SARS-CoV2: should inhibitors of the renin-angiotensin system be withdrawn in patients with COVID-19?
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ABSTRACT:
SUBMITTER: Kuster GM
PROVIDER: S-EPMC7184407 | biostudies-literature | 2020 May
REPOSITORIES: biostudies-literature
Publications
SARS-CoV2: should inhibitors of the renin-angiotensin system be withdrawn in patients with COVID-19?
Kuster Gabriela M GM Pfister Otmar O Burkard Thilo T Zhou Qian Q Twerenbold Raphael R Haaf Philip P Widmer Andreas F AF Osswald Stefan S
European heart journal 20200501 19
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Project description:The functional receptor to SARS-CoV-2, the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, is angiotensin-converting enzyme-2 (ACE-2), the same enzyme that physiologically counters the renin-angiotensin system (RAS) activation. Some researchers have questioned RAS inhibitors' safety in COVID-19 patients since these drugs have demonstrated an increase in ACE-2 expression in preclinical studies; therefore, they may facilitate viral invasion. On the contrary, others have hypothesized a protective role of RAS inhibitors against COVID-19-associated lung injury. Overall, the data are grossly inadequate to reach any conclusion since no human trials have yet evaluated the effects of RAS inhibitors in COVID-19. We review the current data and pathophysiological mechanisms behind this intriguing interplay between the RAS inhibitors and the COVID-19.
| S-EPMC7596458 | biostudies-literature
Project description:AimsTo describe the characteristics of patients hospitalized with COVID-19 (including their long-term at-home medication use), and compare them with regard to the course of the disease. To assess the association between renin-angiotensin system inhibitors (RASIs) and disease progression and critical outcomes.Methods and resultsAll consecutive hospitalized patients with laboratory-confirmed COVID-19 in a university hospital in Amiens (France) were included in this study. The primary composite endpoint was admission to an intensive care unit (ICU) or death before ICU admission. Univariable and multivariable logistic regression models were used to identify factors associated with the composite endpoint. Between 28 February 2020 and 30 March 2020, a total of 499 local patients tested positive for SARS-CoV-2. Of these, 231 were not hospitalized {males 33%; median [interquartile range (IQR)] age: 44 (32-54)}, and 268 were hospitalized [males 58%; median (IQR) age: 73 (61-84)]. A total of 116 patients met the primary endpoint: 47 died before ICU admission, and 69 were admitted to the ICU. Patients meeting the primary endpoint were more likely than patients not meeting the primary endpoint to have coronary heart disease and to have been taking RASIs; however, the two subsets of patients did not differ with regard to median age. After adjustment for other associated variables, the risk of meeting the composite endpoint was 1.73 times higher (odds ratio 1.73, 95% confidence interval 1.02-2.93) in patients treated at baseline with a RASI than in patients not treated with this drug class. This association was confirmed when the analysis was restricted to patients treated with antihypertensive agents.ConclusionsWe highlighted a potential safety signal for RASIs, the long-term use of which was independently associated with a higher risk of severe COVID-19 and a poor outcome. Due to the widespread use of this important drug class, formal proof based on clinical trials is needed to better understand the association between RASIs and complications of COVID-19.
| S-EPMC7314068 | biostudies-literature
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| S-EPMC7224604 | biostudies-literature
Project description:BackgroundThere is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2).MethodsWe assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as a substantial difference.ResultsAmong 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness. A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness. There was no association between any single medication class and an increased likelihood of a positive test. None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive.ConclusionsWe found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.
| S-EPMC7206932 | biostudies-literature
Project description:(1) Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) penetrates respiratory epithelium through angiotensin-converting enzyme-2 binding, raising concerns about the potentially harmful effects of renin-angiotensin system inhibitors (RASi) on Human Coronavirus Disease 2019 (COVID-19) evolution. This study aimed to provide insight into the impact of RASi on SARS-CoV-2 outcomes in patients hospitalized for COVID-19. (2) Methods: This was a retrospective analysis of hospitalized adult patients with SARS-CoV-2 infection admitted to a university hospital in France. The observation period ended at hospital discharge. (3) Results: During the study period, 943 COVID-19 patients were admitted to our institution, of whom 772 were included in this analysis. Among them, 431 (55.8%) had previously known hypertension. The median age was 68 (56-79) years. Overall, 220 (28.5%) patients were placed under mechanical ventilation and 173 (22.4%) died. According to previous exposure to RASi, we defined two groups, namely, "RASi" (n = 282) and "RASi-free" (n = 490). Severe pneumonia (defined as leading to death and/or requiring intubation, high-flow nasal oxygen, noninvasive ventilation, and/or oxygen flow at a rate of ≥5 L/min) and death occurred more frequently in RASi-treated patients (64% versus 53% and 29% versus 19%, respectively). However, in a propensity score-matched cohort derived from the overall population, neither death (hazard ratio (HR) 0.93 (95% confidence interval (CI) 0.57-1.50), p = 0.76) nor severe pneumonia (HR 1.03 (95%CI 0.73-1.44), p = 0.85) were associated with RASi therapy. (4) Conclusion: Our study showed no correlation between previous RASi treatment and death or severe COVID-19 pneumonia after adjustment for confounders.
| S-EPMC7692895 | biostudies-literature
Project description:BackgroundThe effect of renin-angiotensin-aldosterone system (RAAS) inhibitors in coronavirus disease 19 (Covid-19) patients has not been fully investigated. We evaluated the association between RAAS inhibitor use and outcomes of Covid-19.MethodsThis study was a retrospective observational cohort study that used data based on insurance benefit claims sent to the Health Insurance Review and Assessment Service of Korea by May 15, 2020. These claims comprised all Covid-19 tested cases and the history of medical service use in these patients for the past five years. The primary outcome was all-cause mortality, and the rate of ventilator care was compared between the groups.ResultsFrom a total of 7,590 patients diagnosed with Covid-19, two distinct cohorts were generated based on RAAS inhibitors prescribed within 6 months before Covid-19 diagnosis. A total of 1,111 patients was prescribed RAAS inhibitors, and 794 patients were prescribed antihypertensive drugs, excluding RAAS inhibitors. In propensity-score matched analysis, 666 pairs of data set were generated, and all-cause mortality of the RAAS inhibitor group showed no significant difference compared with the non-RAAS inhibitor group (14.6% vs. 11.1%; hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.54-1.15; p = 0.22). The rate of ventilator care was not significantly different between the two groups (4.4% vs. 4.1%; HR, 1.04; 95%CI, 0.60-1.79; p = 0.89).ConclusionsRAAS inhibitor treatment did not appear to increase the mortality of Covid-19 patients compared with other antihypertensive drugs, suggesting that they may be safely continued in Covid-19 patients.
| S-EPMC7951918 | biostudies-literature
Project description:The dysfunction of the renin-angiotensin system (RAS) has been observed in coronavirus infection disease (COVID-19) patients, but whether RAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs), are associated with clinical outcomes remains unknown. COVID-19 patients with hypertension were enrolled to evaluate the effect of RAS inhibitors. We observed that patients receiving ACEI or ARB therapy had a lower rate of severe diseases and a trend toward a lower level of IL-6 in peripheral blood. In addition, ACEI or ARB therapy increased CD3 and CD8 T cell counts in peripheral blood and decreased the peak viral load compared to other antihypertensive drugs. This evidence supports the benefit of using ACEIs or ARBs to potentially contribute to the improvement of clinical outcomes of COVID-19 patients with hypertension.
| S-EPMC7170368 | biostudies-literature
Project description:Background Considering the widespread risk of collider bias and confounding by indication in previous research, the associations between renin-angiotensin aldosterone system (RAAS) inhibitor use and COVID-19 remain unknown. Accordingly, this study tested the hypothesis that RAAS inhibitors influence the summation effect of COVID-19 and its progression to severe outcomes. Methods and Results This nationwide cohort study compared all residents of Sweden, without prior cardiovascular disease, in monotherapy (as of January 1, 2020) with a RAAS inhibitor to those using a calcium channel blocker or a thiazide diuretic. Comparative cohorts were balanced using machine-learning-derived propensity score methods. Of 165 355 people in the analysis (51% women), 367 were hospitalized or died with COVID-19 (246 using a RAAS inhibitor versus 121 using a calcium channel blocker or thiazide diuretic; Cox proportional hazard ratio [HR], 0.97; 95% CI, 0.74-1.27). When each outcome was assessed separately, 335 people were hospitalized with COVID-19 (HR, 0.92; 95% CI, 0.70-1.22), and 64 died with COVID-19 (HR, 1.22; 95% CI, 0.68-2.19). The severity of COVID-19 outcomes did not differ between those using a RAAS inhibitor and those using a calcium channel blocker or thiazide diuretic (ordered logistic regression odds ratio, 1.01; 95% CI, 0.89-1.14). Conclusions Despite potential limitations, this study is among the best available evidence that RAAS inhibitor use in primary prevention does not increase the risk of severe COVID-19 outcomes; presenting strong data from which scientists and policy makers alike can base, with greater confidence, their current position on the safety of using RAAS inhibitors during the COVID-19 pandemic.
| S-EPMC8475700 | biostudies-literature