An increased rate of cardiovascular deaths in patients with type 2 diabetes treated with olmesartan, compared with placebo, in two studies is the focus of a safety review by the Food and Drug Administration, the agency announced last month.
The FDA plans to evaluate the data from the two clinical trials, which are examining whether treatment with olmesartan slows the progression of kidney disease in patients with type 2 diabetes. In both studies, there were more cardiovascular deaths—myocardial infarction, sudden death, or stroke—in those treated with olmesartan than in those on placebo. Olmesartan is an angiotensin II receptor blocker (ARB), marketed as Benicar by Daiichi Sankyo Inc. for hypertension.
“The review is ongoing and the agency has not concluded that Benicar increases the risk of death,” the statement said. “FDA currently believes that the benefits of Benicar in patients with high blood pressure continue to outweigh its potential risks.” The FDA is advising health care professionals to continue to follow the recommendations in the olmesartan label when prescribing the drug and to report adverse events in patients treated with the drug to the agency's MedWatch adverse event reporting program.
Both studies were completed in 2009. One, the Randomized Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study, conducted in Germany, compared the time to first occurrence of microalbuminuria in 4,447 patients with type 2 diabetes and at least one additional cardiovascular risk factor and normoalbuminuria before being randomized to placebo or olmesartan.
The second study—Olmesartan Reducing Incidence of End Stage Renal Disease in Diabetic Nephropathy Trial (ORIENT)—was conducted in China and Japan, and compared the first occurrence of the doubling of serum creatinine level, death, or end-stage renal disease over 5 years in 566 patients with type 2 diabetes and a clinical diagnosis of diabetic nephropathy.
Cardiovascular deaths were secondary end points in both trials. In ROADMAP, 15 cardiovascular deaths occurred in the olmesartan-treated patients, compared with 3 in the placebo patients; 7 of those 15 were sudden cardiac deaths. In ORIENT, 10 cardiovascular deaths occurred in the treated patients, while 3 occurred in the placebo group.