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Review
. 2016 Jul 8;17(3):1470320316656679.
doi: 10.1177/1470320316656679. Print 2016 Jul.

Renin-angiotensin system blockade for the risk of cancer and death

Jian Shen  1 , Yan-Mei Huang  2 , Min Wang  2 , Xue-Zhi Hong  3 , Xin-Nan Song  4 , Xia Zou  2 , Yan-Hong Pan  2 , Wei Ling  2 , Min-Hui Zhu  2 , Xiao-Xi Zhang  2 , Yi Sui  2 , Hai-Lu Zhao  5
Affiliations
Review

Renin-angiotensin system blockade for the risk of cancer and death

Jian Shen et al. J Renin Angiotensin Aldosterone Syst. .

Abstract

Introduction: The effects of renin-angiotensin system blockade with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs) on cancer remain inconsistent.

Methods: We searched existing databases from 1960 to August 2015, for randomised controlled trials and observational studies (case-control studies and cohort studies) of ARB/ACEI therapy with a minimal one year of follow-up. Outcomes were incidence and mortality of cancer.

Results: We included 14 randomised controlled trials and 17 observational studies of 3,957,725 participants (350,329 ARB/ACEI users). The users had a lower incidence of cancer in the observational studies (RR 0.82, 95% CI 0.73-0.93) but not in the randomised controlled trials (RR 1.00, 95% CI 0.92-1.08). The protection persisted for lung cancer (RR 0.85, 95% CI 0.75-0.97) but not for other sites of cancer. The relative risk of cancer associated with renin-angiotensin system blockade was reduced along with time of follow-up. Mortality reduction with ARB/ACEI was marginally significant in the observational studies (RR 0.71, 95% CI 0.55-0.93) but not in the randomised controlled trials (RR 0.99, 95% CI 0.89-1.09).

Conclusions: The significant benefits of renin-angiotensin system blockade observed in case-control studies and cohort studies might diminish in randomised controlled trials. Clinical design, site of cancer and duration of follow-up may affect the clinical outcomes.

Keywords: Angiotensin-converting enzyme inhibitors; angiotensin II receptor blockers; angiotensin-receptor blocker; cancer; renin–angiotensin system.

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Conflict of interest statement

Declaration of conflicting interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Flow chart of selection process in this study.
Figure 2.
Figure 2.
Funnel plots for assessing publication bias.
Figure 3.
Figure 3.
Incidence reduction with angiotensin-converting enzyme inhibitor/angiotensin II type 1 receptor blocker therapy in randomised controlled trials and observational studies.
Figure 4.
Figure 4.
Subgroup analyses of monotherapy with angiotensin-converting enzyme inhibitor/angiotensin II type 1 receptor blocker therapy and dual renin–angiotensin system blockade.
Figure 5.
Figure 5.
Incidence reduction with angiotensin-converting enzyme inhibitor/angiotensin II type 1 receptor blocker therapy in site-specific cancer.
Figure 6.
Figure 6.
Incidence reduction with angiotensin-converting enzyme inhibitor/angiotensin II type 1 receptor blocker therapy stratified by the duration of follow-up. (a) Forest plot; (b) Relative risk ratios.
Figure 7.
Figure 7.
Mortality reduction with angiotensin-converting enzyme inhibitor/angiotensin II type 1 receptor blocker therapy in observational studies and randomised controlled trials.
Figure 8.
Figure 8.
Current view of the renin–angiotensin system cascade.
See this image and copyright information in PMC

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