Reteplase a good alternative to alteplase in acute ischaemic stroke

Treatment with reteplase appears more effective than alteplase in patients with acute ischaemic stroke (AIS) who have been treated within 4.5 hours of symptom onset, according to the results of RAISE, a phase III multicentre, open-label, randomized controlled, noninferiority trial.

“Although patients [who] received reteplase did have an increased rate of any intracranial haemorrhage, we did not find a difference in the fatal safety profile between patients administrated [reteplase] and alteplase,” said the investigators led by Shuya Li from Beijing Tiantan Hospital in Beijing, China.

 In this study, Li and colleagues sought to establish the noninferiority of reteplase to alteplase for patients who were eligible for standard intravenous (IV) thrombolysis. Noninferiority was defined by a longer half-life that allows double-bolus administration with a fixed dosage instead of infusion based on body weight in kilogram.

A total of 1,412 patients were enrolled from 62 centres in China between March 2022 and March 2023. The investigators randomized them in a 1:1 ratio to receive IV reteplase (18+18 mg) or IV alteplase (0.9 mg/kg body weight; max dose, 90 mg). Of the eligible participants, 700 received reteplase and 699 alteplase. [Li S, et al, ISC 2024, abstract LB35]

The proportion of patients who had a modified Rankin scale score of 0‒1 at 90 days was the primary efficacy endpoint, with a noninferiority margin of 0.93 for the risk ratio. For the primary safety outcome, symptomatic intracerebral haemorrhage within 36 hours since symptom onset was used.

Significantly more patients in the reteplase group than those in the alteplase group achieved the primary outcome (80.1 percent vs 71.1 percent, respectively). However, symptomatic intracerebral haemorrhage within 36 hours from disease onset (2.4 percent and 2.0 percent) and mortality within 90 days (4.3 percent vs 3.4 percent) was slightly higher with reteplase than with alteplase.

These findings were consistent with the results of the previous trial.

Safety and efficacy

“Reteplase was well tolerated in patients with AIS within 4.5 hours of onset in China with a similar efficacy profile to alteplase,” said the investigators in their recently published phase II study. In this trial, 180 patients were randomized to reteplase 12+12 mg (n=61), reteplase 18+18 mg (n=67), or alteplase (n=52) between August 2019 and May 2021.

Symptomatic intracerebral haemorrhage occurred in three of 60 (5.0 percent) in the reteplase 12+12 mg group, one of 66 (1.5 percent) in the reteplase 18+18 mg group, and one of 50 (2.0 percent) in the alteplase group (p=0.53). [Stroke 2024;55:366-375]

The proportion of patients achieving the National Institutes of Health Stroke Scale score of no more than 1 or a decrease of at least 4 points from the baseline at 14 days after thrombolysis was 45 of 60 (75.0 percent) in the reteplase 12+12 mg group (odds ratio [OR], 0.85; 95 percent confidence interval [CI], 0.35‒2.06), 48 of 66 (72.7 percent) in the reteplase 18+18 mg group (OR, 0.75; 95 percent CI, 0.32‒1.78), and 39 of 50 (78.0 percent) in alteplase group. [Stroke 2024;55:366-375]

Reteplase is a modified nonglycosylated recombinant form of tissue plasminogen activator (tPA) used to dissolve intracoronary emboli, lysis of acute pulmonary emboli, and manage myocardial infarction. [Adv Biomed Res 2019;20:8:19]

“This protein contains kringle-2 and serine protease domains. The lack of glycosylation means that a prokaryotic system can be used to express reteplase. Therefore, the production of reteplase is more affordable than that of tPA,” according to researchers. [Adv Biomed Res 2019;20:8:19]