香港糖尿病监测数据库（2002-2019 年）中 RAS 抑制剂对所有部位癌症和死亡率的影响。
Effects of RAS inhibitors on all-site cancers and mortality in the Hong Kong diabetes surveillance database (2002-2019).
机构信息
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.
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
出版信息
EBioMedicine. 2022 Sep;83:104219. doi: 10.1016/j.ebiom.2022.104219. Epub 2022 Aug 12.
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.
背景
癌症正在取代心血管疾病成为 2 型糖尿病（T2D）的主要死亡原因。血管紧张素转换酶抑制剂（ACEi）和血管紧张素受体阻滞剂（ARBs）的 RAS 抑制剂（RASi）与癌症之间的关联，以及它们独立于降压作用的关联，在 T2D 中仍不确定。
方法
我们在 2002-2019 年对香港糖尿病监测数据库（HKDSD）中的 253491 例新患者进行了一项队列研究，采用新用户设计。我们评估了随时间变化的 RASi 使用（ACEi 和 ARBs）与所有部位癌症、糖尿病相关癌症以及癌症特异性死亡率的相关性，包括与钙通道阻滞剂（CCBs）新使用者（作为活性对照组）的比较。
结果
在 253491 例患者中，133730 例（52.8%）为新 RASi 使用者，119761 例（47.2%）为非 RASi 使用者，中位随访时间为 6.3 年（四分位间距：3.4-9.2 年）（1678719 患者年）。在进行倾向评分加权和调整随时间变化的协变量后，RASi 使用与较低的所有部位癌症风险相关（HR=0.76，95%CI：0.74-0.79）、糖尿病相关癌症风险（HR=0.79，95%CI：0.75-0.84）、癌症特异性死亡率（HR=0.50，95%CI：0.47-0.53）和糖尿病相关癌症死亡率（HR=0.49，95%CI：0.45-0.54）相比，非 RASi。在 RASi 使用者中，与 ACEi 相比，ARB 使用者的癌症特异性死亡率风险较低（HR=0.77，95%CI：0.66-0.91）。RASi 的使用估计每 1000 人年可预防 2.6（95%CI：2.3-3.0）例所有部位癌症和 2.2（95%CI：2.0-2.5）例癌症相关死亡。与新 CCBs 使用者相比，新 RASi 使用者的癌症特异性死亡率风险降低也同样明显。
结论
RASi 的使用与 T2D 中的癌症风险降低独立相关，在 ARB 使用者中的相关性强于 ACEi。如果其他真实世界研究和试验得到证实，RASi 在糖尿病患者中的益处可能超出心血管-肾脏保护的范围。
资金
杨爱民博士得到了香港中文大学影响研究奖学金计划的支持。
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