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A systematic-search-and-review of registered pharmacological therapies investigated to improve neuro-recovery after a stroke

Lee TH 1 , Uchiyama S 2 , Kusuma Y 3 , Chiu HC 4 , Navarro JC 5 , Tan KS 6 Show all authors , Pandian J 7 , Guo L 8 , Wong Y 8 , Venketasubramanian N 9 , Asian Stroke Advisory Panel

Affiliations 

  • 1 Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
  • 2 Clinical Research Center for Medicine, International University of Health and Welfare, Center for Brain and Cerebral Vessels, Sanno Medical Center, Tokyo, Japan
  • 3 National Brain Center Hospital, Jakarta, Indonesia
  • 4 Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan
  • 5 Jose R. Reyes Memorial Medical Center, Manila, Philippines
  • 6 University of Malaya Medical Center, Kuala Lumpur, Malaysia
  • 7 Christian Medical College and Hospital, Ludhiana, India
  • 8 Singapore Clinical Research Institute, Consortium for Clinical Research and Innovation, Singapore, Singapore
  • 9 Raffles Hospital, Singapore, Singapore
Front Neurol, 2024;15:1346177.
PMID: 38356890 DOI: 10.3389/fneur.2024.1346177

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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