Ammad Mahmood, MBChB
Guaranteed to feature on the program at this year’s stroke meetings (virtual or otherwise), the debate regarding the potential use of tenecteplase for thrombolysis in acute ischemic stroke rolls on. The authors of this commentary present an excellent summary of the pros and cons of choosing tenecteplase over alteplase, summarizing and critiquing the evidence base in both camps, before reaching a balanced conclusion reflecting the current equipoise in the stroke community.
The ‘Yes’ camp cited the following arguments in favor of tenecteplase use:
- A well understood mechanism of action, strong preclinical data and benefit established in myocardial infarction, which is a similar pathology.
- Practical advantages, such as ease of use during hospital transfers; eliminating the gap between bolus and infusion that exists with alteplase; and reduced staff burden with Tenecteplase.
- Meta-analysis1 which suggests that tenecteplase is non-inferior to alteplase on the basis of currently available clinical trial evidence — while they acknowledge superiority is desirable, they argue that other stroke interventions have been approved on the grounds of non-inferiority, such as direct anticoagulants, statins and mechanical thrombectomy devices.
- National practice guidelines in the United States, Europe, Australia, India and China all recognizing tenecteplase as a potential alternative.
The ‘No’ camp discussed the existing completed trial evidence for tenecteplase vs alteplase: 2 phase II trials, TAAIS2 and ATTEST,3 and 2 phase III trials, NOR-TEST4 and EXTEND-IA TNK.5 TAAIS was positive, though only patients with large vessel occlusion (LVO) were included, whilst ATTEST was negative. Similarly, NORTEST, the largest of the trials, showed no benefit of tenecteplase over alteplase (as a superiority trial), whilst EXTEND-IA TNK showed benefit of tenecteplase in LVO strokes prior to thrombectomy. They argue that the combined evidence base may support non-inferiority of tenecteplase in patients with LVO; however, these patients form a minority of those presenting with acute stroke and a move to tenecteplase for all stroke care isn’t warranted at present.
In conclusion, the authors acknowledged that tenecteplase is an alluring option for thrombolysis in acute ischemic stroke; however, they cautioned against a wholesale move to tenecteplase based on current evidence. They highlight many ongoing trials of Tenecteplase, which vary in target population, qualifying criteria and geographic location, which, in time, should provide the stroke community with sufficient evidence to conclude this debate. Until then, off-label use of tenecteplase should be cautious, and recruitment to relevant clinical trials encouraged.
1. Burgos AM, Saver JL. Evidence that Tenecteplase Is Noninferior to Alteplase for Acute Ischemic Stroke. Stroke. 2019;50(8):2156-62.
2. Parsons M, Spratt N, Bivard A, Campbell B, Chung K, Miteff F, et al. A Randomized Trial of Tenecteplase versus Alteplase for Acute Ischemic Stroke. New England Journal of Medicine. 2012;366(12):1099-107.
3. Huang X, Cheripelli BK, Lloyd SM, Kalladka D, Moreton FC, Siddiqui A, et al. Alteplase versus tenecteplase for thrombolysis after ischaemic stroke (ATTEST): a phase 2, randomised, open-label, blinded endpoint study. The Lancet Neurology. 2015;14(4):368-76.
4. Logallo N, Novotny V, Assmus J, Kvistad CE, Alteheld L, Rønning OM, et al. Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial. The Lancet Neurology. 2017;16(10):781-8.
5. Campbell BCV, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Dowling RJ, et al. Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke. N Engl J Med. 2018;378(17):1573-82.