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


RESULTS
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).


CONCLUSIONS
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.
Sipahi
Ilke
I
Harrington-McLaughlin Heart & Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. ilkesipahi@gmail.com
Debanne
Sara M
SM
Rowland
Douglas Y
DY
Simon
Daniel I
DI
Fang
James C
JC
D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000009:adverse effects*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects; D001565:Benzoates / Q000008:administration & dosage / Q000009:adverse effects; D001943:Breast Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D008297:Male; D009369:Neoplasms / Q000139:chemically induced* / Q000453:epidemiology / Q000401:mortality; D011471:Prostatic Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D000077333:Telmisartan
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001565:Benzoates; D000077333:Telmisartan