Effects of RAS inhibitors on all-site cancers and mortality in the Hong Kong diabetes surveillance database (2002-2019)
Aimin Yang,
Hongjiang Wu,
Eric S.H. Lau,
Mai Shi,
Baoqi Fan,
Alice Pik-Shan Kong,
Ronald Ching-Wan Ma,
Andrea On-Yan Luk,
Juliana Chung-Ngor Chan,
Elaine Chow
Affiliations
Aimin Yang
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
Hongjiang Wu
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
Eric S.H. Lau
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
Mai Shi
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
Baoqi Fan
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
Alice Pik-Shan Kong
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
Ronald Ching-Wan Ma
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
Andrea On-Yan Luk
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
Juliana Chung-Ngor Chan
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
Elaine Chow
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China; Corresponding author at: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
Summary: 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.
