title: Peroxisome proliferator-activated receptor gamma agonists for preventing recurrent stroke and other vascular events in patients with stroke or transient ischaemic attack.
abstract: BACKGROUND
  Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists are insulin-sensitising drugs used for the treatment of insulin resistance. In addition to lowing glucose in diabetes, these drugs may also protect against hyperlipidaemia and arteriosclerosis, which are risk factors for stroke.
  
  
  OBJECTIVE
  To assess the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events for people with stroke or transient ischaemic attack (TIA).
  
  
  METHODS
  We searched the Cochrane Stroke Group Trials Register (August 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 9), MEDLINE (1949 to October 2013), EMBASE (1980 to October 2013), CINAHL (1982 to October 2013), AMED (1985 to October 2013) and 11 Chinese databases (October 2013). In an effort to identify further published, unpublished and ongoing trials we searched ongoing trials registers, reference lists and relevant conference proceedings, and contacted authors and pharmaceutical companies. There were no language restrictions.
  
  
  METHODS
  We included randomised controlled trials (RCTs) evaluating PPAR-γ agonists versus placebo for the secondary prevention of stroke and related vascular events in people with stroke or TIA, with the outcomes of recurrent stroke, vascular events and adverse events.
  
  
  METHODS
  Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted eligible data, cross-checked the data for accuracy and assessed the methodological quality.
  
  
  RESULTS
  We identified four eligible studies with 1163 participants; only one study had a low risk of bias for all domains. The participants in different studies were heterogeneous. The number of participants with recurrent stroke was evaluated in two studies, where PPAR-γ agonists reduced the recurrence of stroke compared with placebo (risk ratio (RR) 0.52, 95% confidence interval (CI) 0.34 to 0.80). PPAR-γ agonists given over a mean duration of 34.5 months in a single trial were found to reduce a composite outcome of total events of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke (RR 0.73, 95% CI 0.54 to 0.99). Data on additional composite outcomes reflecting serious adverse events (all-cause death and other major vascular events; all-cause mortality, non-fatal myocardial infarction or non-fatal stroke) were similar although the confidence intervals were wider and the effects were not statistically significant. In addition, two studies respectively measured insulin sensitivity and the ubiquitin-proteasome activity in carotid plaques with significant differences in these outcomes between PPAR-γ agonists and placebo. None of the studies reported the number of participants with disability due to vascular events or improvement in quality of life. Three RCTs reported information about adverse events. Frequent adverse events included oedema, cardiac failure and anaemia. Evidence that adverse events occurred more frequently in participants treated with PPAR-γ agonists when compared with placebo was imprecise and inconsistent (risk difference (RD) 10%, 95% CI -8% to 28%, I² = 86%).
  
  
  CONCLUSIONS
  PPAR-γ agonists were demonstrated to reduce recurrent stroke and total events of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke, and improve insulin sensitivity and the stabilisation of carotid plaques. There is evidence of limited quality that they are well-tolerated. However, the conclusions should be interpreted with caution considering the small number and the quality of the included studies. In future, well-designed, double-blind RCTs with large samples are required to test the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events in people with stroke or TIA.
authors.affiliation: Department of Geriatric Neurology, Chinese PLA General Hospital, Fuxing Road 28, Beijing, China, 100853.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Lu-Ning
authors.initials: LN
authors.lastname: Wang
mesh_terms: D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D002546:Ischemic Attack, Transient / Q000517:prevention & control*; D009203:Myocardial Infarction / Q000401:mortality / Q000517:prevention & control; D047495:PPAR gamma / Q000819:agonists*; D000077205:Pioglitazone; D000077154:Rosiglitazone; D055502:Secondary Prevention / Q000379:methods*; D020521:Stroke / Q000401:mortality / Q000517:prevention & control*; D045162:Thiazolidinediones / Q000627:therapeutic use
chemical_list: D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077205:Pioglitazone