Do common BP-lowering drugs shield users against viral infections?

Treatment with either angiotensin receptor blockers (ARBs) or angiotensin-converting-enzyme inhibitors (ACEIs) not only help control blood pressure (BP) in hypertensive patients but may also confer protection against viral infections, a study has found.

“This is the first study assessing the association between the risk of viral infections and the use of renin–angiotensin system (RAS) blockers… Our results should be verified in further studies investigating the underlying mechanisms of these medications,” according to the investigators.

“A blinded randomized control trial is required, but our data would not suggest change in clinical practice until more rigorous trial data are available,” they added.

The study used data from the National Health Insurance Research Database and included two propensity-score matched cohorts: 20,207 ARB users and 18,029 ACEI users and identical numbers of respective nonusers. The median age of the entire population was 53 years, and about 61 percent were men.

Viral infections occurred less frequently in users of RAS blockers than in nonusers, with incidence rates of 4.59 vs 8.95 per 1,000 person-years in the ARB cohort and 6.10 vs 7.72 per 1,000 person-years in the ACEI cohort. [Clin Infect Dis 2020;doi:10.1093/cid/ciaa734]

In a Cox proportional hazards model, ARB use reduced the risk of developing viral infection by nearly half (adjusted hazard ratio [aHR], 0.53, 95 percent confidence interval [CI], 0.48–0.58) and the risk of related hospitalization by 40 percent (aHR, 0.59, 95 percent CI, 0.42–0.83). Meanwhile, ACEI use yielded about a 20-percent protection against infection incidence (aHR, 0.81, 95 percent CI, 0.74–0.88).

The associations showed a dose–response pattern, such that the longer the duration of drug use, the lower the risk of viral infections in both ARB (>1,200 days: aHR, 0.31; 500–1,200 days: aHR, 0.47; 121–500 days: aHR, 0.70; ≤120 days: aHR, 0.82) and ACEI cohorts (>550 days: aHR, 0.50; 151–550 days: aHR, 0.87).

Finally, the protective effect of RAS­ blockers was consistently observed across all age groups (50–64 years: aHR, 0.82; ≥65 years: aHR, 0.81) and in both sexes (women: aHR, 0.77; men: aHR, 0.83).

“Thus far, no precise basic science data are available that can prove that ACEIs or ARBs could interfere with viral shedding, attachment factors, or co-receptors of viruses. Therefore, the proposed possible mechanism for the lower risk of viral infections among ACEI and ARB users might be that [the drugs] interfere with the local RAS in the body tissues [hence] modulating the body’s immune response to the virus,” the investigators stated. [Circulation 2020;141:1648-1655]

RAS regulates BP and fluid balance in the body. It affects multiple organs, including the heart, kidney, brain, eyes, vascular system, liver, nervous system, reproductive system, and digestive system. [Physiol Rev 2006;86:747-803]

In previous studies, RAS is described as a specific combination of RAS enzymes locally expressed in a tissue, which results in the production of a specific combination of peptides that bind to their corresponding receptors. This generates a locally balanced paracrine/autocrine effect that plays a role in tissue physiology and homeostasis. [J Cardiovasc Dev Dis 2019;6:14]

Taken together, the evidence suggests that an altered dynamic balance between the peptides in the target organs among ACEI or ARB users could explain why these individuals have a lower risk of viral infections compared with nonusers, the investigators said.

“Further studies are needed to clarify the immune-modulating mechanisms of ACEIs and ARBs,” they added.