Skip to main content
Top
Published in: Neurocritical Care 1/2022

29-04-2022 | Stroke | Original work

Safety and Efficacy of Vinpocetine as a Neuroprotective Agent in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

Authors: Prateek Kumar Panda, Aparna Ramachandran, Pragnya Panda, Indar Kumar Sharawat

Published in: Neurocritical Care | Issue 1/2022

Login to get access

Abstract

Background

Vinpocetine as a neuroprotective agent is effective in acute ischemic stroke in some randomized controlled trials (RCTs). Since the last systematic review has been published in 2008, which didn’t find conclusive evidence favoring its use, two more RCTs have also been completed.

Methods

Relevant electronic databases were searched with a suitable combination of Medical Subject Headings terms to detect publications describing RCTs exploring the safety and efficacy of vinpocetine in patients with acute ischemic stroke. The risk of bias was determined by using the Cochrane Collaboration’s tool for assessing the risk of bias in RCTs after full-text review and relevant data extraction. Higgins and Thompson’s I2 method was used to assess heterogeneity in studies. The presence of publication bias was assessed by Egger’s test. We used a random effect model when I2 was more than 50% and a fixed-effect model for other parameters.

Results

Four placebo-controlled RCTs enrolling a total of 601 and 236 patients in vinpocetine and placebo groups, respectively, were included. The number of patients with death or significant disability was lower in the vinpocetine group than that in the placebo group at both 1 and 3 months (relative risk 0.80, 95% confidence interval [CI] 0.65–0.99 and relative risk 0.67, CI 0.48–0.92, p = 0.04 and 0.02, respectively). The degree of disability in participants at 1 month and 3 months was also lower in vinpocetine group than that in the placebo group (standardized mean difference (SMD) 0.49, 95% CI 0.03–0.95 and SMD 1.22, CI 0.23–2.24, p = 0.001 and 0.04, respectively). Change in mini-mental state examination score compared with baseline at trial enrolment was also better in the vinpocetine group than in the placebo group (pooled weighted mean difference 0.92, 95% CI 0.02–1.82, p = 0.04).

Conclusions

Vinpocetine has some promising efficacy in patients with ischemic stroke when used in the acute stage in reducing the disability, but presently there is not enough evidence to suggest that it also reduces case fatality. More double-blind, placebo-controlled RCTs of adequate sample size are needed before making recommendations for the routine administration of vinpocetine for all patients with acute ischemic stroke.
Appendix
Available only for authorised users
Literature
2.
go back to reference Chugh C. Acute ischemic stroke: management approach. Indian J Crit Care Med Peer-Rev Off Publ Indian Soc Crit Care Med. 2019;23:S140–6. Chugh C. Acute ischemic stroke: management approach. Indian J Crit Care Med Peer-Rev Off Publ Indian Soc Crit Care Med. 2019;23:S140–6.
3.
go back to reference Simpkins AN, Tahsili-Fahadan P, Buchwald N, De Prey J, Farooqui A, Mugge LA, et al. Adapting clinical practice of thrombolysis for acute ischemic stroke beyond 4.5 hours: a review of the literature. J Stroke Cerebrovasc Dis Off J Natl Stroke Assoc. 2021;30:106059.CrossRef Simpkins AN, Tahsili-Fahadan P, Buchwald N, De Prey J, Farooqui A, Mugge LA, et al. Adapting clinical practice of thrombolysis for acute ischemic stroke beyond 4.5 hours: a review of the literature. J Stroke Cerebrovasc Dis Off J Natl Stroke Assoc. 2021;30:106059.CrossRef
4.
go back to reference Feske SK. Ischemic Stroke. Am J Med. 2021;134:1457–64. Feske SK. Ischemic Stroke. Am J Med. 2021;134:1457–64.
5.
go back to reference Imran R, Mohamed GA, Nahab F. Acute reperfusion therapies for acute Ischemic stroke. J Clin Med. 2021;10:3677.CrossRef Imran R, Mohamed GA, Nahab F. Acute reperfusion therapies for acute Ischemic stroke. J Clin Med. 2021;10:3677.CrossRef
7.
go back to reference Gupta S, Singh P, Sharma BM, Sharma B. Neuroprotective effects of agomelatine and vinpocetine against chronic cerebral hypoperfusion induced vascular dementia. Curr Neurovasc Res. 2015;12:240–52.CrossRef Gupta S, Singh P, Sharma BM, Sharma B. Neuroprotective effects of agomelatine and vinpocetine against chronic cerebral hypoperfusion induced vascular dementia. Curr Neurovasc Res. 2015;12:240–52.CrossRef
8.
go back to reference Nyakas C, Felszeghy K, Szabó R, Keijser JN, Luiten PGM, Szombathelyi Z, et al. Neuroprotective effects of vinpocetine and its major metabolite cis-apovincaminic acid on NMDA-induced neurotoxicity in a rat entorhinal cortex lesion model. CNS Neurosci Ther. 2009;15:89–99.CrossRef Nyakas C, Felszeghy K, Szabó R, Keijser JN, Luiten PGM, Szombathelyi Z, et al. Neuroprotective effects of vinpocetine and its major metabolite cis-apovincaminic acid on NMDA-induced neurotoxicity in a rat entorhinal cortex lesion model. CNS Neurosci Ther. 2009;15:89–99.CrossRef
9.
go back to reference Feigin VL, Doronin BM, Popova TF, Gribatcheva EV, Tchervov DV. Vinpocetine treatment in acute ischaemic stroke: a pilot single-blind randomized clinical trial. Eur J Neurol. 2001;8:81–5.CrossRef Feigin VL, Doronin BM, Popova TF, Gribatcheva EV, Tchervov DV. Vinpocetine treatment in acute ischaemic stroke: a pilot single-blind randomized clinical trial. Eur J Neurol. 2001;8:81–5.CrossRef
10.
go back to reference Bereczki D, Fekete I. Vinpocetine for acute ischaemic stroke. Cochrane Database Syst Rev. 2008;2008:CD000480. Bereczki D, Fekete I. Vinpocetine for acute ischaemic stroke. Cochrane Database Syst Rev. 2008;2008:CD000480.
11.
go back to reference Zhang W, Huang Y, Li Y, Tan L, Nao J, Hu H, et al. Safety and efficacy of vinpocetine as part of treatment for acute cerebral infarction: a randomized, open-label, controlled, multicenter CAVIN (Chinese Assessment for Vinpocetine in Neurology) Trial. Clin Drug Investig. 2016;36:697–704.CrossRef Zhang W, Huang Y, Li Y, Tan L, Nao J, Hu H, et al. Safety and efficacy of vinpocetine as part of treatment for acute cerebral infarction: a randomized, open-label, controlled, multicenter CAVIN (Chinese Assessment for Vinpocetine in Neurology) Trial. Clin Drug Investig. 2016;36:697–704.CrossRef
12.
go back to reference Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700.CrossRef Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700.CrossRef
13.
go back to reference Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.CrossRef Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.CrossRef
14.
go back to reference Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919.CrossRef Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919.CrossRef
15.
go back to reference Belova LA, Mashin VV, Proshin AN, Ovsyannicova AN. Kostishko BB [Possibilities of cavinton therapy regimen for infusions and cavinton comforte in acute and early recovery periods after ischemic stroke]. Zhurnal Nevrol Psikhiatrii Im SS Korsakova. 2017;117:51–8.CrossRef Belova LA, Mashin VV, Proshin AN, Ovsyannicova AN. Kostishko BB [Possibilities of cavinton therapy regimen for infusions and cavinton comforte in acute and early recovery periods after ischemic stroke]. Zhurnal Nevrol Psikhiatrii Im SS Korsakova. 2017;117:51–8.CrossRef
16.
go back to reference Werner J, Apececha M, Schaltenbrand R, Fenzl E. Clinical study to evaluate the efficacy and tolerance of vinpocetine i.v. added to standard therapy in patients suffering from an acute apoplectic insult. In: Bés A, editor. Senile dementias: early detection. John Libbey Eurotext; 1986. p. 636–41. Werner J, Apececha M, Schaltenbrand R, Fenzl E. Clinical study to evaluate the efficacy and tolerance of vinpocetine i.v. added to standard therapy in patients suffering from an acute apoplectic insult. In: Bés A, editor. Senile dementias: early detection. John Libbey Eurotext; 1986. p. 636–41.
17.
go back to reference Zhang Y-S, Li J-D, Yan C. An update on vinpocetine: new discoveries and clinical implications. Eur J Pharmacol. 2018;819:30–4.CrossRef Zhang Y-S, Li J-D, Yan C. An update on vinpocetine: new discoveries and clinical implications. Eur J Pharmacol. 2018;819:30–4.CrossRef
18.
go back to reference Al-Kuraishy HM, Al-Gareeb AI, Naji MT, Al-Mamorry F. Role of vinpocetine in ischemic stroke and poststroke outcomes: a critical review. Brain Circ. 2020;6:1–10.CrossRef Al-Kuraishy HM, Al-Gareeb AI, Naji MT, Al-Mamorry F. Role of vinpocetine in ischemic stroke and poststroke outcomes: a critical review. Brain Circ. 2020;6:1–10.CrossRef
19.
go back to reference Onwuekwe I, Ezeala-Adikaibe B. Ischemic stroke and neuroprotection. Ann Med Health Sci Res. 2012;2:186–90.CrossRef Onwuekwe I, Ezeala-Adikaibe B. Ischemic stroke and neuroprotection. Ann Med Health Sci Res. 2012;2:186–90.CrossRef
20.
go back to reference Xing C, Arai K, Lo EH, Hommel M. Pathophysiologic cascades in ischemic stroke. Int J Stroke Off J Int Stroke Soc. 2012;7:378–85.CrossRef Xing C, Arai K, Lo EH, Hommel M. Pathophysiologic cascades in ischemic stroke. Int J Stroke Off J Int Stroke Soc. 2012;7:378–85.CrossRef
21.
go back to reference Zhang L, Yang L. Anti-inflammatory effects of vinpocetine in atherosclerosis and ischemic stroke: a review of the literature. Mol Basel Switz. 2014;20:335–47. Zhang L, Yang L. Anti-inflammatory effects of vinpocetine in atherosclerosis and ischemic stroke: a review of the literature. Mol Basel Switz. 2014;20:335–47.
22.
go back to reference Farooq MU, Min J, Goshgarian C, Gorelick PB. Pharmacotherapy for vascular cognitive impairment. CNS Drugs. 2017;31:759–76.CrossRef Farooq MU, Min J, Goshgarian C, Gorelick PB. Pharmacotherapy for vascular cognitive impairment. CNS Drugs. 2017;31:759–76.CrossRef
23.
go back to reference Solovyeva EY, Karneev AN, Chekanov AV, Baranova OA, Choi IV. Complex application 2-ethyl-6-methyl-3-hydroxypyridine-succinate and vinpocetine in cerebrovascular disorder. Zhurnal Nevrol Psikhiatrii Im SS Korsakova. 2017;117:103–8.CrossRef Solovyeva EY, Karneev AN, Chekanov AV, Baranova OA, Choi IV. Complex application 2-ethyl-6-methyl-3-hydroxypyridine-succinate and vinpocetine in cerebrovascular disorder. Zhurnal Nevrol Psikhiatrii Im SS Korsakova. 2017;117:103–8.CrossRef
24.
go back to reference Xu H, Wang E, Chen F, Xiao J, Wang M. Neuroprotective phytochemicals in experimental ischemic stroke: mechanisms and potential clinical applications. Oxid Med Cell Longev. 2021;2021:6687386.PubMedPubMedCentral Xu H, Wang E, Chen F, Xiao J, Wang M. Neuroprotective phytochemicals in experimental ischemic stroke: mechanisms and potential clinical applications. Oxid Med Cell Longev. 2021;2021:6687386.PubMedPubMedCentral
25.
go back to reference Hu C, Li L. Pre-conditions for eliminating mitochondrial dysfunction and maintaining liver function after hepatic ischaemia reperfusion. J Cell Mol Med. 2017;21:1719–31.CrossRef Hu C, Li L. Pre-conditions for eliminating mitochondrial dysfunction and maintaining liver function after hepatic ischaemia reperfusion. J Cell Mol Med. 2017;21:1719–31.CrossRef
26.
go back to reference Liu Y, Yin Y, Lu Q-L, Dan Y, Xu M-S, Song G, et al. Vinpocetine in the treatment of poststroke cognitive dysfunction: a protocol for systematic review and meta-analysis. Medicine (Baltimore). 2019;98:e13685.CrossRef Liu Y, Yin Y, Lu Q-L, Dan Y, Xu M-S, Song G, et al. Vinpocetine in the treatment of poststroke cognitive dysfunction: a protocol for systematic review and meta-analysis. Medicine (Baltimore). 2019;98:e13685.CrossRef
27.
go back to reference Protasov KV, Dzizinskiĭ AA, Shprakh VV, Sinkevich DA, Kuklin SG, Filatova LN. Cavinton forte treatment of cerebral vascular insufficiency in patients with coronary heart disease and arterial hypertension. Zhurnal Nevrol Psikhiatrii Im SS Korsakova. 2006;106:31–4. Protasov KV, Dzizinskiĭ AA, Shprakh VV, Sinkevich DA, Kuklin SG, Filatova LN. Cavinton forte treatment of cerebral vascular insufficiency in patients with coronary heart disease and arterial hypertension. Zhurnal Nevrol Psikhiatrii Im SS Korsakova. 2006;106:31–4.
28.
go back to reference Dutov AA, Gal’tvanitsa GA, Volkova VA, Sukhanova ON, Lavrishcheva TG, Petrov AP. Cavinton in the prevention of the convulsive syndrome in children after birth injury. Zhurnal Nevropatol Psikhiatrii Im SS Korsakova Mosc Russ. 1991;91:21–2. Dutov AA, Gal’tvanitsa GA, Volkova VA, Sukhanova ON, Lavrishcheva TG, Petrov AP. Cavinton in the prevention of the convulsive syndrome in children after birth injury. Zhurnal Nevropatol Psikhiatrii Im SS Korsakova Mosc Russ. 1991;91:21–2.
29.
go back to reference Garza-Morales S, Briceño-González E, Ceja-Moreno H, Ruiz-Sandoval JL, Góngora-Rivera F, Rodríguez-Leyva I, et al. Extended-release vinpocetine: a possible adjuvant treatment for focal onset epileptic seizures. Bol Med Hosp Infant Mex. 2019;76:215–24.PubMed Garza-Morales S, Briceño-González E, Ceja-Moreno H, Ruiz-Sandoval JL, Góngora-Rivera F, Rodríguez-Leyva I, et al. Extended-release vinpocetine: a possible adjuvant treatment for focal onset epileptic seizures. Bol Med Hosp Infant Mex. 2019;76:215–24.PubMed
30.
go back to reference Zhang P, Cao Y, Chen S, Shao L. Combination of vinpocetine and dexamethasone alleviates cognitive impairment in nasopharyngeal carcinoma patients following radiation injury. Pharmacology. 2021;106:37–44.CrossRef Zhang P, Cao Y, Chen S, Shao L. Combination of vinpocetine and dexamethasone alleviates cognitive impairment in nasopharyngeal carcinoma patients following radiation injury. Pharmacology. 2021;106:37–44.CrossRef
31.
go back to reference Valikovics A, Csányi A, Németh L. Study of the effects of vinpocetin on cognitive functions. Ideggyogyaszati Szle. 2012;65:115–20. Valikovics A, Csányi A, Németh L. Study of the effects of vinpocetin on cognitive functions. Ideggyogyaszati Szle. 2012;65:115–20.
Metadata
Title
Safety and Efficacy of Vinpocetine as a Neuroprotective Agent in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis
Authors
Prateek Kumar Panda
Aparna Ramachandran
Pragnya Panda
Indar Kumar Sharawat
Publication date
29-04-2022
Publisher
Springer US
Keyword
Stroke
Published in
Neurocritical Care / Issue 1/2022
Print ISSN: 1541-6933
Electronic ISSN: 1556-0961
DOI
https://doi.org/10.1007/s12028-022-01499-y

Other articles of this Issue 1/2022

Neurocritical Care 1/2022 Go to the issue