FDA: No Clear Sign of Harm With Olmesartan in Diabetics

by Todd Neale, Senior Staff Writer, ��ѻ��ý June 25, 2014

This article is a collaboration between ��ѻ��ý and:

The evidence linking use of the angiotensin II receptor blocker (ARB) olmesartan in patients with diabetes and increased cardiovascular risk is not conclusive, according to a .

The agency said that it believes the benefits of using the drug outweigh the risks, adding that recommendations for use will not change. Information from some of the studies addressing the potential cardiovascular risk will be included on the drug labels, however.

The safety review initially was sparked in 2010 following the results of the 4,447-patient ROADMAP trial, which evaluated olmesartan versus placebo in patients with type 2 diabetes and at least one other cardiovascular risk factor but no overt nephropathy. Patients in the olmesartan arm had a delay on the onset of microalbuminuria -- the primary endpoint -- but at the expense of a greater number of cardiovascular deaths (15 versus three), mostly attributable to sudden cardiac death and myocardial infarction.

That concerning finding also was seen in the smaller 566-patient ORIENT trial, which included patients with type 2 diabetes and overt nephropathy. In that trial, there were 10 cardiac deaths in the olmesartan arm and three in the placebo arm.

The FDA's review included a look at those and other studies, including one using the Clinical Practice Research Datalink, one using Medicare data, and two studies -- a patient-level meta-analysis and an observational analysis -- conducted by the maker of olmesartan, Daiichi Sankyo.

In the Medicare study, a high dose of olmesartan (40 mg) was associated with a greater risk of death in patients with diabetes, but a lower risk of death in patients without diabetes compared with others ARBs, a discrepancy described by the FDA as "not a plausible finding."

"Overall, we determined these studies do not clearly show an increased cardiovascular risk," the agency said. "Thus, the collective evidence available at this time does not support changing our recommendations for olmesartan use and does not support recommending that its use be avoided in patients with diabetes."