Could statins be repurposed to protect against tuberculosis?

The HMG-CoA reductase inhibitor statin may help fight tuberculosis (TB) infection, with a recent study showing that the use of the drug confers substantial protection against TB risk in both individuals with diabetes and the general population.

“Statins are prescribed to hyperlipidaemic patients to cure and prevent coronary heart diseases and strokes by blocking 3-hydroxy-3-methylglutaryl-CoA reductase, one of the main enzymes in cholesterol generation. Diabetic patients also take [them] for various positive outcomes,” according to the investigators.

“However, statins affect the immune system in multiple ways and are related to improved outcomes in many infectious diseases,” they added. [PLoS One 2018;13:e0198263; Clin Res Hepatol Gastroenterol 2017;41:533-542; BMC Infect Dis 2018;18:258; J Clin Med 2018;doi:10.3390/jcm7110381]

To examine the definite effect of statins on the risk of TB, the investigators performed a systematic review and meta-analysis of six articles (four cohort, one nested case–control study, and one abstract), three of which only included diabetic patients while the other three involved both diabetic patients and the general population.

The total population comprised 2,073,968 individuals, with the proportion of women ranging from 31.2 percent to 54.0 percent. Study quality was high in five observational studies, as evaluated using the Newcastle–Ottawa scale.

Pooled data revealed that statin use significantly reduced the risk of TB in patients with diabetes by 22 percent (risk ratio [RR], 0.78, 95 percent confidence interval [CI], 0.63–0.95; I², 76.1 percent) and in the general population by 40 percent (RR, 0.60, 95 percent CI, 0.50–0.71; I², 57.7 percent). [Int J Infect Dis 2020;93:168-174]

“Host cholesterol has been shown to be a critical factor in the occurrence of TB in several ways in vitro, and the removal of membrane cholesterol can specifically prevent TB pathogens from entering host macrophages. Therefore, the reduction of cholesterol by statins is logically expected to have a favourable effect during TB management,” according to the investigators. [J Bacteriol 2009;191:6584-6591; J Biol Chem 2008;283:35745-35755; Indian J Exp Biol 2009;47:407-411; Science 2000;288:1647-1650]

“However, these conclusions should be interpreted with caution,” they continued.

Several key and potential confounders that may factor in the association between statin use and TB, such as prior TB status, obesity, cholesterol levels, smoking status and presence of cardiovascular disease, among others, were not considered in the analysis because of limited available data, the investigators pointed out. “The lack of these confounding factors may have led to a less accurate estimate of the association.”

Additionally, the studies included in the meta-analysis were all from Asia (Taiwan and South Korea), and none of these were randomized controlled trials (RCTs). Also, there was no blinding during quality assessment and study selection.

“Thus, large-size and multicentre RCTs are needed,” the investigators said.