Weighing up the cardiovascular benefits of thiazolidinedione therapy: the impact of increased risk of heart failure.

Type 2 diabetes and heart failure commonly occur together and this combination is associated with poor outcomes. The relationship is likely to be multifactorial and also may involve a specific, though ill-defined, diabetic cardiomyopathy. Glucose-lowering therapies may also be associated with an increased risk of heart failure. Data from recent large-scale clinical trials have drawn particular attention to the thiazolidinediones that appear to increase the risk of heart failure in patients with type 2 diabetes. Although pioglitazone therapy has been shown to decrease the risk of macrovascular events, the overall cardiovascular benefit needs to be addressed together with the apparent increase in heart failure risk. In this review, we provide appropriate context for assessing this balance from several perspectives. First, we consider the high underlying risk of heart failure already present in type 2 diabetes. Secondly, we highlight a potential distinction between genuine heart failure due to cardiac dysfunction and thiazolidinedione-associated oedema that may simply unmask previously undiagnosed cardiac dysfunction without itself having any direct impact on heart muscle. Most importantly, we emphasize the apparent lack of any long-term mortality consequences and a relative improvement in outcomes associated with thiazolidinedione-induced 'heart failure' and discuss the potential mechanisms underlying this apparent paradox. Finally, we review the current guidelines for thiazolidinedione use and heart failure and suggest potential future strategies for avoiding and/or minimizing this association.