Association of Amlodipine with the Risk of In-Hospital Death in Patients with COVID-19 and Hypertension: A Reanalysis on 184 COVID-19 Patients with Hypertension

Abstract

Association between calcium channel blockers (CCBs) or functional inhibitors of acid sphingomyelinase (FIASMAs) use and decreased mortality in people with COVID-19 has been reported in recent studies. Since amlodipine is both a CCB and a FIASMA, the aim of this study was to investigate the association between chronic amlodipine use and the survival of people with hypertension infected with COVID-19. This retrospective cohort study used data extracted from the medical records of adult inpatients with hypertension and laboratory-confirmed COVID-19 between 1 March 2020 and 31 August 2020 with definite outcomes (discharged from hospital or deceased) from Erasme Hospital (Brussels, Belgium). We re-analyzed the data of the retrospective cohort study using only the 184 patients (103 males, 81 females) with a mean age of 69.54 years (SD = 14.6) with hypertension. The fifty-five participants (29.9%) receiving a chronic prescription of amlodipine were compared with the 129 patients who did not receive a chronic prescription of amlodipine. Univariate and multivariate logistic regressions were used to explore the relationships between mortality and sex, age, comorbidities, smoking, and amlodipine status. Out of the 184 participants, 132 (71.7%) survived and 52 (28.3%) died. The mortality rates were, respectively, 12.73% (n = 7) and 34.88% (n = 45) for the amlodipine and non-amlodipine groups. Multivariate logistic regression was significant (Chi square (5) = 29.11; p < 0.0001). Chronic kidney disease and malignant neoplasm were significant predictors as well as amlodipine status. For chronic kidney disease and malignant neoplasm, the odds ratio with 95% confidence interval (95% CI) were, respectively, 2.16 (95% CI: 1.04–4.5; p = 0.039) and 2.46 (95% CI: 1.01–6.01; p = 0.047). For amlodipine status the odds ratio was 0.29 (95% CI: 0.11–0.74; p = 0.009). The result of the present study suggests that amlodipine may be associated with reduced mortality in people with hypertension infected with COVID-19. Further research and randomized clinical trials are needed to confirm the potential protective effect of amlodipine in people with hypertension infected with COVID-19.

A GABA-receptor agonist reduces pneumonitis severity, viral load, and death rate in SARS-CoV-2-infected mice

“…The activation of GABA A -Rs on infected cells could promote Cl - efflux which would oppose Ca 2+ influx and reduce Ca 2+ contents, limiting SARS-CoV-2 replication. Indeed, calcium blockers have been shown to reduce SARS-CoV-2 replication in vitro , but whether they confer beneficial effects to COVID-19 patients has been controversial ( 73 – 75 ). The activation of GABA A -Rs on alveolar and large airway epithelial cells may also have altered 1) the secretion of inflammatory signaling molecules from infected cells, 2) alveolar surfactant production/absorption, and/or 3) altered inflammatory responses and autophagy processes ( 17 ) in ways that limited virus infection and replication.…”

GABA-receptors are a new druggable target for limiting disease severity, lung viral load, and death in SARS-CoV-2 infected mice

“…The activation of GABA A -Rs on infected cells could promote Cl - efflux which would oppose Ca 2+ influx and reduce Ca 2+ contents, limiting SARS-CoV-2 replication. Indeed, calcium blockers have been shown to reduce SARS-CoV-2 replication in vitro , but whether they confer beneficial effects to COVID-19 patients has been controversial (66-68). The activation of GABA A -Rs on alveolar and large airway epithelial cells may also have altered 1) the secretion of inflammatory signaling molecules from infected cells, 2) alveolar surfactant production/absorption, and/or 3) altered inflammatory responses and autophagy processes (15) in ways that limited virus infection and replication.…”

Antihypertensive Drugs Therapy in Hypertension and Covid-19 Comorbidity

“…According to reports, CCBs can reduce SARSCoV-2 multiplication (Zhang et al, 2020;Loas et al, 2022). Amlodipine besylate was observed to decrease the risk of death in hypertension individuals (Zhang et al, 2020).…”