization as a mediator for the association of women with poor outcomes. mRS, modified Rankin Scale; A, the effect of women on failed recanalization; B, the effect of failed recanalization on poor outcomes additionally adjusted for women; C, total effect of women on poor outcomes; C’, direct effect of women on poor outcomes additionally adjusted for failed recanalization; A×B, indirect effect between women and poor functional outcomes via failed recanalization. All analyses were adjusted for age and variables with
Comparison of basic characteristics between women and men
Variable | Women (n=76) | Men (n=97) | |
---|---|---|---|
Age (yr) | 72.0±13.3 | 65.1±12.3 | 0.001a) |
Hypertension | 50 (65.8) | 64 (66.0) | 0.979b) |
Diabetes | 17 (22.4) | 31 (32.0) | 0.162b) |
Hyperlipidemia | 24 (31.6) | 32 (33.0) | 0.844b) |
Prior stroke | 16 (21.1) | 19 (19.6) | 0.812b) |
Ischemic heart disease | 12 (15.8) | 14 (14.4) | 0.804b) |
Atrial fibrillation | 50 (65.8) | 46 (47.4) | 0.016b) |
Current smoking | 1 (1.3) | 27 (27.8) | <0.001c) |
Premorbid independence (pre-stroke mRS ≤2) | 71 (93.4) | 96 (99.0) | 0.088c) |
Previous medication | |||
Antiplatelet | 25 (32.9) | 20 (20.6) | 0.068b) |
Anticoagulant | 12 (15.8) | 11 (11.3) | 0.392b) |
Statin | 18 (23.7) | 14 (14.4) | 0.120b) |
Initial systolic BP (mmHg) | 145.4±25.1 | 148.4±27.4 | 0.459a) |
Initial diastolic BP (mmHg) | 84.4±15.0 | 87.4±17.1 | 0.239a) |
Initial blood glucose (mg/dL) | 147.3±48.8 | 159.3±66.6 | 0.194a) |
Initial NIHSS | 16 (12–19) | 16 (10–19) | 0.378d) |
Onset to ER time (min) | 84 (37–173) | 71 (36–188) | 0.685d) |
ER to groin time (min) | 146 (120–182) | 144 (117–189) | 0.999d) |
Procedure time (min) | 53.4±33.6 | 60.6±38.9 | 0.208a) |
Left-side infarct | 39 (51.3) | 52 (53.6) | 0.764b) |
Location of symptomatic occlusion | 0.274b) | ||
Internal carotid artery | 25 (32.9) | 43 (44.3) | |
M1 | 39 (51.3) | 39 (40.2) | |
M2 | 12 (15.8) | 15 (15.5) | |
CTA-SI ASPECTS | 5 (3–8) | 7 (3–9) | 0.063d) |
Clot burden score on CTA | 6 (4–7) | 6 (4–8) | 0.963d) |
Use of IVT | 36 (47.4) | 48 (49.5) | 0.782b) |
Stroke classification | 0.005b) | ||
Large artery atherosclerosis | 15 (19.7) | 40 (41.2) | |
Cardioembolism | 46 (60.5) | 48 (49.5) | |
Undetermined | 15 (19.7) | 9 (9.3) | |
Large artery atherosclerosis (vs. others) | 15 (19.7) | 40 (41.2) | 0.003b) |
Poor collaterals | 32 (42.1) | 37 (38.1) | 0.597b) |
Values are presented as mean±standard deviation, number (%), or median (interquartile range).
mRS, modified Rankin Scale; BP, blood pressure; NIHSS, National Institutes of Health Stroke Scale; ER, emergency room; CTA-SI ASPECTS, CT (computed tomography) angiography source image Alberta Stroke Program Early CT Score; IVT, intravenous thrombolysis.
Variables were analyzed using a)Independent
Comparison of outcomes between women and men
Variable | Women (n=76) | Men (n=97) | |
---|---|---|---|
Failed recanalization | 34 (44.7) | 25 (25.8) | 0.009 |
Final infarct size | 0.230 | ||
<1/3 MCA territory | 30 (39.5) | 51 (52.6) | |
1/3–2/3 MCA territory | 22 (28.9) | 22 (22.7) | |
>2/3 MCA territory | 24 (31.6) | 24 (24.7) | |
<1/3 MCA territory (vs. others) | 30 (39.5) | 51 (52.6) | 0.086 |
Any intracranial hemorrhage | 44 (57.9) | 63 (64.9) | 0.343 |
HT1 | 12 (16.0) | 16 (16.5) | |
HT2 | 6 (8.0) | 12 (12.4) | |
PH1 | 3 (4.0) | 12 (12.4) | |
PH2 | 23 (30.7) | 23 (23.7) | |
sICH | 13 (17.1) | 13 (13.4) | 0.499 |
Poor outcome (mRS ≥3) | 54 (71.1) | 50 (51.5) | 0.009 |
mRS 0 | 7 (9.2) | 13 (13.4) | |
mRS 1 | 9 (11.8) | 13 (13.4) | |
mRS 2 | 6 (7.9) | 21 (21.6) | |
mRS 3 | 11 (14.5) | 14 (14.4) | |
mRS 4 | 11 (14.5) | 11 (11.3) | |
mRS 5 | 16 (21.1) | 9 (9.3) | |
mRS 6 | 16 (21.1) | 16 (16.5) |
Values are presented as number (%).
MCA, middle cerebral artery; HT, hemorrhagic transformation; PH, parenchymal hemorrhage; sICH, symptomatic intracranial hemorrhage; mRS, modified Rankin Scale.
a)Variables were analyzed using chi-square test.
Comparison between patients with good and poor outcomes
Variable | Good outcome (n=69) | Poor outcome (n=104) | |
---|---|---|---|
Age (yr) | 67.3±13.0 | 68.7±13.3 | 0.488a) |
Women | 22 (31.9) | 54 (51.9) | 0.009b) |
Hypertension | 44 (63.8) | 70 (67.3) | 0.631b) |
Diabetes | 15 (21.7) | 33 (31.7) | 0.151b) |
Hyperlipidemia | 22 (31.9) | 34 (32.7) | 0.911b) |
Prior stroke | 11 (15.9) | 24 (23.1) | 0.253b) |
Ischemic heart disease | 9 (13.0) | 17 (16.3) | 0.552b) |
Atrial fibrillation | 36 (52.2) | 60 (57.7) | 0.475b) |
Current smoking | 8 (11.6) | 20 (19.2) | 0.182b) |
Premorbid independence (pre-stroke mRS ≤2) | 69 (100.0) | 98 (94.2) | 0.082c) |
Previous medication | |||
Antiplatelet | 16 (23.2) | 29 (27.9) | 0.491b) |
Anticoagulant | 5 (7.2) | 18 (17.3) | 0.068b) |
Statin | 13 (18.8) | 19 (18.3) | 0.924b) |
Initial systolic BP (mmHg) | 145.7±28.7 | 147.9±24.9 | 0.588a) |
Initial diastolic BP (mmHg) | 84.2±15.9 | 87.4±16.4 | 0.209a) |
Initial blood glucose (mg/dL) | 148.6±61.6 | 157.5±57.9 | 0.337a) |
Initial NIHSS | 13 (8–17) | 17 (13–21) | <0.001d) |
Onset to ER time (min) | 69 (31–150) | 84 (39–200) | 0.603d) |
ER to groin time (min) | 131 (108–178) | 142 (123–191) | 0.144d) |
Onset to groin time (min) | 212 (172–317) | 260 (185–380) | 0.115d) |
Procedure time (min) | 47.6±33.8 | 64.1±37.3 | 0.004a) |
Location of symptomatic occlusion | 0.043b) | ||
Internal carotid artery | 28 (40.6) | 40 (38.5) | |
M1 | 25 (36.2) | 53 (51.0) | |
M2 | 16 (23.2) | 11 (10.6) | |
M2 vs. others | 16 (23.2) | 11 (10.6) | 0.025b) |
CTA-SI ASPECTS | 8 (6–9) | 4.5 (2–7) | <0.001d) |
Clot burden score on CTA | 6 (4–8) | 6 (4–7) | 0.103d) |
Poor collaterals | 13 (18.8) | 56 (53.8) | <0.001b) |
Use of IVT | 38 (55.1) | 46 (44.2) | 0.162b) |
Stroke classification | 0.679b) | ||
Large artery atherosclerosis | 21 (30.4) | 34 (32.7) | |
Cardioembolism | 40 (58.0) | 54 (51.9) | |
Undetermined | 8 (11.6) | 16 (15.4) | |
Failed recanalization | 9 (13.0) | 50 (48.1) | <0.001b) |
Values are presented as mean±standard deviation, number (%), or median (interquartile range).
mRS, modified Rankin Scale; BP, blood pressure; NIHSS, National Institutes of Health Stroke Scale; ER, emergency room; CTA-SI ASPECTS, CT (computed tomography) angiography source image Alberta Stroke Program Early CT Score; IVT, intravenous thrombolysis.
Variables were analyzed using a)Independent