Effect of angiotensin receptor blockers on the development of cancer: A nationwide cohort study in korea

Abstract

The potential cancer risk associated with long‐term exposure to angiotensin receptor blockers (ARBs) is still unclear. We assessed the risk of incident cancer among hypertensive patients who were treated with ARBs compared with patients exposed to angiotensin‐converting enzyme inhibitors (ACEIs), which are known to have a neutral effect on cancer development. Using the Korean National Health Insurance Service database, we analyzed the data of patients diagnosed with essential hypertension from January 2005 to December 2012 who were aged ≥40 years, initially free of cancer, and were prescribed either ACEI or ARB (n = 293,962). Cox proportional hazard model adjusted for covariates was used to evaluate the risk of incident cancer. During a mean follow‐up of 10 years, 24,610 incident cancers were observed. ARB use was associated with a decreased risk of overall cancer compared with ACEI use (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.72‐0.80). Similar results were obtained for lung (HR 0.73, 95% CI 0.64‐0.82), hepatic (HR 0.56, 95% CI 0.48‐0.65), and gastric cancers (HR 0.74, 95% CI 0.66‐0.83). Regardless of the subgroup, greater reduction of cancer risk was seen among patients treated with ARB than that among patients treated with ACEIs. Particularly, the decreased risk of cancer among ARB users was more prominent among males and heavy drinkers (interaction P < .005). Dose‐response analyses demonstrated a gradual decrease in risk with prolonged ARB therapy than that with ACEI use. In conclusion, ARB use was associated with a decreased risk of overall cancer and several site‐specific cancers.

Association between angiotensin-converting enzyme inhibitors and the risk of lung cancer: a systematic review and meta-analysis

“…Based on the search strategy, 2400 records from the databases were screened, of which 392 duplicated records and 1976 records did not meet the inclusion criteria and were excluded. Finally, 11 clinical studies [12][13][14][23][24][25][26][27][28][29][30], including seven cohort studies [12,14,23,[26][27][28]30] and four case-control studies [13,24,25,29], conducted between 1988 and 2020 were included in the meta-analysis (Fig. 1).…”

“…The 11 studies comprised 11 study groups and 13 control groups. Four groups were extracted from two cohort studies [26,27] according to the different controls. The meta-analysis comprised a total of 13,061,226 patients, including 1,493,225 patients in the ACEI group and 11,568,001 patients in the non-ACEI group.…”

“…The meta-analysis comprised a total of 13,061,226 patients, including 1,493,225 patients in the ACEI group and 11,568,001 patients in the non-ACEI group. These patients mainly resided in Asia [14,27,28], North America [23,26], and Europe [12,13,24,25,30]. Patient and study characteristics of the cohort and case-control studies are described in Table 1.…”

“…In addition, among the included studies, three studies [25,27,30] reported the occurrence of other cancers, such as hepatic cancer, gastric cancer, breast cancer, and prostate cancer, after using ACEIs (all ORs > 1, P < 0.05).…”

The Role of the Renin–Angiotensin System in the Cancer Stem Cell Niche

“…112 A cohort study demonstrates ARB use is associated with a decreased overall risk of cancer compared with patients who use ACEI [hazard ratio (HR) = 0.76, 95% confidence interval (CI): 0.72-0.80] with a gradual dose-response relationship also being observed, and the cancer risk decreasing in those on prolonged ARB regimes compared with ACEI use. 102 Other studies show no improvement of outcomes of cancer patients administered with RASIs (Table 1). For example, a meta-analysis of 138,769 patients concludes that ARB administration does not affect the overall incidence of cancer including lung, breast, and prostate cancer or overall cancer deaths in those treated with ARBs.…”