ABSTRACT
INTRODUCTION: The angiotensin-converting enzyme 2 (ACE2) as well as the transmembrane protease serine type 2 (TMPRSS2) have been found to play roles in cell entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19). SARS-CoV-2 infection risk and severity of COVID-19 might be indicated by the expression of ACE2 and TMPRSS2 in the lung. METHODS: A high-salt diet rat model and renin-angiotensin-aldosterone system (RAAS) blockade were used to test whether these factors affect ACE2 and TMPRSS2 expression in the lung. A normal (0.3% NaCl), a medium (2% NaCl), or a high (8% NaCl) salt diet was fed to rats for 12 weeks, along with enalapril or telmisartan, before examining the lung for histopathological alteration. Using immunofluorescence and qRT-PCR, the localization as well as mRNA expression of ACE2 and TMPRSS2 were investigated. RESULTS: The findings provide evidence that both TMPRSS2 and ACE2 are highly expressed in bronchial epithelial cells as well as ACE2 was also expressed in alveolar type 2 cells. High-salt diet exposure in rats leads to elevated ACE2 expression on protein level. Treatment with RAAS blockers had no effect on lung tissue expression of ACE2 and TMPRSS2. CONCLUSIONS: These findings offer biological support regarding the safety of these drugs that are often prescribed to COVID-19 patients with cardiovascular comorbidity. High salt intake, on the other hand, might adversely affect COVID-19 outcome. Our preclinical data should stimulate clinical studies addressing this point of concern.
Subject(s)
COVID-19 , Renin-Angiotensin System , SARS-CoV-2 , Angiotensin-Converting Enzyme 2 , Animals , Enalapril/pharmacology , Lung , RNA, Messenger/metabolism , Rats , Renin-Angiotensin System/drug effects , Serine Endopeptidases , Sodium Chloride, Dietary/adverse effects , Telmisartan/pharmacologyABSTRACT
BACKGROUND: Sacubitril-valsartan is effective in reducing the N-terminal pro-B-type natriuretic peptide level of hospitalized patients with acute decompensated heart failure, with a high acquisition cost compared with enalapril treatment. OBJECTIVE: This study aimed to determine the cost utility of sacubitril-valsartan compared with enalapril for acute decompensated heart failure treatment. METHODS: A Markov model was constructed to project the total costs, life-years, quality-adjusted life-years (QALYs) of early initiation, and a 2-month delay of sacubitril-valsartan treatment and enalapril treatment in hospitalized patients with acute decompensated heart failure over a lifetime horizon from a Thai healthcare system perspective. Clinical inputs were mainly derived from the PIONEER-HF and PARADIGM-HF trials, together with Thai epidemiological data. Cost data were based on the Thai population. All costs and outcomes were discounted at 3% annually. A series of sensitivity analyses were performed. RESULTS: Compared with enalapril, sacubitril-valsartan incurred a higher total cost per year (THB 42,994 [US$1367.48] vs THB 19,787 [US$629.37]), and it gained more QALYs (4.969 vs 4.755). The incremental cost-effectiveness ratio was THB 108,508/QALY (US$3451.26/QALY). Early initiation of sacubitril-valsartan treatment was more cost effective than delayed treatment. Sensitivity analyses revealed that at a level of willingness to pay of THB 160,000/QALY (US$5089/QALY), sacubitril-valsartan was a cost-effective strategy of about 60%. CONCLUSIONS: Sacubitril-valsartan is cost effective in patients with acute decompensated heart failure. However, the results are highly dependent on the long-term cardiovascular mortality, and they are applicable only to Thailand or countries with a similarly structured healthcare system. Long-term registries should be pursued to decrease the uncertainty around long-term mortality.
Subject(s)
Enalapril , Heart Failure , Aminobutyrates/therapeutic use , Angiotensin Receptor Antagonists/therapeutic use , Biphenyl Compounds , Cost-Benefit Analysis , Drug Combinations , Enalapril/therapeutic use , Heart Failure/diagnosis , Heart Failure/drug therapy , Hospitalization , Humans , Stroke Volume , Tetrazoles/therapeutic use , Thailand , ValsartanSubject(s)
Betacoronavirus/physiology , Coronavirus Infections , Enalapril/pharmacology , Losartan/pharmacology , Pandemics , Peptidyl-Dipeptidase A , Pneumonia, Viral , Serine Endopeptidases , Angiotensin II Type 2 Receptor Blockers/pharmacology , Angiotensin-Converting Enzyme 2 , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , COVID-19 , Coronavirus Infections/metabolism , Coronavirus Infections/virology , Male , Mice , Mice, Inbred C57BL , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/metabolism , Pneumonia, Viral/virology , RNA, Messenger/analysis , SARS-CoV-2 , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism , Tissue DistributionABSTRACT
Based on some publications that associate SARS-CoV-2 infection with the use of anti-hypertensive drug groups such as angiotensin-converting-enzyme inhibitors (e.g. enalapril) or angiotensin II receptor blockers (e.g. losartan), many patients from South America, Central America or Spain, have stopped or intend to interrupt their treatments with these drugs. Hence, it may exist ominous consequences due to this drop out. For this reason, it is necessary to quickly warn about this situation and the risks associated with it.