Dallas, TX - A new consensus statement detailing the safe use of thiazolidinediones (TZDs) in people with suspected or mild heart failure should serve as a tool kit for the growing number of cardiologists treating diabetic patients, according to the lead author on the statement. Among the recommendations set out in the joint American Heart Association/American Diabetes Association statement is the reminder that TZDs should not be used in diabetic patients with NYHA class 3 or 4 heart failure.

The consensus statement outlining TZD use and congestive heart failure (CHF) appears in the December 10, 2003 issue of Circulation.1

Dr Richard W Nesto (Lahey Clinic, Burlington, MA) emphasized to heartwire that the TZDs rosiglitazone and pioglitazone are still believed, on the basis of experimental data, to have cardioprotective effects. In addition to lowering blood glucose in diabetics, the drugs may improve lipid and blood-pressure profiles, inflammatory biomarkers, endothelial function, and fibrinolytic status and potentially limit infarct size and remodeling after ischemia or infarction. These effects, however, may occur only in people with normal hearts and are offset by an increase in fluid retention and weight gain, both possible "harbingers" of CHF. In people with preexisting LV dysfunction, that fluid retention may be problematic, Nesto says. Indeed, in April 2002, the FDA issued an advisory notice warning that TZDs may cause fluid retention that can progress to heart failure and should not be used in people with current or previous HF, fluid retention, or renal disease.

The new statement thus does not necessarily add to the FDA warning but may help physicians translate the available evidence into patient management. "This statement doesn't provide what I would call new informationit is more a sourcebook for doctors setting the record straight on this matter....Cardiologists are getting more tuned into the fact that diabetes is a risk factor for heart disease, so they're seeing more patients with diabetes and they're becoming more conscious of the nuances of care in patients with diabetes," Nesto said.

Trials are currently under way that will clarify the cardiovascular safety of TZDs in patients with diabetes and underlying heart disease; Nesto himself is principal investigator for the ongoing BARI-2D trial, investigating the effects of diabetes drugs, including rosiglitazone, in diabetics with existing cardiovascular disease. In the meantime, Nesto believes it is important for physicians to retain an index of suspicion. "At this point we don't know the real risk because we don't know the actual number of patients with diabetes who are taking a TZD and develop congestive heart failure compared with the actual total number of patients who are taking a TZD," he commented in an AHA press statement. "This risk is probably quite low, but without solid data that's just guesswork."

If anything, Nesto elaborated to heartwire, the statement shouldn't give physicians cause for alarm but rather help them put the potential risk of TZDs in perspective. "A lot of people thought this issue had reached a level where maybe the talk about the problem was greater than the reality of the problem, which may indeed be the case. If you look at the literature, CHF is a pretty rare complication of TZD treatment, even in people who have mild LV dysfunction. My guess is that the denominator [of diabetics taking this drug] is very big, and the numerator [of CHF risk] has gained a lot of attention, but we don't know exactly how big that numerator is. But it's not like I see a patient every day in my office who's developed HF on a TZD. It's pretty uncommon."

The consensus statement will also appear in the January 2004 issue of Diabetes Care.