Abstract

Chronic obstructive pulmonary disease (COPD) is independently associated with an increased risk of developing lung cancer. In this study, we want to evaluate the association of statins as a chemoprevention of lung cancer in COPD patients and investigate which one of statin has larger chemopreventive effect. The study cohort comprised all patients diagnosed with COPD (according to International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes) at healthcare facilities in Taiwan (n = 116,017) from January 1, 2001, to December 31, 2012. Our final study cohort contained 43,802 patients diagnosed with COPD in Taiwan over the 11-year period; 10,086 COPD patients with statins use and 33,716 COPD patients without statins use. Each patient was followed up to assess the risk of lung cancer or protective factors: the demographic characteristics of age and sex; the comorbidities of diabetes, hypertension, dyslipidemia, Charlson Comorbidity Index; urbanization level; monthly income; and non-statins lipid-lowering drugs, metformin, aspirin, and angiotensin-converting enzyme inhibitor (ACEI) use. The index date of statins use was the date of COPD confirmation. To examine the dose–response relationship, we categorized statins use into four groups in each cohort (<28, 28–90, 91–365, and >365 cumulative [c]DDD). Patients who received <28 cDDD were defined as non-statins users. After adjustment for age, sex, Charlson comorbidity index, diabetes, hypertension, dyslipidemia, level of urbanization, Monthly income in propensity score, we analyzed the risk of lung cancer. The adjusted HRs (aHRs) of lung cancer decreased in statins use patients compared with those in non-statins use patients (aHRs = 0.37, 95% CI: 0.31, 0.44). In different individual statins use, lovastatin and fluvastatin could not reduce the risk of lung cancer in COPD patients, statistically. The adjusted HRs of lung cancer decreased in individual statins use patients compared with those in non-statins use patients (rosuvastatin, simvastatin, atorvastatin and pravastatin: aHRs = 0.41, , 0.44, 0.52 and 0.58, respectively). After sensitivity analysis, statins dose-dependently reduced the risk of lung cancer in all subgroups and the main model with additional covariates (non-statins lipid-lowering drugs, metformin, ACEI, or aspirin use). Statins dose-dependently exerts a significant chemopreventive effect against lung cancer in COPD patients. The priority of chemopreventive potent were rosuvastatin, simvastatin, and atorvastatin in this study.

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