FDA alerts to ongoing olmesartan cardiovascular review

Key Points

On June 11, 2010, FDA announced in a drug safety communication that the agency was currently evaluating whether the use of the angiotensin II receptor blocker (ARB) olmesartan (Benicar, Daiichi Sankyo) (also sold in combination with hydrocholorothiazide as Benicar HCT) was associated with increased cardiovascular mortality.

Concerns regarding olmesartan's safety have grown out of unexpected findings in 2 recently completed randomized controlled trials.

In both clinical trials, olmesartan-treated patients were found to have a higher rate of death due to heart attack, sudden death, or stroke than patients taking placebo.

Officials further emphasized "FDA currently believes that the benefits of Benicar in patients with high blood pressure continue to outweigh its potential risks."

In both the Randomized Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study and the Olmesartan Reducing Incidence of End-Stage Renal Disease in Diabetic Nephropathy Trial (ORIENT), patients with type 2 diabetes were given either olmesartan or placebo to determine if treatment with olmesartan would slow their progression to end-stage renal disease.

ROADMAP enrolled 4,447 European patients with at least 1 additional cardiovascular risk factor to accompany diabetes, but without overt evidence of nephropathy to receive either 40 mg of olmesartan or placebo daily.

ORIENT enrolled 566 patients from Japan and Hong Kong with type 2 diabetes and overt nephropathy to receive olmesartan at doses of 10 mg to 40 mg daily or placebo.

In both ROADMAP and ORIENT a greater number of deaths due to cardiovascular causes occurred in olmesartan-treated patients (ROADMAP: 0.67%; ORIENT: 3.5%) compared with placebo (ROADMAP: 0.14%; ORIENT: 1.1%).

FDA ACTION

FDA cautioned, "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."

To further evaluate this possible association between olmesartan and increased cardiovascular death, FDA noted that it plans to further review data from these 2 randomized trials, as well as the totality of clinical trial data involving olmesartan.

SOURCES

FDA. FDA Drug Safety Communication: Ongoing safety review of Benicar and cardiovascular events. June 11, 2010. Available at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm215222.htm. Accessed June 14, 2010.

Olmesartan Medoxomil in Diabetes Mellitus (NCT00185159). Available at: http://www.clinicaltrials.gov/ct2/show/NCT00185159?term=ROADMAP+AND+olmesartan&rank=1. Accessed June 14, 2010.

ORIENT: Olmesartan Reducing Incidence of End Stage Renal Disease in Diabetic Nephropathy Trial (NCT00141453). Available at: http://www.clinicaltrials.gov/ct2/show/NCT00141453?term=ORIENT&rank=1. Accessed June 14, 2010.