The Food and Drug Administration (FDA) is evaluating data from two clinical trials in which patients with type 2 diabetes taking the blood pressure medication olmesartan (Benicar) had a higher rate of death from a cardiovascular cause compared to patients taking a placebo.
There were 15 cardiovascular deaths in the olmesartan arm of the 4,447-patient Randomized Olmesartan and Diabetes Microalbuminuria Prevention Study (ROADMAP) trial versus three in the placebo arm, and in the much smaller Olmesartan Reducing Incidence of End Stage Renal Disease in Diabetic Nephropathy Trial (ORIENT) study (with 566 patients), there were 10 cardiac deaths among patients taking olmesartan versus three in the placebo group.
In announcing the safety review, the FDA said, "The Agency has not concluded that Benicar increases the risk of death. FDA currently believes that the benefits of Benicar in patients with high blood pressure continue to outweigh its potential risks."
The FDA said it planned to review the primary data from the two trials and the total clinical trial data on olmesartan to evaluate the possible association between olmesartan and increased cardiovascular-related death.
"Also, the Agency will evaluate additional ways to understand the findings from ROADMAP and ORIENT, in light of information supporting the use of ARBs and ACE-inhibitors in certain patients at high risk for cardiovascular events," the FDA said.
Both clinical trials were designed to determine if treatment with olmesartan, which is an angiotensin II receptor blocker (ARB), could slow the progression of kidney disease.
The FDA noted that clinical trials of other ARBs as well as other trials of olmesartan have not revealed an excess risk of cardiovascular mortality.
Benicar and Benicar HCT are marketed by Daiichi Sankyo, Inc., which has a U.S. headquarters in Parsippany, N.J.
ROADMAP was a randomized, double-blind, placebo-controlled, multicenter trial conducted in Europe. The trial included 4,447 patients with type 2 diabetes and at least one additional cardiovascular risk factor, but without overt evidence of nephropathy. Patients were randomized to receive either 40 mg of olmesartan or placebo daily. Patients were permitted to receive other antihypertensive medications, but not other ACE inhibitors or ARBs.
The primary objective was to evaluate whether olmesartan could delay the onset of microalbuminuria. The majority of patients had three to five cardiovascular risk factors and 80% of patients were using other antihypertensives. The mean duration of exposure to olmesartan was 39 months.
ORIENT was a randomized, double-blind, placebo-controlled, multicenter trial conducted in Japan and Hong Kong. A total of 566 patients with type 2 diabetes and overt nephropathy were randomized to receive olmesartan 10 mg to 40 mg or placebo daily. Patients were permitted to take additional antihypertensives including ACE-inhibitors, but excluding ARBs. The primary composite endpoint was the time to first event of doubling of serum creatinine, end stage renal disease, and all cause death.
