A second trace: tenecteplase versus alteplase
A Class 1 stroke recommendation, built on non-inferiority and a single bolus.
The second trace is up, on acute ischemic stroke (ICD-10 I63): tenecteplase versus alteplase for thrombolysis.
In January 2026 the AHA/ASA guideline gave a Class 1 recommendation to use either drug within 4.5 hours, an upgrade for tenecteplase from its old “reasonable alternative” status. The trace walks that recommendation down to the trials, and the load-bearing fact is a design choice most readers never see.
What it traces. The strongest head-to-head evidence is non-inferiority, not superiority. The largest precise trial, ATTEST-2, met its pre-specified margin (an odds ratio of 0.75 on the disability scale) and explicitly did not show superiority (p = 0.43); pooled across trials, every functional interval crosses the no-difference line. A non-inferiority result bounds how much worse a drug could be. It cannot, by itself, show it is better. So the Class 1 endorsement, and the stronger “should be preferred” some authors use, rest on equal efficacy within a chosen margin plus a real logistical advantage (one bolus instead of an hour-long infusion), not on demonstrated better outcomes. Naming that claim correctly is the whole exercise.
Read the tenecteplase trace → · All traces by condition →
Every figure is verified against the primary trials and the guideline, with a full source list on the trace.