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FDA Drug Safety Podcast for Healthcare Professionals: Ongoing safety review of Benicar and cardiovascular events

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Welcome, my name is Jennifer Shepherd, a pharmacist in the Division of Drug Information. I am updating you on the ongoing safety review of Benicar and cardiovascular events. The FDA is evaluating data from two clinical trials ROADMAP and ORIENT in which patients with type 2 diabetes taking Benicar, also known as olmesartan, had a higher rate of death from a cardiovascular cause compared to patients taking a placebo.

FDA's review is ongoing and the Agency has not concluded that Benicar increases the risk of death. FDA currently believes that the benefits of Benicar in patients with high blood pressure continue to outweigh its potential risks.

Benicar is in the class of drugs called angiotensin II receptor blockers or ARBs. These drugs and a closely related group of drugs called angiotensin-converting enzyme inhibitors (ACEIs) have been evaluated in many studies involving thousands of patients at high-risk for cardiovascular events, such as patients who had a previous heart attack or had heart failure. No increased risk of cardiovascular-related death has been reported in these trials and, in fact, some of these studies indicate ARBs and ACEIs are useful as treatments for certain patients at high-risk for cardiovascular events.

The Randomized Olmesartan and Diabetes Microalbuminuria Prevention Study or 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 ACEIs or ARBs.

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.

The Olmesartan Reducing Incidence of End Stage Renal Disease in Diabetic Nephropathy Trial or ORIENT was a randomized, double-blind, placebo-controlled, multicenter trial conducted in Japan and Hong Kong. The trial included 566 patients with type 2 diabetes and overt nephropathy who were randomized to receive olmesartan 10 mg to 40 mg or placebo daily. Patients were permitted to take additional antihypertensives including ACEIs, but excluding ARBs. The primary composite endpoint was the time to first event of doubling of serum creatinine, end stage renal disease, and all cause death.

An unexpected finding observed in both trials was a greater number of deaths from a cardiovascular cause, such as heart attack, sudden death, or stroke, in the Benicar-treated patients compared to placebo. In ROADMAP, there were 15 cardiovascular related deaths in the Benicar group compared to 3 in the placebo group. In ORIENT, there were 10 cardiovascular-related deaths in the Benicar group compared to 3 deaths in the placebo group. The summary of findings from these trials can be found in tables which are available in the full drug safety communication on the FDA website at www.fda.gov.

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 ARBs and ACEIs in certain patients at high risk for cardiovascular events.

At this time, FDA recommends that Healthcare Professionals be aware that:

  1. FDA has not concluded that Benicar increases the risk of death. The Agency is reviewing information related to the safety concern and will update the public when additional information is available.
  2. FDA believes the benefits of Benicar in patients with high blood pressure continue to outweigh the potential risks.
  3. In the ROADMAP and ORIENT trials, there were a greater number of cardiovascular-related deaths in the Benicar group compared to the placebo group.
  4. Additional information about ROADMAP and ORIENT can be found at www.clinicaltrials.gov.
  5. Other controlled clinical trials evaluating Benicar and other angiotensin II receptor blockers have not suggested an increased risk of cardiovascular-related death.
  6. Recommendations in the drug label should be followed when prescribing Benicar.
  7. Adverse events involving Benicar can be reported to the FDA MedWatch program at www.fda.gov/medwatch.

Thank you for listening. The FDA is committed to keeping healthcare professionals informed of the latest safety information. If you have questions about this safety communication, you can reach us at the following email address: druginfo@fda.hhs.gov.

 

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