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

Abstract

Background: Tuberculosis remains one of the leading causes of mortality among the infectious diseases, while statins were suggested to confer anti-infective efficacy in experimental studies. We aimed to evaluate the association between statin use and tuberculosis infection in a meta-analysis. Method: Relevant studies were obtained via systematically search of PubMed and Embase databases. A random or a fixed effect model was applied to pool the results according to the heterogeneity among the included studies. Subgroup analyses according to the gender and diabetic status of the participants were performed. We assessed the quality of evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: Nine observational studies were included. Significant heterogeneity was detected among the studies (p for Cochrane's Q test < 0.001, I 2 = 93%). The GRADE approach showed generally low quality of evidence. Pooled results showed that statin use was associated with reduced active tuberculosis infection (risk ratio [RR]: 0.60, 95% confidence interval [CI]: 0.45 to 0.75, p < 0.001). Subgroup analyses showed that the negative association between statin use and active tuberculosis infection was consistent in men (RR: 0.63, p = 0.01) and women (RR: 0.58, p < 0.001), in participants with (RR: 0.63, p = 0.02) and without diabetes (RR: 0.50, p < 0.001), in retrospective cohort studies (RR: 0.56, p = 0.02), prospective cohort studies (RR: 0.76, p = 0.03), nested case-controls studies (RR: 0.57, p < 0.001), and case-control studies (RR: 0.60, p < 0.001), and in studies with statin used defined as any use within 1 year (RR: 0.59, p < 0.001) or during follow-up (RR: 0.61, p < 0.001). Significant publication bias was detected (p for Egger's regression test = 0.046). Subsequent "trim and fill" analyses retrieved an unpublished study to generate symmetrical funnel plots, and meta-analysis incorporating this study did not significantly affect the results (RR: 0.72, 95% CI: 0.68 to 0.76, p < 0.001). Conclusions: Statin use may be associated with reduced active tuberculosis infection. Randomized controlled trials (RCTs) are needed to confirm the potential preventative role of statin use on tuberculosis infection.

The association of atherosclerotic cardiovascular disease and statin use with inflammation and treatment outcomes in tuberculosis

“…Statins are commonly used agents used to reduce serum lipids and systemic inflammation to improve outcomes in patients with a history of or at risk for ASCVD. Prior systematic reviews have shown that statin use reduces TB incidence, both in patients with DM and in the general population 28 , 29 . Preclinical studies in macrophage and mouse models have demonstrated that statins enhance autophagy and phagosome maturation 24 , increase the proportion of NK cells, and increase secretion of the pro-inflammatory cytokines IL-1β and IL-12p70, thereby reducing the lung bacillary burden in M. tuberculosis -infected mice 24 , 49 .…”

“…As adjunctive therapy, statins improve sterilizing activities of the first-line anti-tubercular regimen in murine models 24 – 27 . Though systematic reviews have shown that statin use reduces the incidence of active TB 28 , 29 , there is no clinical evidence on whether statins have salutary effects in TB patients after adjusting for confounding factors 30 .…”

The Association of Atherosclerotic Cardiovascular Disease and Statin Use With Inflammation and Treatment Outcomes in Tuberculosis

“…Statins are commonly used agents used to reduce serum lipids and systemic in ammation in patients with a history of or at risk for ASCVD. Prior systematic reviews have shown that statin use reduces TB incidence both in patients with DM and in the general population 23,24 . Preclinical studies in macrophage and mouse models have demonstrated that statins enhance autophagy and phagosome maturation 19 , increase the proportion of NK cells, and increase secretion of the pro-in ammatory cytokines IL-1β and IL-12p70, thereby reducing the lung bacillary burden in M. tuberculosis-infected mice 19,42 .…”

“…As adjunctive therapy, statins improve sterilizing activities of the rst-line anti-tubercular regimen in murine models [19][20][21][22] . Though systematic reviews have shown that statin use reduces the incidence of active TB 23,24 , there is no clinical evidence on whether statins have salutary effects in TB patients after adjusting for confounding factors 25 .…”

Targeting Molecular Inflammatory Pathways in Granuloma as Host-Directed Therapies for Tuberculosis

“…In C3HeB/FeJ Kramnik mice, adjunctive statins decreased lung CFUs and the percentage of lung surface area involved by inflammation (31). Several population-based studies reported that statin treatment was associated with a decreased risk of TB disease (167)(168)(169)(170). Pravastatin is currently being evaluated in a clinical phase 2b dose-finding study in adults with TB (StAT-TB, ClinicalTrials.gov identifier: NCT03882177).…”