Is Thrombolysis Necessary Before Thrombectomy in Stroke?

January 24, 2017

Now that mechanical thrombectomy has proven to be beneficial in patients with acute ischemic stroke caused by a large vessel occlusion, the question of whether thrombolysis is necessary beforehand has been raised. A new analysis suggests it may not be.

Several randomized trials published in the last 2 years have shown definitive benefit of mechanical removal of the clot in selected stroke patients and in most patients in these trials thrombectomy was performed after thrombolysis.

Writing in a paper published online in JAMA Neurology on January 9, an international group of researchers note that in the recent trials of thrombectomy, of patients randomly assigned to subsequent mechanical thrombectomy after treatment with tissue plasminogen activator (tPA), only a small proportion had vessel patency at the time of the first catheter angiography. This finding suggests that early recanalization in response to thrombolysis is uncommon in this selected patient population with a proximal occlusion.

"In some centers where we have geared up for thrombectomy, we have got the situation now when patients are arriving at the cath lab ready for the procedure but the tPA is still ongoing or has only just been started," senior author, Vitor M. Pereira, MD, Toronto Western Hospital, Ontario, Canada, commented to Medscape Medical News.

"Sometimes we have finished the thrombectomy and the tPA is still running," he said. "That has led us to question if we can get patients to thrombectomy so quickly, do we really need tPA at all? It might be that it just increases bleeding risks and costs and may not add any benefit to the procedure."

He explained that in the five recently published trials that established a benefit of thrombectomy, most patients received tPA beforehand, and there were too few patients who did not get thrombolysis to make a meaningful comparison.

The researchers therefore decided to look at the benefit of thrombolysis in the databases of the STAR and SWIFT trials conducted in 2010 to 2013. The SWIFT trial compared the new Solitaire thrombectomy device (Medtronic Neurovascular) with the older Merci device (Stryker Neurovascular), and the STAR trial was a nonrandomized, single-group study of the Solitaire device. For this analysis, patients from the SWIFT trial treated with the Merci device were excluded because use of that device does not represent current clinical practice.

In both SWIFT and STAR, patients were eligible if thrombectomy was feasible within 8 hours of symptom onset. Thrombolysis was recommended in all patients within 4.5 hours of stroke symptom onset who did not have any contraindication.

Of the 291 patients included in the analysis, 160 (55.0%) underwent thrombectomy after thrombolysis and 131 (45.0%) were treated with thrombectomy alone.

Of the patients who received thrombolysis, this was judged to have failed in 116 (full tPA dose), and 44 received bridging therapy at a mean dose of 0.62 mg/kg.

The median time from symptom onset to hospital arrival was shorter in patients treated with thrombolysis plus thrombectomy (171 vs 190 minutes), but the median time from hospital arrival to groin puncture was similar in both groups.

Results showed no differences in the median number of passes or the rate of modified Thrombolysis in Cerebral Infarction 2b or 3 reperfusion among groups. Vasospasm occurred more often in patients who received thrombolysis (26.9% vs 13.7%). Somewhat counterintuitively, symptomatic intracerebral hemorrhage occurred less frequently in patients treated with thrombolysis (1.3% vs 3.8%), but this was not statistically significant.

Results of the multivariate analyses did not show a statistically significant association between the use of thrombolysis and any of the outcomes studied. However, there were a numerically lower risk for intracerebral hemorrhage, a higher risk for emboli to uninvolved territory, and a higher rate of functional independence (90-day modified Rankin Scale score of 0 to 2: adjusted odds ratio, 1.48; 95% confidence interval, 0.80 - 2.74).

When patients who received bridging-dose tPA were excluded, the results of the multivariate analysis were essentially the same.

Randomized Trials Planned

"We cannot draw any definite conclusions from this post hoc analysis," Dr Pereira commented. "At present, we always give tPA to everyone who is eligible and arrives within 4.5 hours, and we do thrombectomy as well in patients up to 8 hours. But we think our results show that we need to do randomized trials to look at the issue of whether tPA is adding anything if patients arrive early for thrombectomy."

Several such randomized trials are actually now planned. These include the SWIFT DIRECT trial, being run by Dr Pereira's Canadian group in collaboration with a team from Berne, Switzerland. There is also a Dutch trial from the MR CLEAN group, and another trial from Australia. Results should be in by 2020.

"Even if these trails show tPA does not add benefit, it will still be used in many places for patients who won't be able to get to the comprehensive stroke centers in time for thrombectomy," Dr Pereira points out. "But there is a possibility that if patients present early to a hospital where thrombectomy can be done fast, the addition of tPA may not be necessary."

In an accompanying editorial, Gursant S. Atwal, MD, and Adnan H. Siddiqui, MD, State University of New York at Buffalo, say that "Although there are hypothetical benefits [of thrombolysis], such as increased recanalization and thrombolysis of smaller clot fragments, there are also hypothetical concerns regarding increased risk for intracranial hemorrhage and greater fragmentation with reduction in MT [mechanical thrombectomy] effectiveness."

They add that the current study provides the largest well-designed and -conducted multicenter data set to highlight the question and provides critical data that can be used to design a definitive randomized clinical trial.

JAMA Neurol. Published online January 9, 2017. Abstract, Editorial

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