The Food and Drug Administration’s review of the safety of olmesartan has found "no clear evidence" of increased cardiovascular risks associated with the use of the drug in people with diabetes, but some concern remains about the possible risk with high doses, the agency reported on June 24.
The review, prompted by the ROADMAP (Randomized Olmesartan and Diabetes Microalbuminuria Prevention) study of patients with type 2 diabetes – which unexpectedly found an increased risk of cardiovascular death among patients on olmesartan, compared with those on placebo – has been completed, and recommendations for the use of the angiotensin receptor blocker (ARB) in people with diabetes will remain unchanged, according to the FDA.
Information about some of the studies reviewed by the FDA, however, including a large observational study of Medicare patients, will be included in the labels of olmesartan products, which include Benicar, Benicar HCT, AZO, Tribenzor, and generic formulations, the statement said.
"While data from the ROADMAP trial and the Medicare study have suggested that high-dose olmesartan may increase CV risk in diabetic patients, when considering the data from all trials and studies, they are not conclusive," the FDA statement said, adding, "Overall, we determined these studies do not clearly show an increased cardiovascular risk. Thus, the collective evidence available at this time does not support changing our recommendations for olmesartan use and does not support recommending that its use be avoided in patients with diabetes."
The risk of nonfatal MI, however, was lower among those on olmesartan in the ROADMAP study, which was designed to determine whether olmesartan could delay kidney damage in patients with type 2 diabetes (N. Engl. J. Med. 2011;364:907-17).
In the Medicare study of patients aged 65 years and older, the risk of death was increased among patients with diabetes, who received the highest (40 mg/day) dose of olmesartan for more than 6 months (hazard ratio, 2.0). Among patients who did not have diabetes, however, the highest dose was associated with a reduced risk of death (HR, 0.46). The conflicting results in these two patient groups in the study "are difficult to reconcile and raise uncertainty about the credibility of the findings in either group," the FDA said.
Other studies reviewed include a U.K. study of primary care medical records that compared outcomes of patients receiving high-dose olmesartan with those treated with high doses of other ARBs in over 58,000 patients. The study found an increased risk of overall death and of acute myocardial infarction associated with the use of high-dose olmesartan, which was not statistically significant (Pharmacoepidemiol. Drug Saf. 2014;23:340-7).
"Overall, these data raise concern of possible increased cardiovascular risk associated with the use of high-dose olmesartan in diabetic patients," the FDA concluded.
The FDA’s first safety communication on this issue was posted in June 2010, followed by an update in April 2011.
In 2013, about 1.8 million people received a dispensed prescription for olmesartan products from U.S. outpatient retail pharmacies, according to the FDA.
Serious adverse events in patients treated with olmesartan products should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch.