Functional inhibitors of acid sphingomyelinase (FIASMAs) have been shown to augment human immune function in vitro, and the current research presents population-based evidence to uphold that mechanism in real-world clinical practice. The research sought to contrast the risk of acute infection among amlodipine users with that among users of other first-line antihypertensive drugs, namely ramipril (an ACE inhibitor) and bendroflumethiazide (a thiazide diuretic), and to assess whether the use of amlodipine is related to SARS-CoV-2 infection.
This was a cohort study based on data from the UK Clinical Practice Research Datalink (CPRD) GOLD for 2000–2021. Researchers compared new monousers of amlodipine, ramipril, or bendroflumethiazide who were free from preexisting cardiovascular disease at baseline.
Two comparisons were made in pairs:
Follow-up extended to the duration that patients remained under exposure to their allocated drug. The main outcome was the development of acute outpatient infections (respiratory, genitourinary, gastrointestinal infection, and sepsis). A secondary outcome was diagnosed SARS-CoV-2 infection between 2020–2021. Statistical analysis comprised the estimation of incidence rates (IRs) and incidence rate ratios (IRRs) from negative binomial regression, with adjustment for confounders by means of fine stratification on the propensity score.
Key Findings
121,847 amlodipine vs. 122,096 ramipril and 46,368 amlodipine vs. 153,660 bendroflumethiazide users studied.
Incidence rate (IR) of acute infections:
Amlodipine = 38.9/1,000 person-years
Bendroflumethiazide = 51.6/1,000 person-years
Weighted IRR for acute infections:
Amlodipine vs. Ramipril = 0.77 (95% CI 0.75–0.80)
Amlodipine vs. Bendroflumethiazide = 0.78 (95% CI 0.75–0.81)
SARS-CoV-2 infection IRR: 0.57 (95% CI 0.48–0.67)
This large cohort study based on populations showed that amlodipine use was associated with significantly reduced risk of acute infections and SARS-CoV-2 infection when compared to ramipril and bendroflumethiazide. These results indicate that amlodipine, in addition to its antihypertensive effect, may have additional immune-protective effects, and thus its value as a first-line treatment for hypertension.
Reference:
Aebi, N., Meier, C. R., Jick, S. S., Lang, U., & Spoendlin, J. (2025). Risk of acute infections in new users of antihypertensive drugs: An observational cohort study. Journal of the American Heart Association, 14(14), e040242. https://doi.org/10.1161/JAHA.124.040242
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