Giving tPA before thrombectomy still holds in stroke

Outcomes after stroke thrombectomy were no better with tissue plasminogen activator (tPA) withheld in the MR CLEAN-NO IV trial, suggesting that the practice of giving thrombolytics still holds in stroke.

The trial failed to show superiority or noninferiority of direct endovascular treatment (EVT) over tPA (intravenous alteplase) on top of EVT. Functional outcomes were not significantly different and haemorrhage rates with or without tPA prior to EVT were comparable.

“This is very surprising, we have always thought thrombolysis causes an increased bleeding risk,” said co-lead investigator Dr Yvo Roos, professor of neurology at Amsterdam Medical Center, Amsterdam, the Netherlands. “We may have to rethink that idea  now ― perhaps it is not the tPA itself that is causing the bleeding risk but the opening up of the vessel.”

“It looks like, we cannot change standard practice … giving tPA to those eligible still holds. But I think tPA may not be needed in patients who can go straight to EVT,” he added.

Similar results for both approaches  

The MR CLEAN-NO IV trial had 540 acute stroke patients with large vessel occlusion (LVO) randomly assigned to direct EVT alone or tPA on top of EVT.  The mean time from stroke onset to groin puncture was 130 minutes in the direct EVT group and 135 minutes in the tPA group. [ISC 2021, abstract LB3]

Patients randomized to EVT alone did not meet the criteria for superior functional outcomes on the modified Rankin Scale (mRS) at 90 days vs those getting tPA on top of EVT (adjusted common odds ratio [OR], 0.88, 95 percent confidence interval [CI], 0.65-1.19).

Direct EVT failed to meet noninferiority as the lower 95 percent CI bound crossed 0.8.  In addition, a good functional outcome (mRS 0-2) was achieved in 49 percent of patients getting direct EVT and in 51 percent of the tPA group (adjusted OR 0.95, 95 percent CI, 0.65-1.40).

Skipping tPA made no difference in intracerebral haemorrhage (ICH, 35.9 percent vs 36.4 percent for direct EVT)  or symptomatic ICH (5.9 percent vs 5.3 percent). Mortality rates were also similar between groups.

Leave it out if in doubt

“Thrombolytics are critical in hospitals where transfer to thrombectomy centre is going to take some time,” commented Dr Joseph Broderick from the University of Cincinnati in Cincinnati, Ohio, US, who is unaffiliated with the trial.

“On the other hand, if we are not sure whether a patient is suitable for tPA because they have a higher bleeding risk, I think we can be reassured about missing the tPA out and going straight to EVT. So, if in doubt, leave it out,” Roos said.

Previous trials (DEVT, SKIP, DIRECT-MT) in Asian countries of whether thrombolysis can be omitted in patients who can go straight to EVT found no differences in functional outcomes between the two approaches.  

“The results of the two approaches are very similar in this study and in the Asian studies. It doesn’t appear that tPA adds very much, and it is associated with a significant increase in costs,” commented Dr Tudor Jovin from the Cooper University Hospital in Cherry Hill, New Jersey, US. “The answer will probably be that there is not a one-size-fits-all strategy.”

When to skip tPA

Dr Charles Majoie, co-lead investigator of the MR CLEAN-NO IV trial, who is also from the Amsterdam Medical Center, shared the same standpoint as Jovin, saying different patients may require different approaches.

“If we have a young patient and the angiography suite is ready, we could probably skip tPA, but it would be for the neurologist/neuroradiologist to make individualized decisions on that,” he said.