A front-page story in the Wall Street Journal has blown the lid off a highly controversial internal squabble at the FDA involving a popular category of blood pressure medicine. ARBs (angiotensin receptor blockers) are among the most frequently prescribed drugs in the world. Millions of people take such medications daily. In the U.S., nearly $8 billion is spent annually on such drugs.
ARBs ON THE U.S. MARKET
- Atacand (candesartan)
- Avapro (irbesartan)
- Benicar (olmesartan)
- Cozaar (losartan)
- Diovan (valsartan)
- Edarbi (azilsartan)
- Micardis (telmisartan)
- Teveten (eprosartan)
We first became aware of a possible linkage between ARBs and cancer nearly three years ago after reading an article in Lancet Oncology (online, June 14, 2010). The researchers reviewed data from randomized controlled trials (RCTs) and information on cancer deaths. The authors concluded:
“In conclusion, this meta-analysis shows that ARBs are associated with a modestly increased risk of new cancer occurrence. Among the solid organ cancers examined, only the risk of lung cancer was significantly increased. Given limited data, it is not possible to draw conclusions about the exact risk of cancer associated with each particular ARB. Our findings warrant further investigation.”
A year later, on June 2, 2011, the FDA issued its own analysis that contradicted this concern:
“The U.S. Food and Drug Administration today announced that a group of medications used to control high blood pressure, called angiotensin receptor blockers (ARBs), do not increase the risk of developing cancer in patients using the medications…The FDA has determined that any concern about a relationship between ARB use and development of cancer has been resolved by this analysis. People currently taking any antihypertensive medication should not stop taking it without talking to their health care professional first.”
The FDA left little doubt that it had reviewed the matter carefully and declared all clear. No cancer risk and nothing to worry about.
We contacted the author of the original research to try and get a handle on what was going on. We also dug into the data a bit further ourselves. We discovered that the FDA included research that lasted little more than one year. The average follow up was 39 months for the 31 trials included in the FDA analysis. That might not have been long enough to detect a true cancer signal.
After talking to experts at the National Toxicology Program about how long it would take to detect a cancer signal from a known carcinogen, it became clear that 3.5 years was woefully inadequate. These scientists doubted you could prove cigarette smoking caused cancer after such a short period of time. But the FDA was satisfied that its analysis slammed the door on this controversy. We contacted the FDA and posed the following concern:
“If the FDA relies primarily on RCTs [randomized controlled trials] to assess cancer risk and most such studies last no longer than a few years, the agency will be handicapped in its power to evaluate a risk to patients.”
The FDA did not respond to our concern.
Barely three weeks later (June 20, 2011), however, a study from Taiwan published in the Journal of Clinical Oncology revealed that patients with diabetes taking ARBs such as candesartan (Atacand) and telmisartan (Micardis) experienced an increased risk of cancer.
In September of 2011 another study pointed to problems. This time it came from Germany. Researchers detected lung cancer at a significantly higher rate in kidney transplant patients who had smoked and had been given ACE inhibitors or ARBs. In a sense, these people were like canaries in the coal mine. Because of their susceptibility, they were a highly vulnerable population.
Despite such mounting evidence, the FDA has stood by its official conclusion that there is no cancer risk associated with ARBs.
Now the Wall Street Journal has uncovered a substantial rift within the agency itself. Dr. Thomas Marciniak is an FDA reviewer. He was concerned that the data the agency had reviewed might have been incomplete. According to the Wall Street Journal report:
“Dr. Marciniak said in an internal analysis viewed by the Journal that the FDA meta-analysis didn’t count cases of ‘lung carcinomas’ as lung cancers, which they are.”
Dr. Marciniak analyzed the raw data supplied by the drug companies and discovered that there was roughly a 24% increased risk of lung cancer among patients who took ARBs. He encouraged his colleagues at the FDA to inform doctors and patients about this risk.
His FDA bosses, however, discount his research and appear in no mood to issue any warning. If anything, they are circling the wagons. Dr. Marciniak’s boss, Ellis Unger, apparently told the Wall Street Journal that the cancer concerns are a “diversion.” Unger’s position: “We have no reason to tell the public anything new.”
THE PEOPLE’S PHARMACY BOTTOM LINE:
What are we to make of all this? First, we have asked the FDA repeatedly about how it determines if a drug causes cancer. You would be surprised to learn that there are a great many medications on the market that raise the risk of tumors in animals. The FDA lists this in the official prescribing information, but rarely requires drug companies to do long-term follow-up studies to determine if there is a problem in humans. That leaves physicians, pharmacists and patients in the lurch.
Even when there is a clear signal that a drug is linked to cancer, the FDA seems puzzled about what to do about the problem. Just such a concern has been raised with the popular diabetes drug Actos (pioglitazone). A study published in the Journal of the National Cancer Institute (Aug. 9, 2012) suggested that people with type 2 diabetes who took Actos were two to three times more likely to be diagnosed with bladder cancer compared to those taking other antidiabetes drugs.
France and Germany banned Actos in 2011 because of cancer concerns. All the FDA has done is issue a warning:
“The use of the diabetes medication Actos (pioglitazone) for more than one year may be associated with an increased risk of bladder cancer.”
Needless to say, such a warning leaves doctors and patients in a terrible double bind. Another class of drugs for treating diabetes is now also under scrutiny. GLP-1 diabetes drugs rake in over $9 billion each year. They include brands such as Byetta, Januvia, Onglyza and Victoza. An article in the New York Times (May 30, 2013) reveals a fascinating story about a researcher who studied Januvia in animals and found “worrisome changes in the pancreas of the rats that could lead to pancreatic cancer.”
The FDA has issued a warning about “pre-cancerous cellular changes called pancreatic duct metaplasia” linked to the GLP-1 diabetes drugs. But once again, the agency is moving very cautiously. We will have to wait to see whether the millions of people taking such medications are at increased risk for pancreatic cancer.
In the meantime, we do agree that no one should stop taking ARBs, Actos or GLP-1 diabetes drugs without discussing the controversies with the prescribing doctor. That said, we hope patients will bring the articles from the Wall Street Journal and the New York Times to their health professionals’ attention. Doctors, pharmacists and nurses need to be aware of these cancer concerns so they won’t be taken by surprise when the FDA finally takes action.