Low-Dose Tenecteplase Ideal for Stroke Treatment

Bruce Campbell, MBBS, BMedSc, PhD, head of stroke, Royal Melbourne Hospital, and professorial fellow, University of Melbourne

Bruce Campbell, MBBS, BMedSc, PhD

New data presented at the 2020 International Stroke Conference (ISC) suggests that eligible patients with stroke can be treated with tenecteplase at a lower dose of 0.25 mg/kg, and can reduce the need for mechanical clot removal.^1,2

In a randomized controlled trial led by Bruce Campbell, MBBS, BMedSc, PhD, head of stroke, Royal Melbourne Hospital, and professorial fellow, University of Melbourne, the 0.25 mg/kg dose (n = 150) of tenecteplase was just as effective as the 0.40 mg/kg dose (n = 150) in dissolving clots in the 300-patient cohort, all of whom had ischemic stroke patients with large vessel occlusion within 4.5 hours of onset.

All told, clots were largely dissolved prior to mechanical removal in 19.3% of patients in both groups (adjusted risk ratio [aRR], 1.03; 95% CI, 0.66 to 1.61; P = .89). Additionally, functional outcomes, as measured by modified Rankin Scale (mRS) scores, were not statistically different between dose groups (generalized odds ratio [gOR], 0.96; 95% CI, 0.74 to 1.24; P = .73).

“The two doses behaved very similarly overall, and there was no advantage to increasing the dose beyond 0.25mg/kg in this study,” Campbell said in a statement. “These results provide reassurance that there is a window of safety if the weight-based dose is inadvertently overestimated.”

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For both doses, 49% of patients in the groups had an mRS of 0-1 or no change from baseline (P = .69) while 59% and 56% of the 0.25 mg/kg and 0.40 mg/kg groups, respectively, had mRS scores of 0-2 or no change from baseline (P = .40).

“In addition, about 34% of patients treated in rural centers had substantially improved blood flow by the time they arrived at a hospital capable of performing mechanical clot removal,” Campbell added. “This treatment could be particularly important for them.”

As for symptomatic intracranial hemorrhage, the rates of occurrence were numerically lower in those treated with the smaller dose (1.3%) compared to the larger dose (4.7%), although the investigators noted this difference was mostly due to thrombectomy-related wire perforations.

In a statement, Mitchell S.V. Elkind, MD, president-elect, American Heart Association, chair, Advisory Committee of the American Stroke Association, and professor of neurology and epidemiology, Columbia University, called tenecteplase an “exciting” drug due to its ease of use in comparison to alteplase.¹

“It's a modified form of TPA and can be given in a single bolus at 1 point in time, instead of the extended period of 1 hour that we use for intravenous TPA,” Elkind explained. “It's not used much in the United States, though. I think most gastroenterologists in the US still use alteplase and that's because other trials have been a little bit more equivocal about whether tenecteplase is, in fact, better than TPA. So, although there does seem to be evidence here of its benefit in this particular setting together with endovascular therapy, it's not clearly going to be used routinely—at least in the United States."

Last year, the American Stroke Association updated its acute ischemic guidelines with comprehensive recommendations, which included that tenecteplase is OK to administer in place of IV alteplase in those who are ineligible or who have contraindications to receive alteplase.

For more coverage of ISC 2020, click here.

REFERENCES

1. Lower dose of newer clot-buster may be appropriate for some stroke patients [press release]. Los Angeles, CA: American Stroke Association; Published February 20, 2020. newsroom.heart.org/news/lower-dose-of-newer-clot-buster-may-be-appropriate-for-some-stroke-patients. Accessed February 21, 2020.

2. Campbell B, Mitchell P, Davis S, et al. Determining the Optimal Dose of Tenecteplase Before Endovascular Thrombectomy (EXTEND-IA TNK Part 2): A Multicenter, Randomized, Controlled Trial. Presented at: 2020 International Stroke Conference. February 19-21, 2020; Los Angeles, CA.