Popular Blood Pressure Drugs Tied to Slight Rise in Cancer Risk
SUNDAY June 13, 2010 -- Use of a popular class of drugs for high blood pressure and heart failure is associated with a slight boost in cancer risk, a new review of data finds.
The drugs are known as angiotensin-receptor blockers (ARBs) and include medicines such as telmisartan (Micardis), losartan (Cozaar, Hyzaar), valsartan (Diovan) and candesartan (Atacand).
Overall, the researchers looked at trials involving over 223,000 patients. When they concentrated on five trials involving over 60,000 patients, in which cancer was a pre-specified endpoint, "patients assigned to these ARBs had about a 10 percent increase in cancer" relative to those not on the medications, said Dr. Ilke Sipahi, assistant professor of medicine at Case Western Reserve University, lead author of a report in the June 14 online edition of The Lancet Oncology.
The incidence of cancer in people taking an ARB was 7.2 percent, compared to a 6 percent incidence in those taking a placebo, the analysis found. The increase in solid tumors was concentrated in lung cancers, whose incidence was 25 percent higher in those taking an ARB, he said.
Despite the rise in risk, the researchers noted that there was only a slight increase in deaths from cancer among ARB users -- 1.8 percent for those taking ARBs, 1.6 percent for those taking placebo, a difference that was not statistically significant.
Most of the people in the trials -- 85.7 percent -- were taking the ARB telmisartan (Micardis), while the remainder took other ARBs such as losartan, valsartan and candesartan.
The drugs work by blocking cell receptors for angiotensin II, a hormone that plays an important role in regulating blood pressure. Another class of drugs that are used for the same purposes are the ACE inhibitors, which prevent the formation of the active form of angiotensin.
"Experimental studies using cancer cell lines and animal models have implicated the angiotensin system in the proliferation of cells and also tumors," Sipahi said. "Evidence from animal studies show that blockage of angiotensin receptors can stimulate tumor growth by promoting new blood vessel formation in tumors."
But the evidence that ARBs can play a real role in cancer growth remains unclear, he said, and these findings only show an association, not cause-and-effect.
"Before we jump to that conclusion, I feel we need more analysis," Sipahi said.
Several laboratory studies reported by researchers in the United States and Japan have found evidence that ARBs might prevent growth or recurrence of several forms of cancer -- bladder, prostate, breast -- but "I know of no controlled studies that show that," Sipahi said.
Another expert agreed that the data on ARBs and cancer risk is unsettled at best.
Dr. Hwyda Arafat, who has been doing research on the angiotensin system and pancreatic cancer, said there is some evidence from animal models that ARBs can prevent cancer growth.
But it's also possible that ARB treatment could promote cancer growth, said Arafat, who is associate professor of surgery, pathology, anatomy and cellular biology at Thomas Jefferson University. ARB treatment increases the amount of free angiotensin in and around cells, and its possible tumor-promoting effect is unknown, she said. "This kind of investigation is now warranted, especially in lung cancer for example, where the effects were most significantly high," Arafat said.
In the meantime, doctors should be cautious about changing their prescribing practices on the basis of the new report. "Physicians should wait for more intensive examination of our findings," Sipahi said. "Meanwhile, I am urging caution."
A full investigation of the possible risk by the U.S. Food and Drug Administration is needed, he said. "It is the FDA's responsibility to do a thorough analysis of the risk of cancer with ARBs, using the individual patient data they have," he added.
Sipahi said he now includes the possible increased risk of cancer when making decisions about drug prescriptions, but he looks at a drug's benefits, as well.
"I am a heart failure specialist," Sipahi said. "I am looking at benefits versus risks and am making decisions according to that. When necessary, there is an alternative to an ARB -- I can prescribe an ACE inhibitor."
Posted: June 2010