Liu Ju-Chi, Yang Tsung-Yeh, Hsu Yi-Ping, Hao Wen-Rui, Kao Pai-Feng, Sung Li-Chin, Chen Chun-Chao, Wu Szu-Yuan
Division of Cardiovascular Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Oncotarget. 2016 Sep 13;7(37):59618-59629. doi: 10.18632/oncotarget.11162.
Chronic obstructive pulmonary disease (COPD) is associated with increased lung cancer risk. We evaluated the association of statin use with lung cancer risk in COPD patients and identified which statins possess the highest chemopreventive potential.
After adjustment for age, sex, CCI, diabetes, hypertension, dyslipidemia, urbanization level, and monthly income according to propensity scores, lung cancer risk in the statin users was lower than that in the statin nonusers (adjusted hazard ratio [aHR] = 0.37). Of the individual statins, lovastatin and fluvastatin did not reduce lung cancer risk significantly. By contrast, lung cancer risk in patients using rosuvastatin, simvastatin, atorvastatin, and pravastatin was significantly lower than that in statin nonusers (aHRs = 0.41, 0.44, 0.52, and 0.58, respectively). Statins dose-dependently reduced lung cancer risk in all subgroups and the main model with additional covariates (nonstatin drug use).
The study cohort comprised all patients diagnosed with COPD at health care facilities in Taiwan (n = 116,017) between January 1, 2001 and December 31, 2012. Our final study cohort comprised 43,802 COPD patients: 10,086 used statins, whereas 33,716 did not. Patients were followed up to assess lung cancer risk or protective factors. In addition, we also considered demographic characteristics, namely age, sex, comorbidities (diabetes, hypertension, dyslipidemia, and Charlson comorbidity index [CCI]), urbanization level, monthly income, and nonstatin drug use. The index date of statin use was the COPD confirmation date. To examine the dose-response relationship, we categorized statin use into four groups in each cohort: < 28, 28-90, 91-365, and > 365 cumulative defined daily doses (cDDDs). Patients receiving < 28 cDDDs were defined as nonstatin users.
Statins dose-dependently exert a significant chemopreventive effect against lung cancer in COPD patients. Rosuvastatin, simvastatin, and atorvastatin exhibited the highest chemopreventive potential.
慢性阻塞性肺疾病(COPD)与肺癌风险增加相关。我们评估了COPD患者使用他汀类药物与肺癌风险之间的关联,并确定了哪些他汀类药物具有最高的化学预防潜力。
根据倾向评分调整年龄、性别、CCI、糖尿病、高血压、血脂异常、城市化水平和月收入后,他汀类药物使用者的肺癌风险低于未使用者(调整后风险比[aHR]=0.37)。在各单一他汀类药物中,洛伐他汀和氟伐他汀未显著降低肺癌风险。相比之下,使用瑞舒伐他汀、辛伐他汀、阿托伐他汀和普伐他汀的患者肺癌风险显著低于未使用他汀类药物者(aHR分别为0.41、0.44、0.52和0.58)。他汀类药物在所有亚组以及包含额外协变量(非他汀类药物使用)的主要模型中均呈剂量依赖性降低肺癌风险。
研究队列包括2001年1月1日至2012年12月31日期间在台湾医疗机构诊断为COPD的所有患者(n=116,017)。我们最终的研究队列包括43,802例COPD患者:10,086例使用他汀类药物,而33,716例未使用。对患者进行随访以评估肺癌风险或保护因素。此外,我们还考虑了人口统计学特征,即年龄、性别、合并症(糖尿病、高血压、血脂异常和查尔森合并症指数[CCI])、城市化水平、月收入和非他汀类药物使用情况。他汀类药物使用的索引日期为COPD确诊日期。为了研究剂量反应关系,我们将每个队列中的他汀类药物使用情况分为四组:<28、28-90、91-365和>365累积限定日剂量(cDDD)。接受<28 cDDD的患者被定义为未使用他汀类药物者。
他汀类药物在COPD患者中呈剂量依赖性地对肺癌发挥显著的化学预防作用。瑞舒伐他汀、辛伐他汀和阿托伐他汀表现出最高的化学预防潜力。