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Alteplase within 5 hours of stroke onset linked to improved outcomes
When administered within 4 to 5 hours of stroke onset, the thrombolytic drug alteplase significantly increased the likelihood of a positive outcome, researchers reported in The Lancet.
Although treatment with alteplase was associated with increased risk for fatal intracranial hemorrhage within the first days after stroke, the risk was attenuated within a few months, according to the study findings.
“Our results show that alteplase treatment is a very effective means of limiting the degree of disability in stroke patients,” Jonathan Emberson, PhD, of the clinical Trial Service Unit at the University of Oxford, said in a press release.
Jonathan Emberson
In a meta-analysis of individual patient data, researchers collected data on 6,756 patients from nine randomized, phase 3 clinical trials of IV alteplase for the treatment of acute ischemic stroke. The trials randomly assigned patients to receive alteplase (n=3,391) or a control medication (n=3,365).
The primary measure of efficacy was the proportion of participants with a positive stroke outcome, defined as a modified Rankin score of 0 or 1 at 3 to 6 months. This score indicated no symptoms or lingering symptoms with no activity limitations. Secondary outcomes included fatal intracranial hemorrhage within 7 days, symptomatic intracranial hemorrhage and 90-day mortality.
A positive stroke outcome was reported in 31% of all patients at 3 to 6 months. The odds of a positive outcome increased significantly with alteplase use, in proportion with earlier treatment. A positive outcome was achieved by 32.9% of patients treated with alteplase within 3 hours, compared with 23.1% patients treated with control medication (OR=1.75; 95% CI, 1.35-2.27).
Among patients with a treatment delay of more than 3 hours and up to 4.5 hours, a positive outcome was reported in 35.3% of patients treated with alteplase vs. 30.1% treated with a control medication (OR=1.26; 95% CI, 1.05-1.51). Among patients whose treatment was delayed for more than 4.5 hours, a positive outcome was reported in 32.6% of patients treated with alteplase vs. 30.6% of patients treated with a control medication (OR=1.15; 95% CI, 0.95-1.4).
The treatment benefits were consistent regardless of age (P=.53) or stroke severity (P=.06).
In other results, the odds of symptomatic intracranial hemorrhage were significantly increased among patients who received alteplase (type 2 parenchymal hemorrhage within 7 days: 6.8% vs. 1.3%; OR=5.55; 95% CI, 4.01-7.7; type 2 parenchymal hemorrhage within 36 hours: 3.7% vs. 0.6%; OR=6.67; 95% CI, 4.11-10.84). Fatal intracranial hemorrhage within 7 days was also more common among alteplase recipients (2.7% vs. 0.4%; OR=7.14; 95% CI, 3.98-12.79). The relative increase in fatal intracranial hemorrhage did not differ based on treatment delay, age or stroke severity. However, alteplase use was associated with a greater absolute excess risk among patients with severe strokes. Treatment with alteplase did not significantly impact death from other causes. Consequently, the researchers wrote, overall mortality rates at 90 days were similar between the treatment groups: 17.9% among patients who received alteplase vs. 16.5% among patients who received control medication (HR=1.11; 95% CI, 0.99-1.25).
“Although alteplase increased the risk of death from intracranial hemorrhage by about 2% within the first few days after stroke, by a few months, survivors treated with alteplase were less likely to be disabled than those not receiving such treatment,” Emberson said in the release. “Indeed, alteplase increased the proportion who avoided disability altogether by about 10% for patients treated within 3 hours and 5% for those treated between 3 and 4.5 hours.”
Disclosure: See the full study for a list of the researchers’ relevant financial disclosures.