Blood pressure drugs, angiotensin-receptor blockers, and risk of cancer: meta-analysis of randomized controlled trials

A recent study by Sipahi et al. published in The Lancet Oncology suggests that angiotensin-receptor blockers (ARBs) may be associated with a "modestly" increased risk of cancer. However, conclusions about the exact risk of cancer associated with each particular drug were not possible to draw due to study limitations.

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.

This study assessed whether ARBs affect cancer occurrence with a meta-analysis of randomized controlled trials of these drugs by searching 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.* Randomized 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. The following information was available:

• New-cancer data for 61, 590 patients from five trials
• Data on common types of solid organ cancers for 68, 402 patients from five trials
• Data on cancer deaths for 93, 515 patients from eight trials.

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).

This meta-analysis of randomized controlled trials suggested that ARBs were associated with a modestly increased risk of new cancer diagnosis. The researchers concluded that due to the limited data, it was not possible to draw conclusions about the exact risk of cancer associated with each particular drug, and these findings warranted further investigation.

*Drugs in this class include:

• Atacand (candesartan) (AstraZeneca)
• Avapro (irbesartan) (sanofi-aventis and Bristol Myers Squibb)
• Benicar (omesartan) (Daiichi Sankyo) 
• Cozaar (losartan) (Merck & Co.)
• Diovan (valsartan) (Novartis)
• Mycardis (telmisartan) (Boehringer Ingelheim and Astellas)
• Teveten (eprosartan) (Solvay)
  

Reference
Sipahi I, Debanne SM, Rowland DY, et al. Blood pressure drugs, angiotensin-receptor blockers and risk of cancer: meta-analysis of randomized controlled trials. Lancet Oncol, Early Online Publication, 14 June 2010, doi:10.1016/S1470-2045(10)70106-6 .