Meta-analyses contrast CV effects of pioglitazone and rosiglitazone

Latest meta-analyses contrast CV effects of pioglitazone and rosiglitazone


12 September 2007

MedWire News: Two separate meta-analyses of the thiazolidinediones pioglitazone and rosiglitazone published in the Journal of the American Medical Association point to contrasting effects of these glucose-lowering drugs on ischemic cardiovascular disease.

The latest meta-analysis in a series that has provoked much controversy indicates that, in line with some previous reports, rosiglitazone increases the risk for myocardial infarction (MI) by around 40%.

Meanwhile, the meta-analysis of pioglitazone shows that patients taking the drug have almost a 20% lower risk for death, MI, or stroke than those on alternative glucose-lowering medication.

Sonal Singh (Wake University School of Medicine, Winston-Salem, North Carolina, USA) and colleagues systematically reviewed the long-term cardiovascular risks associated with rosiglitazone. Unlike the initial meta-analysis by Steven Nissen and Kathy Wolski, and subsequent re-analyses of that study, Singh and colleagues included only studies of at least 12 months' duration.

Four studies, involving 6421 Type 2 diabetic patients treated with rosiglitazone and 7870 receiving control therapy, and with between 1 and 4 years of follow-up, met all inclusion criteria. The analysis of the pooled data from the four trials showed that rosiglitazone was associated with an increased risk for MI compared with control therapy, at a relative risk (RR) of 1.42 (p=0.02), and for heart failure compared with active control therapy or placebo, at a RR of 2.09 (p<0.001).

However, rosiglitazone did not increase the risk for cardiovascular mortality (RR=0.90) or all-cause mortality (RR=0.99) compared with control treatment.

There was no evidence for heterogeneity among the trials for any of these endpoints, the authors note.

They write: "These data suggest a reversal of the benefit-to-harm balance for rosiglitazone present at the time of approval. Thus, currently there appear to be much safer treatment alternatives."

Singh et al urge physicians not to wait for regulatory action, but to avoid using rosiglitazone in patients at risk for cardiovascular events.

For the second meta-analysis, Michael Lincoff (Cleveland Clinic, Ohio, USA) and colleagues included the complete set of patient-level, time-to-event data from all 19 randomized controlled trials of pioglitazone to date. These involved a total of 16,390 patients.

The primary outcome of death, MI, or stroke was significantly less frequent in the pioglitazone-treated patients, at 4.4% compared with 5.7% in those receiving control therapy (hazard ratio [HR]=0.82, p=0.005).

However, the increased risk for heart failure associated with pioglitazone was underlined, with serious heart failure reported in 2.3% of patients who received pioglitazone compared with 1.8% of control patients (HR=1.41).

The authors say that their findings, following inconclusive results of the PROactive trial, "provide reasonably strong evidence that [pioglitazone] does, in fact, reduce the risk of cardiovascular ischemic endpoints among patients with Type 2 diabetes."

LINK:
JAMA 2007; 298: 1180-1188, 1189-1195