FDA Reviews Olmesartan (Benicar) Safety Record, Cites CV Deaths in Trials

The FDA is conducting a safety review of the angiotensin receptor blocker (ARB) olmesartan (Benicar, Daiichi Sankyo) after determining that diabetic patients taking the drug in two completed phase 3 trials may have had an excess risk of cardiovascular death, the regulatory body has announced [1]…. 

The safety announcement says that the FDA’s review is “ongoing, and 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 agency also notes that “other controlled clinical trials evaluating Benicar and other ARBs have not suggested an increased risk of cardiovascular-related death.”

The primary end points of the two trials were dominated by measures of renal function.

In the Randomized Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study, conducted in Europe, 4,447 patients with diabetes and at least one additional cardiovascular risk factor, but no evidence of renal dysfunction, were randomized to receive either olmesartan at 40 mg/day (n=2232) or placebo (n=2215). The trial, sponsored by Sankyo Pharma, ended in July 2009 [2].

There were 15 cardiovascular deaths — including seven cases of sudden death, five fatal MIs, two fatal strokes, and one death related to coronary revascularization — in the olmesartan group compared with a total of three CV deaths — one sudden death and two fatal strokes –i n the control group.

In the Olmesartan Reducing Incidence of End Stage Renal Disease in Diabetic Nephropathy Trial (ORIENT), conduced in Japan and Hong Kong, 566 patients with diabetes and renal dysfunction were randomized to receive olmesartan at 10 mg/day to 40 mg/day (n=282) or placebo (n=284).

Of the 10 cardiovascular deaths in the olmesartan group, five were sudden death, one was a fatal MI, three were fatal strokes, and one was of unknown CV cause. Three patients in the control group died, two from sudden death and one from MI. ORIENT, sponsored by Daiichi Sankyo, was completed in February 2009 [3].

“In considering the results of these trials, it is important to remember that numerous clinical trials with olmesartan as well as trials with other ARBs have not suggested an increased risk of cardiovascular-related death,” the FDA announcement notes. Still, the “FDA plans to review the primary data from the two trials and the total clinical-trial data on olmesartan. 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 angiotensin-converting enzyme (ACE) inhibitors in certain patients at high risk for cardiovascular events.”

1. Food and Drug Administration. FDA drug safety communication: Ongoing safety review of Benicar and cardiovascular events. June 11, 2010. Available here.
2. Randomized Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study. clinicaltrials.gov. Available here.
3. ORIENT: Olmesartan Reducing Incidence of End Stage Renal Disease in Diabetic Nephropathy Trial. clinicaltrials.gov. Available here.