The Source for Neurovascular News and Education

December 04, 2023


The study demonstrates good safety and clinical outcomes, but larger, multicenter trials are needed to standardize the technique.


Intra-arterial recombinant tPA as a rescue therapy after failed mechanical thrombectomy may safely improve outcomes without increasing the risk of symptomatic hemorrhage or mortality, a small registry trial published recently online ahead of print in Stroke shows.


According to one expert who currently uses intra-arterial recombinant tPA routinely in combination with mechanical thrombectomy, it is high time this approach was evaluated in a large, randomized clinical trial.


“Since the time of effective mechanical thrombectomy devices and techniques, we have something that works very well for large-vessel occlusions [LVOs], in most cases,” William W. Ashley Jr, MD, PhD (Sinai Hospital of Baltimore and LifeBridge Health System, Baltimore, MD), told Neurovascular Exchange in a comment on the study. “The addition of recombinant tPA is useful, but it’s not standard. Many of us use it, but not everyone, and what’s more important is not everyone uses it in a standardized way.”


“We have anecdotal evidence that it works, and I certainly think it works well in clots that are resistant to our standard treatment,” he continued. “It has an additive effect, I think.”


For the study, researchers led by Syed F. Zaidi, MD (University of Toledo Health Science Campus, Toledo, OH), used the North American Solitaire Stent-Retriever Acute Stroke registry to identify 354 patients treated with mechanical thrombectomy for anterior emergent LVOs who required rescue therapy.


Overall, 37 patients received intra-arterial recombinant tPA rescue therapy and 44 did not. Successful revascularization, defined as a modified TICI ≥ 2b, occurred more often in patients who received intra-arterial recombinant tPA as rescue therapy (61.2% vs 46.6%; P = 0.13).


In addition, time to recanalization was numerically shorter and rate of good functional outcome (defined as mRS ≤ 2) was numerically higher among patients who received recombinant tPA, but the difference did not reach statistical significance.


At 90 days, rates of symptomatic intracranial hemorrhage (ICH) and mortality were similar for both groups.


Clinical Outcomes


Recombinant tPA

(n = 37)

No Recombinant tPA

(n = 44)

P Value

Symptomatic ICH









In an exploratory analysis of patients with M1 occlusions only and a time of onset-to-groin puncture ≤ 8 hours, rates of successful revascularization were significantly greater among those who did versus did not receive intra-arterial recombinant tPA rescue therapy (77.8% vs 38.9%; P = 0.02).


Zaidi and colleagues say their findings represent the only multicenter study of intra-arterial recombinant tPA as rescue therapy after failed mechanical thrombectomy.


“We recommend that future studies, including large prospective randomized clinical trials, are needed to establish the proper patient population and protocol for intra-arterial recombinant tPA administration and to determine if intra-arterial recombinant tPA is more advantageous as an adjunctive or [rescue therapy],” they write.


Moving Toward a Standardized Approach


Speaking with Neurovascular Exchange, Ashley said randomized trials are needed to confirm the benefit of the technique and aid in the development of a standardized approach.


In a study published in 2017, he reported on his own use of intra-arterial recombinant tPA with mechanical thrombectomy. Instead of reserving it as a rescue therapy, as was done in this study, he developed a standard protocol for its use. “I give a dose right before I take out the clot to soften it,” he explained. “I give a second dose right after the stent is opened; it helps it become intercalated into the stent. Then I give a third dose once the stent is removed to potentially help deal with any emboli to microperforators. . . . I use it pretty much every time. . . . I think it really does improve outcomes in terms of speed and number of passes, and I have not had a significant increase in the number of post-treatment hemorrhages.”


This study, he said, provides “additional evidence that, in a separate set of hands, this is a potentially efficacious treatment protocol.”




Zaidi SF, Castonguay, AC, Jumaa MA, et al. Intraarterial thrombolysis as rescue therapy for large vessel occlusions: analysis from the North American Solitaire Stent-Retriever Acute Stroke registry. Stroke. 2019;Epub ahead of print.



  • Zaidi reports no relevant conflicts of interest.
  • Ashley reports being a proctor consultant for Medtronic.