The FDA ( Food and Drug Administration ) has not concluded that Olmesartan ( Benicar ) increases the risk of death. In the ROADMAP and ORIENT trials, there were a greater number of cardiovascular-related deaths in the Olmesartan group compared to the placebo group.
Other controlled clinical trials evaluating Olmesartan and other angiotensin II receptor blockers ( also known as sartans ) have not suggested an increased risk of cardiovascular-related death.
The Randomized Olmesartan and Diabetes Microalbuminuria Prevention Study ( ROADMAP ) was a randomized, double-blind, placebo-controlled, multicenter trial conducted in Europe. The trial included 4,447 patients with type 2 diabetes and at least one additional cardiovascular risk factor, but without overt evidence of nephropathy. Patients were randomized to receive either 40 mg of Olmesartan or placebo daily. Patients were permitted to receive other antihypertensive medications, but not angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers.
The primary objective was to evaluate whether Olmesartan could delay the onset of microalbuminuria. The majority of patients had 3 to 5 cardiovascular risk factors and 80% of patients were using other antihypertensives. The mean duration of exposure to Olmesartan was 39 months.
There were 15 cardiovascular deaths ( seven cases of sudden death, five fatal myocardial infarctions, two fatal strokes, and one death related to coronary revascularization ) in the Olmesartan group compared with a total of three cardiovascular deaths ( one sudden death and two fatal strokes ) in the control group.
The Olmesartan Reducing Incidence of End Stage Renal Disease in Diabetic Nephropathy Trial ( ORIENT ) was a randomized, double-blind, placebo-controlled, multicenter trial conducted in Japan and Hong Kong. Patients ( n= 566 ) with type 2 diabetes and overt nephropathy were randomized to receive Olmesartan 10 mg to 40 mg or placebo daily. Patients were permitted to take additional antihypertensives including angiotensin-converting enzyme inhibitors, but excluding angiotensin II receptor blockers. The primary composite endpoint was the time to first event of doubling of serum creatinine, end stage renal disease, and all cause death.
Of the 10 cardiovascular deaths in the Olmesartan group, five were sudden death, one was a fatal myocardial infarction, three were fatal strokes, and one was of unknown cardiovascular cause. Three patients in the control group died, two from sudden death and one from myocardial infarction.
An unexpected finding in both trials was an increased number of cardiovascular deaths in the patients receiving Olmesartan compared to placebo.
In considering the results of these trials, it is important to remember that numerous clinical trials with Olmesartan as well as trials with other sartans have not suggested an increased risk of cardiovascular-related death.
To evaluate the possible association with Olmesartan and increased cardiovascular-related death, 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 sartans and ACE inhibitors in certain patients at high risk for cardiovascular events.
Source: FDA, 2010
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