Prourokinase vs Alteplase for Acute Ischemic Stroke Treatment: Which Is Better?

Recombinant human prourokinase is noninferior to alteplase as a thrombolytic agent after acute ischemic stroke, according to the findings of a study published in The Lancet Neurology.

Guidelines recommend the administration of intravenous (IV) thrombolysis within 4.5 hours of stroke onset. Prourokinase is a glycosylated, single-chain proenzyme that does not dissolve hemostatic thrombus.

The PROST-2 study (ClinicalTrials.gov Identifier: NCT05700591) was an open-label, phase 3, noninferiority trial conducted at 61 sites in China between 2023 and 2024. Patients (N=1552) with acute ischemic stroke and a National Institutes of Health Stroke Scale (NIHSS) score of 4 to 25 presenting within 4.5 hours of stroke onset were randomly assigned in a 1:1 ratio to receive 35 mg IV recombinant human prourokinase (n=775; mean age, 65; men, 64.9%; Han Chinese, 31.2%) or 0.9 mg/kg alteplase (n=777; mean age, 65; men, 68.1%; Han Chinese, 97.0%).

The primary outcome was the proportion of patients who achieved an excellent functional outcome at 90 days, defined as a modified Rankin score (mRS) of 0 or 1.

Among the participants who received prourokinase or alteplase, 31.2% and 35.0% had a history or stroke or transient ischemic attack, 42.9% and 45.4% received the study drug less than 3 hours of stroke onset, and they had an NIHSS score of 7 and 7 at baseline, respectively.

At 90 days, 72.0% of participants who received prourokinase and 68.7% of those who received alteplase achieved an excellent functional outcome (risk ratio [RR], 1.04; 95% CI, 0.98-1.10; P <.0001), indicating noninferiority.

In the subgroup analyses, no significant interactions were observed.

The 2 treatment groups had similar risk for secondary outcomes of achieving an mRS score of 0 to 2 at 90 days (RR, 1.01; 95% CI, 0.96-1.05), early neurological improvement at 24 hours (RR. 1.09; 95% CI, 0.99-1.20) and 7 days (RR. 1.00; 95% CI, 0.94-1.06), and a Barthel Index score of 95 or greater at 90 days (RR. 1.00; 95% CI, 0.95-1.05).

However, compared with alteplase, prourokinase was associated with a greater reduction in NIHSS score from baseline at 7 days (risk difference [RD], -0.8; 95% CI, -1.3 to -0.2; P =.0078).

The safety outcomes were similar with prourokinase and alteplase, with the exceptions that prourokinase was associated with a decreased risk for symptomatic intracranial hemorrhage within 36 hours (RD, -1.0; 95% CI, -2.1 to -0.1; P =.021) and major hemorrhage (RD, -1.5; 95% CI, -2.8 to -0.4; P =.0072) or clinically relevant non-major hemorrhage (RD, -4.6; 95% CI, -9.1 to -0.1; P =.00051) within 7 days.

This study was limited by the lack of diversity in the study population. It remains unclear whether these findings may be generalizable.

“[T]he results of the PROST-2 trial support the use of recombinant human prourokinase as an alternative thrombolytic agent in patients with acute [ischemic] stroke who are eligible for intravenous thrombolysis but ineligible for or who have refused endovascular thrombectomy within 4.5 h of symptom onset,” the researchers concluded.

Disclosure: This research was supported by Tasly Biopharmaceuticals. Please see the original reference for a full list of disclosures