Thrombolysis in stroke despite contraindications or warnings?

BACKGROUND AND PURPOSE: Intravenous thrombolysis with alteplase is approved for acute ischemic stroke, but its use is limited by numerous contraindications and warnings arising from trial selection criteria or expert opinions. We examined outcomes from alteplase-treated versus untreated patients, registered in a trials archive, according to presence or absence of specified contraindications and warnings. METHODS: We analyzed 90-day modified Rankin Scale across the whole distribution of scores using the Cochran-Mantel-Haenszel test, with adjustment for age and baseline National Institutes of Health Stroke Score, followed by proportional odds logistic regression analysis to estimate the odds ratios for preferred outcome. RESULTS: We used data from 9613 ischemic stroke patients of whom 2755 were treated with thrombolysis. Adjusted odds ratios showed a broad trend of more favorable 3-month outcome associated with alteplase treatment versus no treatment in various subgroups of patients with contraindications and warnings; for example, 1.40 (95% confidence interval [CI], 1.14-1.70) in patients aged >80 (n=1805), 1.50 (95% CI, 1.03-2.18) in patients with combined history of prior stroke and diabetes mellitus (n=672), 1.42 (95% CI, 1.19-1.70) in patients on prior single antiplatelet agent (n=1626), 2.20 (95% CI, 1.12-4.32) in patients on oral anticoagulation, and International Normalized Ratio≤1.7 (n=157), 1.50 (95% CI, 1.15-1.97) in patients with baseline glucose >180 (n=879), and 1.57 (95% CI, 1.12-2.18) in patients with pretreatment National Institutes of Health Stroke Score >22 (n=620). CONCLUSIONS: This comprehensive retrospective analysis of various contraindications and warnings provides reassurance about benefits and risks of intravenous alteplase treatment in common clinical situations.

Thrombolysis in very elderly people: controlled comparison of SITS International Stroke Thrombolysis Registry and Virtual International Stroke Trials Archive.

OBJECTIVE: To assess effect of age on response to alteplase in acute ischaemic stroke. DESIGN: Adjusted controlled comparison of outcomes between non-randomised patients who did or did not undergo thrombolysis. Analysis used Cochran-Mantel-Haenszel test and proportional odds logistic regression analysis. SETTING: Collaboration between International Stroke Thrombolysis Registry (SITS-ISTR) and Virtual International Stroke Trials Archive (VISTA). PARTICIPANTS: 23 334 patients from SITS-ISTR (December 2002 to November 2009) who underwent thrombolysis and 6166 from VISTA neuroprotection trials (1998-2007) who did not undergo thrombolysis (as controls). Of the 29 500 patients (3472 aged >80 ("elderly," mean 84.6), data on 272 patients were missing for baseline National Institutes of Health stroke severity score, leaving 29 228 patients for analysis adjusted for age and baseline severity. MAIN OUTCOME MEASURES: Functional outcomes at 90 days measured by score on modified Rankin scale. RESULTS: Median severity at baseline was the same for patients who underwent thrombolysis and controls (median baseline stroke scale score: 12 for each group, P=0.14; n=29 228). The distribution of scores on the modified Rankin scale was better among all thrombolysis patients than controls (odds ratio 1.6, 95% confidence interval 1.5 to 1.7; Cochran-Mantel-Haenszel P<0.001). The association occurred independently among patients aged ≤80 (1.6, 1.5 to 1.7; P<0.001; n=25 789) and in those aged >80 (1.4, 1.3 to 1.6; P<0.001; n=3439). Odds ratios were consistent across all 10 year age ranges above 30, and benefit was significant from age 41 to 90; dichotomised outcomes (score on modified Rankin scale 0-1 v 2-6; 0-2 v 3-6; and 6 (death) v rest) were consistent with the results of the ordinal analysis. CONCLUSIONS: Outcome in patients with acute ischaemic stroke is significantly better in those who undergo thrombolysis compared with those who do not. Increasing age is associated with poorer outcome but the association between thrombolysis treatment and improved outcome is maintained in very elderly people. Age alone should not be a barrier to treatment.