Peroxisome Proliferator-Activated Receptor Gamma Agonists for Preventing Recurrent Stroke and other Vascular Events in Patients with Stroke or Transient Ischaemic Attack

Summary

A Cochrane review [Abstract] 1 included 4 studies with a total of 1163 subjects. Three studies evaluated pioglitazone and one study evaluated rosiglitazone. The number of patients with recurrent stroke was evaluated in 2 studies (n=1103), where peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists reduced the recurrence of stroke compared with placebo (RR 0.52, 95% CI 0.34 to 0.80). PPAR-γ agonists given over a mean duration of 34.5 months in a single trial (n=984) 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 CIs were wider and the effects were not statistically significant. In addition, one study (n=78) measured the ubiquitin-proteasome activity in carotid plaques. Compared with placebo, symptomatic carotid plaques in the rosiglitazone group showed fewer inflammatory cells (p < 0.01); less ubiquitin (p < 0.01), proteasome 20S (p < 0.01) and nuclear factor kappa B (NFkB) (p < 0.01); less nitrotyrosine (p < 0.01) and superoxide anion production (p < 0.01) and more collagen content (p < 0.01), suggesting greater plaque stabilisation.These results show significantly improved results on carotid plaques by PPAR-γ agonists. Insulin sensitivity was measured in one study (n=20) by the composite insulin sensitivity index, which was significantly increased in the pioglitazone group vs. placebo (p < 0.01). Frequent adverse events included oedema, cardiac failure and anaemia. Evidence that adverse events occurred more frequently in participants treated with PPAR-γ agonists vs. placebo was imprecise and inconsistent (risk difference (RD) 10%, 95% CI -8% to 28%, I² = 86%).