Publication date: Jul 14, 2025
Functional inhibitors of acid sphingomyelinase enhance human immune function in vitro. We compared the risk of acute infection in users of amlodipine, a functional inhibitor of acid sphingomyelinase, to users of other first-line antihypertensive drugs. We conducted a cohort study using the UK Clinical Practice Research Datalink GOLD (2000-2021). We included new monousers of amlodipine, ramipril, or bendroflumethiazide without preexisting cardiovascular disease. In 2 pairwise comparisons (amlodipine versus ramipril/bendroflumethiazide), we followed patients for as long as they were exposed to compare risk of the primary outcome (acute outpatient infections including respiratory, genitourinary, gastrointestinal infections, and sepsis) and diagnosed SARS-CoV-2 infections in 2020/2021 (amlodipine versus ramipril). We estimated incidence rates (IR) and IR ratios using negative binomial regression, overall and in subgroup analyses. We controlled for confounding using fine stratification on the propensity score. After propensity score weighting, we included 121 847 amlodipine versus 122 096 ramipril users and 46 368 amlodipine versus 153 660 bendroflumethiazide users. IRs for the primary outcome ranged from 38. 9 per 1000 person-years for amlodipine to 51. 6/1000 person-years for bendroflumethiazide. The weighted IR ratios for acute infections were 0. 77 (95% CI, 0. 75-0. 80) for amlodipine versus ramipril, and 0. 78 (95% CI, 0. 75-0. 81) for amlodipine versus bendroflumethiazide. These results were robust after excluding patients with diabetes, after restriction to patients with diagnosed hypertension, and within other subgroup analyses. Amlodipine (versus ramipril) was associated with an IR ratio for SARS-CoV-2 infection of 0. 57 (95% CI, 0. 48-0. 67). Amlodipine may be associated with a lower risk of acute infections compared with ramipril and bendroflumethiazide.
| Concepts | Keywords |
|---|---|
| Irs | acid sphingomyelinase |
| Outpatient | antihypertensive drug |
| Sphingomyelinase | CPRD |
| infection risk |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | Infections |
| disease | IDO | acute infection |
| drug | DRUGBANK | Amlodipine |
| drug | DRUGBANK | Gold |
| drug | DRUGBANK | Ramipril |
| drug | DRUGBANK | Bendroflumethiazide |
| disease | MESH | cardiovascular disease |
| disease | MESH | sepsis |
| disease | MESH | SARS-CoV-2 infections |
| disease | MESH | hypertension |
| pathway | REACTOME | SARS-CoV-2 Infection |
| disease | IDO | infection |