Thrombolysis Unnecessary in Some Stroke Thrombectomies?

February 25, 2020

LOS ANGELES — A new Japanese study suggests that thrombolysis may not always be necessary in the treatment of acute stroke when a patient is going to receive endovascular therapy.

The SKIP trial found similar functional outcomes at 90 days in patients receiving thrombolysis plus thrombectomy and those receiving thrombectomy alone. However, the study failed to prove non-inferiority.

The trial was presented by Kentaro Suzuki, MD, Nippon Medical School, Japan, at last week's International Stroke Conference (ISC) 2020 in Los Angeles.

For the trial, 200 ischemic stroke patients with an internal carotid artery or M1 middle cerebral artery occlusion, and within 4 hours of symptom onset, were assigned to either mechanical thrombectomy alone or the combination of thrombolysis (alteplase at the Japanese dose of 0.6 mg/kg) plus thrombectomy.

At 90 days, favorable outcomes (defined as modified Rankin score 0-2) were similar: 59% for those who received thrombectomy alone vs 57% for those who received the combination approach. There was no difference in death rates between the two groups.

However, the rate of any intracranial hemorrhage (ICH) within 36 hours was significantly lower for the thrombectomy alone group. Symptomatic ICH was not significantly different between the two groups, although there was a trend toward a reduction in the thrombectomy alone group.    

Table. ICH Rates at 36 Hours

End Point

Thrombectomy alone (n = 101)

Thrombolysis plus thrombectomy (n = 103)

HR (95% CI)

P value

Any ICH   (%)



0.50 (0.28-0.88)


Symptomatic ICH (NINDS criteria) (%)



0.65 (0.25-1.67)


Symptomatic ICH (SITS-MOST criteria) (%)



0.75 (0.25-2.24)


NINDS – National Institute of Neurological Disorders and Stroke
SITS-MOST – Safe Implementation of Thrombolysis in Stroke-Monitoring Study

"We feel that giving alteplase to dissolve clots is not necessary, and mechanical clot removal can be performed immediately," Suzuki said. "If we skip alteplase, we can perform mechanical thrombectomy with low risk of bleeding."

Louise McCullough, MD, PhD, McGovern Medical School, University of Texas Health Science Center at Houston, told Medscape Medical News that with the increased use of thrombectomy, it has been a subject of great debate in the stroke field whether thrombolysis is necessary prior to thrombectomy. McCullough was the co-chair of the ISC session at which the SKIP trial was presented.

"In this study, functional outcomes were similar between IV tPA and mechanical thrombectomy and mechanical thrombectomy alone," McCullough said. However, she pointed out that both groups showed very high recanalization rates of over 90% (compared with around 70% in prior studies) and the lower dose of 0.6 mg/kg alteplase was used rather than the 0.9 mg/kg used in many other countries. "It is possible that ICH rates would have been higher with the higher dose," she added.   

Also commenting for Medscape Medical News, Bruce Campbell, MBBS, PhD, Royal Melbourne Hospital, Australia, who conducted one of the first positive thrombectomy trials, EXTEND-IA, pointed out that SKIP is the first of several trials attempting to address the question of whether IV thrombolysis adds any value to thrombectomy.

"The SKIP trial used the lower 0.6 mg/kg alteplase dose standard in Japan (that failed to show non-inferiority vs 0.9 mg/kg in the ENCHANTED trial), and a much smaller sample size than the other direct thrombectomy trials, leaving it underpowered," he said.

"It is important for the stroke community to remember that these trials only apply to patients presenting to a hospital that has immediate on-site access to thrombectomy (currently the minority of large vessel occlusion stroke patients as most require interhospital transfer). Thrombolysis remains standard care for all eligible patients unless randomizing into one of these trials," Campbell stressed.  

"Overall in the SKIP trial there were no perceptible differences between the direct and bridging (thrombolysis plus thrombectomy) strategies, which will no doubt be variably interpreted as supporting no advantage of continuing with thrombolysis or no advantage of dropping thrombolysis depending on an individual's viewpoint. Asymptomatic hemorrhage was reduced but this is not clinically relevant — the numeric reduction in symptomatic hemorrhage (6% vs 8%) was of small magnitude and did not reach statistical significance," he noted.  

Campbell does not believe the current results will affect practice at present, but will be considered along with the results from several other similar studies currently underway.

"As the results from subsequent direct trials become available, it will be important to scrutinize the workflow times, as the trial randomization procedure may delay IV thrombolysis compared to standard care practices, which would reduce the time that thrombolysis has to work before thrombectomy," Campbell said. "The trials will also mainly be comparing direct thrombectomy vs bridging with alteplase (rather than tenecteplase, which appears to be a more effective thrombolytic for large vessel occlusion ischemic stroke)."

Another stroke endovascular pioneer, Michael Hill, MD, University of Calgary, Canada, added: "It is always incredibly challenging to design a randomized trial where the intervention is withholding of a proven therapy. The non-inferiority design is appropriate here, but even if the team has been able to show non-inferiority, the non-inferiority margin was so large that I am uncertain if it would have had clinical meaning."

"It is likely that in a subgroup of patients with proximal large vessel occlusion and rapid access to endovascular therapy with a technically good endovascular team that can achieve very high rates of reperfusion, intravenous thrombolysis may not be of much benefit," Hill said. "However, a key clinical issue is that the expected benefit of IV thrombolysis will necessarily be limited to the small proportion of patients who undergo early recanalization and the small proportion of patients who benefit from the clean-up effect of IV thrombolysis dealing with small distal emboli in a new territory. Therefore, trial designs need to be statistically robust enough to detect small differences."

The SKIP study was funded by the Japanese Society for Neuroendovascular Therapy. Suzuki has disclosed no relevant financial relationships.

International Stroke Conference (ISC) 2020: Abstract LB18. Presented February 21, 2020.

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