Statins dose-dependently exert a chemopreventive effect against lung cancer in COPD patients: a population-based cohort study
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Ju-Chi Liu1,4,*, Tsung-Yeh Yang1,*, Yi-Ping Hsu1, Wen-Rui Hao1, Pai-Feng Kao1,4, Li-Chin Sung1,4, Chun-Chao Chen1, Szu-Yuan Wu2,3,4,5
1Division of Cardiovascular Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
2Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan
3Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
4Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
5Department of Biotechnology, Hungkuang University, Taichung, Taiwan
*Co-first authors, These authors contributed equally to this work
Szu-Yuan Wu, email: [email protected]
Keywords: statins, COPD, lung cancer
Received: March 09, 2016 Accepted: July 09, 2016 Published: August 09, 2016
Purpose: 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.
Results: 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).
Materials and Methods: 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.
Conclusions: Statins dose-dependently exert a significant chemopreventive effect against lung cancer in COPD patients. Rosuvastatin, simvastatin, and atorvastatin exhibited the highest chemopreventive potential.
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