Thrombectomy after intravenous thrombolysis is the new standard of care in acute stroke with large vessel occlusion

Since the demonstration of the efficacy of intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (rt-PA) 20 years ago with the publication of NINDS, no medical or interventional treatment had shown further clinical benefit in acute cerebral infarction. Although three randomized trials (IMS 3 SYNTHESIS, MR RESCUE) using first-generation devices (MERCI system) failed to show benefit of intra-arterial revascularization,^1–3 the therapeutic management of acute ischemic stroke has been revolutionized by the recent results of six randomized controlled trials (MR CLEAN, ESCAPE, EXTEND-IA, SWIFT PRIME, REVASCAT, THRACE) comparing the usual medical management (including IV thrombolysis within 4.5 h of symptoms onset) with stent retriever thrombectomy in acute anterior ischemic stroke with proximal intracranial artery occlusion (distal internal carotid artery or proximal middle cerebral artery).^4–9

MR CLEAN was published in the New England Journal of Medicine in December 2014 and is so far the only completed trial, while the four other trials were stopped early after positive interim analysis. No upper age limit was imposed in most studies. Imaging selection in MR CLEAN, REVASCAT was based on a conventional vascular and parenchymal study (CT/CTA or MRI/MRA). In other studies, patients who may most likely to have salvageable brain if reperfusion could be obtained were selected: ASPECTS and CTA collateral flow in ESCAPE, CT perfusion/core in EXTEND-IA, and CT perfusion/ASPECTS in SWIFT PRIME. ESCAPE enrolled patients with good collaterals on multiphase CTA and a small core defined by an ASPECTS score >5, and a significant mismatch and a small core on CTP automatically calculated by the RAPID software was required in EXTEND-IA and SWIFT PRIME. At present, a good clinical evaluation, a baseline CT, and CTA are probably sufficient to select patients for endovascular therapy within the current treatment window of thrombolysis of 4.5 h.

Stent retriever thrombectomy improved significantly the rate of favourable functional outcome (mRS ≤2 at 3 months) ranging from 33% in MR CLEAN; 53% in ESCAPE; 71% in EXTEND-IA; 60% in SWIFT PRIME; and 44% in REVASCAT (Figure 1, Table 1). By comparison, the rates of favourable outcome in the medical arm were 19% in MR CLEAN, 29% in ESCAPE; 40% in EXTEND-IA; 36% in SWIFT PRIME; and 28% in REVASCAT. These results are valid for patients receiving IV thrombolysis before the thrombectomy. For the first time in the world of acute ischemic stroke, the mortality was significantly reduced in ESCAPE (10% against 19%, p < 0.05). In addition, subgroup analyses of MR CLEAN and ESCAPE trials demonstrated that the benefit of thrombectomy remained among patients older than 80 years old and with various NIHSS thresholds, as well as among patients with tandem occlusions in ESCAPE and REVASCAT. However, rapid management of brain infarction remains mandatory, requiring the involvement of all healthcare stakeholders, as IV thrombolysis, stent retriever thrombectomy should be performed as soon as possible. In fact, in MR CLEAN and EXTEND-IA, the delay between the imaging and the femoral puncture was 60 min and the delay between the imaging and the first stent deployment was 90 min in ESCAPE. In SWIFT PRIME, the delay between the imaging and the femoral puncture was 90 min. These data highlight the importance of minimizing time to recanalization from the pre-hospital stage to the endovascular suite. In addition, it is suggested that these excellent results were obtained by the fact that thrombectomy procedures were performed at relatively high-volume centres, as reported on consensus statement of ESO, ESMINT and ESNR (ESO-Karolinska Stroke Update 2014). This procedure should be realized by a neurointerventionist with threshold number of cases per year to guarantee the safety and efficacy of the thrombectomy. Thus, there is a need for a centralization of thrombectomy procedure and eligible patients should be transferred early to these interventional neuroradiology centres. Interestingly, the addition of intra-arterial treatment therapy compared with standard treatment alone yielded a lifetime gain of 0.7 QALY for an additional cost of US$9911, which resulted in a cost of US$14,137 per QALY.¹⁰ These findings suggest that there is a strong societal rationale for investment in intra-arterial treatment systems of care.

Figure 1.

Rate of reperfusion (TICI 2b-3), good clinical outcome (mRS 0–2 at 3 months) and mortality in intra-arterial thrombectomy (TBY) and control (CTL) groups.

Table 1.

Baseline characteristics of patients in intra-arterial thrombectomy (TBY) and control (CTL) groups.

TBY/CTL	MR CLEAN	ESCAPE	EXTEND-IA	SWIFT PRIME	RESVASCAT
Number of patients	233/267	165/150	35/35	98/98	103/103
Median NIHSS	17/18	16/17	17/13	17/17	17/17
rt-PA IV before TBY (%)	87	76	100	98	73
M1 occlusion (%)	66	68	51	68	65
Tandem occlusion (%)	32	13	–	0	19
Reperfusion onset (min)	260	241	210	224	269
NNT (mRS ≤2 at 3 months)	8	4	3	4	–
sICH (%)	7/6	4/3	0/6	0/3	2/2

TBY: thrombectomy group; CTL: control group; sICH: symptomatic intracranial haemorrhage; ESCAPE: Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times; EXTEND-IA: Extending the Time for Thrombolysis in Emergency Neurological Deficits—Intra-Arterial; MR CLEAN: Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; SWIFT PRIME: Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment Trial; REVASCAT: Randomized Trial of Revascularization With the Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset.

In conclusion, a new therapeutic era is now opening since it is now clear that stent retriever thrombectomy, in combination with IV thrombolysis, significantly increases neurological recovery at 3 months. These results validate thrombectomy in combination with IV thrombolysis as the new standard treatment of acute ischemic stroke with proximal arterial occlusion within 6 h. Each eligible patient will be able to benefit from this new brain revascularization technique in the shortest possible time, which will require a re-organization of care pathways and strengthening teams of interventional neuroradiologists.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.