Tenecteplase a promising alternative to alteplase for stroke thrombolysis

Intravenous thrombolysis with tenecteplase is noninferior to that with alteplase, with the functional outcome and safety profile being similar, according to the results of the ORIGINAL study.

Analysis of data from Chinese patients with acute ischaemic stroke (AIS) eligible for intravenous thrombolysis within 4.5 hours after the index event showed a similar proportion of patients with a modified Rankin Scale (mRS) score of 0 or 1 (no symptoms or no significant disability) at day 90 in the tenecteplase and alteplase arms (72.7 percent vs 70.3 percent; risk ratio [RR], 1.03, 95 percent confidence interval [CI], 0.97–1.09; p=0.003 for noninferiority). [JAMA 2024;332:1437-1445]

Likewise, the tenecteplase and alteplase arms did not significantly differ in terms of the proportion of patients with an mRS score of 0 to 2 at day 90 (80.9 percent vs 79.9 percent; RR, 1.01, 95 percent CI, 0.96–1.06), those who achieved major neurologic improvement at 24 hours (48.0 percent vs 45.0 percent; RR, 1.07, 95 percent CI, 0.96–1.19), and those who had a Barthel Index score of at least 95 on day 90 (75.7 percent vs 73.9 percent; RR, 1.02, 95 percent CI, 0.96–1.08).

Symptomatic intracerebral haemorrhage occurred in 1.2 percent of patients in each treatment arm (RR, 1.01, 95 percent CI, 0.37–2.70). The 90-day mortality was 4.6 percent among tenecteplase-treated patients vs 5.8 percent among those who received alteplase (RR, 0.80, 95 percent CI, 0.51–1.23), and the proportion of patients with an mRS score of 5 or 6 was 6.8 percent vs 7.8 percent, respectively (RR, 0.92, 95 percent CI, 0.66–1.29).

“Results of this study in Chinese patients with AIS were consistent with those of investigator-initiated trials, including the AcT trial, a phase 3, pragmatic, registry-linked, randomized controlled study conducted in Canada, and ATTEST-2, a prospective, randomized, controlled, parallel-group trial completed in the UK,” the investigators said. [Lancet 2022;400:161-169; Muir K, et al, WSC 2023]

The 2023 TRACE-2 study conducted in China also demonstrated the noninferiority of tenecteplase to alteplase in Chinese patients with AIS eligible for standard intravenous thrombolysis. However, the study excluded patients eligible for endovascular thrombectomy and those with an NIHSS score of 4 or below. [Lancet 2023;401:645-654]

ORIGINAL involved 1,465 Chinese adults (median age 66 years, 30.4 percent female, median NIHSS score 6.0) with acute ischaemic stroke, measurable neurologic deficit, who had been symptomatic for at least 30 minutes without significant improvement, and who were able to receive thrombolytic therapy within 4.5 hours of symptom onset. Patients considered for endovascular thrombectomy were included, but those who presented with intracranial haemorrhage on noncontrast CT imaging were excluded.

Within 4.5 hours of stroke onset, the patients were randomly assigned to receive intravenous thrombolytic treatment with tenecteplase 0.25 mg/kg or alteplase 0.9 mg/kg. A total of 373 patients (25.5 percent) in both treatment arms had CT or MR angiography performed at baseline based on physician assessment. Among these, 130 patients (35 percent) had an occlusion, mainly in the M1 segment.

“[ORIGINAL] strengthens the understanding of tenecteplase in AIS by further building on the results from previous trials, including TAAIS, TNK-S2B, ATTEST, NOR-TEST, and EXTEND-IA TNK, as well as the large clinical trial AcT. Together, these studies have provided evidence on the use of tenecteplase, including the optimal dosing and use in clinical subgroups, such as patients with large vessel occlusion,” the investigators said. [N Engl J Med 2012;366:1099-1107; Lancet Neurol 2015;14:368-376; Stroke 2002;33:2243-2246; Int J Stroke 2018;13:328-334; Lancet 2022;400:161-169]

“The overall treatment effect in this study of Chinese patients can be expected to be similar to other populations beyond China, given the comparability of the current result with existing studies, which comprise non-Asian populations across various stroke severities,” they added. [Lancet 2022;400:161-169; Lancet 2023;401:645-654; N Engl J Med 2008;359:1317-1329; Lancet 2007;369:275-282]