Johannes Kaesmacher, University Institute of Diagnostic and Interventional Neuroradiology, University Hospital Bern and Diana Aguiar de Sousa, Departamento de Neurociências, Hospital de Santa Maria
Patient selection is a key issue when planning and performing randomized controlled trials (RCT), because the treatment effect observed and, logically, the sample size required to detect this effect in a statistical meaningful manner, will severely depend on the selection of the cohort under study. Accordingly, better definition of the criteria for patient selection, with subsequent restriction in inclusion, was considered as one of the most important factors leading to the positive results of recent pivotal thrombectomy trials. Once evidence is established, however, the problem usually quickly turns, especially if significant results for large effect sizes, as for mechanical thrombectomy, were observed. While restriction was necessary to detect treatment effects in the artificial scenery of RCTs, the question of how many more patients not meeting these restrictive criteria may potentially benefit from this new therapy is usually quickly been put forward. Authors of organizational recommendations are thus often confronted with recommendations and opinions on topics of smaller treatment effect sizes (“the not-so-easy-to-pluck fruits”1), which have not yet been answered by unambiguous results of multiple RCTs.
Like other more recent ESO guidelines, the new ESO/ESMINT guidelines2 have addressed these questions using a transparent approach that follows a PICO-guided design (GRADE methodology). While the strong recommendations remain derived from RCT data without exception, some weaker recommendations and consensus expert opinions also incorporate observational data, generally supporting more inclusive treatment selection.
- Incorporating latest synopses and RCT post-hoc data, the new guidelines make a clear recommendation not to restrict mechanical thrombectomy to patients younger than 80 years of age and have now incorporated a clear recommendation for attempting Thrombolysis in Cerebral Infarction grade 3 whenever possible in order to maximize the therapy benefits achievable.
- Maybe most importantly, there is unambiguous expert opinion (11/11 agreed) on recommending the treatment of M2 and basilar artery occlusions, both formally lacking RCT evidence until today. These will further reassure many centres practices, which already subject patients with these types of occlusion to mechanical thrombectomy on a regular basis.
- There is large agreement (10/11 experts) that patients within the 6-12 hours time window can be treated if ASPECTS is ≥6 and there is evidence of moderate to good collateral circulation (ESCAPE criteria). This is particularly important in hospitals in which there is limited or no access to CT perfusion or MRI.
It is also good news for many centres lacking RAPID® that concurrent software applications and simple volumetry on high quality DWI scans was considered as an acceptable option by the experts.
For societies, they say, “If you do not have the lens that has been trained to look at how various forms of discrimination were put together, you are unlikely to develop a set of policies that will be as inclusive as they need to be.” For one of the most prominent emerging stroke therapies, it appears the authors found the right lens on the right subject, cautiously balancing the striving for inclusion against the danger of overly unrealistic expectations and enthusiasm.
1 Goyal, M., Simonsen, C.Z. & Fisher, M. Neuroradiology (2018) 60: 123. https://doi.org/10.1007/s00234-017-1966-0
2 Turc, G., Bhogal, P., Fischer, U., Khatri, P., Lobotesis, K., Mazighi, M., … Fiehler, J. (2019). European Stroke Organisation (ESO) – European Society for Minimally Invasive Neurological Therapy (ESMINT) Guidelines on Mechanical Thrombectomy in Acute Ischaemic StrokeEndorsed by Stroke Alliance for Europe (SAFE). European Stroke Journal. https://doi.org/10.1177/2396987319832140 This article is co-published in the Journal of NeuroInterventional Surgery (JNIS) in February 2019