AUTHOR=Lee Tsong-Hai , Uchiyama Shinichiro , Kusuma Yohanna , Chiu Hou Chang , Navarro Jose C. , Tan Kay Sin , Pandian Jeyaraj , Guo Liang , Wong Yoko , Venketasubramanian Narayanaswamy , for the Asian Stroke Advisory Panel TITLE=A systematic-search-and-review of registered pharmacological therapies investigated to improve neuro-recovery after a stroke JOURNAL=Frontiers in Neurology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1346177 DOI=10.3389/fneur.2024.1346177 ISSN=1664-2295 ABSTRACT=Background

Stroke burden is largely due to long-term impairments requiring prolonged care with loss of productivity. We aimed to identify and assess studies of different registered pharmacological therapies as treatments to improve post-stroke impairments and/or disabilities.

Methods

We performed a systematic-search-and-review of treatments that have been investigated as recovery-enhancing or recovery-promoting therapies in adult patients with stroke. The treatment must have received registration or market authorization in any country regardless of primary indication. Outcomes included in the review were neurological impairments and functional/disability assessments. “The best available studies” based on study design, study size, and/or date of publication were selected and graded for level of evidence (LOE) by consensus.

Results

Our systematic search yielded 7,801 citations, and we reviewed 665 full-text papers. Fifty-eight publications were selected as “the best studies” across 25 pharmacological classes: 31 on ischemic stroke, 21 on ischemic or hemorrhagic stroke, 4 on intracerebral hemorrhage, and 2 on subarachnoid hemorrhage (SAH). Twenty-six were systematic reviews/meta-analyses, 29 were randomized clinical trials (RCTs), and three were cohort studies. Only nimodipine for SAH had LOE A of benefit (systematic review and network meta-analysis). Many studies, some of which showed treatment effects, were assessed as LOE C-LD, mainly due to small sample sizes or poor quality. Seven interventions had LOE B-R (systematic review/meta-analysis or RCT) of treatment effects.

Conclusion

Only one commercially available treatment has LOE A for routine use in stroke. Further studies of putative neuroprotective drugs as adjunctive treatment to revascularization procedures and more confirmatory trials on recovery-promoting therapies will enhance the certainty of their benefit. The decision on their use must be guided by the clinical profile, neurological impairments, and target outcomes based on the available evidence.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=376973, PROSPERO, CRD42022376973.