Stroke represents the fourth leading cause of death in industrialized nations, after
and chronic lower respiratory disease.
The overall burden of stroke will rise dramatically in the next 20 years due to an ageing population. The projections in the Burden of Stroke report indicate that between 2015 and 2035, overall there will be a 34% increase in total number of stroke events in the European Union from 613,148 in 2015 to 819,771 in 20351.
Approximately one-quarter of the patients suffering a stroke die within one year after the initial event and stroke is a leading cause of serious long-term disability. Direct medical costs related to stroke in the United States is an estimated $28.3 billion per year3. In the EU the total cost of stroke in 2015 was calculated as €45 billion1. We can then conclude that stroke brings a dramatic financial and personal burden to society.
Proximal intracranial arterial occlusions cause the most disabling types of ischemic strokes and are predictive of poor neurological outcomes2.
In population-based studies, patients presenting with minor or mild stroke symptoms represent about two-thirds of stroke patients, and almost one-third of these patients are unable to ambulate independently at the time of discharge4,5.
Although mechanical thrombectomy (MT) has become the standard of care for acute ischemic stroke with proximal large vessel occlusion (LVO) in the anterior circulation, the management of patients harboring proximal occlusion but presenting minor-to-mild stroke symptoms, has not yet been determined by these recent randomized clinical trials6,7. Indeed, the majority of patients presented with major clinical impairment, with a median NIHSS of 178. Thus, American Heart Association (AHA) gives level 1a evidence for MT performed only for patients with baseline NIHSS score ≥69.
However, patients with proximal occlusions may present with a low NIHSS10, a proximal intra-arterial occlusion being present in up to 28% when considering patients with an NIHSS ≤ 411. In observational study, patient with minor or mild stroke symptoms and LVO have a high risk of both clinical worsening and bad outcome12.
The STAIR (Stroke Treatment Academic Industry Roundtable) meeting aims to advance acute stroke therapy development through collaboration between academia, industry, and regulatory institutions13. In pursuit of this goal and building on the available level I evidence of benefit from endovascular therapy (EVT) in large vessel occlusion stroke, STAIR IX consensus recommendations were developed that outline priorities for future research in EVT. Three key directions for advancing the field were identified:
(1) Development of systems of care for EVT in large vessel occlusion stroke
(2) Development of therapeutic approaches adjunctive to EVT
(3) Exploring clinical benefit of EVT in patient population insufficiently studied in recent trials and explore whether patient eligibility could be expanded
Recent AHA/ASA guidelines have also highlighted the need to gain more evidence to determine whether there is an overall net benefit from endovascular therapy (EVT) in patients with LVO and minor stroke9.
The effectiveness and safety of MT, in the subgroup of minor stroke with LVO in the anterior circulation, is still open to debate. Data about MT in this subgroup of patients are sparse, and their optimal management has not yet been defined14.
A retrospective study conducted in France has analyzed the data extracted from 3 prospective clinical registries of all consecutive patients with acute cerebral infarct and minor-to-mild symptoms treated by MT, with or without intravenous thrombolysis, between January 2012 and March 201615. The purpose of this study was to evaluate the impact of reperfusion on functional outcome after MT. Regarding patient selection, it corresponds to those used in several studies, both for minor (NIHSS ≤ 3)16,17 and mild strokes (NIHSS <8)18.
The study shows that the reperfusion status achieved with MT strongly impacts the functional outcome among minor to-mild stroke patients with LVO. The excellent outcome (mRS 0-1) rate increased with reperfusion grades, with 34.6% of patients with no successful reperfusion having excellent outcome in comparison to 61.7% in patients with TICI 2B reperfusion and 78.5% in patients with TICI 3 reperfusion (p for trend <0.001). There are already known the limitations inherent to a retrospective design, added to a relatively small sample size extracted from 3 different centers but, the main limitation is the absence of a control group undergoing optimal medical management alone.
One previous study with a relatively small sample size (n = 33) has already shown that clinical outcome is predominately favorable for minor stroke patients having undergone MT19. Excellent and favorable outcomes were achieved in 42.4 and 63.6%19.
Another recent small case–control study (n=10 in the MT group and 22 in the medical group) suggested that MT may lead to a shift towards a lower NIHSS at discharge than due to medical management alone (rate of excellent outcome, MT, 70% versus BMT, 55%)20. An analysis from STOPStroke and GESTOR cohorts (n=30 in the MT group and 88 in the medical group) similarly concludes that in patients presenting with minimal stroke symptoms (NIHSS score ≤5) and large vessel occlusion strokes, MT appears to be associated with a favorable shift of NIHSS at discharge, as well as higher rates of independence at discharge and long-term follow-up21.
Another retrospective study 378 patients with minor strokes in the anterior circulation; 54 (14.2%) of these had proved large-vessel occlusions. Eight of 54 (14.8%) were immediately treated with mechanical thrombectomy, 6/54 (11.1%) after early neurologic deterioration, and the rest were treated with standard thrombolysis only. Rates of successful recanalization were similar between the 2 mechanical thrombectomy groups (75% versus 100%). Rates of excellent outcome (modified Rankin Scale 0–1) were higher in patients with immediate thrombectomy (75%) compared with patients with delayed thrombectomy (33.3%) and thrombolysis only (55%). No symptomatic intracranial hemorrhage occurred in either group22.
A multicenter cohort study of minor and mild AIS patients harboring LVO in the anterior circulation, conducted in 4 comprehensive stroke centers with two therapeutic approaches (urgent MT associated with BMT versus BMT first and MT if worsening occurs) included 301 patients (170 with urgent MT associated with BMT and 131 with BMT alone as first line treatment). The primary end-point was the rate of excellent outcome defined as the achievement of a mRS score of 0–1 at 3 months23. In an intention-to-treat analysis, patients treated with urgent MT were younger, more often received intravenous thrombolysis, and had shorter time to imaging. Twenty-four patients (18.0%) in the BMT group had rescue MT due to neurologic worsening. Overall, excellent outcome was achieved in 64.5% of patients, with no difference between the two groups. Stratified analysis according to key subgroups did not find heterogeneity in the treatment effect size. Study conclusion was that minor-to-mild stroke patients with LVO achieved excellent and favorable functional outcomes at 3 months in similar proportions between urgent MT versus delayed MT associated with BMT.