Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: a meta-analysis of randomised clinical trials

Background The overall clinical benefit of thiazolidinediones (TZDs) as a treatment for hyperglycaemia can be difficult to assess because of the risk of congestive heart failure due to TZD-related fluid retention. Since prediabetic and diabetic patients are at high cardiovascular risk, the outcome and natural history of such risks need to be better understood. We aimed to examine the risk of congestive heart failure and of cardiac death in patients given TZDs. Methods We used a search strategy to identify 3048 studies. 3041 were excluded, and we did a systematic review and meta-analysis of the seven remaining randomised double-blind clinical trials of drug-related congestive heart failure in patients given TZDs (either rosiglitazone or pioglitazone). We calculated pooled random-effects estimates of the risk ratios for development of congestive heart failure in patients given TZDs compared with controls. The main outcome measures were development of congestive heart failure and the risk of cardiovascular death. Findings 360 of 20191 patients who had either prediabetes or type 2 diabetes had congestive heart failure events (214 with TZDs and 146 with comparators). Results showed no heterogeneity of effects across studies (I-2=22.8%; p for interaction=0.26), which indicated a class effect for TZDs. Compared with controls, patients given TZDs had increased risk for development of congestive heart failure across a wide background of cardiac risk (relative risk [RR] 1.72, 95% CI 1.21-2.42, p=0.002). By contrast, the risk of cardiovascular death was not increased with either of the two TZDs (0.93, 0.67-1.29, p=0.68). Interpretation Congestive heart failure in patients given TZDs might not carry the risk that is usually associated with congestive heart failure which is caused by progressive systolic or diastolic dysfunction of the left ventricle. Longer follow-up and better characterisation of such patients is needed to determine the effect of TZDs on overall cardiovascular outcome.