To examine thrombolysis outcomes for acute ischemic stroke in patients with pre-stroke disability compared to those without.

Randomized-controlled trials of intravenous thrombolysis with alteplase in acute ischemic stroke had little representation of patients who had pre-morbid disability. The role of thrombolysis in this population remains uncertain and they are often excluded from treatment in practice. Observational studies may help inform discussions about thrombolysis in these patients.

In this meta-analysis (PROSPERO CRD42021240499, MOOSE-compliant), we searched Medline and Ovid-Embase for studies reporting thrombolysis in patients with acute ischemic stroke with and without pre-morbid disability (modified Rankin Scale [mRS] ≥2). The primary outcome was the return to pre-morbid mRS at 90-days in each group. Secondary outcomes included achievement of favorable functional outcome at 90-days, defined as mRS 0-2 or return to pre-morbid mRS, symptomatic intracerebral hemorrhage (sICH), and 90-day mortality. 

Six observational studies were included, representing 103,988 patients, of whom 5,403 (5.2%) had pre-morbid disability. 35.9% of patients with pre-morbid disability returned to pre-morbid level of function compared to 26.3% of patients without pre-morbid disability (OR:1.57, 95%CI:0.93-2.66). 39.1% of patients with pre-morbid disability achieved favorable outcome vs 57.2% without disability (OR:0.47, 95%CI:0.34-0.65). The rates of sICH were 6.4% versus 4.2% in patients with and without pre-morbid disability (OR:1.63, 95%CI:1.20-2.21). Mortality was three times higher in patients with pre-morbid disability than in those without pre-morbid disability; 37.6% versus 12.6%, respectively (OR:3.96, 95%CI:3.18-4.93).

The use of alteplase in patients with pre-existing disability was associated with comparable odds for return to baseline level of function compared to those without disability. However, discussions regarding thrombolysis in this group should acknowledge their much higher mortality and potentially higher sICH risk, although it is unknown if this can be attributed to treatment. High-quality data comparing treated versus untreated patients with pre-morbid disability are needed to clarify this issue.