Previous studies have suggested that taking certain drugs to lower blood pressure may reduce the risk of infections. One possible reason for this could be that some blood pressure drugs inhibit the production of certain enzymes, which promote the death of important immune cells. Thus, certain blood pressure drugs may prevent immune cells from dying, which in turn can help the body fight infections. Laboratory studies have shown that the blood pressure drug amlodipine inhibits this enzyme, while others, such as ramipril or bendroflumethiazide, have no such effect. However, it is not known whether use of amlodipine actually prevents infections in the general population.
The potential association between blood pressure drugs and infections is of particular interest given the ongoing COVID-19 pandemic and the subsequent search for medications that can prevent infections. We plan to use data from the Clinical Practice Research Datalink (CPRD) GOLD to compare the risk of infection among patients with new use of several different blood pressure drug treatments in the United Kingdom (UK).
In addition to its antihypertensive effect, the antihypertensive drug amlodipine (a calcium channel blocker) has a pleiotropic mechanism of action by which it inhibits the acid sphingomyelinase (ASM), thereby lowering ceramide concentrations and consequently reducing apoptosis of important immune cells. However, it remains unknown whether amlodipine improves immune function in a clinically relevant manner. In a retrospective cohort study, we will use CPRD GOLD data to determine the incidence rate of acute infections (i.e. respiratory, genitourinary, gastrointestinal infections, septicemia, and in an additional analysis we will further look at the outcome SARS-CoV-2) in patients with amlodipine treatment compared to users of one of two other first-line antihypertensive drugs: 1) ramipril (angiotensin-converting enzyme inhibitor), or 2) bendroflumethiazide (thiazide diuretic) which are not known to reduce apoptosis of important immune cells. We will then compare the risk of acute infection between amlodipine and 1) ramipril and 2) bendroflumethiazide in pairwise comparisons by calculating incidence rate ratios (IRRs) with 95% confidence intervals (CIs). We will control for multiple baseline covariates by weighting the comparison patients according to fine strata of the propensity score in the amlodipine group (exposed group). Based on this study, it may be possible to conclude whether amlodipine, by possibly inhibiting acid sphingomyelinase, demonstrates a beneficial effect on the immune system and therefore a reduction in infections compared with other antihypertensive drugs, thus benefiting general public health.
The incidence rates of any of the following acute infections (Read codes will be counted as separate episodes of infections if they are recorded at least 14 days apart, in Appendix):
- Respiratory infections
- Genitourinary infections
- Gastrointestinal infections
- Septicemia
- SARS-CoV-2 infection (additional analysis between 01.01.2020 and 31.12.2021)
Susan Jick - Chief Investigator - BCDSP - Boston Collaborative Drug Surveillance Program
Noah Aebi - Corresponding Applicant - University of Basel
- Collaborator -
Christoph Meier - Collaborator - University of Basel
Johannes Kornhuber - Collaborator - Friedrich-Alexander Universitat Erlangen-Nurnberg
Undine Lang - Collaborator - University of Basel