Tenecteplase speeds up stroke thrombolysis compared to alteplase.
Understanding the differences in treatment times between tenecteplase and alteplase can enhance acute ischemic stroke management and improve patient outcomes. Tenecteplase led to significantly shorter door-to-needle times (47.0 vs 52.7 minutes) and improved other workflow metrics compared to alteplase. These findings suggest tenecteplase may optimize stroke thrombolysis workflow, offering advantages over alteplase, though integration into practice will require careful consideration of local protocols. Tenecteplase improves thrombolysis workflow times in acute ischemic stroke compared to alteplase.
Authors: Warach SJ, Weber JM, Alhanti B, Messé SR, Schwamm LH, Fonarow GC, Sheth KN, Smith EE, Mullen MT, Silva GS, Mac Grory B, Xian Y, Saver JL
Citation: Warach SJ, Weber JM, Alhanti B, et al. Tenecteplase vs Alteplase and Time to Treatment for Acute Ischemic Stroke. JAMA network open. 2026;9(7):e2623260. doi:10.1001/jamanetworkopen.2026.23260
Article Links: PubMed · Journal / DOI
Confirmatory Impact 3/5
A very large nationwide registry consistently confirms tenecteplase's plausible single-bolus workflow advantage over alteplase, but the observational design, site-level channeling, and modest 3–6 minute effect sizes prevent it from being practice-changing.
Evidence Grade: Low
Despite the large sample and precise estimates, the nonrandomized unblinded registry design with confounding by indication and concentration of tenecteplase at high-resource early-adopter centers introduces serious risk of bias limiting certainty.
Registry-based observational cohort study using the American Heart Association's Get With The Guidelines–Stroke (GWTG-Stroke) database from July 1, 2020, to June 30, 2022. No trial registration (observational registry study); reported per Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Funded in part by GWTG-Stroke, American Heart Association/American Stroke Association.
133,228 adults with a principal discharge diagnosis of acute ischemic stroke (AIS) treated with intravenous (IV) thrombolysis across 2,092 US hospitals. Mean (SD) age 68.3 (14.8) years; 48.2% female; median (IQR) National Institutes of Health Stroke Scale (NIHSS) score 7 (3–14). Excluded in-hospital stroke onset, low-volume sites (<5 thrombolysis cases), sites with <75% data completeness, and investigational-treatment recipients. 10.5% received tenecteplase (TNK); 89.5% received alteplase.
| Characteristic | Tenecteplase | Alteplase |
|---|---|---|
| Age, mean (SD), years | 69.4 (14.6) | 68.2 (14.8) |
| Female, % | 47.2% | 48.3% |
| NIHSS, median (IQR) | 7 (4–15) | 7 (3–14) |
| Arrived directly to reporting hospital, % | 81.8% | 75.2% |
| Vascular/perfusion imaging before thrombolytic, % | 55.7% | 46.7% |
| Underwent mechanical thrombectomy, % | 21.3% | 17.3% |
| Black race, % | 11.9% | 14.8% |
| Asian race, % | 5.1% | 2.7% |
Door-to-needle time (DTN) among directly arriving patients who did not transfer out; and door-in-door-out time (DIDO) among transferred MT candidates (Index stroke admission (July 2020–June 2022))
| Comparison | Effect Measure | Effect Size (95% CI) | p‑value | Favors |
|---|---|---|---|---|
| Tenecteplase vs alteplase, DTN adjusted | MD | -3.13 min (-3.84 to -2.42) | significant at alpha 0.05 | tenecteplase |
| Tenecteplase vs alteplase, DIDO (MT candidates) adjusted | MD | -5.94 min (-9.10 to -2.77) | significant at alpha 0.05 | tenecteplase |
Generalized linear mixed models with a random site intercept were used for all workflow outcomes; continuous outcomes used a normal distribution with identity link and binary outcomes a binomial distribution with logit link. Both unadjusted and covariate-adjusted estimates were produced (demographics, medical history, prior medications, arrival data, admission vitals, hospital characteristics). Missing outcome data were not imputed (assumed missing at random). Extreme implausible time values were excluded from models. Confidence intervals were not corrected for multiplicity. Hospital-switch effects were assessed by paired t test comparing pre- and post-switch site means.
| Outcome | Result | Effect (95% CI) | p‑value | Sig? |
|---|---|---|---|---|
| DTN within 30 minutes (direct arrivals)Favors tenecteplase | 29.9%20.4% | aOR 1.34 (1.25–1.44) | significant | Yes |
| DTN within 45 minutes (direct arrivals)Favors tenecteplase | 58.3%48.6% | aOR 1.24 (1.17–1.32) | significant | Yes |
| DTN within 60 minutes (direct arrivals)Favors tenecteplase | 77.5%70.7% | aOR 1.25 (1.17–1.33) | significant | Yes |
| DIDO, all transferred patients (adjusted)Favors tenecteplase | 113.7 min117.8 min | MD -3.76 min (-6.42 to -1.09) | significant | Yes |
| Door-to-puncture, same-hospital thrombolysis+MT (adjusted)Favors tenecteplase | 84.4 min92.8 min | MD -5.93 min (-7.76 to -4.11) | significant | Yes |
| Door-to-puncture, transferred-in MT patients (adjusted)Favors tenecteplase | 34.7 min47.9 min | MD -6.47 min (-9.42 to -3.51) | significant | Yes |
| Door-to-reperfusion, same-hospital (adjusted)Favors tenecteplase | 116.7 min127.2 min | MD -8.28 min (-11.02 to -5.54) | significant | Yes |
| DTN change after hospital switch to tenecteplase (unadjusted paired)Favors tenecteplase | 51.1 min52.7 min | MD -1.52 min (-2.88 to -0.15) | significant | Yes |
Not reported. This analysis was restricted to workflow time metrics and did not assess hemorrhage, mortality, or functional outcomes. The authors note a companion GWTG-Stroke analysis (Rousseau et al) found no overall functional benefit of tenecteplase on discharge status.
| Subgroup | Comparison | Effect (95% CI) | p‑value | Interaction p |
|---|---|---|---|---|
| Transferred-out patients (any reason), DTN within 45 min | Tenecteplase vs alteplase | aOR 1.18 (1.01–1.37) | significant | NR |
| Transferred-out patients (any reason), DTN within 30 min | Tenecteplase vs alteplase | aOR 1.23 (0.98–1.55) | not significant | NR |
| Transferred-out MT candidates, DTN within 60 min | Tenecteplase vs alteplase | aOR 1.18 (0.96–1.46) | not significant | NR |
| Same-hospital MT, door-to-deployment within 60 min | Tenecteplase vs alteplase | OR 2.05 (1.42–2.97) | significant (adjusted model nonconvergent) | NR |
Observational, nonrandomized, unblinded registry data with no external verification of data accuracy or completeness, leaving residual and unmeasured confounding despite adjustment. Findings predominantly reflect early-adopter centers, which were disproportionately certified stroke centers and high-volume academic hospitals, limiting generalizability to smaller or later-adopting sites. Missing time-metric values were not imputed and may not be missing at random; DIDO analysis was available for only 64% of eligible transferred patients.
The evidence establishes a consistent, statistically significant association between tenecteplase use and faster thrombolytic and transfer workflow times, biologically plausible given single-bolus administration versus a 60-minute infusion. However, the observational design and channeling of tenecteplase to higher-resource centers preclude causal attribution, and the absolute time savings (roughly 3–6 minutes) are modest. This study confirms an operational advantage but does not itself demonstrate improved clinical outcomes.
Supports the American Heart Association/American Stroke Association trend toward accepting tenecteplase as a reasonable alternative to alteplase for eligible AIS patients, consistent with the AcT and ATTEST-2 noninferiority trials. This study adds real-world workflow evidence (faster DTN/DIDO) that randomized trials did not capture, reinforcing but not altering current guideline positioning.
Not applicable to this workflow analysis. In practice, standard post-thrombolysis monitoring applies: serial neurologic assessments, blood pressure control per protocol, and vigilance for symptomatic intracranial hemorrhage; institutions should track DTN and DIDO as quality metrics against Target: Stroke goals (<60, <45, <30 minutes).
Tenecteplase patients differed at baseline: more Asian, fewer Black patients; more frequently ambulatory pre-stroke; more likely to receive advanced vascular/perfusion imaging (55.7% vs 46.7%) and to undergo MT (21.3% vs 17.3%). Because tenecteplase concentrated at comprehensive stroke centers and higher-volume academic hospitals, the observed workflow advantages may reflect site-level capabilities in part. Effects in low-volume or rural settings remain uncharacterized, though the authors hypothesize DIDO gains could be larger where critical-care transport for infusions is scarce.
The central tension is that these workflow savings have not appeared in head-to-head randomized trials (AcT, ATTEST-2, EXTEND-IA TNK, TASTE), which the authors attribute to trial-related enrollment tasks obscuring real-world logistics advantages. Whether the modest 3–6 minute reductions translate into measurable functional benefit is unresolved, particularly since the companion Rousseau analysis found no discharge-outcome difference. A follow-up study of later-adopting, lower-volume centers is needed to confirm generalizability.
Not discussed in detail. Tenecteplase offers logistical savings in pharmacy and nursing labor by removing infusion setup and monitoring; acquisition cost differences and formulary implications were not addressed in this analysis.
Safety and functional-outcome data are absent by design; the reported clinical relevance of time savings is inferred from prior time-to-treatment literature rather than measured here. The switching-hospital DTN comparison used an unadjusted paired analysis and should be interpreted cautiously. Baseline imbalances and channeling of tenecteplase to high-resource centers warrant editor attention as sources of confounding.
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