TZD’s and Congestive Heart Failure in Pre-Diabetics and Type 2 Patients

Congestive heart failure in patients with prediabetes and type 2 diabetes given TZDs might not carry the risk that is usually associated with congestive heart failure. The overall clinical benefit of thiazolidinediones (TZDs) as a treatment for hyperglycemia 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. The researchers from the USA aimed to examine the risk of congestive heart failure and of cardiac death in patients given TZDs. They used a search strategy to identify 3048 studies. 3041 were excluded, and they did a systematic review and meta-analysis of the seven remaining randomized double-blind clinical trials of drug-related congestive heart failure in patients given TZDs (either rosiglitazone or pioglitazone). Note: It was incredible that only 7 of 3048 studies were found adequate to use. They 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.

They found that 360 of 20,191 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 (I2=22·8%), 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). By contrast, the risk of cardiovascular death was not increased with either of the two TZDs (0·93).

The researchers concluded: ”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.”

The Lancet Vol 370, Issue 9593 29 September 2007 Pp 1129-1136: Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: a meta-analysis of randomised clinical trials, Rodrigo M Lago MD, Premranjan P Singh MD and Richard W Nesto MD

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