NEW YORK (Reuters Health) – A Danish observational study provides no evidence that use of angiotensin receptor blockers (ARBs) is associated with an increased risk of incident cancer overall or of lung cancer.

Concern about increased risks of cancer was raised by results of a meta-analysis of nine randomized trials that appeared in the Lancet Oncology in 2010. (Sipahi et al, Lancet Oncol 2010;11:627-636). The analysis found a modestly increased risk of incident cancer overall (rate ratio [RR] 1.08) and a significantly increased risk of lung cancer (RR 1.25), compared with placebo or comparator drugs.

The findings prompted the U.S. Food and Drug Administration and the European Medicines Agency to initiate a review of ARB safety.

The new study, Dr. Bjorn Pasternak, of Statens Serum Institut, Copenhagen, Denmark, told Reuters Health, “provides solid observational support for an absence of association between use of ARBs and the risk of cancer overall or lung cancer, as compared to use of angiotensin-converting enzyme (ACE) inhibitors.” The study appears in the April 26 issue of Circulation.

Among 107,466 new ARB users, 3,954 cases of cancer were detected during 312,753 person-years of follow-up compared with 6,214 cases during 435,207 person-years of follow-up in 209,692 ACE inhibitor users, yielding an adjusted RR of 0.99.

Based on narrow confidence intervals, “an increase in the risk of cancer of more than 3% seems unlikely,” Dr. Pasternak told Reuters Health.

The risk of incident cancer did not increase with increasing duration of ARB exposure and was similar for men and women and across individual ARBs.

In subgroup analyses, an association between ARB use and cancer of the male genital organs (RR 1.15) emerged, but the researchers caution that this could represent a chance finding. There was no significantly increased risk of any of 15 other cancer subgroups, including lung cancer (RR 0.92).

Based on these data, together with data from two other meta-analyses published this year – one in Lancet Oncology by Bangalore et al and one in the Journal of Hypertension by the ARB Trialists Collaboration – “there is now strong evidence for an absence of association between ARB exposure and cancer,” Dr. Pasternak wrote in an e-mail.

He noted that differences between observational studies and meta-analyses of randomized trials (the 2010 analysis) probably explain the differing results. “In contrast to randomized studies, which often include stringent inclusion criteria for selection of patients, an observational cohort study such as our represents data from a real-world setting, and thereby reflects what is actually happening in clinical practice,” he noted.

Key strengths of the current analysis, Dr. Pasternak noted, include use of nationwide registries and individual-level information from several independent data sources and detailed information about all cancers in Denmark. Moreover, the study was specifically designed to research the question raised by the results from 2010 meta-analysis.

“Clinicians can continue to prescribe ARBs without concern about an excess risk of cancer,” the researchers conclude.

Circulation 2011;123:1729-1736.