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Linger et al. Vessel Plus 2020;4:36 I http://dx.doi.org/10.20517/2574-1209.2020.51 Page 5 of 9

and Randomized Controlled Trial to Optimize Patient’s Selection for Endovascular Treatment in Acute
Ischemic Stroke (SELECT-2), NCT03876457] are currently underway to assess this possible benefit.
Undoubtedly, rates of functional independence (defined as mRS 0-2) will be substantially lower compared
to the imaging-selected randomized controlled thrombectomy trials, such as EXTEND-IA, DAWN and
DEFUSE 3. However, mRS 3 outcomes that allow patients to return home with some supports are clinically
and economically meaningful compared to death and requirement for fulltime nursing care. Another
potential positive outcome may be a reduction in the requirement for hemicraniectomy.

ENDOVASCULAR THROMBECTOMY FOR BASILAR ARTERY OCCLUSIONS
Basilar artery occlusion is associated with very high levels of morbidity and mortality. Meta-analysis
of observational data demonstrated lower rates of death (HR = 0.49, 95%CI: 0.44-0.55) and improved
modified Rankin scale 4-6 (HR = 0.67, 95%CI: 0.63-0.72) with thrombectomy as compared to best
[35]
medical management . Unfortunately, prospective randomized controlled data are less robust. The BEST
randomized trial demonstrated improved outcomes with thrombectomy in an as-treated analysis (mRS
0-2; 39 vs. 19%, OR = 2.81, 95%CI: 1.23-6.41) but was confounded by high crossover rate from medical
[36]
management to thrombectomy, resulting in a neutral intention-to-treat analysis . The BASICS (Basilar
Artery International Cooperation Study) randomized trial has been reported in abstract form and did not
demonstrate a significant benefit in favorable outcome with thrombectomy (mRS ≤ 3; 44.2 vs. 37.7%, RR 1.18,
95%CI: 0.92-1.50). However, the subgroup with severe clinical deficit (NIHSS ≥ 10) appeared to benefit.
[37]
Critical details including the rate of successful reperfusion have not yet been released .

THROMBOLYSIS FOLLOWED BY THROMBECTOMY VS. DIRECT THROMBECTOMY
The current standard of care in a patient presenting with a LVO, even in a thrombectomy-capable center,
is to give thrombolysis prior to proceeding with thrombectomy. Thrombolysis is more widely available
than thrombectomy and should be given at primary stroke centers, if no contraindications exist, prior
to transfer to a thrombectomy-capable center. Studies looking at whether thrombolysis can be withheld
in patients who present directly to a thrombectomy-capable center are currently underway [Solitaire
With the Intention For Thrombectomy Plus Intravenous t-PA Versus DIRECT Solitaire Stent-retriever
Thrombectomy in Acute Anterior Circulation Stroke (SWIFT DIRECT), NCT03192332; A Randomized
Controlled Trial of DIRECT Endovascular Clot Retrieval Versus Standard Bridging Thrombolysis With
Endovascular Clot Retrieval (DIRECT SAFE), NCT03494920 and Multicenter Randomized CLinical trial
of Endovascular treatment for Acute ischemic stroke in the Netherlands investigating the added benefit of
intravenous alteplase prior to intra-arterial thrombectomy in stroke patients with an intracranial occlusion
of the anterior circulation (MR CLEAN-NO IV), ISRCTN80619088]. The first trial published on this
topic, Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke [DIRECT-MT],
found similar results between direct thrombectomy and combined thrombolysis-thrombectomy arms.
Technically, direct thrombectomy narrowly met the specified non-inferiority margin of the lower bound of
the 95% confidence interval for the common odds ratio > 0.80. However, this margin was overly generous
and does not provide reassurance that omitting thrombolysis would be appropriate, even in patients who
directly present to a thrombectomy center . The rate of successful reperfusion at end of thrombectomy
[38]
was numerically higher in the alteplase pre-treated group and there were no significant differences in
adverse events, including symptomatic intracerebral hemorrhage, between groups . Other factors that
[38]
confound the interpretation of the direct to thrombectomy trials are the use of alteplase rather than the
more effective thrombolytic tenecteplase [39,40] and potentially distorted acute stroke workflow. Usually,
thrombolysis can be given in parallel with thrombectomy decision-making, whereas in these trials, all
imaging must be completed and the patients accepted by the interventionist for thrombectomy before they
can be randomized and eventually receive thrombolysis. The delay in commencing thrombolysis reduces its
opportunity to induce reperfusion prior to thrombectomy.