炎症性肠病患者使用他汀类药物与结直肠癌风险
Statin use and risk of colorectal cancer in patients with inflammatory bowel disease.
作者信息
Sun Jiangwei, Halfvarson Jonas, Bergman David, Ebrahimi Fahim, Roelstraete Bjorn, Lochhead Paul, Song Mingyang, Olén Ola, Ludvigsson Jonas F
机构信息
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
出版信息
EClinicalMedicine. 2023 Aug 24;63:102182. doi: 10.1016/j.eclinm.2023.102182. eCollection 2023 Sep.
BACKGROUND
Statin use has been linked to a reduced risk of advanced colorectal adenomas, but its association with colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD) - a high risk population for CRC - remains inconclusive.
METHODS
From a nationwide IBD cohort in Sweden, we identified 5273 statin users and 5273 non-statin users (1:1 propensity score matching) from July 2006 to December 2018. Statin use was defined as the first filled prescription for ≥30 cumulative defined daily doses and followed until December 2019. Primary outcome was incident CRC. Secondary outcomes were CRC-related mortality and all-cause mortality. Cox regression estimated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs).
FINDINGS
During a median follow-up of 5.6 years, 70 statin users (incidence rate (IR): 21.2 per 10,000 person-years) versus 90 non-statin users (IR: 29.2) were diagnosed with incident CRC (rate difference (RD), -8.0 (95% CIs: -15.8 to -0.2 per 10,000 person-years); aHR = 0.76 (95% CIs: 0.61 to 0.96)). The benefit for incident CRC was duration-dependent in a nested case-control design: as compared to short-term use (30 days to <1 year), the adjusted odd ratios were 0.59 (0.25 to 1.43) for 1 to <2 years of use, 0.46 (0.21 to 0.98) for 2 to <5 years of use, and 0.38 (0.16 to 0.86) for ≥5 years of use ( = 0.016). Compared with non-statin users, statin users also had a decreased risk for CRC-related mortality (IR: 6.0 vs. 11.9; RD, -5.9 (-10.5 to -1.2); aHR, 0.56 (0.37 to 0.83)) and all-cause mortality (IR: 156.4 vs. 231.4; RD, -75.0 (-96.6 to -53.4); aHR, 0.63 (0.57 to 0.69)).
INTERPRETATION
Statin use was associated with a lower risk of incident CRC, CRC-related mortality, and all-cause mortality. The benefit for incident CRC was duration-dependent, with a significantly lower risk after ≥2 years of statin use.
FUNDING
This research was supported by Forte (i.e., the Swedish Research Council for Health, Working Life and Welfare).
背景
他汀类药物的使用与晚期结直肠腺瘤风险降低有关，但其在炎症性肠病（IBD）患者（结直肠癌高危人群）中与结直肠癌（CRC）的关联仍不明确。
方法
从瑞典全国性IBD队列中，我们在2006年7月至2018年12月期间确定了5273名他汀类药物使用者和5273名非他汀类药物使用者（1:1倾向评分匹配）。他汀类药物的使用定义为首次开具累计≥30个限定日剂量的处方，并随访至2019年12月。主要结局是新发结直肠癌。次要结局是结直肠癌相关死亡率和全因死亡率。Cox回归估计调整后的风险比（aHRs）和95%置信区间（CIs）。
研究结果
在中位随访5.6年期间，70名他汀类药物使用者（发病率（IR）：每10000人年21.2例）与90名非他汀类药物使用者（IR：29.2例）被诊断为新发结直肠癌（率差（RD），-8.0（95%CI：每10000人年-15.8至-0.2）；aHR = 0.76（95%CI：0.61至0.96））。在巢式病例对照设计中，他汀类药物对新发结直肠癌的益处与用药持续时间有关：与短期使用（30天至<1年）相比，使用1至<2年的调整后比值比为0.59（0.25至1.43），使用2至<5年的为0.46（0.21至0.98），使用≥5年的为0.38（0.16至0.86）（P = 0.016）。与非他汀类药物使用者相比，他汀类药物使用者的结直肠癌相关死亡率风险也降低（IR：6.0对11.9；RD，-5.9（-10.5至-1.2）；aHR，0.56（0.37至0.83））和全因死亡率风险降低（IR：156.4对231.4；RD，-75.0（-96.6至-53.4）；aHR，0.63（0.57至0.69））。
解读
他汀类药物的使用与新发结直肠癌、结直肠癌相关死亡率和全因死亡率的较低风险相关。他汀类药物对新发结直肠癌的益处与用药持续时间有关，使用他汀类药物≥2年后风险显著降低。
资助
本研究由Forte（即瑞典卫生、工作生活和福利研究理事会）资助。
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