Objective:

We aimed to investigate the role of reteplase compared to alteplase in AIS patients presenting within 4.5 h of symptom onset.

Background:

The demand for more effective and safer thrombolytic agents for acute ischemic stroke (AIS) has been increasingly recognized. Reteplase is a mutant form of alteplase with practical advantages. Nevertheless, the role of reteplase in patients with AIS is uncertain.

Design/Methods:

We searched electronic databases to identify randomised clinical trials (RCTs) comparing reteplase to alteplase in AIS patients presenting within 4.5 h. The primary outcomes were the 90-day excellent functional outcome (modified Rankin scale [mRS] of 0–1) and symptomatic intracerebral hemorrhage (sICH). Secondary outcomes included 90-day good functional outcome (mRS 0–2), early neurological improvement (ENI), and 90-day mortality. Odds ratios (ORs) with 95 % confidence intervals (CIs) were pooled using the fixed-effects model.

Results:

Of the 544 identified records, we included two high-quality RCTs (1588 patients). A total of 833 patients received reteplase (60 with 12 + 12 mg and 773 with 18 + 18 mg), while 755 patients received alteplase 0.9 mg/kg. Reteplase was associated with higher rates of excellent functional outcomes (OR, 1.55 [95 % CI, 1.23–1.95]), good functional outcomes (OR, 1.36 [95 % CI, 1.04–1.77]), and ENI (OR, 1.42 [95 %CI, 1.16–1.73]) compared to alteplase. Similar rates of sICH (OR, 1.25 [95 %CI, 0.64–2.47]) and mortality (OR, 1.18 [95 %CI, 0.72–1.92]) were noted. Optimal benefits were reported in patients treated with 18 + 18 mg of reteplase.

Conclusions:

In this meta-analysis, reteplase, particularly at the 18 + 18 mg dose, was more effective than alteplase with comparable safety profiles. These findings suggest that reteplase could be a viable alternative to alteplase for stroke thrombolysis. Multinational trials are needed to validate the generalizability of these results to a broader population.