Parent Category: Public


Cardiovascular risk

Two studies have prompted safety reviews of olmesartan (Benicar), but hypertension experts attending the European Society of Hypertension (ESH) European Meeting on Hypertension in June 2010 did not appear to be particularly concerned about possible risk of cardiac death. See ROADMAP presented; hypertension experts react to FDA review of olmesartan safety. (You may be asked to register for free access to the story about ROADMAP study.)

Hypertension experts thought the supposed increased risk of cardiac death from olmesartan in the ROADMAP and ORIENT studies could be due to chance. They noted that the drug has proven no real danger since it went on the market in 2002. The FDA is evaluating data from the two studies.

The FDA's ongoing safety review of Benicar and cardiovascular events states:

"Do not stop your treatment with Benicar unless told to do so by your healthcare professional."

4/14/11 safety review update: FDA Drug Safety Communication: Safety Review Update of Benicar (olmesartan) and cardiovascular events

The results of this well-powered 2013 study do not raise concerns for the risk of SCD or death from all causes among olmesartan users in comparison with users of other ARBs or ACE inhibitors:
Cardiac mortality in users of olmesartan, other angiotensin-receptor blockers and angiotensin-converting enzyme inhibitors

06/26/2014 The U.S. Food and Drug Administration (FDA) has completed its safety review and has found no clear evidence of increased cardiovascular risks associated with use of the blood pressure medication olmesartan in diabetic patients. As a result, recommendations for use of olmesartan (Benicar, Benicar HCT, Azor, Tribenzor, and generics) will remain the same. Patients should discuss any questions they have with their health care professionals. It is important to take olmesartan and other blood pressure medicines because uncontrolled high blood pressure increases the risks of cardiovascular problems. Do not stop taking olmesartan or any blood pressure medication without first discussing it with your health care professional. This safety review was prompted by the results of the ROADMAP trial. The ROADMAP (Randomized Olmesartan and Diabetes Microalbuminuria Prevention) clinical trial examined the effects of olmesartan in patients with type 2 diabetes, to see whether olmesartan could delay kidney damage. There was an unexpected finding of increased risk of cardiovascular death in the olmesartan group compared to the group taking a placebo, or sugar pill. However, the risk of non–fatal heart attack was lower in the olmesartan–treated patients. The collective evidence available at this time does not support changing recommendations for olmesartan use and does not support recommending that its use be avoided in patients with diabetes.

FDA Drug Safety Communication: FDA review of cardiovascular risks for diabetics taking hypertension drug olmesartan not conclusive; label updates required
This information is in follow-up to the FDA Drug Safety Communication: Safety Review Update of Benicar (olmesartan) and cardiovascular events.

Cancer riskBenicar_Safety

The US FDA also announced this month that it will be conducting a safety review of olmesartan after a paper about a meta-analysis, published in Lancet Oncology, suggested that angiotensin receptor blockers, as a class of drugs, may be linked to a small increase in cancer risk. There was no increased risk of death from cancer.

Most patients included in the meta-analysis, 86 percent, were taking telmisartan (Micardis), so the applicability of this analysis to other or all ARBs is not known. The data analyzed was limited to only four FDA-approved ARBs (telmisartan, losartan, valsartan, and candesartan), and none of the data was based on use of olmesartan, irbesartan or eprosartan.

The German drug maker of Micardis noted that the meta-analysis relied mainly on data from a combination of Micardis with an angoitensin-converting enzyme (ACE) inhibitor called ramipril. The manufacturer of Micardis does not recommend this combination. The drug maker also pointed out that no analysis was provided for the available data from the trial arms using each compound separately.

In its safety alert, the FDA says it has "not concluded that ARBs increase the risk of cancer." The agency is reviewing information related to this safety concern and will update the public when additional information is available. At this time, FDA believes the benefits of ARBs continue to outweigh their potential risks.

The European Medicines Agency has announced plans to review the possible risk of cancer in patients taking angiotensin-receptor blockers (ARBs), based on a meta-analysis in the June 2010 issue of Lancet Oncology, which suggested a "modest but significant" link between ARBs and cancer.

This article states:

"data analysed in the study was limited to 3 out of 7 US Food and Drug Administration-approved ARBs (telmisartan, losartan, and candesartan), so it is unknown if valsartan, irbesartan, olmesartan, and eprosartan are linked to a higher risk of new cancer incidence."

At the same time, hypertension experts are up in arms about the paper, calling it deeply flawed. See EMA to review ARBs and cancer, infuriating experts, who point to missing data and adverse consequences.

The FDA has not concluded that ARBs increase the risk of cancer. The Agency is reviewing information related to this safety concern and will update the public when additional information is available. FDA believes the benefits of ARBs continue to outweigh their potential risks. See Angiotensin Receptor Blockers (ARBs): Ongoing Safety Review for Cancer Risk.

Editorial: Meta-Analysis Concludes Angiotensin Receptor Blocker Use Increases the Risk of Developing Cancer: Concerns About the Science and the Message.

"In conclusion, we think that this situation highlights the need for us to better educate the mass media about levels of evidence. The fact that the publication of this finding from a study with a low weight of evidence was given such widespread national attention is troubling. According to well-established rules of evidence-based medicine, studies such as this should never dictate clinical care and should remain hypothesis-generating. Perhaps the American Society of Hypertension (ASH) should develop a panel of experts that could be available to help the media appropriately evaluate the strength and significance of publications related to hypertension.

We feel that based on the evidence presented to date, there is no need for physicians to change their prescribing of ARBs or for any regulatory change to occur at this time. We do recommend the following steps be taken to clarify the issue of a potential link between ARBs and incident cancer: (1) a better-designed patient level meta-analysis of all relevant ARB studies, including VALUE, be performed; (2) administrative claims databases such as those available from the Veterans Administration (VA) should be examined to determine whether there is an association between ARB use and incident cancer; (3) any clinical investigators with cancer-related data and ARB use should contact the authors of the present study so they can perform an updated meta-analysis (submitted as a Letter to the Editor of Lancet Oncology); and (4) future trials using ARBs should collect cancer data as a pre-specified end point of interest. Societies such as ASH need to work with the media to properly position and explain the results"

This study states "In conclusion, long-term use of ARBs is associated with a lower incidence of cancer occurrence, thereby suggesting that ARBs may prevent cancer development."
Angiotensin II Receptor Blockers and Risk of Cancer in Patients With Systemic Hypertension.

Angiotensin Receptor Blockers (ARBs): Drug Safety Communication - Drug Safety Review Completed
FDA's meta-analysis of 31 randomized controlled trials comparing ARBs to other treatment found no evidence of an increased risk of incident cancer, cancer-related death, breast cancer, lung cancer, or prostate cancer in patients receiving ARBs.

Renal risk

The concern about kidney damage while taking Benicar with an NSAID is unfounded. This only refers to the angiotensin receptor blockers that are combined with a diuretic (e.g., olmesartan with hydrochlorothiazide). These combination products are often prescribed to treat high blood pressure. Inflammation Therapy uses only single ingredient Benicar.

See: Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: nested case-control study

Long-term safety of high-dose angiotensin receptor blocker therapy in hypertensive patients with chronic kidney disease.

Sprue-like enteropathy risk

Olmesartan Medoxomil: Drug Safety Communication - Label Changes To Include Intestinal Problems (Sprue-Like Enteropathy)

The sprue-like enteropathy recently associated with Benicar involves severe and protracted diarrhea. This puzzling sundrome has been experienced by only a small subset of users and we've not seen it in any patients on Inflammation Therapy.

Stearates are used in many drugs (including Benicar), as a lubricant and stabilizer. In sensitive individuals, stearates could coat the lining of the intestines and prevent proper digestive actions from taking place, thus causing gastroenteritis.

Sprue-like enteropathy

Benicar (olmesartan medoxomil) has recently been linked with development of sprue-like enteropathy in a small subset of users. The gastrointestinal symptoms are not celiac disease because a gluten-free diet did not affect them, the patients did not have the usual antibodies and their symptoms resolved when olmesartan was discontinued. Benicar's prodrug activity occurs in the small bowel but the etiology of this phenomenon is unknown. It could be a consequence of the prodrug action, the infectious theory of systemic inflammation (i.e., Herxheimer reaction) or inactive ingredients in the formulated medication.

Anyone who is experiencing severe and protracted diarrhea should discuss with their doctor the possibility it being caused by Benicar.

This September 2014 study concluded:
"Our findings suggest that neither olmesartan nor other ARBs were associated with diarrhea among patients undergoing endoscopy. The spruelike enteropathy recently associated with olmesartan is likely a rare adverse effect and milder presentations are unlikely."
Olmesartan, Other Antihypertensives, and Chronic Diarrhea Among Patients Undergoing Endoscopic Procedures: A Case-Control Study.


See also Lies, Damned Lies, and Medical Science.