Patients with type 2 diabetes or prediabetes are more likely to develop congestive heart failure (CHF) when given rosiglitazone or pioglitazone, as compared with controls. However these drugs did not increase the risk of cardiovascular death (CVD) for these patients.
These are the conclusions of authors of an Article published in The Lancet.
Additionally, a linked Editorial and two accompanying Comments discuss the importance of basing clinical decisions on trials which assess outcomes which most matter to patients - such as micro- and macro-vascular complications and quality and quantity of life - rather than simply the “surrogate outcome” of blood glucose control which all trials in the Article’s analysis are based.
In the Article, Dr Richard Nesto, Lahey Clinic Medical Centre, Burlington, MA, USA and colleagues did a meta-analysis (a combined analysis of previous studies) of seven randomised double-blind clinical trials of drug related congestive heart failure in patients with type 2 diabetes or prediabetes, who were given rosiglitazone or pioglitazone, from a family of drugs known as thiazolidinediones (TZDs). These trials featured 20191 patients. The main outcome measures were development of CHF and the risk of CVD.
The researchers found that the 72% increase in relative risk for CHF was observed across a wide background of cardiovascular risk – in patients with prediabetes, those with type 2 diabetes but no cardiovascular disease, those with both type 2 diabetes and cardiovascular disease, and those with type 2 diabetes and documented CHF. According to the authors, the absolute risk for CFH varied a great deal across these patient groups which should help clinicians select appropriate patients for TZDs when these drugs are prescribed.
The authors say that since the drug exposures in these trials were relatively short, and most patients did not have previous histories of CHF or evidence of left ventricular dysfunction at entry, the excess of CHF events related to TZDs was probably the result of TZD-related fluid retention and diastolic dysfunction in susceptible patients. They add, however, that the natural history of congestive heart failure when caused by TZD-related fluid retention is unknown.
They say: “Despite the glucose-lowering effect of TZDs, our data indicate that these drugs should not be used in patients with heart failure and should be cautiously used for glycaemic control in patients with cardiovascular disease who do not have heart failure. In patients with type 2 diabetes without cardiovascular disease in whom the absolute risk for CHF is much lower, the use of TZDs should be weighed against the risks and benefits of other antidiabetic medications.”
They conclude with a note of caution, saying: “Insufficient follow-up durations could have affected our conclusions about the association between CHF and cardiovascular mortality. We also did not have sufficient data to assess whether the risk of congestive heart failure differed between the two TZDs. We need longer follow-up and better characterisation of patients in whom CHF develops because of fluid retention to determine the effect of TZDs on overall cardiovascular outcome and whether CHF should be regarded as an adverse event or a characteristic cardiovascular endpoint.”