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Peroxisome proliferator-activated receptor gamma agonists for preventing recurrent stroke and other vascular events in patients with stroke or transient ischaemic attack

  1. Jia Liu*,
  2. Lu-Ning Wang

Editorial Group: Cochrane Stroke Group

Published Online: 8 JAN 2014

Assessed as up-to-date: 14 OCT 2013

DOI: 10.1002/14651858.CD010693.pub2


How to Cite

Liu J, Wang LN. Peroxisome proliferator-activated receptor gamma agonists for preventing recurrent stroke and other vascular events in patients with stroke or transient ischaemic attack. Cochrane Database of Systematic Reviews 2014, Issue 1. Art. No.: CD010693. DOI: 10.1002/14651858.CD010693.pub2.

Author Information

  1. Chinese PLA General Hospital, Department of Geriatric Neurology, Beijing, China

*Jia Liu, Department of Geriatric Neurology, Chinese PLA General Hospital, Fuxing Road 28, Beijing, 100853, China. Jason_liu1984@163.com.

Publication History

  1. Publication Status: New
  2. Published Online: 8 JAN 2014

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This is not the most recent version of the article. View current version (29 OCT 2015)

 
Characteristics of included studies [ordered by study ID]
J-SPIRIT

MethodsA multicentre, randomised, double-blind, placebo-controlled trial to test the effect of pioglitazone on the reduction of recurrent stroke in patients with abnormal glucose metabolism and insulin resistance after ischaemic stroke


ParticipantsPeople aged 35 to 85 years with symptomatic ischaemic stroke and no history of diabetes and no evidence of diabetes by initial blood test were included

119 eligible people from 3 hospitals in Tokyo or neighbouring cities in Japan were randomised


InterventionsPioglitazone or matching placebo


OutcomesRecurrence of stroke; recurrence of ischaemic stroke


NotesMean observation periods were 25 ± 19.9 months in the pioglitazone group and 30 ± 16 months in the control group


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMethod of random sequence generation was not described

Allocation concealment (selection bias)Unclear riskAllocation concealment was not reported

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskInsufficient information to judge

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskInsufficient information to judge

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskInsufficient information to judge

Selective reporting (reporting bias)Unclear riskInsufficient information to judge

Other biasUnclear riskInsufficient information to judge

Kernan 2003

MethodsA randomised, double-blind, placebo-controlled trial to test the effect of pioglitazone compared with placebo for improving insulin sensitivity among non-diabetic patients with a recent TIA or non-disabling ischaemic stroke


ParticipantsNon-diabetic men and women aged > 45 years with TIA or non-disabling ischaemic stroke were included. 20 eligible patients from 3 hospitals were randomised as 1:1 into the trial


InterventionsPioglitazone 45 mg per day or placebo was given for 3 months


OutcomesMean proportional changes in insulin sensitivity; mean C-reactive protein concentration; adverse events


NotesA repeated oral glucose tolerance test was done at the endpoint of the 3-month therapy. The mean age was 66 years among participants assigned to pioglitazone and 67 years among participants assigned to placebo


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskA master schedule of computer-generated random treatment assignments (placebo or pioglitazone) was stored at the investigational pharmacy at Yale-New Haven hospital

Allocation concealment (selection bias)Low riskAfter screening for eligibility, a research associate contacted the investigational pharmacist, who assigned the participant to the next available treatment as specified by the master schedule

Blinding of participants and personnel (performance bias)
All outcomes
Low riskParticipants were blinded to treatment assignment throughout the study

Blinding of outcome assessment (detection bias)
All outcomes
Low riskResearch staff and investigators were blinded to treatment assignment throughout the study

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo participant permanently discontinued the treatment

Selective reporting (reporting bias)Low riskAll pre-specified outcomes were reported

Other biasLow riskNo other bias was found

Marfella 2006

MethodsA randomised, placebo-controlled trial


Participants40 patients who presented with symptoms of cerebral ischaemic attack were included and randomised as 1:1 into the trial


InterventionsRosiglitazone 8 mg per day or placebo was given for 4 months


OutcomesUbiquitin-proteasome activity


Notes38 patients with asymptomatic carotid stenosis were not included in this review


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMethod of random sequence generation was not described

Allocation concealment (selection bias)Unclear riskAllocation concealment was not reported

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskInsufficient information to judge

Blinding of outcome assessment (detection bias)
All outcomes
Low riskThe specimens were analysed by an expert pathologist blinded to the participant's diagnosis

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo participant in either group discontinued the treatment

Selective reporting (reporting bias)Low riskAll pre-specified outcomes were reported

Other biasLow riskNo other bias was found

PROactive

MethodsA multicentre, randomised, double-blind, placebo-controlled trial


ParticipantsPatients aged 35 to 75 years with type 2 diabetes and a previous stroke (6 months before randomisation) were included
984 eligible patients were randomised into the trial, with 486 in the pioglitazone group and 498 in the placebo group


InterventionsPioglitazone titration from 15 to 45 mg per day depending on tolerability or placebo was given until the first occurrence of any of the events described in primary outcomes. The mean duration was 34.5 months


OutcomesPrimary outcomes: all-cause mortality, non-fatal myocardial infarction (including silent myocardial infarction), stroke, acute coronary syndrome, cardiac intervention (including coronary artery bypass graft surgery or percutaneous coronary intervention), leg revascularisation and amputation above the ankle

Secondary outcomes: all-cause death, non-fatal myocardial infarction or non-fatal stroke; adverse events


NotesData for patients without previous stroke were not included


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMethod of random sequence generation was not described

Allocation concealment (selection bias)Unclear riskAllocation concealment was not reported

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskInsufficient information to judge

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskInsufficient information to judge

Incomplete outcome data (attrition bias)
All outcomes
High risk882 of 984 (90%) participants completed the final visit: 439 (90%) of 486 in the pioglitazone group and 443 (89%) in the placebo group

Intention-to-treat analysis was used

Selective reporting (reporting bias)Low riskAll pre-specified outcomes were reported

Other biasLow riskNo other bias was found

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

CIMT TrialThe intervention was not PPAR-γ agonist

Dehnavi 2005The participants were not eligible

Forst 2008There was no subgroup of stroke patients for whom separate results were available

Hedblad 2007The participants were not eligible

Koshiyama 2001The participants were not eligible

Meisner 2006The participants were not eligible

Sidhu 2004The participants were not eligible

TARTThe participants were not eligible

TIDEThere was no subgroup of stroke patients for whom separate results were available

TRIPODThe participants were not eligible

Varghese 2009The participants were not eligible

 
Characteristics of ongoing studies [ordered by study ID]
IRIS

Trial name or titleInsulin Resistance Intervention after Stroke Trial (IRIS)

MethodsA randomised, interventional, placebo-controlled trial

ParticipantsThose aged 40 years or older with ischaemic stroke or TIA no less than 14 days and no more than 6 months before randomisation and insulin resistance as defined by a value over 3.0 on the homeostasis model assessment of insulin sensitivity

InterventionsPioglitazone versus placebo

OutcomesPrimary outcome: time to occurrence of recurrent fatal or non-fatal stroke, or fatal or non-fatal myocardial infarction

Starting dateFebruary 2005

Contact informationWalter N Kernan, MD, Principal Investigator, Yale University School of Medicine, USA

NotesEstimated enrolment: 3936; estimated study completion date: August 2015

 
Comparison 1. Efficacy in the secondary prevention of stroke

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Recurrence of stroke21103Risk Ratio (M-H, Random, 95% CI)0.52 [0.34, 0.80]

 
Comparison 2. Safety in the secondary prevention of stroke

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Reported adverse events31044Risk Difference (M-H, Random, 95% CI)0.10 [-0.08, 0.28]