Population-Based Case-Control Study Assessing the Association between Statins Use and Pulmonary Tuberculosis in Taiwan

Abstract

Background and Objectives: Little evidence is available about the relationship between statins use and pulmonary tuberculosis in Taiwan. The aim of the study was to explore this issue.Methods: Using the database of the Taiwan National Health Insurance Program, we conducted a population-based case-control study to identify 8,236 subjects aged 20 years and older with newly diagnosed pulmonary tuberculosis from 2000 to 2013 as the cases. We randomly selected 8,236 sex-matched and age-matched subjects without pulmonary tuberculosis as the controls. Subjects who had at least one prescription of statins before the index date were defined as “ever use.” Subjects who never had one prescription of statins before the index date were defined as “never use.” The odds ratio (OR) and 95% confidence interval (CI) for pulmonary tuberculosis associated with statins use was estimated by a multivariable logistic regression model.Results: After adjustment for co-variables, the adjusted OR of pulmonary tuberculosis was 0.67 for subjects with ever use of statins (95% CI 0.59, 0.75). In a sub-analysis, the adjusted ORs of pulmonary tuberculosis were 0.87 (95% CI 0.69, 1.10) for subjects with cumulative duration of statins use <3 months, 0.77 (95% CI 0.58, 1.03) for 3–6 months, and 0.59 (95% CI 0.51, 0.68) for ≥6 months, compared with subjects with never use of statins.Conclusions: Statins use correlates with a small but statistically significant risk reduction of pulmonary tuberculosis. The protective effect is stronger for longer duration of statins use. Due to a case-control design, a causal-relationship cannot be established in our study. A prospective cohort design is needed to confirm our findings.

Statin Use May Be Associated With Reduced Active Tuberculosis Infection: A Meta-Analysis of Observational Studies

“…Of these, 12 were further excluded because two of them did not treat statin use as the exposure, six did not report tuberculosis infection as the outcome, one study did not provide available outcome data, and the other three were abstracts of already included studies. Finally, nine observational studies were included (10)(11)(12)(13)(14)(15)(16)(17)(18).…”

“…These studies were published between 2014 and 2019, and all of them included Asian people. Regarding the study design, five studies were retrospective cohort studies (10,(15)(16)(17)(18), one was a prospective cohort study (11), two were nested case-control studies (12,14), and another one was a retrospective case-control study (13).…”

“…The mean ages of the patients varied between 51 and 65 years, with the proportions of male ranging from 44 to 70%. Statin use was defined as any stain use within 1 year before the end of follow-up in six studies (10,(12)(13)(14)(15)17), and any stain use during follow-up in three studies (11,16,18). The follow-up durations varied from 1 to 12 years, and the outcome of active tuberculosis infection was validated via the International Classification for Diseases codes and records of antituberculosis prescription.…”

“…Moreover, statins may also synergistically increase the treatment efficacy of antituberculosis, such as rifampin (9). However, an early cohort study did not show a significant association between statin use and tuberculosis infection (10), while subsequent studies indicated that use of statins may be associated with reduced tuberculosis infection (11)(12)(13)(14)(15)(16)(17)(18). The potential reasons for the inconsistencies of the above findings remain unknown.…”

Anti-tuberculous Effects of Statin Therapy: A Review of Literature

“…A reduction in membrane cholesterol decreases the entry of TB pathogen inside macrophages [8]. Retrospective human studies and experimental animal studies have shown beneficial effects of statins in both treatment and prevention of TB [10][11][12]. Classic first-line TB treatment consists of four drugs: rifampicin, isoniazid, pyrazinamide, and ethambutol.…”