IV alteplase alone good enough- add on argatroban may not further improve outcomes in acute ischemic stroke

In a new study by Hui-Sheng Chen and team it was shown that argatroban with intravenous alteplase compared to alteplase therapy alone did not substantially increase functional outcome at 90 days in individuals with acute ischemic stroke. The findings of this study were published in the Journal of American Medical Association.

Prior research revealed that individuals with acute ischemic stroke (AIS) could benefit from combining argatroban with alteplase (recombinant tissue-type plasminogen activator). However, there is a lack of solid evidence in studies with high sample sizes. As a result, this study was carried out to evaluate the effectiveness of argatroban + alteplase for AIS.

50 hospitals in China participated in an open-label, multicenter, blinded end point, randomized clinical study, which included 808 patients with AIS from January 18, 2019, through October 30, 2021, with the last follow-up occurring on January 24, 2022. Within 4.5 hours after the beginning of symptoms, suitable patients were randomly allocated to one of two groups: alteplase alone (n = 415) or alteplase + argatroban (n = 402), each of whom received intravenous argatroban one hour after alteplase. Both groups got care based on recommended protocols.

The main outcome was an excellent functional result, which was determined by a modified Rankin Scale score of 0 to 1 at 90 days (range, 0 [no symptoms] to 6 [death]). All end points underwent blinded evaluation and comprehensive analysis set analysis.

The key findings of this study were:

760 (93.0%) of the 817 eligible AIS patients who were randomized to receive the treatment finished the trial. 

At 90 days, 238 of 367 people in the alteplase alone group had a good functional result compared to 210 of 329 participants (63.8%) in the argatroban + alteplase group. 

In the argatroban plus alteplase group, the percentages of participants with symptomatic intracranial hemorrhage, parenchymal hematoma type 2 and major systemic bleeding were 2.1% (8/383), 2.3% (9/383), and 0.3% (1/383), respectively. 

In the alteplase alone group, the percentages were 1.8% (7/397), 2.5% (10/397), and 0.5% (2/397).

In conclusion, treatment with argatroban with intravenous alteplase in AIS patients did not substantially increase the chance of a good functional status at 90 days compared to alteplase alone.

Reference: 

Chen, H.-S., Cui, Y., Zhou, Z.-H., Dai, Y.-J., Li, G.-H., Peng, Z.-L., Zhang, Y., Liu, X.-D., Yuan, Z.-M., Jiang, C.-H., Yang, Q.-C., Duan, Y.-J., Ma, G.-B., Zhao, L.-W., Wang, R.-X., Sun, Y.-L., Shen, L., Wang, E.-Q., … Wang, L.-H. (2023). Effect of Argatroban Plus Intravenous Alteplase vs Intravenous Alteplase Alone on Neurologic Function in Patients With Acute Ischemic Stroke. In JAMA. American Medical Association (AMA). https://doi.org/10.1001/jama.2023.0550