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• W3107263100 abstract "HomeStrokeVol. 51, No. 12Response by Doubal et al to Letter Regarding Article, “Cilostazol for Secondary Prevention of Stroke and Cognitive Decline: Systematic Review and Meta-Analysis” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessLetterPDF/EPUBResponse by Doubal et al to Letter Regarding Article, “Cilostazol for Secondary Prevention of Stroke and Cognitive Decline: Systematic Review and Meta-Analysis” Fergus N. Doubal, PhD, Gordon Blair, MBChB and Joanna M. Wardlaw, MD Fergus N. DoubalFergus N. Doubal Centre for Clinical Brain Sciences and UK Dementia Research Institute, University of Edinburgh, Scotland. Search for more papers by this author , Gordon BlairGordon Blair Centre for Clinical Brain Sciences and UK Dementia Research Institute, University of Edinburgh, Scotland. Search for more papers by this author and Joanna M. WardlawJoanna M. Wardlaw https://orcid.org/0000-0002-9812-6642 Centre for Clinical Brain Sciences and UK Dementia Research Institute, University of Edinburgh, Scotland. Search for more papers by this author Originally published23 Nov 2020https://doi.org/10.1161/STROKEAHA.120.032520Stroke. 2020;51:e377In Response:We thank Xu et al for their interest in our article and agree that cilostazol has promise as potential secondary prevention in stroke, particularly in combination with other antiplatelets and that further trials are required.There are several rejoinders to the points raised:In the subgroup analysis of the effect of time from stroke on effectiveness of cilostazol in preventing recurrent stroke, we made conclusions based upon the pooled estimate from each subgroup, for example, up to 2 weeks or >2 weeks per protocol rather than the total pooled estimate as suggested.1 We agree with Xu that the variance in the design and reporting of the included studies will limit the strength of any conclusions drawn from this review and have emphasized this in the discussion. The number of adverse events in trials is often low, and there were not sufficient numbers to stratify events by confounders. Furthermore, we considered any bleeding event to be significant and used this rather than gastrointestinal bleeding for our sensitivity analysis.The statistical plan for this study had been to study the effect of cilostazol upon outcomes compared to a range of different controls. We found that in the overall combined analysis cilostazol reduced hemorrhagic stroke compared to controls (Figure 3); however, Xu et al are correct in suggesting that this association might be driven by the comparison between cilostazol and aspirin as demonstrated in the sensitivity analysis.We agree that the I2 statistic is a measure of statistical heterogeneity and not a measure of study heterogeneity and that although widely used it can occasionally (like all statistical methods) be susceptible to bias. We would also agree that there is variation in the study design (which is an unavoidable limitation of the published literature). We address this in the discussion of the article. Furthermore, any interpretation of the results of this meta-analysis should be cautious, the benefit of cilostazol versus placebo is only demonstrated in one trial,2 and we would stress the need for careful trials with relevant outcomes.Sources of FundingSupported by Chest Heart Stroke Scotland (Res 14/A157); European Union Horizon 2020 ‘[email protected]’ (No. 666881); Fondation Leducq Transatlantic Network on Perivascular Spaces in Small Vessel Disease (16CVD05); UK Dementia Research Institute (DRI Ltd, UK Medical Research Council, Alzheimer’s Society, Alzheimer’s Research UK); Alzheimer’s Society (AS-PG-14-033); Stroke Association (Princess Margaret Research Development Fellowship, Stroke Association-Garfield Weston Foundation Senior Clinical Lectureship); National Health Service Research Scotland; British Heart Foundation (CS/15/5/31475).DisclosuresJ.M. Wardlaw, G. Blair, and F.N. Doubal worked on the LACI-1 and LACI-2 trials (Lacunar Intervention Trials 1 and 2) testing cilostazol in lacunar stroke.FootnotesFor Disclosures, see page e377.References1. McHutchison C, Blair GW, Appleton JP, Chappell FM, Doubal F, Bath PM, Wardlaw JM. Cilostazol for secondary prevention of stroke and cognitive decline: systematic review and meta-analysis.Stroke. 2020; 51;2374–2385. doi: 10.1161/STROKEAHA.120.029454LinkGoogle Scholar2. Gotoh F, Tohgi H, Hirai S, Terashi A, Fukuuchi Y, Otomo E, Shinohara Y, Itoh E, Matsuda T, Sawada T, et al.. Cilostazol stroke prevention study: a placebo-controlled double-blind trial for secondary prevention of cerebral infarction.J Stroke Cerebrovasc Dis. 2000; 9:147–157. doi: 10.1053/jscd.2000.7216CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails December 2020Vol 51, Issue 12Article InformationMetrics Download: 208 © 2020 American Heart Association, Inc.https://doi.org/10.1161/STROKEAHA.120.032520PMID: 33226926 Originally publishedNovember 23, 2020 PDF download Advertisement SubjectsCerebrovascular Disease/StrokeCognitive Impairment" @default.
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• W3107263100 title "Response by Doubal et al to Letter Regarding Article, “Cilostazol for Secondary Prevention of Stroke and Cognitive Decline: Systematic Review and Meta-Analysis”" @default.
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