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1.
Vascul Pharmacol ; 143: 106955, 2022 04.
Article in English | MEDLINE | ID: covidwho-1641722

ABSTRACT

Interactions between anti-hypertensive agents (ACEI), comorbidities, inflammation, and stress status may impact hospital stay duration in COVID-19 patients. This retrospective study analyzed epidemiological data, comorbidities, metabolic/inflammatory markers, and clinical information from 165 SARS-CoV-2 positive patients. In a multiple linear regression model, an IL-6 higher than 100 mg/L, glucose at admission (baseline levels at the hospital entry), and the interaction between ACEI administration and LDH predicted the days of hospital admission (P < 0.001). In conclusion, hypertensive patients suffering more severe inflammatory condition assessed by LDH levels clinically benefited more and reduced the hospital stay when prescribed ACEI agents than those with lower systemic baseline inflammation at admission.


Subject(s)
Antihypertensive Agents , COVID-19 , Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Antihypertensive Agents/adverse effects , COVID-19/diagnosis , COVID-19/drug therapy , Humans , Retrospective Studies , SARS-CoV-2
2.
Elife ; 102021 11 23.
Article in English | MEDLINE | ID: covidwho-1622815

ABSTRACT

Background: Potential therapy and confounding factors including typical co-administered medications, patient's disease states, disease prevalence, patient demographics, medical histories, and reasons for prescribing a drug often are incomplete, conflicting, missing, or uncharacterized in spontaneous adverse drug event (ADE) reporting systems. These missing or incomplete features can affect and limit the application of quantitative methods in pharmacovigilance for meta-analyses of data during randomized clinical trials. Methods: Data from patients with hypertension were retrieved and integrated from the FDA Adverse Event Reporting System; 134 antihypertensive drugs out of 1131 drugs were filtered and then evaluated using the empirical Bayes geometric mean (EBGM) of the posterior distribution to build ADE-drug profiles with an emphasis on the pulmonary ADEs. Afterward, the graphical least absolute shrinkage and selection operator (GLASSO) captured drug associations based on pulmonary ADEs by correcting hidden factors and confounder misclassification. Selected drugs were then compared using the Friedman test in drug classes and clusters obtained from GLASSO. Results: Following multiple filtering stages to exclude insignificant and noise-driven reports, we found that drugs from antihypertensives agents, urologicals, and antithrombotic agents (macitentan, bosentan, epoprostenol, selexipag, sildenafil, tadalafil, and beraprost) form a similar class with a significantly higher incidence of pulmonary ADEs. Macitentan and bosentan were associated with 64% and 56% of pulmonary ADEs, respectively. Because these two medications are prescribed in diseases affecting pulmonary function and may be likely to emerge among the highest reported pulmonary ADEs, in fact, they serve to validate the methods utilized here. Conversely, doxazosin and rilmenidine were found to have the least pulmonary ADEs in selected drugs from hypertension patients. Nifedipine and candesartan were also found by signal detection methods to form a drug cluster, shown by several studies an effective combination of these drugs on lowering blood pressure and appeared an improved side effect profile in comparison with single-agent monotherapy. Conclusions: We consider pulmonary ADE profiles in multiple long-standing groups of therapeutics including antihypertensive agents, antithrombotic agents, beta-blocking agents, calcium channel blockers, or agents acting on the renin-angiotensin system, in patients with hypertension associated with high risk for coronavirus disease 2019 (COVID-19). We found that several individual drugs have significant differences between their drug classes and compared to other drug classes. For instance, macitentan and bosentan from endothelin receptor antagonists show major concern while doxazosin and rilmenidine exhibited the least pulmonary ADEs compared to the outcomes of other drugs. Using techniques in this study, we assessed and confirmed the hypothesis that drugs from the same drug class could have very different pulmonary ADE profiles affecting outcomes in acute respiratory illness. Funding: GJW and MJD accepted funding from BioNexus KC for funding on this project, but BioNexus KC had no direct role in this article.


Subject(s)
Antihypertensive Agents/adverse effects , COVID-19/complications , Data Mining/methods , Drug-Related Side Effects and Adverse Reactions , Hypertension/drug therapy , Pharmacovigilance , Adverse Drug Reaction Reporting Systems , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Antihypertensive Agents/therapeutic use , Bayes Theorem , Calcium Channel Blockers/adverse effects , Fibrinolytic Agents/adverse effects , Humans , Hypertension/complications , SARS-CoV-2
3.
High Blood Press Cardiovasc Prev ; 29(2): 155-161, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1568427

ABSTRACT

INTRODUCTION: Cardiovascular risk seems not to be greater in patients with white coat uncontrolled hypertension (WUCH) than in patients with sustained blood pressure (BP) control. Therefore, its detection is important to avoid overtreatment. The COVID-19 pandemic determined a massive migration of hypertension consultations from the face-to-face modality to teleconsultations, and it is unknown whether WUCH exists in this context. AIM: We aimed to evaluate the prevalence of WUCH through home BP monitoring (HBPM) in treated hypertensive patients evaluated by teleconsultation. METHODS: We included treated hypertensive patients that owned a digital BP monitor. During teleconsultation, patients were asked to perform two BP measurements and then a 7-day HBPM, using the same device. Patients were classified as having WUCH if BP was ≥ 140 and/or 90 mmHg in teleconsultation and < 135/85 mmHg on HBPM. The prevalence of WUCH and its 95% confidence interval were estimated. One-way ANOVA, the Chi-square test or Fisher's exact test were used to compare the characteristics of these patients with the other groups. RESULTS: We included 341 patients (45.2% male, mean age 62.3 years). The prevalence of WUCH was 33.1% (95% CI 28.3-38.3%). Significant differences were found in terms of age, the number of antihypertensive drugs and the use of calcium channel blockers, all lower in the WUCH group as compared with the groups with elevated BP on HBPM. CONCLUSION: WUCH exists in teleconsultation and is very frequent. It can be easily detected though HBPM, thus avoiding overmedication, and its potential impact on side-effects and health costs.


Subject(s)
COVID-19 , Hypertension , Remote Consultation , White Coat Hypertension , Antihypertensive Agents/adverse effects , Blood Pressure , Blood Pressure Monitoring, Ambulatory , Female , Humans , Hypertension/diagnosis , Hypertension/drug therapy , Hypertension/epidemiology , Male , Middle Aged , Pandemics , White Coat Hypertension/diagnosis , White Coat Hypertension/drug therapy , White Coat Hypertension/epidemiology
4.
Korean J Intern Med ; 36(Suppl 1): S123-S131, 2021 03.
Article in English | MEDLINE | ID: covidwho-1369806

ABSTRACT

BACKGROUND/AIMS: There are concerns that the use of renin-angiotensin system (RAS) blockers may increase the risk of being infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or progressing to a severe clinical course after infection. This this study aimed to investigate the influence of RAS blockers on the risk and severity of SARS-CoV-2 infection. METHODS: We conducted a retrospective cohort study analyzing nationwide claims data of 215,184 adults who underwent SARS-CoV-2 tests in South Korea. The SARS-CoV-2 positive rates and clinical outcomes were evaluated according to the use of RAS blockers in patients with hypertension (n = 64,243). RESULTS: In total, 38,919 patients with hypertension were on RAS blockers. The SARS-CoV-2 positive rates were significantly higher in the RAS blocker group than in the control group after adjustments (adjusted odds ratio [OR], 1.22; 95% confidence interval [CI], 1.10 to 1.36; p < 0.001), and matching by propensity score (adjusted OR, 1.16; 95% CI, 1.03 to 1.32; p = 0.017). Among the 1,609 SARS-CoV-2-positive patients with hypertension, the use of RAS blockers was not associated with poor outcomes, such as mortality (adjusted OR, 0.81; 95% CI, 0.56 to 1.17; p = 0.265), and a composite of admission to the intensive care unit and mortality (adjusted OR, 0.95; 95% CI, 0.73 to 1.22; p = 0.669). Analysis in the propensity scorematched population showed consistent results. CONCLUSION: In this Korean nationwide claims dataset, the use of RAS blockers was associated with a higher risk to SARS-CoV-2 infection but not with higher mortality or other severe clinical courses.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , COVID-19/therapy , Hypertension/drug therapy , Renin-Angiotensin System/drug effects , Administrative Claims, Healthcare , Aged , Aged, 80 and over , Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Antihypertensive Agents/adverse effects , COVID-19/diagnosis , COVID-19/mortality , Databases, Factual , Female , Humans , Hypertension/diagnosis , Hypertension/mortality , Hypertension/physiopathology , Male , Middle Aged , Retrospective Studies , Risk Assessment , Risk Factors , Severity of Illness Index , Treatment Outcome
5.
BMJ Case Rep ; 14(8)2021 Aug 17.
Article in English | MEDLINE | ID: covidwho-1361973

ABSTRACT

Hydralazine is a commonly prescribed antihypertensive agent. Some of its labelled adverse reactions include lupus-like syndrome, tachycardia, headache and fever. Despite its well-known side effects, little is known about hydralazine's hepatotoxic effects. We report the case of a 54-year-old female patient who was started on hydralazine for hypertension management but later presented with hydralazine-induced liver injury. Her initial presentation consisted of non-specific symptoms and a hepatocellular injury pattern. Liver biopsy revealed hepatic steatosis. Three weeks after discontinuation of hydralazine, the patient's liver enzymes normalised, and her symptoms resolved. Few studies have examined the incidence and mechanism by which hydralazine induces a liver injury pattern. With this case, we review the literature, the pathogenesis involved and the eventual management of hydralazine-induced liver injury. We propose close monitoring of liver enzymes for patients on hydralazine throughout their treatment course.


Subject(s)
Chemical and Drug Induced Liver Injury, Chronic , Chemical and Drug Induced Liver Injury , Hypertension , Antihypertensive Agents/adverse effects , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury, Chronic/drug therapy , Female , Humans , Hydralazine/adverse effects , Hypertension/drug therapy , Middle Aged
6.
Drugs Aging ; 38(10): 921-930, 2021 10.
Article in English | MEDLINE | ID: covidwho-1361350

ABSTRACT

BACKGROUND: There is ongoing debate about the associations between drug therapies targeting the renin-angiotensin-aldosterone system (RAAS) and adverse outcomes in coronavirus disease 2019 (COVID-19). OBJECTIVE: This study aims to examine the associations between using medications for the cardiovascular system and the risks associated with COVID-19 in middle-aged and older adults. METHODS: A total of 77,221 participants (aged 50-86 years) from UK Biobank were tested for SARS-CoV-2 RNA. The medications included angiotensin-converting enzyme inhibitors (ACEI), angiotensin-receptor blockers (ARB), ß-blockers, calcium channel blockers (CCB), statins, and aspirin. COVID-19 outcomes comprised a positive test result and severity of COVID-19 (defined as mild, hospitalization or death). We evaluated the risk among total participants and for sub-groups based on sex. Propensity score matching was performed 1:1 and logistic regression models were used. RESULTS: Among the middle- and older aged participants, no significant associations between any class of medications and the likelihood of COVID-19 infection were observed. ACEI were associated with a higher mortality risk from COVID-19 (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.01-1.32) and CCB were associated with a lower hospitalization risk for COVID-19 (OR 0.87, 95% CI 0.79-0.96) among the male patients with COVID-19, while a lower mortality risk from COVID-19 (OR 0.67, 95% CI 0.47-0.96) was observed with ARB among the female patients with COVID-19. CONCLUSIONS: The study suggested sex differences in the risk of death from COVID-19 with the use of ACEI and ARB among middle-aged and older adults. Sex differences in the risk of hospitalization for COVID-19 with the use of CCB was observed as well. It is of clinical importance that clinicians adopt different CVD treatment approaches for female and male patients with COVID-19.


Subject(s)
COVID-19 , Hypertension , Aged , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Antihypertensive Agents/adverse effects , Female , Humans , Hypertension/drug therapy , Male , Middle Aged , RNA, Viral , Retrospective Studies , Risk Factors , SARS-CoV-2 , Sex Characteristics
7.
Hipertens Riesgo Vasc ; 37(4): 169-175, 2020.
Article in Spanish | MEDLINE | ID: covidwho-1322115

ABSTRACT

The first case of COVID-19 was reported on 31 December 2019 in Wuhan, China. Ever since there has been unprecedented and growing interest in learning about all aspects of this new disease. Debate has been generated as to the association between antihypertensive therapy with renin-angiotensin-aldosterone system (RAAS) inhibitors and SARS-CoV-2 infection. While many questions as yet remain unanswered, the aim of this report is to inform health professionals about the current state of knowledge. Because this is an ever-evolving topic, the recommendation is that it be updated as new evidence becomes available. Below, we provide a review of pre-clinical and clinical studies that link coronavirus to the RAAS.


Subject(s)
Betacoronavirus , Coronavirus Infections/physiopathology , Pandemics , Pneumonia, Viral/physiopathology , Renin-Angiotensin System/physiology , ADAM17 Protein/physiology , Angiotensin II/physiology , Angiotensin Receptor Antagonists/adverse effects , Angiotensin Receptor Antagonists/pharmacology , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme 2 , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/adverse effects , Antihypertensive Agents/pharmacology , Antihypertensive Agents/therapeutic use , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/complications , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Humans , Hypertension/complications , Hypertension/physiopathology , Lung/physiopathology , Models, Biological , Pandemics/prevention & control , Peptidyl-Dipeptidase A/drug effects , Peptidyl-Dipeptidase A/physiology , Pneumonia, Viral/complications , Pneumonia, Viral/immunology , Pneumonia, Viral/prevention & control , Receptors, Virus/drug effects , Renin-Angiotensin System/drug effects , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/physiopathology , SARS-CoV-2 , Serine Endopeptidases/physiology , Viral Vaccines , Virus Internalization/drug effects
8.
Sci Rep ; 11(1): 13349, 2021 06 25.
Article in English | MEDLINE | ID: covidwho-1281740

ABSTRACT

Hypertension is a recognized comorbidity for COVID-19. The association of antihypertensive medications with outcomes in patients with hypertension is not fully described. However, angiotensin-converting enzyme 2 (ACE2), responsible for host entry of the novel coronavirus (SARS-CoV-2) leading to COVID-19, is postulated to be upregulated in patients taking angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs). Here, we evaluated the occurrence of pulmonary adverse drug events (ADEs) in patients with hypertension receiving ACEIs/ARBs to determine if disparities exist between individual drugs within the respective classes using data from the FDA Spontaneous Reporting Systems. For this purpose, we proposed the proportional reporting ratio to provide a statistical summary for the commonality of an ADE for a specific drug as compared to the entire database for drugs in the same or other classes. In addition, a statistical procedure, multiple logistic regression analysis, was employed to correct hidden confounders when causative covariates are underreported or untrusted to correct analyses of drug-ADE combinations. To date, analyses have been focused on drug classes rather than individual drugs which may have different ADE profiles depending on the underlying diseases present. A retrospective analysis of thirteen pulmonary ADEs showed significant differences associated with quinapril and trandolapril, compared to other ACEIs and ARBs. Specifically, quinapril and trandolapril were found to have a statistically significantly higher incidence of pulmonary ADEs compared with other ACEIs as well as ARBs (P < 0.0001) for group comparison (i.e., ACEIs vs. ARBs vs. quinapril vs. trandolapril) and (P ≤ 0.0007) for pairwise comparison (i.e., ACEIs vs. quinapril, ACEIs vs. trandolapril, ARBs vs. quinapril, or ARBs vs. trandolapril). This study suggests that specific members of the ACEI antihypertensive class (quinapril and trandolapril) have a significantly higher cluster of pulmonary ADEs.


Subject(s)
Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Antihypertensive Agents/adverse effects , COVID-19 , Hypertension , Indoles/adverse effects , Quinapril/adverse effects , COVID-19/drug therapy , COVID-19/epidemiology , Comorbidity , Hospital Mortality , Humans , Hypertension/drug therapy , Hypertension/epidemiology , Retrospective Studies
9.
BMC Infect Dis ; 21(1): 527, 2021 Jun 05.
Article in English | MEDLINE | ID: covidwho-1251747

ABSTRACT

BACKGROUND: Reports on the effects of renin-angiotensin-aldosterone system (RAAS) inhibitors on the clinical outcomes of coronavirus disease-19 (COVID-19) have been conflicting. We performed this meta-analysis to find conclusive evidence. METHODS: We searched published articles through PubMed, EMBASE and medRxiv from 5 January 2020 to 3 August 2020. Studies that reported clinical outcomes of patients with COVID-19, stratified by the class of antihypertensives, were included. Random and fixed-effects models were used to estimate pooled odds ratio (OR). RESULTS: A total 36 studies involving 30,795 patients with COVID-19 were included. The overall risk of poor patient outcomes (severe COVID-19 or death) was lower in patients taking RAAS inhibitors (OR = 0.79, 95% CI: [0.67, 0.95]) compared with those receiving non-RAAS inhibitor antihypertensives. However, further sub-meta-analysis showed that specific RAAS inhibitors did not show a reduction of poor COVID-19 outcomes when compared with any class of antihypertensive except beta-blockers (BBs). For example, compared to calcium channel blockers (CCBs), neither angiotensin-I-converting enzyme inhibitors (ACEIs) (OR = 0.91, 95% CI: [0.67, 1.23]) nor angiotensin-II receptor blockers (ARBs) (OR = 0.90, 95% CI: [0.62, 1.33]) showed a reduction of poor COVID-19 outcomes. When compared with BBs, however, both ACEIs (OR = 0.85, 95% CI: [0.73, 0.99) and ARBs (OR = 0.72, 95% CI: [0.55, 0.94]) showed an apparent decrease in poor COVID-19 outcomes. CONCLUSIONS: RAAS inhibitors did not increase the risk of mortality or severity of COVID-19. Differences in COVID-19 clinical outcomes between different class of antihypertensive drugs were likely due to the underlying comorbidities for which the antihypertensive drugs were prescribed, although adverse effects of drugs such as BBs could not be excluded.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , COVID-19/drug therapy , COVID-19/mortality , Hypertension/drug therapy , Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Antihypertensive Agents/adverse effects , Calcium Channel Blockers/adverse effects , Calcium Channel Blockers/therapeutic use , Comorbidity , Humans , Hypertension/complications , Odds Ratio , Renin-Angiotensin System/drug effects , Risk Factors , Severity of Illness Index , Treatment Outcome
10.
Lancet ; 395(10238): 1705-1714, 2020 05 30.
Article in English | MEDLINE | ID: covidwho-1217628

ABSTRACT

BACKGROUND: Concerns have been raised about the possibility that inhibitors of the renin-angiotensin-aldosterone system (RAAS) could predispose individuals to severe COVID-19; however, epidemiological evidence is lacking. We report the results of a case-population study done in Madrid, Spain, since the outbreak of COVID-19. METHODS: In this case-population study, we consecutively selected patients aged 18 years or older with a PCR-confirmed diagnosis of COVID-19 requiring admission to hospital from seven hospitals in Madrid, who had been admitted between March 1 and March 24, 2020. As a reference group, we randomly sampled ten patients per case, individually matched for age, sex, region (ie, Madrid), and date of admission to hospital (month and day; index date), from Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP), a Spanish primary health-care database, in its last available year (2018). We extracted information on comorbidities and prescriptions up to the month before index date (ie, current use) from electronic clinical records of both cases and controls. The outcome of interest was admission to hospital of patients with COVID-19. To minimise confounding by indication, the main analysis focused on assessing the association between COVID-19 requiring admission to hospital and use of RAAS inhibitors compared with use of other antihypertensive drugs. We calculated odds ratios (ORs) and 95% CIs, adjusted for age, sex, and cardiovascular comorbidities and risk factors, using conditional logistic regression. The protocol of the study was registered in the EU electronic Register of Post-Authorisation Studies, EUPAS34437. FINDINGS: We collected data for 1139 cases and 11 390 population controls. Among cases, 444 (39·0%) were female and the mean age was 69·1 years (SD 15·4), and despite being matched on sex and age, a significantly higher proportion of cases had pre-existing cardiovascular disease (OR 1·98, 95% CI 1·62-2·41) and risk factors (1·46, 1·23-1·73) than did controls. Compared with users of other antihypertensive drugs, users of RAAS inhibitors had an adjusted OR for COVID-19 requiring admission to hospital of 0·94 (95% CI 0·77-1·15). No increased risk was observed with either angiotensin-converting enzyme inhibitors (adjusted OR 0·80, 0·64-1·00) or angiotensin-receptor blockers (1·10, 0·88-1·37). Sex, age, and background cardiovascular risk did not modify the adjusted OR between use of RAAS inhibitors and COVID-19 requiring admission to hospital, whereas a decreased risk of COVID-19 requiring admission to hospital was found among patients with diabetes who were users of RAAS inhibitors (adjusted OR 0·53, 95% CI 0·34-0·80). The adjusted ORs were similar across severity degrees of COVID-19. INTERPRETATION: RAAS inhibitors do not increase the risk of COVID-19 requiring admission to hospital, including fatal cases and those admitted to intensive care units, and should not be discontinued to prevent a severe case of COVID-19. FUNDING: Instituto de Salud Carlos III.


Subject(s)
Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Antihypertensive Agents/adverse effects , Coronavirus Infections/epidemiology , Hospitalization/statistics & numerical data , Pneumonia, Viral/epidemiology , Renin-Angiotensin System , Aged , Aged, 80 and over , COVID-19 , Comorbidity , Coronavirus Infections/complications , Female , Humans , Male , Middle Aged , Mineralocorticoid Receptor Antagonists/adverse effects , Pandemics , Pneumonia, Viral/complications , Renin/antagonists & inhibitors , Risk Factors , Spain/epidemiology
11.
J Zhejiang Univ Sci B ; 22(4): 330-340, 2021 Apr 15.
Article in English | MEDLINE | ID: covidwho-1175476

ABSTRACT

Epidemiological evidence suggests that patients with hypertension infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are at increased risk of acute lung injury. However, it is still not clear whether this increased risk is related to the usage of renin-angiotensin system (RAS) blockers. We collected medical records of coronavirus disease 2019 (COVID-19) patients from the First Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou, China), and evaluated the potential impact of an angiotensin II receptor blocker (ARB) on the clinical outcomes of COVID-19 patients with hypertension. A total of 30 hypertensive COVID-19 patients were enrolled, of which 17 were classified as non-ARB group and the remaining 13 as ARB group based on the antihypertensive therapies they received. Compared with the non-ARB group, patients in the ARB group had a lower proportion of severe cases and intensive care unit (ICU) admission as well as shortened length of hospital stay, and manifested favorable results in most of the laboratory testing. Viral loads in the ARB group were lower than those in the non-ARB group throughout the disease course. No significant difference in the time of seroconversion or antibody levels was observed between the two groups. The median levels of soluble angiotensin-converting enzyme 2 (sACE2) in serum and urine samples were similar in both groups, and there were no significant correlations between serum sACE2 and biomarkers of disease severity. Transcriptional analysis showed 125 differentially expressed genes which mainly were enriched in oxygen transport, bicarbonate transport, and blood coagulation. Our results suggest that ARB usage is not associated with aggravation of COVID-19. These findings support the maintenance of ARB treatment in hypertensive patients diagnosed with COVID-19.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Antibodies, Viral/blood , COVID-19/complications , Hypertension/drug therapy , Viral Load , Aged , Aged, 80 and over , Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme 2/blood , Antihypertensive Agents/adverse effects , Antihypertensive Agents/therapeutic use , Biomarkers , China , Female , Humans , Hypertension/complications , Intensive Care Units , Length of Stay , Male , Middle Aged , Retrospective Studies , Transcriptome
12.
JAMA Netw Open ; 4(3): e213594, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-1159048

ABSTRACT

Importance: The chronic receipt of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) has been assumed to exacerbate complications associated with COVID-19 and produce worse clinical outcomes. Objective: To conduct an updated and comprehensive systematic review and meta-analysis comparing mortality and severe adverse events (AEs) associated with receipt vs nonreceipt of ACEIs or ARBs among patients with COVID-19. Data Sources: PubMed and Embase databases were systematically searched from December 31, 2019, until September 1, 2020. Study Selection: The meta-analysis included any study design, with the exception of narrative reviews or opinion-based articles, in which COVID-19 was diagnosed through laboratory or radiological test results and in which clinical outcomes (unadjusted or adjusted) associated with COVID-19 were assessed among adult patients (≥18 years) receiving ACEIs or ARBs. Data Extraction and Synthesis: Three authors independently extracted data on mortality and severe AEs associated with COVID-19. Severe AEs were defined as intensive care unit admission or the need for assisted ventilation. For each outcome, a random-effects model was used to compare the odds ratio (OR) between patients receiving ACEIs or ARBs vs those not receiving ACEIs or ARBs. Main Outcomes and Measures: Unadjusted and adjusted ORs for mortality and severe AEs associated with COVID-19. Results: A total of 1788 records from the PubMed and Embase databases were identified; after removal of duplicates, 1664 records were screened, and 71 articles underwent full-text evaluation. Clinical data were pooled from 52 eligible studies (40 cohort studies, 6 case series, 4 case-control studies, 1 randomized clinical trial, and 1 cross-sectional study) enrolling 101 949 total patients, of whom 26 545 (26.0%) were receiving ACEIs or ARBs. When adjusted for covariates, significant reductions in the risk of death (adjusted OR [aOR], 0.57; 95% CI, 0.43-0.76; P < .001) and severe AEs (aOR, 0.68; 95% CI, 0.53-0.88; P < .001) were found. Unadjusted and adjusted analyses of a subgroup of patients with hypertension indicated decreases in the risk of death (unadjusted OR, 0.66 [95% CI, 0.49-0.91]; P = .01; aOR, 0.51 [95% CI, 0.32-0.84]; P = .008) and severe AEs (unadjusted OR, 0.70 [95% CI, 0.54-0.91]; P = .007; aOR, 0.55 [95% CI, 0.36-0.85]; P = .007). Conclusions and Relevance: In this systematic review and meta-analysis, receipt of ACEIs or ARBs was not associated with a higher risk of multivariable-adjusted mortality and severe AEs among patients with COVID-19 who had either hypertension or multiple comorbidities, supporting the recommendations of medical societies. On the contrary, ACEIs and ARBs may be associated with protective benefits, particularly among patients with hypertension. Future randomized clinical trials are warranted to establish causality.


Subject(s)
Angiotensin Receptor Antagonists/pharmacology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Antihypertensive Agents/pharmacology , COVID-19/mortality , Hypertension/drug therapy , Renin-Angiotensin System , Severity of Illness Index , Adult , Aged , Aged, 80 and over , Angiotensin Receptor Antagonists/adverse effects , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/adverse effects , Antihypertensive Agents/therapeutic use , COVID-19/epidemiology , Comorbidity , Female , Humans , Hypertension/epidemiology , Male , Middle Aged , SARS-CoV-2
13.
Korean J Intern Med ; 36(Suppl 1): S114-S122, 2021 03.
Article in English | MEDLINE | ID: covidwho-1143662

ABSTRACT

BACKGROUND/AIMS: Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, there have been concerns about the association between exposure to renin-angiotensin-aldosterone system (RAAS) inhibitors and the risk and severity of COVID-19. METHODS: We performed a case-control study that utilized up-to-date data on the South Korean population provided by the Korean National Health Insurance System. Of the 62,909 patients with hypertension or heart failure tested for COVID-19, there were 1,644 (2.6%) confirmed cases. After case-control matching, multivariable-adjusted conditional logistic regression analysis was performed. RESULTS: Comparison between patients exposed to RAAS inhibitors and those not exposed to RAAS inhibitors revealed that the adjusted odds ratio (OR) and 95% confidence interval (CI) for COVID-19 infection and death were 0.981 (95% CI, 0.849 to 1.135) and 0.875 (95% CI, 0.548 to 1.396), respectively. Subgroup analysis for the major confounders, age and region of diagnosis, resulted in OR of 0.912 (95% CI, 0.751 to 1.108) and 0.942 (95% CI, 0.791 to 1.121), respectively. CONCLUSION: The present study demonstrated no evidence of association between RAAS inhibitor exposure and risk and severity of COVID-19.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , COVID-19/epidemiology , Heart Failure/drug therapy , Hypertension/drug therapy , Renin-Angiotensin System/drug effects , Aged , Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Antihypertensive Agents/adverse effects , COVID-19/diagnosis , Case-Control Studies , Databases, Factual , Female , Heart Failure/diagnosis , Heart Failure/epidemiology , Humans , Hypertension/diagnosis , Hypertension/epidemiology , Male , Middle Aged , Republic of Korea/epidemiology , Risk Assessment , Risk Factors , Severity of Illness Index
14.
Hypertens Res ; 44(8): 955-968, 2021 08.
Article in English | MEDLINE | ID: covidwho-1139738

ABSTRACT

Angiotensin-converting enzyme 2 (ACE2) protects against organ damage in hypertension and cardiovascular diseases by counter regulating the renin-angiotensin system (RAS). ACE2 is also the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on the claim that RAS inhibitors (RASIs) cause ACE2 overexpression in some animal experiments, concerns have arisen that RASIs may aggravate SARS-CoV-2 infection and coronavirus disease-2019 severity in RASI-treated patients. To achieve a comprehensive review, a systematic search of MEDLINE/PubMed was conducted regarding the effects of RASIs on tissue ACE2 mRNA/protein expression in healthy animals and animal models of human diseases. We identified 88 eligible articles involving 168 experiments in the heart, kidneys, lungs, and other organs. Three of 38 experiments involving healthy animals showed ACE2 expression greater than twice that of the control (overexpression). Among 102 disease models (130 experiments), baseline ACE2 was overexpressed in 16 models (18 experiments) and less than half the control level (repression) in 28 models (40 experiments). In 72 experiments, RASIs did not change ACE2 levels from the baseline levels of disease models. RASIs caused ACE2 overexpression compared to control levels in seven experiments, some of which were unsupported by other experiments under similar conditions. In 36 experiments, RASIs reversed or prevented disease-induced ACE2 repression, yielding no or marginal changes. Therefore, ACE2 overexpression appears to be a rare rather than common consequence of RASI treatment in healthy animals and disease models. Future studies should clarify the pathophysiological significance of RASI-induced reversal or prevention of ACE2 repression in disease models.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Antihypertensive Agents/adverse effects , Gene Expression/drug effects , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Antihypertensive Agents/pharmacology , COVID-19 , Disease Models, Animal , MEDLINE , Renin-Angiotensin System/drug effects
15.
BMC Infect Dis ; 21(1): 262, 2021 Mar 15.
Article in English | MEDLINE | ID: covidwho-1136209

ABSTRACT

INTRODUCTION: Renin-angiotensin system (RAS) inhibitors have been postulated to influence susceptibility to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). This study investigated whether there is an association between their prescription and the incidence of COVID-19 and all-cause mortality. METHODS: We conducted a propensity-score matched cohort study comparing the incidence of COVID-19 among patients with hypertension prescribed angiotensin-converting enzyme I (ACE) inhibitors or angiotensin II type-1 receptor blockers (ARBs) to those treated with calcium channel blockers (CCBs) in a large UK-based primary care database (The Health Improvement Network). We estimated crude incidence rates for confirmed/suspected COVID-19 in each drug exposure group. We used Cox proportional hazards models to produce adjusted hazard ratios for COVID-19. We assessed all-cause mortality as a secondary outcome. RESULTS: The incidence rate of COVID-19 among users of ACE inhibitors and CCBs was 9.3 per 1000 person-years (83 of 18,895 users [0.44%]) and 9.5 per 1000 person-years (85 of 18,895 [0.45%]), respectively. The adjusted hazard ratio was 0.92 (95% CI 0.68 to 1.26). The incidence rate among users of ARBs was 15.8 per 1000 person-years (79 out of 10,623 users [0.74%]). The adjusted hazard ratio was 1.38 (95% CI 0.98 to 1.95). There were no significant associations between use of RAS inhibitors and all-cause mortality. CONCLUSION: Use of ACE inhibitors was not associated with the risk of COVID-19 whereas use of ARBs was associated with a statistically non-significant increase compared to the use of CCBs. However, no significant associations were observed between prescription of either ACE inhibitors or ARBs and all-cause mortality.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , COVID-19/complications , Calcium Channel Blockers/therapeutic use , Hypertension/complications , Hypertension/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Antihypertensive Agents/adverse effects , COVID-19/mortality , Calcium Channel Blockers/adverse effects , Cohort Studies , Female , Humans , Incidence , Male , Middle Aged , Mortality , Propensity Score , Proportional Hazards Models , Renin-Angiotensin System , United Kingdom , Young Adult
16.
Diabetes Metab J ; 45(3): 430-438, 2021 05.
Article in English | MEDLINE | ID: covidwho-1094277

ABSTRACT

BACKGROUND: Angiotensin-converting enzyme 2 facilitates the entry of severe acute respiratory syndrome coronavirus 2 into the human body. We investigated the association of renin-angiotensin-aldosterone system (RAAS) inhibitor use with severe coronavirus disease 2019 (COVID-19) outcomes in hypertensive patients. METHODS: We identified hypertensive patients with confirmed COVID-19 from the Korean Health Insurance Review and Assessment Service from inception to May 15, 2020. The primary outcome was the composite of intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), continuous renal replacement therapy (CRRT), extracorporeal membrane oxygenation (ECMO), and death from COVID-19. The individual components were evaluated as secondary outcomes. RESULTS: Of 1,374 hypertensive patients with COVID-19, 1,076 (78.3%) and 298 (21.7%) were users and never-users of RAAS inhibitors, respectively. The RAAS inhibitor users were not associated with the risk of the primary outcome (adjusted odds ratio [aOR], 0.72; 95% confidence interval [CI], 0.46 to 1.10). The risk of ICU admission was significantly lower in the users than the never-users (aOR, 0.44; 95% CI, 0.24 to 0.84). The RAAS inhibitors were beneficial only in ICU admissions that did not require IMV (aOR, 0.28; 95% CI, 0.14 to 0.58). The risk of death from COVID-19 was comparable between the groups (aOR, 1.09; 95% CI, 0.64 to 1.85). We could not evaluate the risks of CRRT and ECMO owing to the small number of events. CONCLUSION: RAAS inhibitor use was not associated with the composite of severe outcomes in the hypertensive patients with COVID-19 but significantly lowered the risk of ICU admission, particularly in patients who did not require IMV.


Subject(s)
Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , COVID-19/epidemiology , Hypertension/epidemiology , Aged , Antihypertensive Agents/adverse effects , Cohort Studies , Female , Hospitalization/statistics & numerical data , Humans , Hypertension/complications , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Republic of Korea/epidemiology , Risk Factors
18.
Korean J Intern Med ; 36(Suppl 1): S123-S131, 2021 03.
Article in English | MEDLINE | ID: covidwho-1076708

ABSTRACT

BACKGROUND/AIMS: There are concerns that the use of renin-angiotensin system (RAS) blockers may increase the risk of being infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or progressing to a severe clinical course after infection. This this study aimed to investigate the influence of RAS blockers on the risk and severity of SARS-CoV-2 infection. METHODS: We conducted a retrospective cohort study analyzing nationwide claims data of 215,184 adults who underwent SARS-CoV-2 tests in South Korea. The SARS-CoV-2 positive rates and clinical outcomes were evaluated according to the use of RAS blockers in patients with hypertension (n = 64,243). RESULTS: In total, 38,919 patients with hypertension were on RAS blockers. The SARS-CoV-2 positive rates were significantly higher in the RAS blocker group than in the control group after adjustments (adjusted odds ratio [OR], 1.22; 95% confidence interval [CI], 1.10 to 1.36; p < 0.001), and matching by propensity score (adjusted OR, 1.16; 95% CI, 1.03 to 1.32; p = 0.017). Among the 1,609 SARS-CoV-2-positive patients with hypertension, the use of RAS blockers was not associated with poor outcomes, such as mortality (adjusted OR, 0.81; 95% CI, 0.56 to 1.17; p = 0.265), and a composite of admission to the intensive care unit and mortality (adjusted OR, 0.95; 95% CI, 0.73 to 1.22; p = 0.669). Analysis in the propensity scorematched population showed consistent results. CONCLUSION: In this Korean nationwide claims dataset, the use of RAS blockers was associated with a higher risk to SARS-CoV-2 infection but not with higher mortality or other severe clinical courses.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , COVID-19/therapy , Hypertension/drug therapy , Renin-Angiotensin System/drug effects , Administrative Claims, Healthcare , Aged , Aged, 80 and over , Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Antihypertensive Agents/adverse effects , COVID-19/diagnosis , COVID-19/mortality , Databases, Factual , Female , Humans , Hypertension/diagnosis , Hypertension/mortality , Hypertension/physiopathology , Male , Middle Aged , Retrospective Studies , Risk Assessment , Risk Factors , Severity of Illness Index , Treatment Outcome
19.
Am J Hypertens ; 33(12): 1102-1111, 2020 12 31.
Article in English | MEDLINE | ID: covidwho-1066252

ABSTRACT

BACKGROUND: There is an ongoing controversy about harms and benefits of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in hypertensive patients with coronavirus disease 2019 (COVID-19). Given the unresolved debate, we investigated the association of ARBs with in-hospital outcomes of these patients. METHODS: In this retrospective observational study, we studied patients with COVID-19 who referred to Sina Hospital in Tehran, Iran, from 20 February to 29 May 2020. Patients with either positive real-time reverse-transcriptase polymerase-chain-reaction test of swab specimens, or high clinical suspicion according to the World Health Organization's interim guidance were included. We followed-up patients for incurring death, severe COVID-19, and in-hospital complications. RESULTS: We evaluated 681 patients with COVID-19 of whom 37 patients were excluded due to incomplete medical records and 8 patients who used ACEIs which left 636 patients in the analysis. In this cohort, 108 (17.0%) patients expired and 407 (64.0%) patients incurred severe COVID-19. Of 254 (39.9%) patients with hypertension, 122 (48.0%) patients were receiving an ARB. After adjustment for possible confounders, we found no independent association between taking ARBs and in-hospital outcomes except for acute kidney injury (AKI), in patients with confirmed or clinically suspected COVID-19, either hypertensive or not-hypertensive. We found that discontinuation of ARBs during hospitalization was associated with a greater risk of mortality, invasive ventilation, and AKI (all P ˂ 0.002). CONCLUSIONS: We found that taking ARBs by patients with hypertension and confirmed or clinically suspected COVID-19 is not associated with poorer in-hospital outcomes after adjustment for possible confounders.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Antihypertensive Agents/therapeutic use , COVID-19/therapy , Hypertension/drug therapy , Acute Kidney Injury/mortality , Aged , Angiotensin Receptor Antagonists/adverse effects , Antihypertensive Agents/adverse effects , COVID-19/diagnosis , COVID-19/mortality , Female , Hospital Mortality , Hospitalization , Humans , Hypertension/diagnosis , Hypertension/mortality , Iran , Male , Middle Aged , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
20.
High Blood Press Cardiovasc Prev ; 28(1): 5-11, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1064648

ABSTRACT

The COVID-19 infection has rapidly spread around the world and a second wave is sweeping in many countries. Different clinical and epidemiological aspects characterize the disease and their understanding is necessary to better face the management of the pandemic in progress. The Italian society of arterial hypertension with the SARS-RAS study has contributed significantly to the knowledge of the interaction between inhibition of the renin-angiotensin system and COVID-19 infection. Furthermore, the study results help to understand some of the main aspects related to mortality and morbidity deriving from the infection through a multicentre analysis throughout the national territory.


Subject(s)
Antihypertensive Agents/therapeutic use , Arterial Pressure/drug effects , COVID-19/therapy , Hypertension/drug therapy , Renin-Angiotensin System/drug effects , Antihypertensive Agents/adverse effects , COVID-19/diagnosis , COVID-19/mortality , Comorbidity , Cross-Sectional Studies , Frailty/mortality , Humans , Hypertension/diagnosis , Hypertension/mortality , Hypertension/physiopathology , Italy/epidemiology , Risk Assessment , Risk Factors , Severity of Illness Index , Sex Factors , Treatment Outcome
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