Policy

FDA will review angiotensin-receptor blockers (ARBs) for cancer risk

The Food and Drug Administration (FDA) has joined the ranks of public health agencies reviewing a popular class of blood pressure medicines and its possible link to cancer, despite criticism about using the method of meta-analysis to establish such a link. Researchers at Cleveland, Ohio’s, University Hospitals Harrington-McLaughlin Heart & Vascular Institute blew the whistle […]

The Food and Drug Administration (FDA) has joined the ranks of public health agencies reviewing a popular class of blood pressure medicines and its possible link to cancer, despite criticism about using the method of meta-analysis to establish such a link.

Researchers at Cleveland, Ohio’s, University Hospitals Harrington-McLaughlin Heart & Vascular Institute blew the whistle on angiotensin-receptor blockers (ARBs) for posing a heightened cancer risk in a June 13 Lancet article. Brand names of these drugs, which also are used to treat heart failure, diabetic nephropathy and cardiovascular risk, include Atacand, Avapro, Benicar, Cozaar, Diovan, Micardis and Teveten, according to the FDA.

The researchers did a meta-analysis of more than 60,000 patients randomly assigned to take either an ARB or a control medication. The researchers found that patients who took ARBs had a modest but “significantly increased risk of new cancer” compared to patients who didn’t take the drugs.

“We have found the risk of new cancers was increased with these medications by 8 [percent] to 11 percent,” said Dr. Ilke Sipahi, associate director of heart failure and transplantation at University Hospitals Case Medical Center in a release on the Lancet article. “Most importantly, risk of lung cancer was increased by 25 percent.”

The research did not establish links between ARBs and other types of cancer, such breast cancer. “This is the first time an association between ARBs and cancer development is suggested, said Sipahi, who also is an assistant professor at Case Western Reserve University School of Medicine. “While our findings are robust, they need to be replicated in other studies before they can be considered as definitive.”

A week after the Lancet article was published (pdf), the Committee for Medicinal Products for Human Use of the European Medicines Agency said it would review ARBs for their potential to cause cancer.

The FDA already had been looking at ARB Benicar (generic name olmesartan) for its potential to raise the risk of cardiac deaths among diabetic patients. That review began after two published articles uncovered a potential risk.

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A Deep-dive Into Specialty Pharma

A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.

Cleveland Clinic cardiologist Steven Nissen, who used meta-analyses to blow the whistle on diabetes drug Avandia, among others, called the University Hospitals analysis “disturbing and provocative” in a June 13 Lancet article.

But Boehringer Ingelheim group, which makes ARB Micardis (telmisartan), said it “strongly disagrees” with the conclusions of the meta-analysis. The German drugmaker has studied its drug in more than 50,000 patients, finding it safe for up to five years.

It also said the meta-analysis was based on combining telmisartan with an angiotensin-converting enzyme (ACE) inhibitor called ramipril. The drugmaker does not recommend such a combination.

“We were roundly criticized for making even soft conclusions on safety issues using meta-analysis,” said Dr. Dan Simon, chief of Cardiovascular Medicine at UH Case Medical Center, director of the Case Cardiovascular Center and a co-author of the Lancet study.

“The problem is, we did meta-analysis on 40,000 to 90,000 patients. No drugmaker is going to do a safety study on the numbers of patients that you need to get a safety signal,” Simon said.

“So, yes, randomized, prospective trials are the best way to understand safety signals. The problem is, they’re not realistic,” he said. “No one is going to ever do an ACE versus ARB cancer study. The country struggles with what post-marketing approval data there is to tell you about the safety of drugs or devices. This is the best you have.”