You may have mastered all the latest changes affecting management of sepsis, STEMI, and opiate-use disorder, but there’s no stopping the relentless revisions to our approach to neurologic emergencies.

The first bit of news is good news, however: a “negative” study in which no change in practice is needed. This comes out of INTERACT-4, a trial testing the efficacy of blood pressure reduction in undifferentiated acute stroke syndromes.¹ Our prior INTERACT family of trials are those whose results have influenced our current practice of blood pressure control following intracranial hemorrhage, demonstrating reductions in hematoma size associated with prompt blood pressure control. The hypothesis tested in INTERACT-4 is whether antihypertensive treatment might be started even earlier, in the pre-hospital setting, reducing any time-dependent negative effects.

In this trial conducted in China, the antihypertensive of choice was urapidil, primarily an alpha-1 receptor antagonist, and provided by the trial sponsor. Without delving into too much detail, approximately half of the over 2,300 patients in the trial suffered ischemic stroke, and the remainder hemorrhagic stroke. The intervention was, indeed, successful at lowering blood pressure in those randomized. However, the overall trial itself was “negative” in that there was no overall difference between groups. Looking more closely, there is a very clear demarcation within these results in which the intensive blood pressure control harmed those patients suffering ischemic stroke, but benefitted those suffering hemorrhagic stroke. These results suggest there is yet no role for prehospital antihypertensives until the specific stroke syndrome is diagnosed, as with one of the mobile CT scanners.

The next question addressed in recent trials continues to be refinement of the thrombolytic of choice. The last few years have been consistently spotlighting tenecteplase as superior to alteplase, both with respect to efficacy and safety. This is not unwelcome in the slightest, as tenecteplase administration in stroke is more straightforward than the bolus-plus-infusion requirement for alteplase. The most recent spotlight for tenecteplase is whether it can be used in extended time windows up to 24 hours. Two recent trials have looked at this same question: TIMELESS and TRACE-III.^2,3

These trials lend themselves to discussion in the same breath because they have, effectively, the same study concept. Each trial enrolled patients presenting with acute ischemic stroke in a large-vessel territory and favorable perfusion imaging. Each trial included patients in the 4.5 to 24 hour treatment window, outside of traditional indications for thrombolysis. How these trials differ, however, is important.