FDA announces ongoing cardiovascular safety review of olmesartan

July 15, 2010

FDA has announced that the agency is 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.

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 the safety of olmesartan 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 sudden death and death from heart attack or stroke than patients taking placebo.

"This communication is in keeping with FDA's commitment to inform the public about its ongoing safety review of drugs," noted FDA officials, adding, "FDA's review is ongoing and the Agency has not concluded that Benicar increases the risk of death." Officials further emphasized that "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 whether 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 the ROADMAP and ORIENT studies, a greater number of deaths from cardiovascular causes occurred in olmesartan-treated patients (ROADMAP: 0.67%; ORIENT: 3.5%) compared with placebo (ROADMAP: 0.14%; ORIENT: 1.1%).

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 explore further the possible association between olmesartan and increased cardiovascular death, FDA anounced, it will continue to review data from these 2 randomized trials, as well as to examine the totality of clinical trial data involving olmesartan.

References

1. FDA. FDA Drug Safety Communication: Ongoing safety review of Benicar and cardiovascular events. FDA website (

Benicar safety review

). June 11, 2010. Accessed June 30, 2010.
2. Olmesartan Medoxomil in Diabetes Mellitus (nct00185159). ClinicalTrials.gov website (

Olmesartan Medoxomil

). Accessed June 30, 2010.
3. ORIENT: Olmesartan Reducing Incidence of End Stage Renal Disease in Diabetic Nephropathy Trial (NCT00141453). ClinicalTrials.gov website (

ORIENT

). Accessed June 30, 2010.