Background: Recent concern about rosiglitazone (Avandia) started with a 2007 meta-analysis associating its use with higher rates of myocardial infarction (MI) and congestive heart failure (CHF). There is some concern about whether pioglitazone (Actos)—as a related drug—might also pose similar risks. One study reported a lower incidence of a combined end point of MI, stroke, and cardiovascular mortality with pioglitazone, but did not examine these outcomes individually. Head-to-head comparisons of these two drugs have been rare, and have generally not addressed long-term clinical outcomes. Winkelmayer and colleagues compared cardiovascular outcomes and mortality rates between patients starting rosiglitazone and pioglitazone.

The Study: The authors conducted a population-based cohort study of U.S. Medicare beneficiaries older than 65 years. They reviewed medical claims data over a seven-year period, using National Drug Code numbers to identify patients who were started on rosiglitazone or pioglitazone, as well as comorbidities, cardiac procedures, and hospitalizations. The primary end point was all-cause mortality, with secondary end points of MI, stroke, and hospitalization for CHF.

Results: Of the 28,361 eligible patients, 50.3 percent were started on pioglitazone and 49.7 percent on rosiglitazone. Baseline traits were similar between the groups, although the rosiglitazone group had slightly more diagnoses of coronary artery disease and CHF at baseline. Rosiglitazone users had a 15 percent greater mortality rate compared with pioglitazone users, but whether this was specifically of cardiovascular origin could not be determined. Rosiglitazone users also had a 13 percent greater risk of hospitalization for CHF compared with pioglitazone users. Risks of MI or stroke were comparable using either medication.

Conclusion: The authors conclude that patients started on rosiglitazone have higher rates of all-cause mortality and hospitalization for CHF than those using pioglitazone. The risks of MI or stroke are comparable for the two drugs. This study confirms the safety concerns of rosiglitazone relative to pioglitazone, although pioglitazone has also been shown to increase risk of CHF.

editor's note: Although this study shows that pioglitazone may be ‘safer’ than rosiglitazone, this is a relative distinction only; both drugs are linked with higher rates of CHF.¹ For this reason, the American Diabetes Association (ADA) has advised caution with the use of either agent, especially with class III or IV heart failure. New guidelines from the ADA and the European Association for the Study of Diabetes recommend a “back-to-basics” approach for treating diabetes. Lifestyle modification and metformin (Glucophage) should be used initially, followed by insulin, sulfonylureas, or both if further control is needed. Thiazolidinediones and other drug classes should be reserved for cases in which the initial treatments are unsuccessful in achieving target glycemic goals.²—k.t.m.