CardioExchange Archive

Although thrombolysis for ischemic stroke has been widely recognized as beneficial, its use has been limited because of concerns about its effects in patients treated after 3 hours, in older patients, and in patients with mild and with severe strokes. Now a meta-analysis published in the Lancet offers evidence that the use of thrombolysis should be more aggressively pursued.

Researchers from the Stroke Thrombolysis Trialists’ Collaborative Group combined patient data from nine randomized trials testing alteplase against placebo or open control in 6756 patients. Thrombolysis was more likely to lead to a good stroke outcome, defined as no significant disability at 3 to 6 months, in patients treated within 4.5 hours:

• Treatment within 3 hours: 32.9% for alteplase versus 23.1% for control (OR 1.75, CI 1.35–2.27)
• Treatment between 3 and 4.5 hours: 35.3% versus 30.1% (OR 1.26, CI 1.05–1.51)
• Treatment after 4.5 hours: 32.6% versus 30.6% (OR 1.15, CI 0.95–1.40)

The chief disadvantage to thrombolysis was an early and significant increase in intracranial hemorrhage (fatal ICH at 1 week: 2.7% vs 0.4%). This resulted in a significant increase in early mortality, but this difference was no longer significant at 90 days, although a trend remained (17.9% versus 16.5%, HR 1.11, CI 0.99–1.25, p=0·07).

There were no significant variations in benefit and risk based on age or stroke severity. Despite the early increase in mortality, the authors concluded that thrombolysis was associated with an average absolute increase in disability-free survival of approximately 10% and 5% for patients treated within 3 hours and between 3 and 4.5 hours, respectively.

In an accompanying editorial, Michael Hill and Shelagh Coutts write that the finding of the meta-analysis is “definitive.” “The question now,” they write, “is not whether we can extend the window for treatment. Rather, how do we get everyone treated faster and how do we dispel preconceived notions about not treating older patients or those with milder strokes? We must move from the proven science to policy and systems of care.”