ACEIs and ARBs and Their Correlation with COVID-19: A Review.
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ABSTRACT:
SUBMITTER: Yehualashet AS
PROVIDER: S-EPMC7502385 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
ACEIs and ARBs and Their Correlation with COVID-19: A Review.
Yehualashet Awgichew Shewasinad AS Belachew Teshome Fentik TF
Infection and drug resistance 20200916
Although some animal studies suggested that the use of ACEIs/ARBs could contribute for the prevention and treatment of the effects of the COVID-19 infection, there are also contradictory scenarios indicating that their use may exacerbate the deleterious conditions of the infection. As a result of the paradoxical issue of using ACEIs/ARBs during COVID-19, it is still an area requiring extended investigation to prove. Additionally, a trial evidence of their efficacy and the possible benefit risk a ...[more]
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Project description:ObjectivesAngiotensin-converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARBs), and HMG-CoA reductase inhibitors ("statins") have been hypothesized to affect COVID-19 severity. However, up to now, no studies investigating this association have been conducted in the most vulnerable and affected population groups (ie, older adults residing in nursing homes). The objective of this study was to explore the association of ACEi/ARB and/or statins with clinical manifestations in COVID-19-infected older adults residing in nursing homes.DesignWe undertook a retrospective multicenter cohort study to analyze the association between ACEi/ARB and/or statin use with clinical outcome of COVID-19. The outcomes were (1) serious COVID-19 defined as long-stay hospital admission or death within 14 days of disease onset, and (2) asymptomatic (ie, no disease symptoms in the whole study period while still being diagnosed by polymerase chain reaction).Setting and participantsA total of 154 COVID-19-positive subjects were identified, residing in 1 of 2 Belgian nursing homes that experienced similar COVID-19 outbreaks.MeasuresLogistic regression models were applied with age, sex, functional status, diabetes, and hypertension as covariates.ResultsWe found a statistically significant association between statin intake and the absence of symptoms during COVID-19 (odds ratio [OR] 2.91; confidence interval [CI] 1.27-6.71), which remained statistically significant after adjusting for covariates (OR 2.65; CI 1.13-6.68). Although the effects of statin intake on serious clinical outcome were in the same beneficial direction, these were not statistically significant (OR 0.75; CI 0.24-1.87). There was also no statistically significant association between ACEi/ARB and asymptomatic status (OR 2.72; CI 0.59-25.1) or serious clinical outcome (OR 0.48; CI 0.10-1.97).Conclusions and implicationsOur data indicate that statin intake in older, frail adults could be associated with a considerable beneficial effect on COVID-19 clinical symptoms. The role of statins and renin-angiotensin system drugs needs to be further explored in larger observational studies as well as randomized clinical trials.
| S-EPMC7294267 | biostudies-literature
Project description:BackgroundWe explored the effect of discontinuing versus continuing angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) on clinical outcomes in patients with COVID-19 according to baseline disease severity.MethodsWe randomized 659 patients with a confirmed diagnosis of COVID-19 and classified them as having mild or moderate COVID-19 disease severity at hospital presentation using blood oxygen saturation and lung imaging. The primary outcome was the mean ratio of number of days alive and out of the hospital at 30 days according to disease severity.ResultsAt presentation, 376 patients (57.1%) had mild and 283 (42.9%) had moderate COVID-19. In patients with mild disease, there was no significant difference in the number of days alive and out of the hospital between ACEI/ARB discontinuation (mean 23.5 [SD 6.3] days) and continuation (mean 23.8 [SD 6.5] days), with a mean ratio of 0.98 (95% CI 0.92-1.04). However, in patients with moderate disease, there were fewer days alive and out of the hospital with ACEI/ARB discontinuation (mean 19.6 [SD 9.5] days) than continuation (mean 21.6 [SD 7.6] days), with a mean ratio of 0.90 (95% CI 0.81-1.00; P-interaction = .01). The impact of discontinuing versus continuing ACEIs/ARBs on days alive and out of hospital through 30 days differed according to baseline COVID-19 disease severity.ConclusionsUnlike patients with mild disease, patients with moderate disease who continued ACEIs/ARBs had more days alive and out of hospital through 30 days than those who discontinued ACEIs/ARBs. This suggests that ACEIs/ARBs should be continued for patients with moderate COVID-19 disease severity.Clinical trial registrationClinicalTrials.gov (NCT04364893).
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Project description:Diabetic nephropathy (DN) is a serious complication of both type 1 and type 2 diabetes mellitus. The disease is now the most common cause of end-stage kidney disease (ESKD) in developed countries, and both the incidence and prevalence of diabetes mellitus is increasing worldwide. Current treatments are directed at controlling hyperglycemia and hypertension, as well as blockade of the renin angiotensin system with angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers. Despite these therapies, DN progresses to ESKD in many patients. As a result, much interest is focused on developing new therapies. It has been over two decades since ACEIs were shown to have beneficial effects in DN independent of their blood pressure-lowering actions. Since that time, our understanding of disease mechanisms in DN has evolved. In this review, we summarize major cell signaling pathways implicated in the pathogenesis of diabetic kidney disease, as well as emerging treatment strategies. The goal is to identify promising targets that might be translated into therapies for the treatment of patients with diabetic kidney disease.
| S-EPMC4652076 | biostudies-literature
Project description:ObjectivesThe widespread use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) by patients with chronic conditions raised early concerns on the potential exacerbation of COVID-19 severity and fatality. Previous studies addressing this question have used standard methods that may lead to biased estimates when analysing hospital data because of the presence of competing events and event-related dependency. We investigated the association of ACEIs/ARBs' use with COVID-19 disease outcomes using time-to-event data in a multistate setting to account for competing events and minimise bias.SettingNationwide surveillance data from 119 Belgian hospitals.ParticipantsMedical records of 10 866 patients hospitalised from 14 March 2020to 14 June 2020 with a confirmed SARS-CoV-19 infection and information about ACEIs/ARBs' use.Primary outcome measureMultistate, multivariate Cox-Markov models were used to estimate the hazards of patients transitioning through health states from admission to discharge or death, along with transition probabilities calculated by combining the baseline cumulative hazard and regression coefficients.ResultsAfter accounting for potential confounders, there was no discernable association between ACEIs/ARBs' use and transfer to intensive care unit (ICU). Contrastingly, for patients without ICU transfer, ACEIs/ARBs' use was associated with a modest increase in recovery (HR 1.07, 95% CI 1.01 to 1.13, p=0.027) and reduction in fatality (HR 0.83, 95% CI 0.75 to 0.93, p=0.001) transitions. For patients transferred to ICU admission, no evidence of an association between ACEIs/ARBs' use and recovery (HR 1.16, 95% CI 0.97 to 1.38, p=0.098) or in-hospital death (HR 0.91, 95% CI 0.73 to 1.12, p=0.381) was observed. Male gender and older age were significantly associated with higher risk of ICU admission or death. Chronic cardiometabolic comorbidities were also associated with less recovery.ConclusionsFor the first time, a multistate model was used to address magnitude and direction of the association of ACEIs/ARBs' use on COVID-19 progression. By minimising bias, this study provided a robust indication of a protective, although modest, association with recovery and survival.
| S-EPMC8449849 | biostudies-literature
Project description:To evaluate the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) vs calcium channel blockers (CCBs) on the progression of Corona Virus Disease 2019 (COVID-19) patients with hypertension in Wuhan. This retrospective single-center case series analyzed COVID-19 patients with hypertension, treated with ACEIs/ARBs or CCBs at the Tongji Hospital of Wuhan City, China from 25th January to 15th March 2020. After propensity score matching analysis, 76 patients were selected into two groups. Univariate and multivariable analyses were conducted to determine factors related to improvement measures and outcome measures by Cox proportional hazard regression models. Among 157 patients with confirmed COVID-19 combined hypertension, including 73 males and 84 females, a median age of 67.28 ± 9.11 vs 65.39 ± 10.85 years. A univariable analysis indicated that clinical classification, lymphocyte count, and interleukin-2 receptor were associated with a lengthened negative time of nucleic acid, with a significant difference between two groups (P = .036). Furthermore, we found no obvious difference in nucleic acid conversion time between ACEIs/ARBs and CCBs groups (hazard ratio [HR]: 0.70; 95% confidence interval [CI]: [0.97, 3.38]; P = .18) in the multivariable analysis as well as chest computed tomography improved time (HR: 0.73; 95% CI [0.45, 1.2]; P = .87), and hospitalization time between ACEIs/ARBs and CCBs groups (HR: 1.06; 95% CI [0.44, 1.1]; P = .83). Our study provided additional evidence of no obvious difference in progress and prognosis between ACEIs/ACEIs and CCBs group, which may suggest ACEIs/ARBs may have scarcely influence on increasing the clinical severe situations of COVID-19 patients with hypertension.
| S-EPMC7405149 | biostudies-literature
Project description:The COVID-19 pandemic has prompted an international effort to develop and repurpose medications and procedures to effectively combat the disease. Several groups have focused on the potential treatment utility of angiotensin-converting-enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) for hypertensive COVID-19 patients, with inconclusive evidence thus far. We couple electronic medical record (EMR) and registry data of 3,643 patients from Spain, Italy, Germany, Ecuador, and the US with a machine learning framework to personalize the prescription of ACEIs and ARBs to hypertensive COVID-19 patients. Our approach leverages clinical and demographic information to identify hospitalized individuals whose probability of mortality or morbidity can decrease by prescribing this class of drugs. In particular, the algorithm proposes increasing ACEI/ARBs prescriptions for patients with cardiovascular disease and decreasing prescriptions for those with low oxygen saturation at admission. We show that personalized recommendations can improve patient outcomes by 1.0% compared to the standard of care when applied to external populations. We develop an interactive interface for our algorithm, providing physicians with an actionable tool to easily assess treatment alternatives and inform clinical decisions. This work offers the first personalized recommendation system to accurately evaluate the efficacy and risks of prescribing ACEIs and ARBs to hypertensive COVID-19 patients.
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Project description:BackgroundHypertension and diabetes mellitus are independent risk factors for cardiovascular diseases. Due to the cardioprotective nature of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), they are recommended for patients with comorbid hypertension and diabetes. However, poor adherence to ACEIs/ARBs among older adults is a major public health concern. This study aimed to assess the effectiveness of a telephonic motivational interviewing (MI) intervention conducted by pharmacy students among a nonadherent older population (≥ 65 years old) with diabetes and hypertension.MethodsPatients continuously enrolled in a Medicare Advantage Plan who received an ACEI/ARB prescription between July 2017 and December 2017 were identified. Group-based trajectory modeling (GBTM) was used to identify distinct patterns of ACEI/ARB adherence during the 1-year baseline period: adherent, gaps in adherence, gradual decline, and rapid decline in adherence. Patients from the three nonadherent trajectories were randomized into MI intervention or control group. The intervention consisted of an initial call and five follow-up calls administered by MI-trained pharmacy students and tailored to the baseline ACEI/ARB adherence trajectories. The primary outcome was adherence to ACEI/ARB during the 6- and 12-month periods post-MI implementation. The secondary outcome was discontinuation, defined as no refills for ACEI/ARB during the 6- and 12-month periods post-MI implementation. Multivariable regression analyses examined the impact of MI intervention on ACEI/ARB adherence and discontinuation while adjusting for baseline covariates.ResultsA total of 240 patients in the intervention group and 480 patients as randomly selected controls were included in this study. At 6 months, patients receiving the MI intervention had significantly better adherence (β = 0.06; p = 0.03) compared with the controls. Linear and logistic regression models also showed patients in the intervention group were more likely to be adherent than controls within 12 months of intervention implementation (β = 0.06; p = 0.02 and OR: 1.46; 95% CI 1.05-2.04, respectively). MI intervention did not have any significant impact on the ACEI/ARB discontinuation.ConclusionPatients who received the MI intervention were more likely to be adherent at 6 and 12 months following the intervention initiation, despite gaps in the follow-up calls due to COVID-19. Pharmacist-led MI intervention is an effective behavioral strategy to improve medication adherence among older adults and tailoring the intervention to past adherence patterns may enhance the intervention effectiveness. This study was registered with the United States National Institutes of Health (ClinicalTrials.gov identifier NCT03985098).
| S-EPMC9969383 | biostudies-literature
Project description:BackgroundIn peritoneal dialysis (PD) patients, whether angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) could protect residual renal function is still controversial. To assess the effects of ACEIs and ARBs on the residual renal function and cardiovascular (CV) events in peritoneal dialysis patients, we performed a meta-analysis of randomized controlled trials.Materials and methodsWe searched PubMed, EMBASE, the Cochrane Library, the CNKI database, and the Wanfang database for relevant articles from database inception to November 30, 2019. Randomized controlled trials were included. The primary outcome was the decline in the residual renal function (RRF).ResultsThirteen trials with 625 participants were included in the meta-analysis. The average residual GFR declined by 1.79 ml/min per 1.73 m2 in the ACEI/ARB group versus 1.44 ml/min per 1.73 m2 in the placebo or active control group at 3 mo. The average residual GFR declined by 2.02 versus 2.06, 2.16 versus 2.72, and -0.04 versus 2.74 ml/min per 1.73 m2 in the placebo or active control group at 6 months (mo), 12 mo, and 24 mo, respectively. The decline in residual GFR showed a significant difference between the ACEI/ARB group and the placebo or active control group at 12 mo (MD = -0.64 ml/min per 1.73 m2; 95% CI: -0.97~-0.32; I 2 = 44%; P < 0.0001). No significant difference was observed in Kt/V, urinary protein excretion, weekly creatinine clearance, CV events, or serum potassium levels.ConclusionsIn the present study, we found that the use of ACEIs and ARBs, especially long-term treatment, decreased the decline of RRF in patients on PD. ACEIs and ARBs do not cause an additional risk of side effects.
| S-EPMC7532381 | biostudies-literature
Project description:The discovery of angiotensin converting enzyme-2 (ACE-2) as the receptor for SARS- CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) has implicated the renin-angiotensin-aldosterone system in acute respiratory distress syndrome (ARDS) and respiratory failure in patients with coronavirus disease-19 (COVID-19). The angiotensin converting enzyme-1-angiotensin II-angiotensin AT1 receptor pathway contributes to the pathophysiology of ARDS, whereas activation of the ACE-2-angiotensin(1-7)-angiotensin AT2 receptor and the ACE-2-angiotensin(1-7)-Mas receptor pathways have been shown to be protective. Here we propose and discuss therapeutic considerations how to increase soluble ACE-2 in plasma in order for ACE-2 to capture and thereby inactivate SARS-CoV-2. This could be achieved by administering recombinant soluble ACE-2. We also discuss why and how ACEIs and ARBs provide cardiovascular, renal and also pulmonary protection in SARS-CoV-2- associated ARDS. Discontinuing these medications in COVID-19 patients may therefore potentially be harmful.
| S-EPMC7198232 | biostudies-literature
Project description:Purpose Due to the affinity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for the human angiotensin converting enzyme 2 (ACE2) receptor, use of angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) has been a major concern for clinicians during the 2020 pandemic. Meta-analyses have affirmed that these agents do not worsen clinical outcomes in SARS-CoV-2 infection. To date, only a limited number of studies have directly looked at the safety of inpatient prescription of ACEi/ARBs during acute COVID-19 illness. Methods A retrospective cohort analysis was conducted to investigate the impact of inpatient provision of ACEi/ARBs on morbidity and mortality in patients admitted to hospital with COVID-19. Relationships were explored using linear and logistic regression. Findings Six hundred and twelve adult patients met our inclusion criteria of which 151 (24.7%) patients were established on ACEi/ARBs. Despite correction for known confounders, discontinuation of ACEi/ARBs was highly predictive of worsened outcomes in COVID-19. The proportion of doses omitted in hospital was significantly associated with increased mortality (p<0.001, OR=9.59 [2.55-36.09]), maximum National Early Warning Score (NEWS-2; p<0.001, OR=1.66 [1.27-2.17]), maximum oxygen requirements (p<0.001, OR=3.00 [1.83-4.91]), and maximum C-Reactive Protein concentration (CRP; p=0.030, OR=1.83 [1.06-3.17]). Implications Our data demonstrates a strong association between missed ACEi/ARB doses with increased morbidity and mortality. The available evidence supports continuation of current accepted practice surrounding ACEi/ARB therapy in acute illness – which is to limit drug omission to established acute contraindications, to actively monitor such decisions and to restart therapy as soon as it is safe to do so.
| S-EPMC7906507 | biostudies-literature