Abstract
PurposeChronic 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.ResultsAfter 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).MATERIALS AND METHODSThe 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.ConclusionsStatins dose-dependently exert a significant chemopreventive effect against lung cancer in COPD patients. Rosuvastatin, simvastatin, and atorvastatin exhibited the highest chemopreventive potential.
Highlights
Chronic obstructive pulmonary disease (COPD) is the seventh leading cause of death in Taiwan [1]
After adjustment for age, sex, Charlson comorbidity index (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
Compared with the statin nonusers, the statin users exhibited a higher prevalence of pre-existing medical comorbidities including diabetes, hypertension, and dyslipidemia, along with a higher CCI
Summary
Chronic obstructive pulmonary disease (COPD) is the seventh leading cause of death in Taiwan [1]. COPD is independently associated with increased lung cancer risk, which is probably associated with the inflammation and scarring that occurs during COPD development [2,3,4]. Lung cancer is the leading cause of cancer death in Taiwan [1]. Statins can reduce COPD-induced inflammation and scarring and further decrease lung cancer risk in patients with COPD. A meta-analysis indicated that statin use has no effect on lung cancer risk [17]. Because patients with COPD have a high lung cancer risk, the effect of statins may differ from that observed previously [17]
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