Zivin Lecture: Debate Rages on tPA vs. tNK for Acute Stroke

Is it time to switch from alteplase (tPA) to tenecteplase (tNK) to treat acute stroke? There are data on both sides, but no large head-to-head trials have reported to date.

Cardiologists have been using tNK to lyse clots in acute myocardial infarction for two decades. That is nearly as long as stroke specialists have been using tPA to lyse clots in acute stroke.

tNK is cheaper than tPA in many locales. tNK requires a bolus injection over five to 10 seconds rather than the infusion required to administer tPA. And clinical trials show similar results in thrombolysis. Should stroke neurologists switch to tNK?

Yes, said Mark Parsons, professor and director of neurology, and The Royal Melbourne Hospital Chair of Neurology at the University of Melbourne in Australia. He pointed out that two Australian states have already replaced tPA with tNK for pre-thrombectomy care of acute stroke patients.

“tPA really doesn’t work very well in vascular occlusion,” Parsons said. “You are more likely to get early response with tNK, hence improved canalization. We know that early recanalization translates to better clinical outcomes. And tNK is infinitely more practical to give in the stroke ambulance.”

Not so fast, countered James Grotta, MD, director of Mobile Stroke Unit Consortium at the Clinical Innovation and Research Institute at Memorial Mermann Hospital-TMC in Houston.

“Just because something is newer and faster doesn’t mean it is better. tNK may be equivalent to tPA, but it’s not better, and we need to do better,” he said. “The best way to improve on tPA is not to try a different thrombolytic but to get whatever thrombolytic we are using into more patients, faster.”

Parsons and Grotta led opposing sides on tPA vs. tNK for acute stroke during The Justin Zivin Memorial Session: “The Tried and Tested vs. The New Kid on the Block: The tPA vs. tNK Debate.”

New study data may help settle the question. Parsons noted the Tenecteplase versus Alteplase for Stroke Thrombolysis Evaluation (TASTE) trial for treatment within 45 hours of the onset of symptoms is nearly completed. TASTE-A, comparing treatment when used on the stroke ambulance, is about to begin.

Parsons was joined by Shelagh Coutts, MD, MSc, stroke neurologist, clinical investigator in stroke and associate professor of neurology at the University of Calgary in Canada, on the switch-to-tNK side.

“TNK is at least as good as tPA; it is easier to use; and it works well for drip-and-ship models,” Coutts said. “It is a question of when, not if, we switch to tNK.”

The data are clear, she said. In MI use, tNK is equivalent to tPA in terms of mortality, more potent in a patient with longer duration of MI and has a reduced rate of major bleeds.

tNK has been trialed in more than 27,000 patients worldwide, she continued. Stroke trials of tNK are smaller, but the data are similarly positive with better outcomes from tNK vs. tPA and better recanalization rates at one and 24 hours with no increased rate in intracerebral hemorrhage.

A formal meta-analysis of tNK stroke trials to date was presented at the International Stroke Conference. The data show similar disability-free rates for the two agents and demonstrate non-inferiority for tNK. The pooled data also suggest that the 0.25 mg/kg dose of tNK is more effective with fewer adverse events compared to other doses.

Grotta was joined by Christopher Lewandowski, MD, vice chair of emergency medicine at Henry Ford Hospital and clinical professor of emergency medicine at Wayne State University, on the stick-with-tPA side.

“As an ER doc, I can tell you that stroke is not the same as acute MI,” Lewandowski said. “The hemorrhage rate in stroke can be three, five, 10 times higher than in MI. TNK in acute MI is not better, it is equivalent. It is a little cheaper, and the bolus makes it nicer for nurses to use. But ER docs won’t start using tNK until a solid study supports superiority and ease of use over tPA. We just don’t have the experience with tNK that we have with tPA.”