EMA Review Concludes: No Cancer Risk With ARBs

Shelley Wood


October 20, 2011

October 20, 2011 (London, United Kingdom) — In a decision mirroring that of the US FDA in June, the European Medicines Agency (EMA) released the results of a review by its Committee for Medicinal Products for Human Use (CHMP) today, concluding that there is likely no increased risk of cancer associated with use of angiotensin-receptor blockers (ARBs) [1].

"The European Medicines Agency concludes that benefit/risk balance of angiotensin-II–receptor antagonists remains positive," a press release from the EMA states today.

The EMA's review was prompted by a controversial 2010 meta-analysis, reported by heartwire , pointing to a 7.2% increased risk of new cancers--lung cancer in particular--as compared with a 6% increased risk in patients taking placebo or other heart drugs.

"The CHMP reviewed all available data on the risk of cancer in patients taking ARBs, including the meta-analysis," the statement reads. "It found that the evidence from the meta-analysis was weak, noting several problems with the quality of the data, specifically that patients in the trials were not followed up for long enough to clearly establish a link between ARBs and cancer, information on the risk of cancer before start of treatment was lacking, and there was a possibility of publication bias, whereby studies that showed a link with cancer were more likely to have been included in the analysis."

As chronicled by heartwire over the past year, researchers have published a raft of studies and analyses either supporting or rejecting a link between ARBs and cancer, the most recent in the October 4, 2011 issue of CMAJ, by Dr Chan Yoon (Seoul National University of Medicine, South Korea) and colleagues, actually pointing to a beneficial effect of ARBs and ACE inhibitors on the risk of cancer [2]. Another recent study, however, in diabetic patients treated with ARBs, suggested that candesartan (Atacand, AstraZeneca) was associated with a significant risk of cancer, while there was a trend toward an increased risk with telmisartan (Micardis, Boehringer Ingelheim).

Commenting on the announcement, Dr Ilke Sipahi (University Hospitals Case Medical Center, Cleveland, OH), whose 2010 meta-analysis first brought this issue into the spotlight, told heartwire that he believes both the EMA and FDA "fumbled the ball."

Both agencies, he notes, had the opportunity to request patient-level data from the companies and to conduct analyses that took into account drug dose, patient compliance, and duration of exposure--but neither did.

"So I am very disappointed. The EMA had a total of 16 months to do this review. . . . Unfortunately, all they could do in 16 months was review the publications that came after my own. And even that review is incomplete, since there have been several studies that have come out since then supporting our findings."

Repeating the criticism he had of the FDA's decision back in June, Sipahi observed that cancer biologists and epidemiologists trying to determine the cancer risk of something like smoking or an environmental toxin will pay "extreme attention" to intensity and duration of exposure. "So it's really surprising that neither of the agencies did that," he said.