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Eur J Intern Med. 2019 Jun;64:1-9. doi: 10.1016/j.ejim.2019.04.019. Epub 2019 May 3.

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.

Author information

1
National Center for Tumour Diseases, Dresden, Germany. Electronic address: thomas.datzmann@nct-dresden.de.
2
Department for Gynaecology and Obstetrics, Kreiskrankenhaus Freiberg, Freiberg, Germany.
3
Department of Medicine, Spital Limmattal, Zurich, Switzerland.
4
Nephrological Center Villingen-Schwenningen, Villingen-Schwenningen, Germany; TU Dresden, Medizinische Fakultät Carl Gustav Carus, Medical Clinic 3, Division of Nephrology, Dresden, Germany. Electronic address: bernd.hohenstein@uniklinikum-dresden.de.
5
TU Dresden, Medizinische Fakultät Carl Gustav Carus, Center for Evidence-Based Healthcare, Dresden, Germany; National Center for Tumour Diseases, Dresden, Germany. Electronic address: jochen.schmitt@uniklinikum-dresden.de.
6
Hannover Medical School, Clinical Research Center Hannover & MHH Center for Pharmacology and Toxicology, Hannover Medical School, Hannover, Germany. Electronic address: schindler.christoph@mh-hannover.de.

Abstract

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.

KEYWORDS:

Angiotensin receptor blockers; Cancer; Cardiovascular pharmacology; Medication safety; Meta-analysis; Renin-angiotensin-system

PMID:
31060961
DOI:
10.1016/j.ejim.2019.04.019

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