To give or not to give IV t-PA: That is the question

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By Joshua A Hirsch

Joshua Hirsch_main
Joshua A Hirsch

The year 2015 was a remarkable one for long-term proponents of endovascular therapy for strokes resultant from emergent large vessel occlusion (ELVO). The excitement of the current multiple positive trials was amplified by the failure in 2013 of Interventional Management of Stroke (IMS) III, Synthesis Expansion and MR RESCUE to demonstrate a benefit for endovascular therapy.  

In January 2016, the Journal of NeuroInterventional Surgery featured a comment primarily authored by Ronil Chandra and Thabele Leslie-Mazwi (with a multi-disciplinary group of co-authors) that in its title posed the question, “Does the use of IV t-PA in the current era of rapid and predictable recanalisation by mechanical embolectomy represent good value?”

The authors concede upfront that the administration of IV t-PA is the current standard of care for eligible patients presenting with stroke up to 4.5 hours from symptom onset. They point out that IV t-PA may produce recanalisation and reperfusion on its own, thereby allowing the patient to avoid embolectomy. Further, IV t-PA may also help by preventing downstream microvascular thrombosis. Finally, they note that there might be patients that cannot be successfully approached with mechanical embolectomy. Conversely, they comment that t-PA is ineffective in the majority of patients with ELVO and might increase the risk of intracranial or systemic haemorrhage, and allergic reactions. In addition, in this era of time-critical reperfusion, t-PA could theoretically prolong the time interval from imaging to groin puncture.

The authors were focused on the point that embolectomy could be completed and reperfusion achieved prior to completion of the one-hour long t-PA infusion. This is not uncommon in comprehensive stroke centres where patients have rapid access to embolectomy. In that particular scenario, they query whether the money spent on t-PA a good investment. This, the authors believe, is an appropriate question in the present day healthcare milieu.

The authors point to the work of Michael Porter from Harvard Business School who defines healthcare value as outcome divided by cost. The trials make clear that marked improvement in patient outcomes and overall reduced post-acute care cost have improved the value proposition of performing mechanical embolectomy.

Thus, for patients who present directly to a comprehensive stroke centre who are able to access embolectomy rapidly, perhaps eliminating the additional cost and potential harms of t-PA will further enhance healthcare value. Groups treating stroke from around the world are actively engaged in a multitude of quality improvement initiatives with a focus on workflow optimisation for patients destined to receive intra-arterial therapy. As parallel processing opportunities continue to reduce treatment delay, they suggest that routine median door-to-groin puncture times at comprehensive stroke centres within 60 minutes are achievable. When one considers that a recent analysis of participating hospitals in the “Get With The Guidelines—Stroke” (GWTG)showed a median door-to-needle time for t-PA of 67 min (IQR 51–87 min), it is evident that patients might be mechanically reperfused while t-PA is still running.

Lee Schwamm, one of the architects of the GWTG programme, thinks that the issue may be more nuanced. “While we know that patients with LVO receive great benefit from embolectomy, most of the data have been in patients who first received t-PA and those who did not were not eligible for t-PA. Additionally, at the high performing centres that were included in the embolectomy trials, median door-to-needle times are very fast and it is, nonetheless, still quite unusual for the t-PA to still be dripping when the groin is punctured”. Schwamm continues that “since the patients undergoing embolectomy after t-PA have very low haemorrhage rates, t-PA is not adding risk as a first line agent. It may be helpful in promoting successful TIC 2b3 reperfusion, and it avoids the need for endovascular treatment in ~5–15% of cases enrolled in the major trials. Lastly, 25% of all t-PA in GWTG hospitals is given in a drip and ship paradigm”. His greatest concern would be limiting access to t-PA and believes the only way forward would be in developing a thoughtfully constructed trial.

Chandra, Leslie-Mazwi et al argue that all of this sets the stage for a randomised controlled trial comparing t-PA and embolectomy against embolectomy alone for patients with ELVO presenting directly within 4.5 hours of last known well to neuroendovacular equipped centres of excellence. We believe that this would be an exciting trial indeed.

Joshua A Hirsch is at Massachusetts General Hospital, Boston, USA and can be found tweeting @JoshuaAHirsch