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In patients presenting at thrombectomy-capable stroke centers, the benefit associated with thrombolysis plus thrombectomy vs thrombectomy alone was time dependent and statistically significant only if the time from symptom onset to expected administration of thrombolysis was short, new data suggested.

These results, from a new individual participant data meta-analysis conducted by the Improving Reperfusion Strategies in Ischemic Stroke collaboration, showed that thrombolysis plus thrombectomy was significantly associated with a favorable shift in functional outcome at 90 days vs thrombectomy alone if the time from symptom onset to expected administration of thrombolysis was within 2 hours 20 minutes. Thereafter, there was no statistically significant association.

The findings were presented on February 7, 2024, at the International Stroke Conference 2024 being held in Phoenix, Arizona. They were also simultaneously published online in JAMA.

"Our results suggest a reasonably large benefit associated with thrombolysis plus thrombectomy if thrombolysis was administered early. However, similar to trials comparing thrombolysis vs placebo, we observed a rapid increase in the estimated number of patients needed to treat to achieve benefit when there were longer treatment delays," the authors stated.

They suggested that the time between symptom onset and expected administration of thrombolysis should be considered in the decision-making process on whether to give thrombolysis for patients who are directly admitted at stroke centers to undergo thrombectomy.

The researchers, led by Johannes Kaesmacher, MD, University Hospital Bern, Bern, Switzerland, noted that the benefit of thrombolysis for acute ischemic stroke declines with longer time from symptom onset, but it is not known whether a similar time dependency exists for thrombolysis followed by thrombectomy.

Current guidelines recommend administration of thrombolysis before thrombectomy in all eligible patients with large-vessel anterior circulation stroke, they noted. However, previous pooled data from randomized clinical trials comparing thrombolysis plus thrombectomy vs thrombectomy alone in participants presenting directly to a thrombectomy-capable center have been inconclusive.

They suggested that certain subgroups of patients may benefit from a treatment strategy that combines thrombolysis with thrombectomy while other subgroups may not, and time from stroke onset to treatment is one potential influencing factor.

To investigate this issue, the researchers conducted the current individual participant data meta-analysis from six randomized clinical trials comparing thrombolysis plus thrombectomy with thrombectomy alone. All participants were eligible for both thrombolysis and thrombectomy and presented directly at thrombectomy-capable stroke centers.

Results showed that the median time from symptom onset to expected administration of thrombolysis was 2 hours 28 minutes.

There was a statistically significant interaction between the time from symptom onset to expected administration of thrombolysis and the association of allocated treatment with functional outcomes.

The benefit of thrombolysis plus thrombectomy decreased with longer times from symptom onset to expected administration of thrombolysis; adjusted common odds ratio for a 1-step modified Rankin Scale (mRS) score shift toward improvement was 1.49 at 1 hour, 1.25 at 2 hours, and 1.04 at 3 hours.

For an mRS score of 0-2, the predicted absolute risk difference was 9% at 1 hour, 5% at 2 hours, and 1% at 3 hours. After 2 hours 20 minutes, the benefit associated with thrombolysis plus thrombectomy was not statistically significant, and the point estimate crossed the null association at 3 hours 14 minutes.

The authors said there appeared to be equipoise among practicing clinicians on the issue of giving thrombolysis before thrombectomy, and they cited a recent analysis of a German stroke registry showing that 37% of patients directly admitted to a comprehensive stroke center did not receive thrombolysis before thrombectomy despite the absence of contraindications.

Based on times from stroke onset to thrombolysis administration, they estimated that depending on the geographic setting, up to approximately 50% of patients eligible for thrombectomy may receive a treatment, thrombolysis, that showed no statistically significant association with better outcomes according to the data in the current study.

If the current study's findings are validated, they can help stratify cohorts of patients undergoing thrombectomy for whom thrombolysis is likely associated with a significant benefit, those for whom there is very unlikely to be benefit, and those for whom there is uncertainty on this issue, they concluded.

The research was supported by an unrestricted grant from Stryker and institutional funds from the Amsterdam University Medical Centers and the University Hospital Bern. Kaesmacher reported receiving grants from the Swiss National Science Foundation paid to the University of Bern.