Dihydropyridine CCBs keep users from catching tuberculosis

Dihydropyridine (DHP) calcium channel blockers (CCBs), commonly used to manage hypertension, also help lower the risk of developing tuberculosis (TB), as shown in a study.

DHP CCBs have a stronger protective effect than non-DHP CCBs, whereas β-blockers and loop diuretics have no association with active TB risk, according to researchers from the National Taiwan University Hospital.

The analysis used data from the National Health Insurance Research Database of Taiwan and included 824,564 individuals followed for 6.37 years on average. Of these, 36,643 were non-DHP CCB users and 69,205 were DHP CCB users. Compared with nonusers, users of either type of CCBs tended to have a higher burden of comorbidities, more risk factors for TB, use healthcare services more frequently, and take more comedications. [Hypertension 2020;doi:10.1161/HYPERTENSIONAHA.120.15534]

Overall, 8,164 incident TB cases were documented. In multivariable conditional logistic regression models, CCB users had a 32-percent lower risk of catching the infection compared with nonusers (relative risk [RR], 0.68, 95 percent confidence interval [CI], 0.58–0.78). The corresponding estimates for DHP and non-DHP CCBs were 0.63 (95 percent CI, 0.53–0.79) and 0.73 (95 percent CI, 0.57–0.94).

Moreover, the longer the duration of CCB use, the lower the risk of active TB was (91–365 vs 7–30 days: RR, 0.63, 95 percent CI, 0.54–0.72; p<0.0001). Daily doses of nifedipine 20 mg or 30 mg conferred substantial protection (RR, 0.32, 95 percent CI, 0.14–0.70 and RR, 0.38, 95 percent CI, 0.17–0.84, respectively), although the association was not dose-dependent (p<0.44).

In contrast, β-blockers (RR, 0.99, 95 percent CI, 0.83–1.12) or loop diuretics (RR, 0.88, 95 percent CI, 0.62–1.26) had a null effect on the risk.

Finally, the TB benefit associated with CCBs was consistent in subgroups defined by age, sex, heart failure, cerebrovascular diseases, renal diseases, and diabetes.

“CCBs are known to reduce the availability of iron—an important mineral for intracellular pathogens,” including Mycobacterium tuberculosis, the researchers said.

Iron acquisition is essential for pathogen growth, promoting infection, replication, and progression to clinical disease and death. For M. tuberculosis, specifically, deprivation of iron may reduce its viability, “and this concept may be applicable to preventing latent TB reactivation,” they explained. [J Infect Dis 2007;195:1745-1753; Nat Commun 2014;5:4730; J Bacteriol 2016;198:2399-2409; FEMS Immunol Med Microbiol 2005;45:103-1126]

Some scientists postulate that CCBs may boost the host immune system and alter pathogen life cycles and antibiotic tolerances by modulating calcium-dependent regulatory pathways. Additional mechanistic studies will be necessary to elucidate the TB benefit of CCBs and why DHPs have a stronger effect than non-DHPs, according to the researchers. [Curr Top Med Chem 2013;13:2291-2305]

“The strong effect, biological plausibility, high safety, and affordability of CCBs may justify a definitive randomized trial to determine whether the preventive use of CCBs in patients at high risk for tuberculosis is warranted,” they said.