Statins are independently associated with a decreased risk of interstitial lung disease (ILD) and idiopathic pulmonary fibrosis (IPF) in a dose-responsive manner, researchers reported in the European Respiratory Journal.
The longitudinal, population-based study sought to determine whether statin use is associated with the prevention of ILD and IPF with use of the Korean National Health Insurance Service-Health Screening Cohort.
Patients aged 40 years and older with ILD and IPF were identified by diagnosis codes. The participants were followed up from January 1, 2004, to the date of ILD and IPF or death from any other cause or the end of the study on December 31, 2015, whichever occurred first.
Statin use was defined with a documented prescription from a physician. The cumulative use of statins was evaluated with a 2-year latent period, and cumulative defined daily dose (cDDD) was calculated every 2 years. The participants were divided into 5 categories (1) those who did not use statins (“nonusers”); and those with a cDDDs of (2) less than 182.5; (3) 182.5 to 365.0; (4) 365.0 to 547.5; and (5) 547.5 or more.
The number of participants who had ever used statins was 192,799 (39.6%) of 486,813 in the ILD study, and 193,131 (39.7%) of 486,995 in the IPF study. For the ILD and IPF analyses, 52.1% were female in the statin group.
During the follow-up, 1949 ILD and 1003 IPF cases were identified. The incidence rates for ILD among those who had ever used statins and those never using statins per were 20.0/100,000 person-years and 44.8/100,000 person-years, respectively. Incidence rates for IPF among those who had ever used statins and those never using statins were 15.6/100,000 person-years and 19.3/100,000 person-years, respectively. Use of statins had a significant protective association with ILD and IPF.
Compared with those never using statins, the associations were significant for patients with a statin use cDDD of less than 182.5 (adjusted hazard ratio [aHR] 1.05; 95% CI, 0.87-1.20), cDDD 182.5 to 365.0 (aHR 0.60; 95% CI, 0.47-0.77), cDDD 365.0 to 547.5 (aHR 0.27; 95% CI, 0.16-0.45), and cDDD of 547.5 or greater (aHR 0.24; 95% CI, 0.13-0.42) in relation to ILD in a dose-response fashion (P for trends <.001).
For IPF, the associations with statin use for those using statin vs those who had never used statin were as follows:
- cDDD less than 182.5: aHR 1.29; 95% CI, 1.07-1.57;
- cDDD 182.5 to 365.0: aHR 0.74; 95% CI, 0.57-0.96;
- cDDD 365.0 to 547.5: aHR 0.40; 95% CI, 0.25-0.64; and
- cDDD of 547.5 or greater: aHR 0.21; 95% CI, 0.11-0.41
All had a dose-response pattern (P for trends <.001).
A consistent dose-response fashion was observed in univariate Cox regression and 2 multivariate Cox regression models for the ILD and IPF protective association with statins. Age (aHR 1.07; 95% CI, 1.06-1.07), male sex (aHR 2.27; 95% CI, 1.92-2.70), having formerly smoked (aHR 1.29; 95% CI, 1.10-1.51), and smoking currently (aHR, 1.53; 95% CI, 1.36-1.72) also were significantly associated with ILD and IPF incidence.
Study limitations include use of diagnosis codes to identify ILD and IPF diagnoses and other comorbidities; the inability to control for all variables; potentially unaccounted for information on the duration and timing of statin administration for the varying dosages; and the potential for time-related bias.
Investigators concluded that statin use is associated with “a lower risk of ILD and IPF development, independent of age, sex, smoking status, and comorbidities.” The study authors further noted that “Statins use was associated with ILD and IPF development in a dose-response manner, with an approximate reduction of 40%, 36%, respectively, in participants who used statins greater than or equal to cDDD 182.5 within a 2-year interval.”
This article originally appeared on Pulmonology Advisor
Jang HJ, Lee DY, Loloci G, Jeong J, Choi W-I. Association between the use of statins and risk of interstitial lung disease/idiopathic pulmonary fibrosis: time-dependent analysis of population-based nationwide data. Eur Respir J. Published online May 18, 2023. doi:10.1183/13993003.00291-2023