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Fulltext Severity of COVID-19 infection in ACEI/ARB users in specialty hospitals: A retrospective cohort study

Alrashed AA, Khan TM, Alhusseini NK, Asdaq SMB, Enani M, Alosaimi B, et al.

J Infect Public Health, 2021 Jun;14(6):726-733.
PMID: 34020213 DOI: 10.1016/j.jiph.2021.03.004

BACKGROUND: The uncertainty about COVID-19 outcomes in angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) users continues with contradictory findings. This study aimed to determine the effect of ACEI/ARB use in patients with severe COVID-19.
METHODS: This retrospective cohort study was done in two Saudi public specialty hospitals designated as COVID-19 referral facilities. We included 354 patients with a confirmed diagnosis of COVID-19 between April and June 2020, of which 146 were ACEI/ARB users and 208 were non-ACEI/ARB users. Controlling for confounders, we conducted multivariate logistic regression and sensitivity analyses using propensity score matching (PSM) and Inverse propensity score weighting (IPSW) for high-risk patient subsets.
RESULTS: Compared to non-ACEI/ARB users, ACEI/ARB users had an eight-fold higher risk of developing critical or severe COVID-19 (OR = 8.25, 95%CI = 3.32-20.53); a nearly 7-fold higher risk of intensive care unit (ICU) admission (OR = 6.76, 95%CI = 2.88-15.89) and a nearly 5-fold higher risk of requiring noninvasive ventilation (OR = 4.77,95%CI = 2.15-10.55). Patients with diabetes, hypertension, and/or renal disease had a five-fold higher risk of severe COVID-19 disease (OR = 5.40,95%CI = 2.0-14.54]. These results were confirmed in the PSM and IPSW analyses.
CONCLUSION: In general, but especially among patients with hypertension, diabetes, and/or renal disease, ACEI/ARB use is associated with a significantly higher risk of severe or critical COVID-19 disease, and ICU care.

Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/adverse effects
Unilateral tongue angioedema caused by angiotensin-converting enzyme inhibitor

Ee YS, Sow AJ, Goh BS

J Laryngol Otol, 2010 Dec;124(12):1337-9.
PMID: 20529395 DOI: 10.1017/S002221511000143X

We report a case of an elderly man receiving treatment with perindopril, who presented with angioedema of the left side of the tongue, floor of the mouth and upper neck. This affected his speech and swallowing, and occurred one day after a burr hole and evacuation procedure undertaken to treat a subdural haematoma. The patient was kept under close observation and treated with intravenous hydrocortisone. The angioedema resolved completely in two days. This is the third reported case of unilateral tongue angioedema occurring secondary to angiotensin-converting enzyme inhibitor use.

Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/adverse effects*
Fulltext Renin-angiotensin system inhibitor use and the risk of mortality in hospitalized patients with COVID-19: a meta-analysis of randomized controlled trials

Kow CS, Ming LC, Hasan SS

Hypertens Res, 2021 Aug;44(8):1042-1045.
PMID: 34017093 DOI: 10.1038/s41440-021-00670-w
Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/adverse effects*
Fulltext Is It Still Relevant to Discover New ACE Inhibitors from Natural Products? YES, but Only with Comprehensive Approaches to Address the Patients' Real Problems: Chronic Dry Cough and Angioedema

Manoharan S

Molecules, 2023 Jun 02;28(11).
PMID: 37299008 DOI: 10.3390/molecules28114532

Despite many publications related to the identification of new angiotensin-I-converting enzyme (ACE) inhibitors, especially peptides from natural products, the actual reason/s for why new ACE inhibitors need to be discovered are yet to be fully understood. New ACE inhibitors are pivotal to address serious side effects caused by commercially available ACE inhibitors in hypertensive patients. Despite the effectiveness of commercial ACE inhibitors, due to these side effects, doctors often prescribe angiotensin receptor blockers (ARBs). Recent evidence has shown the benefits of ACE inhibitors over ARBs in hypertensive patients and hypertensive-diabetes mellitus patients. In order to address these side effects, the somatic ACE's enzyme structures need to be revisited. The peptides isolated from the natural products need to be verified for their stability against ACE and several important gastrointestinal enzymes. The stable peptides sequence with the presence of favourable ACE inhibitory-related amino-acids, such as tryptophan (W), at the C-terminal need to be subjected to molecular docking and dynamics analyses for selecting ACE inhibitory peptide/s with C-domain-specific inhibition instead of both C- and N-domains' inhibition. This strategy will help to reduce the accumulation of bradykinin, the driving factor behind the formation of the side effects.

Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/adverse effects
Spot urine potassium as a potential screening test for aldosterone breakthrough

Sakthiswary R, Wong M, Isa ZM, Nor Azmi K

Clin Ter, 2012;163(3):195-8.
PMID: 22964690

Treatment with angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) may suppress aldosterone production only in the initial phase of treatment and subsequently lead to a rising level of aldosterone to baseline or higher. This phenomenon is described as aldosterone breakthrough. Apart from serial plasma aldosterone levels, there are no other test to identify this condition. The purpose of this study was to evaluate the role of spot urine potassium as a potential screening test for aldosterone breakthrough.

Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/adverse effects
Acute Ischemic Stroke and Acute on Chronic Kidney Disease

Aftab RA, Khan AH, AbdulRazzaq HA, Adnan AS

JNMA J Nepal Med Assoc, 2016 12 10;54(202):85-87.
PMID: 27935930

Ischemic stroke is due to either local thrombus formation or emboli that occlude a cerebral artery, together with chronic kidney disease represent major mortality and morbidity.Here we present a case of 53 years old Malay man, admitted to a hospital in Malaysia complaining of sudden on set of weakness on right sided upper and lower limb associated with slurred speech. Patient was also suffering from uncontrolled hypertension, hyperlipidemia, chronic kidney disease stage 4, and diabetes mellitus (uncontrolled). He was diagnosed with acute ischemic stroke with cranial nerve 7 palsy (with right hemiparesis), acute on chronic kidney disease precipitated by dehydration and ACE inhibitor, and hyperkalemia. Patients with ischemic disease and chronic kidney disaese require constant monitering and careful selected pharmacotherapy. Patient was placed under observation and was prescribed multiple pharamacotherpay to stabalise detoriating condition.

Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/adverse effects
Incidence of risk factors for developing hyperkalemia when using ACE inhibitors in cardiovascular diseases

Amir O, Hassan Y, Sarriff A, Awaisu A, Abd Aziz N, Ismail O

Pharm World Sci, 2009 Jun;31(3):387-93.
PMID: 19255869 DOI: 10.1007/s11096-009-9288-x

STUDY OBJECTIVE: To determine the incidence of and the risk factors associated with hyperkalemia, induced by ACEI-drug interactions among cardiac patients.
SETTING: Five medical and cardiology wards of a tertiary care center in Malaysia.
SUBJECTS: Five hundred cardiac inpatients, who received ACEIs concomitantly with other interacting drugs.
METHOD: This was a prospective cohort study of 500 patients with cardiovascular diseases admitted to Penang Hospital between January to August 2006, who received ACEIs concomitantly with other interacting drugs. ACEI-drug interactions of clinical significance were identified using available drug information resources. Drug Interaction Probability Scale (DIPS) was used to assess the causality of association between ACEI-drug interactions and the adverse outcome (hyperkalemia).
MAIN OUTCOME MEASURE: Hyperkalemia as an adverse clinical outcome of the interaction was identified from laboratory investigations.
RESULTS: Of the 489 patients included in the analysis, 48 (9.8%) had hyperkalemia thought to be associated with ACEI-drug interactions. Univariate analysis using binary logistic regression revealed that advanced age (60 years or more), and taking more than 15 medications were independent risk factors significantly associated with hyperkalemia. However, current and previous smoking history appeared to be a protective factor. Risk factors identified as predictors of hyperkalemia secondary to ACEI-drug interactions by multi-logistic regression were: advanced age (adjusted OR 2.3, CI 1.07-5.01); renal disease (adjusted OR 4.7, CI 2.37-9.39); hepatic disease (adjusted OR 5.2, CI 1.08-25.03); taking 15-20 medications (adjusted OR 4.4, CI 2.08-9.19); and taking 21-26 medications (adjusted OR 9.0, CI 1.64-49.74).
CONCLUSION: Cardiac patients receiving ACEIs concomitantly with potentially interacting drugs are at high risk of experiencing hyperkalemia. Old age, renal disease, hepatic disease, and receiving large number of medications are factors that may significantly increase their vulnerability towards this adverse outcome; thus, frequent monitoring is advocated.

Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/adverse effects*
Blood-pressure lowering efficacy of winged bean seed hydrolysate in spontaneously hypertensive rats, peptide characterization and a toxicity study in Sprague-Dawley rats

Chay SY, Salleh A, Sulaiman NF, Zainal Abidin N, Hanafi MA, Zarei M, et al.

Food Funct, 2018 Mar 01;9(3):1657-1671.
PMID: 29469915 DOI: 10.1039/c7fo01769c

Winged bean seed (WBS) is an underutilized tropical crop. The current study evaluates its potential to reduce blood pressure (BP) in spontaneously hypertensive rats and finds that it reduces BP significantly, in a dose-dependent manner. Five peptides with the sequences, RGVFPCLK, TQLDLPTQ, EPALVP, MRSVVT and DMKP, have been characterized in terms of their stability against ACE via in vitro and in silico modelling. All peptides exhibited IC50 values between 0.019 and 6.885 mM and various inhibitory modes, including substrate, prodrug and true inhibitor modes. The toxicity status of non-Current Good Manufacturing Practice (non-CGMP) peptides is evaluated and the results show that such peptides are toxic, and thus are not suitable to be tested in animals, particularly in repeated-dose studies. In short, WBS hydrolysate demonstrated in vitro ACE inhibitory properties and in vivo blood pressure lowering efficacy in rat models, fostering its potential as a functional food ingredient. Non-CGMP grade peptides are toxic and unfit for testing in animal models.

Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/adverse effects
Fulltext COVID-19 and hypertension-evidence and practical management: Guidance from the HOPE Asia Network

Kario K, Morisawa Y, Sukonthasarn A, Turana Y, Chia YC, Park S, et al.

J Clin Hypertens (Greenwich), 2020 Jul;22(7):1109-1119.
PMID: 32643874 DOI: 10.1111/jch.13917

There are several risk factors for worse outcomes in patients with coronavirus 2019 disease (COVID-19). Patients with hypertension appear to have a poor prognosis, but there is no direct evidence that hypertension increases the risk of new infection or adverse outcomes independent of age and other risk factors. There is also concern about use of renin-angiotensin system (RAS) inhibitors due to a key role of angiotensin-converting enzyme 2 receptors in the entry of the SARS-CoV-2 virus into cells. However, there is little evidence that use of RAS inhibitors increases the risk of SARS-CoV-2 virus infection or worsens the course of COVID-19. Therefore, antihypertensive therapy with these agents should be continued. In addition to acute respiratory distress syndrome, patients with severe COVID-19 can develop myocardial injury and cytokine storm, resulting in heart failure, arteriovenous thrombosis, and kidney injury. Troponin, N-terminal pro-B-type natriuretic peptide, D-dimer, and serum creatinine are biomarkers for these complications and can be used to monitor patients with COVID-19 and for risk stratification. Other factors that need to be incorporated into patient management strategies during the pandemic include regular exercise to maintain good health status and monitoring of psychological well-being. For the ongoing management of patients with hypertension, telemedicine-based home blood pressure monitoring strategies can facilitate maintenance of good blood pressure control while social distancing is maintained. Overall, multidisciplinary management of COVID-19 based on a rapidly growing body of evidence will help ensure the best possible outcomes for patients, including those with risk factors such as hypertension.

Matched MeSH terms: Angiotensin-Converting Enzyme Inhibitors/adverse effects*