Key result
RAS inhibitor use was associated with a lower risk of all-site cancer (HR 0.76) and cancer-specific mortality (HR 0.50) compared to non-use in patients with type 2 diabetes.
Why the study?
The association between RAS inhibitors and cancer, including differences between ACE inhibitors and ARBs as well as blood-pressure-independent associations, remains inconclusive in type 2 diabetes.
Does the use of RAS inhibitors reduce the incidence of cancer and cancer-specific mortality in patients with type 2 diabetes?
Cohort (n=253,491)
Does the use of RAS inhibitors reduce the incidence of cancer and cancer-specific mortality in patients with type 2 diabetes?
Hazard Ratio: 0.76 (95% CI 0.74–0.79)
Absolute Event Rate: 9.2% vs 9.1%
In patients with type 2 diabetes, the use of RAS inhibitors is associated with a significantly lower risk of cancer incidence and cancer-related mortality compared to non-use or calcium-channel blockers.
BACKGROUND: Cancer is replacing cardiovascular-disease as a leading cause of death in type 2 diabetes (T2D). The association of RAS-inhibitors (RASi) and cancer, including differences between angiotensin-converting-enzyme-inhibitor (ACEi) and angiotensin-receptor-blocker (ARBs) as well as their associations independent of blood pressure lowering, remains inconclusive in T2D. METHODS: We conducted a cohort study with new-user design in 253,491 patients in the Hong-Kong-Diabetes-Surveillance-Database (HKDSD) in 2002-2019. We evaluated the associations of time-varying RASi use (ACEi and ARBs) with all-site cancer, diabetes-related cancers, and cancer-specific mortality including comparison with new-users of calcium-channel-blockers (CCBs) as an active-comparator group. FINDINGS: Of 253,491, 133,730 (52.8%) were new-RASi and 119,761 (47.2%) were non-RASi users with a median follow-up period of 6.3 (interquartile ragne: 3.4-9.2) years (1,678,719 patient-years). After propensity-score weighting and adjustment for time-varying covariables, RASi use was associated with lower risk of all-site cancer (HR=0.76, 95%CI: 0.74-0.79), diabetes-related cancer (HR=0.79, 95%CI: 0.75-0.84), cancer-specific mortality (HR=0.50, 95%CI: 0.47-0.53), and diabetes-related cancer mortality (HR=0.49, 95%CI: 0.45-0.54) versus non-RASi. Amongst RASi users, ARBs use was associated with lower risk of cancer-specific mortality versus ACEi (HR=0.77, 95%CI: 0.66-0.91). Use of RASi was associated with an estimated-prevention of 2.6 (95%CI: 2.3-3.0) all-site cancer per-1000-person-years and 2.2 (95%CI: 2.0-2.5) cancer-related mortality per-1000-person-years. Lower risk of cancer-specific mortality was similarly observed in new-RASi compared with new-CCBs users. INTERPRETATION: RASi use was independently associated with lower cancer risk in T2D with stronger associations in users of ARBs than ACEi. The benefits of RASi in patients with diabetes might go beyond cardiovascular-renal protection if confirmed by other real-world studies and trials. FUNDING: Dr. Aimin Yang was supported by a CUHK Impact-Research-Fellowship Scheme.
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Yang et al. (2022) conducted a cohort in Type 2 diabetes (n=253,491). RAS inhibitors vs. Non-RASi users was evaluated on All-site cancer (HR 0.76, 95% CI 0.74-0.79). RAS inhibitor use was associated with a lower risk of all-site cancer (HR 0.76) and cancer-specific mortality (HR 0.50) compared to non-use in patients with type 2 diabetes.
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