Rosiglitazona y Riesgo Cardiovascular

Long-term Risk of Cardiovascular Events With Rosiglitazone

A Meta-analysis

Sonal Singh, MD; Yoon K. Loke, MBBS, MD; Curt D. Furberg, MD, PhD 

JAMA. 2007;298:1189-1195.

Context  Recent reports of serious adverse events with rosiglitazone use have raised questions about whether the evidence of harm justifies its use for treatment of type 2 diabetes.

Objective  To systematically review the long-term cardiovascular risks of rosiglitazone, including myocardial infarction, heart failure, and cardiovascular mortality.

Data Sources  We searched MEDLINE, the GlaxoSmithKline clinical trials register, the US Food and Drug Administration Web site, and product information sheets for randomized controlled trials, systematic reviews, and meta-analyses published in English through May 2007.

Study Selection  Studies were selected for inclusion if they were randomized controlled trials of rosiglitazone for prevention or treatment of type 2 diabetes, had at least 12months of follow-up, and monitored cardiovascular adverse events and provided numerical data on all adverse events. Four studies were included after detailed screening of 140 trials for cardiovascular events.

Data Extraction  Relative risks (RRs) of myocardial infarction, heart failure, and cardiovascular mortality were estimated using a fixed-effects meta-analysis of 4 randomized controlled trials (n = 14 291, including 6421 receiving rosiglitazone and 7870 receiving control therapy, with a duration of follow-up of 1-4 years).

Results  Rosiglitazone significantly increased the risk of myocardial infarction (n = 94/6421 vs 83/7870; RR, 1.42; 95% confidence interval [CI], 1.06-1.91; P = .02) and heart failure (n = 102/6421 vs 62/7870; RR, 2.09;95% CI, 1.52-2.88; P < .001) without a significant increase in risk of cardiovascular mortality (n = 59/6421 vs 72/7870; RR, 0.90; 95% CI, 0.63-1.26; P = .53). There was no evidence of substantial heterogeneity among thetrials for these end points (I² = 0% for myocardial infarction, 18% for heart failure, and 0% for cardiovascularmortality).

Conclusion  Among patients with impaired glucose tolerance or type 2 diabetes, rosiglitazone use for at least 12 months is associated with a significantly increased risk of myocardial infarction and heart failure, without a significantly increased risk of cardiovascular mortality.

Author Affiliations: Department of Medicine (Dr Singh) and Division of Public Health Sciences (Dr Furberg), Wake Forest University School of Medicine, Winston-Salem, North Carolina; and School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, England (Dr Loke).

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