Hyperglycemia worsens outcome after rt-PA primarily in the large-vessel occlusive stroke subtype.

Hyperglycemia at the time of ischemic stroke has been associated with poorer outcomes. Preclinical literature suggests that hyperglycemia is an independent prognostic factor and the vasculature is more vulnerable to reperfusion injury. We applied a method to match subjects on important baseline factors to test whether, independent of stroke severity, stroke subtype influences the effect of hyperglycemia on outcome after recombinant tissue plasminogen activator (rt-PA). We reanalyzed the NINDS rt-PA dataset with respect to matching variables baseline NIHSS, age, and investigator-determined stroke subtypes small-vessel occlusive stroke (SVS), large-vessel occlusive stroke (LVS), and cardioembolic stroke (CES), above and below a glucose threshold of 150 mg/dl. Ninety-day outcomes were compared. Post hoc baseline matching was excellent in most cases. Hyperglycemia was associated with worsened functional outcome mostly in the LVS subtype with increased mortality in the placebo arm (15.3% mortality normoglycemia vs. 30.6% hyperglycemia; p = .046), worse functional outcome in the rt-PA arm (modified Rankin Score (mRS) 0-1; 46.3 vs. 22.0%; p = .034), and no improvement in functional outcome with rt-PA compared to placebo (mRS 0-1; 25% in both groups). Among hyperglycemic subjects, CES subjects showed significant improvement following rt-PA (p = .027). After matching for baseline severity, the influence of hyperglycemia on outcome was primarily in the LVS subtype, especially after rt-PA. This finding is consistent with a deleterious effect of hyperglycemia on ischemia/reperfusion of symptomatic large arteries. If confirmed, the particular vulnerability of the LVS subtype is important in understanding the role of stroke subtype in the mechanism of worsening and potential treatment of hyperglycemic stroke patients.

Explicit consideration of baseline factors to assess recombinant tissue-type plasminogen activator response with respect to race and sex.

BACKGROUND AND PURPOSE: Sex and race reportedly influence outcome after recombinant tissue-type plasminogen activator (rtPA). It is, however, unclear whether baseline imbalances (eg, stroke severity) or lack of response to thrombolysis is responsible. We applied balancing methods to test the hypothesis that race and sex influence outcome after rtPA independent of baseline conditions. METHODS: We mapped group outcomes from the National Institute of Neurological Disorders and Stroke (NINDS) dataset based on race and sex onto a surrogate-control function to assess differences from expected outcomes at their respective National Institutes of Health Stroke Scale and age. Outcomes were also compared for subjects matched individually on key baseline factors using NINDS and 2 recent datasets from southeastern United States. RESULTS: At similar National Institutes of Health Stroke Scale and age, 90-day good outcomes (modified Rankin Score, 0-2) in NINDS were similarly improved after rtPA for white men and women. There was a strong trend for improvement in black men. Conversely, black women treated with rtPA showed response rates no different from the controls. After baseline matching, there were nonsignificant trends in outcomes except for significantly fewer good outcomes in black versus matched white women (37% versus 63%; P=0.027). Pooling the 3 datasets showed a similar trend for poorer short-term outcome for black women (P=0.054; modified Rankin Score, 0-1). CONCLUSIONS: Matching for key baseline factors indicated that race and sex influence outcome most strikingly in black women who demonstrated poorest outcomes after rtPA. This finding supports the hypothesis that poor response to rtPA, rather than differences in baseline conditions, contributes to the worse outcome. This finding requires prospective confirmation.