Review: Diabetes drug trials should add HF hospitalization as outcome
Trials of new glucose-lowering drugs should consider hospitalization for heart failure as an outcome, according to a Personal View article published online March 13 in The Lancet. The authors argued that heart failure has not received much attention as an outcome in clinical trials of these drugs, but results have associated them with an increased risk of heart failure.
John J. V. McMurray, MD, of McMaster University and Population Health Research Institute in Hamilton, Canada, and co-authors analyzed numerous clinical trials published through December 2013 to examine the relationship between diabetes and hospitalization for heart failure.
While it is not clear whether diabetes causes heart failure or the two are comorbid conditions, the authors explained that the data suggest heart failure is a more common occurrence in diabetics than other cardiovascular conditions. In one study, for example, investigators found that among diabetics treated with insulin, the rate of heart failure was 243 per 10,000, compared with 97 per 10,000 for MI and 151 per 10,000 for stroke.
In addition, studies have found heart failure in patients with diabetes to be associated with a poor prognosis. Several clinical trials found mortality to be high among diabetics admitted to the hospital with heart failure, with one trial showing an association between the development of heart failure in diabetics and a six-fold increase in mortality risk.
And while to date few if any new glucose-lowering drugs have been associated with MI or stroke, pioglitazone (Actos, Takeda), rosiglitazone (Avandia, GlaxoSmithKline) and saxagliptin (Onglyza, Bristol-Myers Squibb and AstraZeneca) have been linked to an increased risk of heart failure. A trial evaluating alogliptin (Nesina, Takeda) found a greater number of heart failure admissions among participants taking the drug, but this finding was not statistically significant.
“Admission to hospital for heart failure should have equal status to myocardial infarction and stroke as an important cardiovascular outcome in studies of new diabetic therapies, and even added as a component to the primary composite cardiovascular outcome of trials to more fully capture the potential cardiovascular risks and benefits,” the authors wrote.