Systematic review and meta-analysis of randomised controlled clinical trial evidence refutes relationship between pharmacotherapy with angiotensin-receptor blockers and an increased risk of cancer

Thomas Datzmann, Susanne Fuchs, Daniel Andree, Bernd Hohenstein, Jochen Schmitt, Christoph Schindler
European Journal of Internal Medicine 2019, 64: 1-9

AIMS: The potential influence of angiotensin-receptor blockers (ARBs) on carcinogenesis is a much-debated topic. Both observational, as well as preclinical studies in rodent carcinogenic assays, suggest a major role of the Renin-Angiotensin-Aldosterone-System (RAAS) in cancer development. Therefore, a systematic review and meta-analysis with available study data on ARBs and carcinogenicity in general as primary outcome were conducted. Secondary outcomes were defined as tumour-specific mortality rates and the frequency of new cases of specific tumour types with particular emphasis on lung, breast, and prostate cancer.

METHODS: A systematic literature research was performed in MEDLINE, EMBASE, Cochrane Library, and TOXLINE. We used a combination of MeSH terms, keywords and substance names of ARBs and searched between 1950 and 2016. At least 100 participants in each study arm and a minimum follow-up for one year were necessary for study inclusion. Odds ratios (OR) were calculated by a random-effects model.

RESULTS: A total of 8818 potentially eligible publications were identified of whom seven randomised controlled trials, four case-control studies and one cohort study met our inclusion criteria. As a key result, we found no effect on carcinogenesis in randomised controlled trials for ARB usage. (OR 1.02, 95% CI 0.87-1.19; p = .803). Conflicting results with observational studies could be explained by poor reporting- and study qualities.

CONCLUSIONS: The results of our meta-analysis focusing only on high evidence levels and study designs (RCTs) did not reveal any relationship between pharmacotherapy with an ARB and an increased risk for cancer in general.

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