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1. In a randomized controlled trial of patients who suffered an acute ischemic stroke, the reteplase group reported a greater number of patients experiencing an excellent functional score compared to the alteplase group.

2. A greater proportion of patients reported intracranial hemorrhages within 90 days in the reteplase group compared to the alteplase group. 

Evidence Rating Level: 1 (Excellent)

Study Rundown: One proven intercession for ischemic strokes is reperfusion therapy, currently done by intravenous infusion of alteplase within 4.5 hours of symptoms. Diverse, effective, affordable therapies are needed, and several are in testing, including reteplase, a 30-minute separated double-bolus, recombinant plasminogen activator. A previous meta-analysis has shown no increase in mortality or disabling strokes in patients with acute myocardial infarction with reteplase treatment over alteplase. The Reteplase versus Alteplase for Acute Ischemic Stroke (RAISE) was a phase two randomized control trial that showed higher levels of excellent functional outcome at higher doses of reteplase without an increase in the risk of fatal bleeding. To assess the effectiveness of reteplase versus alteplase, the excellent functional outcome, which meant a modified Rankin scale score of 0 or 1 at 90 days, was measured as the primary outcome. The secondary outcome was a good functional outcome, meaning a modified Rankin scale score of 0 to 2 during the 90 days. One study limitation was the open-label design, which could have increased the risk of potential biases. Overall, reteplase was a better treatment than alteplase for patients with acute ischemic stroke, with an excellent functional outcome within 90 days. However, there was comparatively increased intracranial hemorrhage in the reteplase group.

Click to read the study in NEJM

In-Depth [randomized controlled trial]: This randomized controlled trial enrolled 1,412 patients with acute ischemic stroke between March 21, 2022, and June 22, 2023. The participants were randomly separated, with 707 patients in the reteplase group and 705 in the alteplase group. The median age of the participants was 63 years (interquartile range, 56 to 70), and the majority (70.5%) were men. The reteplase group had an excellent functional outcome in 79.5% of the patients, while the alteplase group reported this outcome in 70.4% of the patients (risk ratio, 1.13; 95% confidence interval [CI], 1.05 to 1.21; p<0.001 for noninferiority and p=0.002 for superiority). When comparing a good functional outcome, the reteplase reported this in 85.3% of patients, while the alteplase group reported it in 79.8% (risk ratio, 1.07; 95% CI, 1.02 to 1.12). Safety was measured as a secondary outcome, with intracranial hemorrhage being a measurable outcome. A total of 17 (2.4%) and 14 (2.0%) patients in the reteplase and alteplase groups, respectively, suffered a symptomatic intracranial hemorrhage within 36 hours (risk ratio, 1.21; 95% CI, 0.54 to 2.75; p=0.64). Similarly, parenchymal hemorrhage type two was seen in 1.7% and 1.4% of patients in the reteplase and alteplase groups, respectively (risk ratio, 1.20; 95% CI, 0.36 to 4.03). Ultimately, the worst adverse outcome was death (within 90 days), which was unfortunately seen in 4.3% (30 patients) of the reteplase group and 3.4% (24 patients) of the alteplase group (risk ratio, 1.25; 95% CI, 0.66 to 2.35).

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