Issue 181 Item 4 More Evidence: Thiazolidinediones Increase Risk of Heart Failur

Physicians should use TZDs with caution in patients with heart failure, [and] remain vigilant for manifestation of heart failure in those receiving these drugs.

Use of thiazolidinediones may increase the risk of heart failure by 60%, according to a recent American study.

Thiazolidinediones (TZDs), which include troglitazone, pioglitazone, and rosiglitazone, are commonly used oral antihyperglycemic agents that function by increasing insulin-stimulated glucose disposal. TZD therapy has been associated with weight gain, increased plasma volume, and oedema, but previous studies have not addressed a potential relationship with heart failure.

Thomas E. Delea, MBA, with Policy Analysis, Brookline, Massachusetts, and colleagues conducted a retrospective cohort analysis to compare the incidence of heart failure in type 2 diabetes patients receiving TZDs (n=5441; males, 56.6%; mean age, 57.2 years) with patients receiving other oral antihyperglycemic treatments (n=28,103; males, 57.2%; mean age, 58.8 years).

Patient data were identified from a health insurance claims database, and patients with a prior incidence of heart failure were excluded from the study. Each patient receiving TZD therapy was compared with five randomly selected patients receiving non-TZD oral antihyperglycemics.

One hundred twenty-six TZD patients (2.3%) and 397 non-TZD patients (1.4%) experienced heart failure during follow up, and statistical analyses revealed that TZD use increased the likelihood of heart failure. After adjusting for other risk factors, the incidence of heart failure at 40 months was 8.2% for TZD patients and 5.3% for non-TZD patients.

TZD use was also found to be associated with coronary artery disease, diabetes complications, and hyperglycemic emergencies. Furthermore, TZD patients were more likely to receive ACE inhibitors, Beta-blockers, metformin, insulin, HbA1c tests, and dilated eye exams.

The researchers did not observe a dose-dependent relationship between TZD use and heart failure. However, the dosages were characterized on index prescription only, and so it remains possible that patients may have changed dosages over time.

"The results of a single observational study are not sufficient to establish causality," the researchers advise. However, they suggest that, "physicians should use TZDs with caution in patients with heart failure, [and] remain vigilant for manifestation of heart failure in those receiving these drugs." Diabetes Care 2003 Nov;26:11:2983-9.

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DID YOU KNOW: The prevalence of heart disease and stroke is approximately two to four times greater among adults with diabetes compared to those without diabetes. For instance:
25 percent of adults with diabetes compared to 7 percent of adults without diabetes reported having coronary heart disease. 9 percent compared to 3 percent reported having had a stroke. 18 percent compared to 8 percent reported having some other heart condition. 37 percent compared to 14 percent reported having at least one of these conditions. CDC Nov, 2003