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Comparison of statins for secondary prevention in patients with ischemic stroke or transient ischemic attack: a systematic review and network meta-analysis

BACKGROUND: Statins may prevent recurrent ischemic events after ischemic stroke. Determining which statin to use remains controversial. We aimed to summarize the evidence for the use of statins in secondary prevention for patients with ischemic stroke by comparing benefits and harms of various stati...

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Autores principales: Tramacere, Irene, Boncoraglio, Giorgio B., Banzi, Rita, Del Giovane, Cinzia, Kwag, Koren H., Squizzato, Alessandro, Moja, Lorenzo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436237/
https://www.ncbi.nlm.nih.gov/pubmed/30914063
http://dx.doi.org/10.1186/s12916-019-1298-5
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author Tramacere, Irene
Boncoraglio, Giorgio B.
Banzi, Rita
Del Giovane, Cinzia
Kwag, Koren H.
Squizzato, Alessandro
Moja, Lorenzo
author_facet Tramacere, Irene
Boncoraglio, Giorgio B.
Banzi, Rita
Del Giovane, Cinzia
Kwag, Koren H.
Squizzato, Alessandro
Moja, Lorenzo
author_sort Tramacere, Irene
collection PubMed
description BACKGROUND: Statins may prevent recurrent ischemic events after ischemic stroke. Determining which statin to use remains controversial. We aimed to summarize the evidence for the use of statins in secondary prevention for patients with ischemic stroke by comparing benefits and harms of various statins. METHODS: We searched for randomized controlled trials (RCTs) assessing statins in patients with ischemic stroke or transient ischemic attack (TIA) in MEDLINE, EMBASE, and CENTRAL up to July 2017. Two authors extracted data and appraised risks of bias. We performed pairwise meta-analyses and trial sequential analyses (TSA) to compare statins versus placebo/no statin, and network meta-analyses using frequentist random-effects models to compare statins through indirect evidence. We used GRADE to rate the overall certainty of evidence. Primary outcomes were all-cause mortality and all strokes. Secondary outcomes were different types of strokes, cardiovascular events, and adverse events. RESULTS: We identified nine trials (10,741 patients). No head-to-head RCTs were found. The median follow-up period was 2.5 years. Statins did not seem to modify all stroke and all-cause mortality outcomes; they were associated with a decreased risk of ischemic stroke (odds ratio, OR, 0.81 [95% CI, 0.70 to 0.93]; absolute risk difference, ARD, − 1.6% [95% CI, − 2.6 to − 0.6%]), ischemic stroke or TIA (OR, 0.75 [95% CI, 0.64 to 0.87]; ARD, − 4.2% [95% CI, − 6.2 to − 2.1%]), and cardiovascular event (OR, 0.75 [95% CI, 0.69 to 0.83]; ARD, − 5.4% [95% CI, − 6.8 to − 3.6%]), and did not seem to modify rhabdomyolysis, myalgia, or rise in creatine kinase. In the comparison of different statins, moderate- to high-quality evidence indicated that differences between pharmaceutical products seemed modest, with high doses (e.g., atorvastatin 80 mg/day and simvastatin 40 mg/day) associated with the greatest benefits. TSA excluded random error as a cause of the findings for ischemic stroke and cardiovascular event outcomes. Evidence for increased risk of hemorrhagic stroke was sensitive to the exclusion of the SPARCL trial. CONCLUSIONS: Evidence strongly suggests that statins are associated with a reduction in the absolute risk of ischemic strokes and cardiovascular events. Differences in effects among statins were modest, signaling potential therapeutic equivalence. TRIAL REGISTRATION: PROSPERO CRD42018079112 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12916-019-1298-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-64362372019-04-10 Comparison of statins for secondary prevention in patients with ischemic stroke or transient ischemic attack: a systematic review and network meta-analysis Tramacere, Irene Boncoraglio, Giorgio B. Banzi, Rita Del Giovane, Cinzia Kwag, Koren H. Squizzato, Alessandro Moja, Lorenzo BMC Med Research Article BACKGROUND: Statins may prevent recurrent ischemic events after ischemic stroke. Determining which statin to use remains controversial. We aimed to summarize the evidence for the use of statins in secondary prevention for patients with ischemic stroke by comparing benefits and harms of various statins. METHODS: We searched for randomized controlled trials (RCTs) assessing statins in patients with ischemic stroke or transient ischemic attack (TIA) in MEDLINE, EMBASE, and CENTRAL up to July 2017. Two authors extracted data and appraised risks of bias. We performed pairwise meta-analyses and trial sequential analyses (TSA) to compare statins versus placebo/no statin, and network meta-analyses using frequentist random-effects models to compare statins through indirect evidence. We used GRADE to rate the overall certainty of evidence. Primary outcomes were all-cause mortality and all strokes. Secondary outcomes were different types of strokes, cardiovascular events, and adverse events. RESULTS: We identified nine trials (10,741 patients). No head-to-head RCTs were found. The median follow-up period was 2.5 years. Statins did not seem to modify all stroke and all-cause mortality outcomes; they were associated with a decreased risk of ischemic stroke (odds ratio, OR, 0.81 [95% CI, 0.70 to 0.93]; absolute risk difference, ARD, − 1.6% [95% CI, − 2.6 to − 0.6%]), ischemic stroke or TIA (OR, 0.75 [95% CI, 0.64 to 0.87]; ARD, − 4.2% [95% CI, − 6.2 to − 2.1%]), and cardiovascular event (OR, 0.75 [95% CI, 0.69 to 0.83]; ARD, − 5.4% [95% CI, − 6.8 to − 3.6%]), and did not seem to modify rhabdomyolysis, myalgia, or rise in creatine kinase. In the comparison of different statins, moderate- to high-quality evidence indicated that differences between pharmaceutical products seemed modest, with high doses (e.g., atorvastatin 80 mg/day and simvastatin 40 mg/day) associated with the greatest benefits. TSA excluded random error as a cause of the findings for ischemic stroke and cardiovascular event outcomes. Evidence for increased risk of hemorrhagic stroke was sensitive to the exclusion of the SPARCL trial. CONCLUSIONS: Evidence strongly suggests that statins are associated with a reduction in the absolute risk of ischemic strokes and cardiovascular events. Differences in effects among statins were modest, signaling potential therapeutic equivalence. TRIAL REGISTRATION: PROSPERO CRD42018079112 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12916-019-1298-5) contains supplementary material, which is available to authorized users. BioMed Central 2019-03-26 /pmc/articles/PMC6436237/ /pubmed/30914063 http://dx.doi.org/10.1186/s12916-019-1298-5 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Tramacere, Irene
Boncoraglio, Giorgio B.
Banzi, Rita
Del Giovane, Cinzia
Kwag, Koren H.
Squizzato, Alessandro
Moja, Lorenzo
Comparison of statins for secondary prevention in patients with ischemic stroke or transient ischemic attack: a systematic review and network meta-analysis
title Comparison of statins for secondary prevention in patients with ischemic stroke or transient ischemic attack: a systematic review and network meta-analysis
title_full Comparison of statins for secondary prevention in patients with ischemic stroke or transient ischemic attack: a systematic review and network meta-analysis
title_fullStr Comparison of statins for secondary prevention in patients with ischemic stroke or transient ischemic attack: a systematic review and network meta-analysis
title_full_unstemmed Comparison of statins for secondary prevention in patients with ischemic stroke or transient ischemic attack: a systematic review and network meta-analysis
title_short Comparison of statins for secondary prevention in patients with ischemic stroke or transient ischemic attack: a systematic review and network meta-analysis
title_sort comparison of statins for secondary prevention in patients with ischemic stroke or transient ischemic attack: a systematic review and network meta-analysis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436237/
https://www.ncbi.nlm.nih.gov/pubmed/30914063
http://dx.doi.org/10.1186/s12916-019-1298-5
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