Feature: Experts clash on ARBs potential link to cancer

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Angiotensin-receptor blockers (ARBs) are commonly administered as a treatment to high-blood pressure, heart failure (HF) and other complex patient conditions and have been shown to reduce incidence of stroke, MI and HF. However, a new analysis featured in Lancet Oncology this week suggests that the use of these drugs may increase the rates of new cancers in patients by 8-11 percent.

The analysis pooled data from nine randomized controlled trials that were published before November 2009, had a follow-up of at least one year and included at least 100 patients. The researchers assessed whether or not the use of ARBs affected cancer occurrence.

Today, the ARB market consists of seven FDA-approved drugs: olmesartan, telmisartan, losartan, candesartan, valsartan, irbesartan and eprosartan. However, the studies in the Lancet analysis focused mainly on the assessment of telmisartan (Micardis; Boehringer Ingelheim), losartan (Cozaar; Merck) and candesartan (Atacand; AstraZeneca).

The study's lead author, Ilke Sipahi, MD, of the University Hospitals Case Medical Center in Cleveland, told Cardiovascular Business News that the ONTARGET trial (25,620 patients) showed a “statistically significant excess in cancers” in patients who received the ARB candesartan plus an ACE inhibitor compared to those administered an ACE inhibitor alone.

And, when examining the LIFE trial, which administered losartan to 9,193 patients, researchers found a "statistically significant excess in lung cancer,” while the CHARM-Overall trial, which administered candesartan to 7,599 patients, showed an increase in the risk of fatal cancers, Sipahi said in an interview.

However, William B. White, MD, president-elect of the American Society of Hypertension (ASH), told Cardiovascular Business News, “The analysis was not definitive and that it actually asks more questions than it gives answers.

“You have to be careful because this analysis is not really a comparison of one drug versus another,” said White, who also is chief of the division of hypertension and clinical pharmacology at the University Of Connecticut School of Medicine in Farmington, Conn.

White said that studies within the meta-analysis were not projected to specifically evaluate rates of cancer and that each study populations within the nine evaluated studies were “vastly different.” For example, some looked at patients with HF, some with hypertension and some with hypertension and vascular disease. “There was a lot of heterogeneity,” said White.

While Sipahi agreed that not all the trials were performed primarily to look at cancer, three trials in the analysis—LIFE, TROPHY and TRANCEND—enrolled over 40,000 patients to specifically examine cancer risk and its association with ARBs.

Additionally, Sipahi said that while the trial populations did differ, the majority of patients in the trials were in their upper 60s, were mostly white and the cohorts were “not that heterogeneous.” However, smoking status did vary from 9-21 percent across the evaluated, randomized, large-scale, clinical trials, said Sipahi.

White said that because lung cancer takes a “very long time to develop—an estimated 20-40 years—it would be highly unlikely that a drug could actually either stimulate the growth of one of these or could cause cancer.”

While Sipahi acknowledged that “cancer is a slow phenomenon, it doesn't always take 40 years to develop. People get testicular cancer at age 10 and kids have brain tumors at age three. Perhaps these drugs are increasing the growth of pre-existing tumors and they become prominent and cause symptoms that end in the clinical diagnosis of cancer.”

But, White said that the analysis “lacks clarity and that it should not be emphasized in practice at this time.” He added that ASH would not recommend that a patient stop taking ARBs or other anti-hypertension drugs because of these study findings.

Because data were pooled and not taken from individual cases, “there could be underlying confounders that could cause the problem than the actual drug itself,” explained White.

If there was a higher percentage of patients who were smokers in the cohort administered an ARB plus an ACE inhibitor, this could be the potential cause of the higher rates of lung cancers found, he said. “You have to evaluate these kinds of studies with substantial caution because of the way they are done and because of the lack of knowledge related to individual patients in their findings.”