Assessment of statin-induced interstitial pneumonia in patients treated for hyperlipidemia using a health insurance claims database in Japan.

PURPOSE: This study aimed to determine the frequency and risk factors for statin-induced interstitial pneumonia (IP).

METHOD: We conducted a retrospective cohort study using a large Japanese health insurance claims database. We determined the statin-induced IP incidence in patients treated with statins for hyperlipidemia (n = 194,814) with 12-month screening and 3-month observation periods. Statin-induced IP was defined as: (1) diagnosis with IP (ICD-10 codes: J70.2-J70.4, J84.1, and J84.9) within 3 months after starting statins; (2) steroid administration starts after starting statins; (3) undergoing laboratory tests for sialylated carbohydrate antigen Krebs von den Lungen-6 or pulmonary surfactant protein-D; and (4) undergoing high-resolution computed tomography (HRCT). Risk factors for IP were defined as presence of lung-related diseases including lung cancer and IP (ICD-10 codes: A15-16, J12-18, 43-46, 60-70, and 80-99) that were known to the risk factors inducing IP during the screening period.

RESULTS: Cohort 1 had no IP-inducing risk factors; based on lung-related disease history, we identified 4 cases (male/female: 0/4, 61 ± 2.5 years) and 46,574 controls (male/female: 29,677/16,897, 51.3 ± 9.5 years). In cohort 1, all cases were female and average age was older than that of controls (p < 0.01). Cohort 2 had lung-related disease history that were known to the risk factors inducing IP; we identified 25 cases (male/female: 11/14, 52.8 ± 11.3 years) and 4005 controls (male/female: 2305/1,700, 51.0 ± 10.4 years). IP incidence was higher in cohort 2 than in cohort 1, who had no IP risk factors (0.6% vs. 0.009%, p < 0.01). The adjusted case/control odds ratio in cohort 2 was 3.8 (1.7-8.5) in patients who had taken atorvastatin and 2.5 (1.1 - 5.6) with diabetes mellitus.

DISCUSSION: We clarified the incidence (0.009% and 0.6% in patients without and with lung-related disease history that were known to the risk factors inducing IP, respectively) and risk factors for statin-induced IP (elderly females without lung-related disease history; atorvastatin administration in those with lung-related disease history). Physicians and pharmacists should pay close attention to female patients starting atorvastatin, especially those with past histories of lung-related diseases that were known to the risk factors for IP.