Systematic Review - Combining Neuroprotection With Reperfusion in Acute Ischemic Stroke

Abstract

BackgroundClinical trials of neuroprotection in acute ischemic stroke (AIS) have provided disappointing results. Reperfusion may be a necessary condition for positive effects of neuroprotective treatments. This systematic review provides an overview of efficacy of neuroprotective agents in combination with reperfusion therapy in AIS.MethodsA literature search was performed on the following databases, namely PubMed, Embase, Web of Science, Cochrane Library, Emcare. All databases were searched up to September 23rd 2021. All randomized controlled trials in which patients were treated with neuroprotective strategies within 12 h of stroke onset in combination with intravenous thrombolysis (IVT), endovascular therapy (EVT), or both were included.ResultsWe screened 1,764 titles/abstracts and included 30 full reports of unique studies with a total of 16,160 patients. In 15 studies neuroprotectants were tested for clinical efficacy, where all patients had to receive reperfusion therapies, either IVT and/or EVT. Heterogeneity in reported outcome measures was observed. Treatment was associated with improved clinical outcome for: 1) uric acid in patients treated with EVT and IVT, 2) nerinetide in patients who underwent EVT without IVT, 3) imatinib in stroke patients treated with IVT with or without EVT, 4) remote ischemic perconditioning and IVT, and 5) high-flow normobaric oxygen treatment after EVT, with or without IVT.ConclusionStudies specifically testing effects of neuroprotective agents in addition to IVT and/or EVT are scarce. Future neuroprotection studies should report standardized functional outcome measures and combine neuroprotective agents with reperfusion therapies in AIS or aim to include prespecified subgroup analyses for treatment with IVT and/or EVT.

Efficacy of Cerebrolysin Treatment as an Add-On Therapy to Mechanical Thrombectomy in Patients With Acute Ischemic Stroke Due to Large Vessel Occlusion: Study Protocol for a Prospective, Open Label, Single-Center Study With 12 Months of Follow-Up

“…First, there is a lack of clinical trials on cytoprotective agents in combination with reperfusion therapy in AIS. Preliminary results from different studies indicate a high potential for some neuroprotective treatments in addition to reperfusion; however more data is needed ( 75 ). Second, Cerebrolysin has been regarded as an ideal agent for functional recovery after AIS because of its multiple attributes including cytoprotective properties and neurotrophic activity.…”

Neuroprotection in Acute Ischemic Stroke: A Battle Against the Biology of Nature

“…Furthermore, studies show the importance of neuroprotection therapy together with reperfusion modalities. In this context, a recent systematic review showed that 5 out of 15 clinical trials indicated that patients treated with neuroprotection and reperfusion therapy had good clinical outcomes ( 65 ). These findings indicate the promising clinical future of using neuroprotection therapy for patients with AIS.…”

The BE COOL Treatments (Batroxobin, oxygEn, Conditioning, and cOOLing): Emerging Adjunct Therapies for Ischemic Cerebrovascular Disease

“…Novel pharmaceutical and non-pharmaceutical methods for recovering cerebral perfusion and neuroprotection are highly sought. Although some drugs were promising in preclinical models for improving cerebral perfusion and rescuing ischemic areas, their use has not translated to clinical settings due to the failure to include stroke models with significant comorbidities and a lack of testing in older animal models [ 9 , 15 , 16 ]. Still, several clinical trials have yielded positive results and indicated beneficial effects in stroke patients, such as the use of human urinary kallidinogenase (HUK) (NCT03431909 Phase IV China), edaravone (NCT02430350 Phase III China/Japan), and nerinetide (NA-1) (NCT02930018 Phase III Canada and USA) [ 17 ].…”