Tenecteplase Could Lower Bleeding Risk vs Alteplase in Acute Stroke

Steven J. Warach, MD, PhD

Analysis of a registry including patients from New Zealand, Australia, and the US is providing clinicians with insight into the real-world effects of tenecteplase versus alteplase as a treatment in patients with acute stroke.

Using deidentified patient-level data from the ongoing CERTAIN collaboration, results of the study demonstrate use of tenecteplase was associated with a 43% lower rate of symptomatic intracranial hemorrhage (sICH) than alteplase, with a 59% lower rate among those who required thrombectomy and a 42% lower rate among those who did not undergo thrombectomy.

“No single trial has proved that tenecteplase is superior, however, in combination, the evidence has shown that tenecteplase is at least as good as alteplase in preventing long-term disability after a stroke and is more effective in dissolving large clots,” said lead investigator Steven J. Warach, MD, PhD, professor of neurology at the Dell Medical School at the University of Texas at Austin, medical director for Ascension hospitals in Texas and chair of Ascension’s national stroke group, in a statement.

Although phase 3 trials are ongoing, Warach and a team of colleagues sought to examine the safety of tenecteplase for thrombolysis. With this in mind, investigators designed their study as an analysis of data from patients with stroke treated with thrombolytics within a registry from the ongoing CERTAIN collaboration.

Launched in 2021, the CERTAIN collaboration included information dating back to July 2018. Using data from all patients treated from July 2018-June 2021, a total of 7891 patients were identified for inclusion, with 6429 receiving alteplase and 1462 receiving tenecteplase. The alteplase cohort had a mean age of 70 years and 48.7% were female. The tenecteplase cohort had a mean age of 73 years and 44.1% were female. Compared to the alteplase cohort, the tenecteplase cohort had a higher NIHSS score (7 [IQR, 4-15] vs 9 [IQR, 5-17]) and more frequently require mechanical thrombectomy (18% vs 36.7%; P <.001).

For the purpose of analysis, sICH was defined as clinical worsening of at least 4 points on NIHSS, attributed to parenchymal hematoma, subarachnoid or intraventricular hemorrhage. Investigators used logistic regression for binary variables and Mann-Whitney test for continuous baseline variables.

Results demonstrated the sICH rate among patients treated with alteplase and 2.13% among patients treated with tenecteplase (OR, 0.49 [95% CI, 0.31-0.76]; P=.002). Among patients who did not require thrombectomy following thrombolytic, the rate of sICH was 3.00% in the alteplase cohort and 1.74% among the tenecteplase cohort (OR, 0.48 [95% CI, 0.27-0.87]; P=.016). Among those who did require thrombectomy, the sICH rate was 6.80% in the alteplase cohort and 2.80% in the tenecteplase cohort, OR, 0.60 [95% CI, 0.31-1.16]; P=.129).

“The significantly lower rates of sICH surprised us. Our finding that tenecteplase had about half the risk of sICH when compared with alteplase in routine clinical practice provides reassurance that tenecteplase does not result in harmful bleeding when used routinely for stroke treatment,” Warach added.

This study, “Comparative Effectiveness Of Routine Tenecteplase Thrombolysis In Acute Stroke Compared With Alteplase: An INternational Collaboration (CERTAIN Collaboration): Rates Of Symptomatic Intracranial Hemorrhage,” was presented at ISC 2022.