Use of RAS inhibitors associated with lower cancer risk in T2D | Latest news for doctors, nurses and pharmacists

A real-world study of over 250,000 type 2 diabetes (T2D) patients in Hong Kong found that the use of renin-angiotensin system inhibitors (RASI) is independently associated with a reduced risk of cancer, including diabetes-related cancers and specific cancers. mortality in diabetes.

Compared to the general population, patients with T2D are 1.3 to 3 times more likely to develop cancer. [N Engl J Med 2011;364:829-841] However, RASIs, which are commonly prescribed to diabetic patients for cardiovascular (CV) and renal protection, are believed to have anticancer effects by blocking the angiotensin II pathway associated with angiogenesis, adhesion, invasion and cell proliferation. [Sci Rep 2019;9:8565;
BMC Cancer 2021;21:1338; Curr Cancer Drug Targets 2005;5:307-323]

“Despite this biological plausibility, compared to the large body of evidence on the benefits of RASIs on CV disease, their anticancer benefits in diabetes remain controversial,” the researchers from the Chinese University of Hong Kong wrote. “In this study, we used real data from a territory-wide electronic medical record system and assessed time-varying risk associations between RASI use and cancer events and associated mortality. .” [EBioMedicine 2022;doi:10.1016/j.ebiom.2022.10421]

The researchers organized a cohort of 253,491 patients with T2DM (mean age, 61.1 years; male, 47.5%) from the Hong Kong Diabetes Surveillance Database, including 133,730 (52, 8%) new RASI users, of which 73,596 were
Angiotensin converting enzyme (ACEI) inhibitor only users, 21,103 were angiotensin receptor blocker (ARB) only users, and 39,031 were ACEI/ARB users.

During a mean follow-up of 6.5 years, 15,030 (5.9%) and 6,863 (2.7%) patients were diagnosed with multisite cancer and diabetes-related cancer, respectively. A total of 24,768 (9.8%) patients died, including 6,590 (2.6%) cancer deaths and 2,845 (1.1%) diabetes-related cancer deaths.

Use of time-varying RASI was associated with a reduced risk of all-site and diabetes-related cancers compared with no use of RASI (all sites: hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.74–0.79; related to diabetes: RR, 0.79; 95% CI, 0.75 to 0.84). “For site-specific cancers, RASI use was associated with a lower risk of liver disease [HR, 0.71; 95 percent CI, 0.63–0.81]lung [HR, 0.64; 95 percent CI, 0.59–0.71]colorectal [HR, 0.82; 95 percent CI, 0.76–0.90] and pancreatic cancers [HR, 0.63; 95 percent CI, 0.52–0.76]and breast risk neutral [HR, 0.93; 95 percent CI, 0.82–1.06] and prostate cancer [HR, 0.86; 95 percent CI, 0.72–1.02]“, underlined the researchers.

In addition, RASI use was associated with a lower risk of all-cause mortality (HR, 0.52; 95% CI, 0.50-0.53), cancer-specific mortality (HR, 0 .50; 95% CI, 0.47-0.53) and diabetes. cancer-related mortality (HR, 0.49; 95% CI, 0.45-0.54).

Compared with ACEI use alone, ARB use alone was associated with a lower risk of cancer at all sites (HR, 0.90; 95% CI, 0.81-0.99 ), all-cause mortality (HR, 0.71; 95% CI, 0.66-0.78), cancer-specific mortality (HR, 0.77; 95% CI, 0.66-0 .91) and diabetes-related cancer mortality (HR, 0.73; 95% CI, 0.57 to 0.94).

“Due to the more complete RAS blockade with ARBs, the larger effect size with ARBs compared to ACEI is plausible,” the researchers commented. “In addition to directly blocking the effects of angiotensin-II on the AT1 receptor, ARBs [but not ACEIs] increase angiotensin-II levels. This increase is accompanied by an upregulation of ACE2, which converts angiotensin-II to angiotensin which possesses anti-proliferative, anti-inflammatory and anti-cancer effects. Also, side effects, such as coughing, are more common with ACEIs than with ARBs, which may lead to poorer compliance. »

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