Aristeidis H. Katsanos, MD, PhD
According to the current guidelines from the American Heart Association/American Stroke Association, endovascular thrombectomy (EVT) should be implemented in the treatment of acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) who have a measurable neurological deficit of at least 6 points in the National Institutes of Health Stroke Scale (NIHSS) on admission, providing however weak support for the use of EVT in AIS patients with internal carotid artery (ICA) or proximal middle cerebral artery (MCA-M1) occlusion and a baseline NIHSS score less than 6. In the October issue of Stroke, two independent multicenter study groups aimed to answer the question on the utility of EVT in patients with LVO and mild AIS severity (NIHSS <6).
Nagel et al. performed a retrospective analysis of prospectively collected data on the safety and efficacy outcomes of 300 AIS patients with LVO and NIHSS scores of 0 to 5 on admission, who were treated with either immediate EVT (n=80) or best medical care (n=220). Patients receiving immediate EVT were younger, with higher rates of atrial fibrillation, higher baseline NIHSS score, and higher Alberta Stroke Program Early CT Score (ASPECTS), and had more frequent proximal M1-MCA occlusions. Using propensity score matching to account for the aforementioned imbalances in baseline characteristics, the authors found that patients receiving immediate EVT had significantly higher rates of good clinical outcome [defined as a modified Rankin Scale (mRS) score of 0 to 2] at 90 days compared to patients treated non-endovascularly, with no excess in the risks of symptomatic intracranial hemorrhage (sICH) or mortality. It also needs to be highlighted that 11.3% of patients in the conservative group finally received delayed EVT as a rescue therapy due to neurological deterioration after admission.
Likewise, in the retrospective analysis of prospectively collected data by Sarraj et al., AIS patients with LVO and NIHSS scores of 0 to 5 on admission who received immediate EVT (n=124) were also found to have higher NIHSS scores on admission and higher prevalence of proximal occlusions compared to non-endovascularly treated patients (n=90). In multivariable logistic regression models, they found no differences between groups in either the rates of excellent (mRS 0–1) or independent (mRS 0-2) 3-month outcome. Similarly, in the analysis of propensity score matched groups, no difference in the efficacy outcomes was found for patients who received EVT compared to patients receiving medical treatment, while EVT was associated with a higher likelihood of sICH.
Compared to the study by Nagel et al., Sarraj et al. included a significant proportion of patients with distal (M3/M4/ACA) occlusions that were significantly more prevalent in the non-endovascular group. Although Nagel et al. reported no significant differences according to thrombus location, a signal of efficacy for EVT on the likelihood of mRS 0-1 at 3-months was present for patients with proximal (M1/ICA) occlusions (adjusted Odds Ratio= 2.68; 95% CI: 0.98–7.32; p=0.05), which is fairly in line with the adjusted odds ratio of 3.1 (95% CI: 1.4–6.9) on the likelihood of 3-month mRS 0-2 with EVT reported by Nagel et al.
It should be highlighted that despite the rigorous statistical analyses performed in both studies, the validity of their outcomes is limited by the retrospective protocol design and the presence of confounding by indication, as suggested by the higher NIHSS scores and the more frequent presence of proximal occlusions in the EVT groups in both studies. The discrepancies of reported outcomes between the propensity score matched analyses of the two studies can also be attributed to the presence of unmeasured, non-balanced factors and the relatively small number of patients included in each strata, increasing the risk for residual confounding due to remaining variability. Despite the aforementioned limitations and until forthcoming randomized clinical trials provide an indefinite (hopefully) answer to the utility of EVT in patients with LVO and mild AIS severity, observational studies on the topic can provide invaluable information to guide therapeutic management, if perceived within a skeptical and combinational approach.
