Angiotensin-receptor blockers (ARBs), drugs commonly used in the treatment of high blood pressure, heart failure, and kidney damage due to diabetes, are associated with a modestly increased risk of developing cancer. Although the limited data makes it impossible to calculate the exact cancer risk associated with each individual drug, these findings demand further investigation, concludes an Article published Online First in The Lancet Oncology.
ARBs work by blocking the receptors for angiotensin II, a hormone that increases blood pressure. Although there are no major safety concerns associated with ARBs at present, a previous trial had reported a significantly increased risk of fatal cancers in patients receiving the ARB candesartan compared with placebo.
To further examine the effect of ARBs on the occurrence of new cancers, Ilke Sipahi and colleagues from Case Western Reserve University School of Medicine, Cleveland, USA, performed a meta-analysis of all publicly available data from randomised trials of ARBs published before November 2009. They analysed new cancer data in five trials involving 61 590 patients, common types of solid-organ cancers (lung, prostate, breast) in five trials of 68 402 patients, and cancer deaths in eight trials including 93 515 patients. Most patients in the trials examined received the ARB telmisartan (85.7%).
Overall, findings showed that patients taking ARBs had a significantly increased likelihood of new cancer diagnosis compared with patients in control groups (7.2% vs 6.0%).
Among the solid-organ cancers examined, only the risk of lung cancer was significantly increased in patients taking ARBs compared with controls (0.9% vs 0.7%). No significant excess in cancer deaths was found (1.8% vs 1.6%), although the authors point out that tumour growth and treatment failure followed by death is a slow process and might not be recorded in trials with a short follow-up.
Additionally, data analysed in the study was limited to three out of seven FDA approved ARBs (telmisartan, losartan, and candesartan), so it is unknown if the other ARBs (valsartan, irbesartan, olmesartan, and eprosartan) are linked to a higher risk of new cancer incidence. The authors say: "Given the limited data, it is not possible to draw conclusions about the exact risk of cancer associated with each ARB."
They conclude: "The increased risk of new cancer occurrence is modest but significant…[However] the finding of a 1.2% increase in absolute cancer risk over an average of 4 years needs to be interpreted in view of the estimated 41% background lifetime cancer risk."
In an accompanying Comment, Steven E Nissen from the Cleveland Clinic, Cleveland, USA, says that these findings raise crucial drug safety questions. He calls for pharmaceutical companies to supply complete ARB trial datasets to the regulatory authorities so they can urgently review the possible link between ARB use and cancer and in the interim urges ARBs to be used with more caution.
Dr Ilke Sipahi, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, USA. T) +1 216 844 1639 E) firstname.lastname@example.org
Dr Steven Nissen at the Cleveland Clinic, Cleveland, USA. Via Brian Kolonick, Department of Media Relations T) +1 216 444 0898 email@example.com
For full Article and Comment, see: http://press.thelancet.com/tloarb.pdf
The Lancet Oncology