The results aren’t inconsistent with previous meta-analyses.
The thiazolidinediones (TZDs) rosiglitazone and pioglitazone are known to increase fluid retention and congestive heart failure. Concern about the cardiovascular safety of these drugs has risen since May 2007, when results of a meta-analysis indicated that patients randomized to rosiglitazone had significantly increased risk for myocardial infarction (Journal Watch May 24 2007).
In a new meta-analysis, researchers reviewed seven randomized trials involving 20,191 patients with type 2 diabetes or prediabetes who were randomized to a TZD or a comparator drug or placebo for 12 to 48 months and were studied for outcomes including CHF and cardiovascular death. Patients who received a TZD had significantly increased risk for CHF compared with controls (2.3% vs. 1.4%), but their risk for cardiovascular death was not significantly increased.
Comment: The authors suggest that increased CHF events with the thiazolidinediones likely resulted from fluid retention superimposed on diastolic dysfunction and that such CHF events may have different prognostic implications than those caused by primary deterioration of myocardial function. The absence of increased cardiovascular mortality in this analysis is consistent with the results of both the aforementioned meta-analysis (in which increased mortality failed to reach statistical significance) and subsequent meta-analyses showing no increased mortality with either rosiglitazone or pioglitazone (Journal Watch Sep 11 2007). Noting the complexity of cardiovascular pathophysiology and the limitations
of meta-analyses, editorialists decry the paucity of trials powered to measure "patient-centered" outcomes such as cardiovascular events, the overreliance on surrogate endpoints such as HbA1c, and the premature approval of drugs with multiple poorly understood long-term effects. Clinically, says one editorialist, "the jury is still out for the thiazolidinediones."
Published in Journal Watch General Medicine October 11, 2007
Lago RM et al. Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: A meta-analysis of randomised clinical trials. Lancet 2007 Sep 29; 370:1129.