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Review
. 2010 Jul;11(7):627-36.
doi: 10.1016/S1470-2045(10)70106-6. Epub 2010 Jun 11.

Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials

Ilke Sipahi  1 , Sara M Debanne, Douglas Y Rowland, Daniel I Simon, James C Fang
Affiliations
Review

Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials

Ilke Sipahi et al. Lancet Oncol. 2010 Jul.

Abstract

Background: Angiotensin-receptor blockers (ARBs) are a widely used drug class approved for treatment of hypertension, heart failure, diabetic nephropathy, and, recently, for cardiovascular risk reduction. Experimental studies implicate the renin-angiotensin system, particularly angiotensin II type-1 and type-2 receptors, in the regulation of cell proliferation, angiogenesis, and tumour progression. We assessed whether ARBs affect cancer occurrence with a meta-analysis of randomised controlled trials of these drugs.

Methods: We searched Medline, Scopus (including Embase), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and the US Food and Drug Administration website for studies published before November, 2009, that included any of the seven currently available ARBs. Randomised controlled trials with an ARB given in at least one group, with a follow-up of at least 1 year, and that enrolled at least 100 patients were included. New-cancer data were available for 61,590 patients from five trials. Data on common types of solid organ cancers were available for 68,402 patients from five trials, and data on cancer deaths were available for 93,515 patients from eight trials.

Findings: Telmisartan was the study drug in 30,014 (85.7%) patients who received ARBs as part of the trials with new cancer data. Patients randomly assigned to receive ARBs had a significantly increased risk of new cancer occurrence compared with patients in control groups (7.2%vs 6.0%, risk ratio [RR] 1.08, 95% CI 1.01-1.15; p=0.016). When analysis was limited to trials where cancer was a prespecified endpoint, the RR was 1.11 (95% CI 1.04-1.18, p=0.001). Among specific solid organ cancers examined, only new lung-cancer occurrence was significantly higher in patients randomly assigned to receive ARBs than in those assigned to receive control (0.9%vs 0.7%, RR 1.25, 1.05-1.49; p=0.01). No statistically significant difference in cancer deaths was observed (1.8%vs 1.6%, RR 1.07, 0.97-1.18; p=0.183).

Interpretation: This meta-analysis of randomised controlled trials suggests that ARBs are associated with a modestly increased risk of new cancer diagnosis. Given the limited data, it is not possible to draw conclusions about the exact risk of cancer associated with each particular drug. These findings warrant further investigation.

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Figures

Figure 1
Figure 1. Flow diagram of literature search to identify randomised controlled trials of angiotensin-receptor blockers
See webappendix for search terms used in the different databases. FDA=Food and Drug Administration. ARB=angiotensin-receptor blocker.
Figure 2
Figure 2. Funnel plot for assessing publication bias for cancer occurrence
Diamond represents log risk ratio (RR) for cancer occurrence (0·07, 95% CI 0·01–0·14).
Figure 3
Figure 3. Cancer occurrence reported in all included trials of angiotensin-receptor blockers (A) and trials in which cancer was a prespecified endpoint (B)*
ARB=angiotensin-receptor blocker. *To obtain the meta-analytic risk ratio, hazard ratios from the ONTARGET and TRANSCEND trials were combined with the risk ratio from the LIFE trial.
Figure 4
Figure 4. Cancers in randomised controlled trials, in patients with (A) and without (B) background ACE-inhibitor treatment
ACE=angiotensin-converting enzyme. ARB=angiotensin-receptor blocker.
Figure 5
Figure 5. Cancer deaths reported in randomised controlled trials of angiotensin-receptor blockers
ARB=angiotensin-receptor blocker.
See this image and copyright information in PMC

Comment in

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