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

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.

Lung cancer risk and the inhibitors of angiotensinconverting enzyme: A mini-review of recent evidence

“…Accordingly, probable anti-cancer mechanisms of RAS blockers may be due to stimulation of angiostatin (only captopril), and diminish the aggregation of tumour-related macrophages by MCP-1 decrement, finally directing to reduced micro-vessel compactness and lessening of the tumour inflammatory location, and also tumour development reversion. These important findings should keep in mind when we talk about the impact of ACEIs on lung cancer (31)(32)(33)(34). In fact, the study by Hicks et al (4), needs further investigation by more multi-centric, multi-ethnic studies.…”

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“…4The role attributed to bradykinin as potential mediator of the increased risk of lung cancer in ACEI users is considered to have low plausibility. 5Several previous meta-analyses have reported either no effect or a protective effect of ACEIs against lung cancer in prospective randomized controlled trials as well as observational studies [8,20]. Thus, the British observation may well be a chance finding.…”

Renin–Angiotensin Inhibition in Combating Malignancy: A Review

“…A meta-analysis of 17 observational studies (case-control studies and cohort studies) with a total of 3,833,261 participants, of whom 289,858 were ACEI/ARB users with long follow-up (2.4-7.8 years), concluded monotherapy with ACEI/ARB might have protective effects on cancer, showing reduced incidence and mortality from cancer (15).…”