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Statins are widely used to lower cholesterol levels and cardiovascular risk. Further, studies have shown that statins may decrease the risks of infectious diseases and infection-related mortality; however, the association between statin use and active TB disease remains unclear.Using the Taiwan National Health Insurance Research Database, we conducted a nationwide population-based study. Patients taking statins between 2000 and 2013, without antecedent TB disease, were included. Data from 102,424 statin users and 202,718 age-, sex-, and enrollment date–matched subjects were analyzed. The two cohorts were monitored until December 31, 2013, for incident TB disease. The definition of TB disease was validated using the claims database of Taipei Veterans General Hospital.The statin and matched cohorts were observed for 571,568 and 1,027,385 person-years, respectively. Of the total 305,142 subjects, 1,264 (0.41%) developed subsequent TB disease. Validation study confirmed the accuracy of the definition of TB disease (sensitivity, 96.3%), with excellent interobserver agreement (κ = 1.00). Multivariate analysis revealed a reduced risk of TB disease among the statin cohort (hazard ratio [HR], 0.53; 95% CI, 0.47-0.61; P < .001). Compared with the matched group, statin use showed a dose-response relationship with the incident TB disease risk (<180 cumulative defined daily doses [cDDDs]: HR, 1.06; 95% CI, 0.91-1.24; P = .477; 180 to 365 cDDDs: HR, 0.57; 95% CI, 0.45-0.72; P < .001; >365 cDDDs: HR, 0.27; 95% CI, 0.22-0.33; P < .001).Statin use associates with a lower risk of incident TB disease.