Written by Clay Smith
Spoon Feed
Tenecteplase (TNK) vs. usual care in non-large vessel occlusion (non-LVO) stroke patients 4.5–24 hours from onset, with perfusion mismatch, had better outcome but slightly more intracranial hemorrhage.
Good to have OPTIONs…
This was a randomized, open-label, assessor-blinded study of 556 patients in China with non-LVO acute ischemic stroke, presenting 4.5–24 hours from onset with perfusion mismatch on imaging, comparing TNK vs. standard care. More patients who received TNK had an excellent neurological outcome (modified Rankin Scale, mRS 0-1): TNK 43.6% (123/282 patients) vs. control 34.2% (97/284); (RR 1.28, 95%CI 1.04-1.57, P = .02). Symptomatic intracranial hemorrhage (sICH) occurred in 2.8% with TNK vs. 0% with standard care: 0% (risk difference 2.85%, 95%CI 1.16%-5.54%, P = 0.004). 90-day mortality was higher with TNK vs. control, though this was not statistically significant: 5.0% vs. 3.2%, respectively (RR 1.57, 95%CI 0.69-3.57, P = .28).
How will this change my practice?
So, this is a NNT = 11, and NNH = 35, which is consistent with prior delayed TNK trials and a recent meta-analysis of 4 RCTs. I used our new software, PubMetric®, and did my own custom meta-analysis in just a few minutes. Here is the Forest plot when you add the OPTION RCT by Ma et al. to the other 4 RCTs in the recent meta-analysis in Stroke: NNT = 15 for mRS 0-1; NNH = 50 for sICH.
Figure edited March 13, 2026, 10:32AM
We received a comment asking us to run the outcome of mortality on the PubMetric software. Please see below. All statistical analyses were performed using R (R Foundation for Statistical Computing) via the ‘meta’ package executed within a WebR virtualized environment. Dichotomous outcomes were synthesized to calculate pooled Risk Ratios (RR). We utilized a random-effects model utilizing the Restricted Maximum Likelihood estimator for between-study variance (τ²) to calculate pooled effects and 95% confidence intervals (CI). Statistical heterogeneity was assessed using the Cochran Q statistic and quantified using the I² statistic. All statistical tests were two-sided with a significance threshold of P < 0.05.
The nice thing about PubMetric is, I was simply able to toggle from RR to odds ratio, for parallelism with the Stroke meta-analysis, and the overall effect was OR 1.11 (95%CI 0.82 to 1.50). You can learn more about PubMetric® here.
Figure added April 6, 2026.
Source
OPTION Investigators. Tenecteplase for Acute Non-Large Vessel Occlusion 4.5 to 24 Hours After Ischemic Stroke: The OPTION Randomized Clinical Trial. JAMA. 2026 Feb 5:e260210. doi: 10.1001/jama.2026.0210. Epub ahead of print. PMID: 41642827; PMCID: PMC12878635.
Clay, thanks for the summary. I believe the data, both the NNT as well as the NNH…. Sadly, every time I pushed TNK (I’m 67 and semi-retired to urgent care last year) I spent the next several hours praying for no hemorrhage. All the best.
Honest question: when you use the new software to answer what happens to mortality, what happens?
That is always my main concern w/ thrombolysis: the increased all-cause mortality sign in several RCTs…
Bernardo, I ran the analysis on PubMetric to answer your question about mortality. See the post above. I added overall or 90-day mortality Forest plot. RR 1.09 (95%CI 0.84 to 1.41); OR 1.11 (95%CI 0.82 to 1.50). Bottom line: a non-significant increase in 90-day mortality was seen with delayed TNK.