Jennifer Harris, MD

Uchida K, Yoshimura S, Sakai N, Yamagami H, Morimoto T, and RESCUE-Japan Registry 2 Investigators. Sex Differences in Management and Outcomes of Acute Ischemic Stroke With Large Vessel Occlusion. Stroke. 2019;50:1915–1918.

Stroke affects men and women. We know that sex differences affect many aspects of stroke and have profound implications for effective prevention and treatment. However, how sex differences are affected in the management and outcomes of acute ischemic stroke with large vessel occlusion in the era of endovascular therapy (EVT) has been largely unknown.

This is the aim of the study by Uchida et al. In this study, data was analyzed from the RESCUE (Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism)-Japan Registry 2 database. The RESCUE trial was a prospective, multicenter registry that enrolled 2420 consecutive patients with acute ischemic stroke with LVO from 46 centers across Japan. Among 2399 patients enrolled in the registry, females accounted for 1087 (45.3%) patients.

The primary outcome was defined as modified Rankin Scale (mRS) score of 0 to 2 at 90 days, and the secondary outcomes were mortality at 90 days, any intracranial hemorrhage, symptomatic intracranial hemorrhage within 72 hours after onset, defined as neurological worsening of >4 points on the National Institutes of Health Stroke Scale (NIHSS), and the recurrence of stroke or transient ischemic attack within 90 days. Variables collected included patient characteristics, mRS before the onset of stroke, NIHSS, the time from onset to arrival at the hospital, the use of EVT and intravenous r-tPA (recombinant tissue-type plasminogen activator), stroke classification, and the spread of stroke using the Alberta Stroke Program Early CT Score (ASPECT) as assessed by diffusion-weighted image in magnetic resonance imaging or noncontrast computed tomography. The degree of reperfusion of the EVT was classified by the Thrombolysis in Cerebral Infarction grading system (TICI).

The study found that female patients were significantly less likely to receive EVT (47.9% versus 57.7%; P<0.0001); the adjusted OR was 0.71 (95% CI, 0.59-0.86; P=0.0005). In regards to outcomes, they found mRS was worse in female patients than male patients at 90 days. Good outcome was observed in 27.3% and 44.2% of female and male patients, respectively (P<0.0001). The adjusted OR for good outcome among females was 0.80 (95% CI, 0.65-0.99; P=0.04). Females had a lower incident of Intracranial hemorrhage within 72 hours than males (21.5% versus 23.6%; P=0.24); the adjusted OR for females was 0.79 (95% CI, 0.58-0.99; P=0.04). Interestingly, the tendency for a poor outcome among female patients was observed in both patients who received EVT (adjusted OR, 0.83; 95% CI, 0.63-1.09) and those who did not receive EVT (adjusted OR, 0.73; 95% CI, 0.52-1.04).

Several differences in baseline characteristics were notable, though, such as that females were older, had higher NIHSS on presentation, were less likely to have mRS <2 at baseline, and were less likely to have an aspect >6 on presentation. In addition, the time from onset of stroke to the hospital door was also longer in female patients. All these factors need to be considered since they could be associated with the lower utilization of EVT and poorer prognosis.

Interestingly, even after adjustment for these factors, female patients were still less likely to receive EVT and more likely to show poor functional prognosis at 90 days, raising the possibility of other factors contributing to the differences observed.

This study clearly highlights the sex differences in the management and subsequent clinical outcomes of patients with acute stroke with LVO. Limitations of this study include inherent limitations of registry studies, as well as lack of generalizability.