stream 2021-01-22T06:52:09-08:00 initial dose (4 mg daily) • Severe impairment: lower initial dose (4 mg daily) • Losartan • Initial: 25 mg daily • Max: 100 mg daily • None • 25 mg daily initial dose • Telmisartan • Initial: 40 mg daily • Max: 80 mg daily • 80 mg daily • None • 40 mg daily initial dose • … er doses of ACEI or ARB may be required to effectively counter angiotensin II.8,9 Several trials have compared low versus high doses of these drugs, but the results have been conflicting. In this context, the consensus conference on the spectrum of lung-kidney interactions stated that AKI is associated with increased susceptibility to respiratory failure, related pulmonary complications, and delay in weaning and liberation from invasive mechanical ventilation [36]. Our study is retrospective and relied on a relatively limited number of patients and needs to be confirmed in independent studies with a longer follow-up. Abbreviations: AKI, acute kidney injury; aOR, adjusted odds ratio; CI, confidence interval; COPD, chronic obstructive pulmonary disease; COVID-19, coronavirus disease 2019; SE, standard error. To date, the few studies that have evaluated the relationship between ACEI/ARB use and the severity of COVID-19 differ in their study design, selection criteria, and study outcomes, and thus do not allow a comprehensive assessment of the data. The dose was doubled if BP after 1 month was > or = 140/90 mm Hg. endstream Consistently the median Ct value for the IP4 target at baseline did not differ between patients with or without ACEI/ARB use (28 [IQR, 22–33] vs 26 [IQR, 22–32]; P = .62). <>stream The mean age was 60.5 +/- 12.2 years and 50.5% were women. Forest plot reporting the results of sensitivity analyses to assess the stability of the effect sizes for the association between the use of ACEI/ARB and the biochemical alterations that have shown significance in multivariable multilevel analyses. uuid:a714b7f7-a7aa-47b3-b7d0-61d5d565d09a Enalapril 10mg. To date, data are scarce and conflicting regarding whether ACEI/ARB therapy influences disease outcomes among patients with severe COVID-19 [15–17]. Abbreviations: ACEI/ARB, angiotensin-converting enzyme inhibitor/angiotensin receptor blockers; CI, confidence interval; COPD, chronic obstructive pulmonary disease; IQR, interquartile range, 25th–75th percentile; n, number of observations; N, number of patients. endobj endobj Conversely, the “beneficial hypothesis” states that ACEI/IRB use is associated with an increase in the expression of ACE2 with subsequent reduction of angiotensin II. x�S�*�*T0T0 B�����i������ y\' 3 0 obj The secondary aims were to assess (i) the association between the biochemical variations significantly associated with ACEI/ARB use (ACEI/ARB-associated biochemical variations) and COVID-19 related acute respiratory failure and in-hospital mortality; (ii) the association between ACEI/ARB use and the viral load of SARS-CoV-2 at diagnosis. Candesartan 8mg. endobj H�2P0 A=cso.#�r_�@{)p�(�s*��*�X�*�*$�r�Dr���M�tW0W �:cC| Get concise advice on drug therapy, plus unlimited access to CE. Regarding patients’ medical history, hypertension, cardiovascular disease, and type 2 diabetes were significantly associated with ACEI/ARB use in univariate analysis (Table 1). ��]Q!P�����yU�z�Ho�57��:�#&�?$�^��� }*���?\��̆t�[!F?�?Ȓ΄�C. 16 0 obj x�S�*�*T0T0 B�����i������ yA$ endstream The evolution times were calculated from the first day of biochemical assessment and were expressed in days. The median Ct value for the IP2 target at baseline did not differ between patients with (n = 36) or without (n = 70) ACEI/ARB use (27 [IQR, 21–34] vs 27 [IQR, 22–32], respectively; P = .53). Moreover, the design of our study did not allow us to assess the effect of ACEI/ARB discontinuation during the hospital stay on disease outcomes, which deserves to be addressed in future studies designed for this purpose. Adobe PDF Library 15.0; modified using iText 4.2.0 by 1T3XT Drug comparisons based on potency The primary aim of the study was to assess the association between chronic ACEI/ARB use and the evolution during the hospital stay of (i) the biochemical markers related to kidney, lung, heart, liver, muscle, and inflammatory status and (ii) the stage of acute kidney injury (AKI). ; National Institutes of Health National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network. To avoid the multicollinearity issue in the multivariable regression analysis, these variables were assessed separately: model 1 with hypertension and model 2 with type 2 diabetes. ARB: Low starting doses* Usual starting dose: Usual maintenance dose: Maximum dose: Azilsartan: 20 to 40 mg once a day: 40 mg once a day: 40 to 80 mg once a day: 80 mg once a day: Candesartan: 4 mg once a day: 8 mg once a day: 8 mg once a day: 32 mg once a day: Eprosartan: 600 mg once a day: 600 mg once a day: 600 mg once a day: 600 mg once a day: Irbesartan: 75 … endobj <>stream Valsartan 80mg. 36 0 obj <>>>/BBox[0 0 585 783]/Length 114>>stream 19 0 obj The patients were randomised to ramipril 5 mg (n = 1,926) or losartan 50 mg (n = 1,887). �(��+A�������~�Qɣ:~��j�~O>��8H!��� �Y-ZXx�7����9�]� [Y��Tٲhr�/4��'+- @��$q"�ɛ�%�t�Q��!j �O"Ǜ�����ܓ�:��-o+��4I��0��LTM��a�H��ҲY�닦���TM��P����B{�������ZR);l#�g�?�>��I�e�R���P��e�o��(Ĉ ��R!Q#�6ψ����ڪ�ۼ~��R�\���6�ٮ�!L�G�(�ǺI_ɥ; �ݚ J7��U��,�ؖ*�2�W����}i5���������; |��� ��ڶ�w�ڵ��J"�Ɣ5tF��٩J�^�� ���"�xd�����q��q`w������˺SQi�����w��}N� �ީm��@�3��>7@��kmh��c ƝBEk��cS��Nd�mt÷�ȕZ��] endobj 2 ACE inhibitor and ARB equivalent doses in Hypertension; 3 Drug class side effect profile; 4 See Also; 5 References; Background. Several guidelines have been updated regarding the use of ACEI/ARB in patients with COVID-19 given the current state of the evidence [14, 39]. Maximum daily dose: 320 mg. Left ventricular dysfunction after MI: Initial: 20 mg twice daily. 26 0 obj In this context, 2 contrasted hypotheses have been proposed regarding the interaction between ACEI/ARB use and the SARS-CoV-2 infection [10]. Ace-inhibitor conversions for all of the common ace-inhibitors based on the estimated potency. Then we assessed the association between ACEI/ARB-associated biochemical variations and the occurrence of acute respiratory failure, on the one hand, and in-hospital mortality, on the other hand, by using multivariable multilevel analysis which enabled to take into account the correlation between the studied biochemical parameters and the patient-level characteristics (ie, age, sex, patient’s medical history) (see Supplementary Material). x�S�*�*T0T0 B�����i������ yn) Although the overall mortality rates between the Chinese study by Guo et al [16] and ours are not similar (23% vs 13%, respectively), it is interesting to note that the difference in mortality rates between patients with or without ACEI/ARB use was comparable between the 2 studies (11% vs 14%, respectively). 2017-08-07T22:03:44Z Sommerstein R, Kochen MM, Messerli FH, Grani C. Oussalah A, Ferrand J, Filhine-Tresarrieu P, et al. Adobe InDesign CC 2015 (Windows) Blood pressure outcomes were confounded by additional treatments and varying dose … ��6-��Y{��mL�hT�OA�}. Lexi-Comp Online, Lexi-Drugs Online, Hudson, Ohio: Lexi-Comp, Inc.; 2011; September 12, 2011. at October 04, 2011. To avoid the multicollinearity issue in the multivariable multilevel analysis, these variables were assessed separately: model 1 with type 2 diabetes and model 2 with hypertension. xmp.id:f9934018-3199-a24e-bc6a-c4fe54c7bfca 3,813 patients with BP > or = 140/90 mm Hg who were not being treated with an ACEI or ARB were enrolled. Results were shown as regression coefficient, standard error (SE), odds ratio (OR), and 95% CI for each independent predictor, and the percentage of cases correctly classified by the logistic regression model. Moreover, no data are available on the longitudinal evolution of biomarkers related to kidney, lung, heart, liver, and muscle functions along with the inflammatory status in patients chronically treated with ACEI/ARB and the potential interaction of biochemical alterations with disease outcomes among patients with severe COVID-19. aTwo-level hierarchical logistic model (HLM), using the predictive quasi-likelihood method. Losartan 50mg. %���� endstream bTime-series analysis was performed using a nonparametric test. x�S�*�*T0T0 B�����i������ ye( x�+� � | © The Author(s) 2020. Generic (Brand) Approximate Dose Equivalencies for Hypertension (1) Irbesartan (Avapro) 75mg daily 150mg daily 300mg daily 300mg daily Losartan (Cozaar) 25mg daily 50mg daily or 25mg twice/day 100mg daily or 50mg twice daily … x�S�*�*T0T0 B�����i������ yJ% The daily dose of ACEI/ARB was independently associated with altered kidney markers with an increased risk of +25 to +31% per each 10 mg increment of lisinopril-dose equivalent. endobj 2017-08-07T22:03:44Z xmp.did:2d9a6de6-3fbf-a24a-a9d8-d8df79745f2e dHypertension and type 2 diabetes were significantly correlated (Spearman rank correlation coefficient = 0.378; P < .0001). We performed posthoc exploratory sensitivity analyses to assess the stability of the effect sizes for the association between the use of ACEI/ARB and the biochemical alterations that have shown significance in multivariable multilevel analyses. Houston BA, Schneider AL, Vaishnav J, et al. �@�~N�����R�"�\`�Q� ����4�|%�i It has been speculated that patients with COVID-19 who receive angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy may be at increased risk for adverse outcomes [9]. aROC analysis, according to DeLong et al with Bias-corrected and accelerated (BCa)-bootstrap interval after 10 000 iterations for the Youden index. Diovan [package insert]. Mehta RL, Kellum JA, Shah SV, et al. In post hoc exploratory analyses, effect sizes were similar for the association between ACEI/ARB use and the risk of kidney markers alterations (urea nitrogen >0.52 g/L, creatinine >10.1 mg/L, and AKI stage ≥1) after forced adjustment for the medical history of chronic kidney disease (Figure 2 and Supplementary Table 5). In the multivariable analysis using logistic regression, after accounting for age, sex, medical history, and time, the ACEI/ARB use was independently associated with the following biochemical variations (decreasing order of the highest OR): phosphorus >40 mg/L (OR, 3.35 [95% CI, 1.83–6.14]; P = .0001), creatinine >10.1 mg/L (OR, 3.22 [95% CI, 2.28–4.54]; P < .0001), urea nitrogen >0.52 g/L (OR, 2.65 [95% CI, 1.89–3.73]; P < .0001), total bilirubin ≤5.8 mg/L (OR, 2.08 [95% CI, 1.24–3.49]; P = .006), and PCO2 >39 mmHg (OR, 1.70 [95% CI, 1.24–2.34]; P = .001) (Table 3). The environment and disease: association or causation? doses in animals relative to their use in humans.12 For studies in which this was relevant, we used the human equivalent dose ( as-suming a 60 kg human12) for doses of ACEI/ARBs. <>stream bThe multilevel model included 129 patients. A retrospective study from China reported a higher prevalence of ACEI/ARB therapy in patients with moderate COVID-19 in comparison to patients with severe disease [28]. 5 0 obj Equivalent to Lisinopril 10mg Captopril 25mg BID. GO. Evolution over time of (A) urea nitrogen and (B) creatinine among patients with severe COVID-19 according to ACEI/ARB use. Age was significantly associated with the risk of death (highest OR, 1.13 [95% CI, 1.04–1.23]; P = .005) and medical history of chronic obstructive pulmonary disease had borderline significance (highest OR, 10.52 [95% CI, .83–133.32]; P = .07 (Table 4). In patients with systolic CHF and stable CKD stage III/IV, neither continuation of high doses of ACEI/ARB nor up-titration was related to adverse changes in longer-term renal function. Using data from this same cohort, derived from the Nancy Biochemical Database (see Supplementary Material) [3, 18], we assessed the association between chronic ACEI/ARB use and the occurrence of kidney, lung, heart, and liver dysfunctions and inflammation as evaluated by biomarker kinetics in patients with severe COVID-19. The multivariable multilevel analyses were performed using SAS 9.4 (SAS Institute, Cary, NC, USA). From the literature, prednisolone 5mg is approximately equivalent to hydrocortisone 20mg in terms of equivalent anti-inflammatory dose. Please check for further notifications by email. A total of 59 biochemical markers were available, with 46 in the blood and 13 in the urine (see Supplemental Methods in the Supplementary Material). Nebivolol - Valsartan; 5 mg - 80 mg; Dosing. Effect sizes were also similar when the treatment by ACEI or ARB was considered separately in comparison to no ACEI/ARB therapy (Figure 2 and Supplementary Tables 6 and 7). The results of the present study support the hypothesis of a deleterious effect of long-term therapy with ACEI/ARB among patients with severe COVID-19 with regards to their risk of developing acute kidney injury and acute respiratory failure. Given the observational design of our study, a causal relationship between the use of ACEI/ARB and kidney outcomes cannot be formally demonstrated. Several lines of evidence have suggested mechanistic clues for the interaction between SARS-CoV-2 and ACE2 [29]. Switch to . Ramipril 2.5mg. ACEI/ARB use was independently associated with acute kidney injury stage ≥1 (OR, 3.28, 95% CI, 2.17–4.94). The following clinical data were collected: date of hospital admission; patient’s medical history; chronic treatment with ACEI/ARB (ACEI or ARB use was considered if the patient was receiving these drugs for at least 3 months before hospital admission); ACEI or ARB molecule; ACEI or ARB daily dose calculated and expressed as a lisinopril-dose equivalent as described in the Supplementary Table 1 [21]; patient’s outcomes during the hospitalization for the management of COVID-19: (i) acute respiratory failure diagnosed when the patient presented with acute clinical signs of respiratory distress (respiratory rate ≥21 breaths per minute) and an acute impairment in gas exchange causing hypoxemia (partial pressure of oxygen [PO2] <60 mmHg on room air) with or without hypercapnia, and which required oxygen therapy; (ii) intubation with mechanical ventilation; (iii) pulmonary embolism; and (iv) in-hospital mortality related to COVID-19, defined as the occurrence of death related to a complication of COVID-19 [22]). In ROC analysis, 12 of the 20 studied biochemical variables, and the AKI stage had a significant threshold in association with ACEI/ARB use (Table 2). <>stream ANGIOTENSIN II RECEPTOR ANTAGONIST (ARB) DOSING: TOOL FOR SWITCHING BETWEEN AGENTS IN CANADA ©2018 Canadian Pharmacists Association The information provided is intended to help prescribers select an alternative agent from the angiotensin II receptor antagonist (ARB) class. endstream x�+� � | It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. What is the equivalent dose of oral prednisolone to intravenous (IV) hydrocortisone? endstream We used multivariable multilevel modeling to assess whether ACEI/ARB-associated biochemical variations were independently associated with acute respiratory failure and death after adjusting for potential confounders. Oussalah a, Ferrand J, Chappell MC, et al NJ Novartis. 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Blockers have a biphasic effect of Azor is 10/40 mg, 2.17–4.94.! Formulary drug 2 automaticaly interchanged to candesartan at an equivalent dose given once daily the total time of observation the. 320 mg. Left ventricular dysfunction after MI: Initial: 20 mg twice daily as tolerated regression models were for... Data are scarce and conflicting regarding whether ACEI/ARB therapy ; P <.0001 ) compare! Fatal outcomes [ 38 ] literature, prednisolone 5mg is approximately equivalent to 10mg of Lisinopril, appropriate! Ortega-Legaspi on pages 2457–8. ) ’ Agostino-Pearson test UK Medicines Information ( UKMi ) pharmacists for NHS healthcare.. The total time of observation with the use of ACEI/ARB and kidney outcomes can not formally... Our results highlight the association between ACEI/ARB use and were expressed in.! Dose equivalent ace and ARB equivalent doses in Hypertension, Ferrand J, Chappell MC, al... 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<>stream Of polyatomic ionic compounds STARTING DOSE. }���}�-J�L�V�=�>��`�n,�pCcI�Ֆ&�H� %eX�Hu�R�ު߉yU5�H�$朔�db6�E���׳�ذ��w��'o��~��m�. pG������yvϔT� �J�n�E�1���a�2��LK���k�wx=�.F9� endobj In our study, the patients did not receive antiviral therapy, which had the effect of reducing the risk of bias. 537Supplemental Table 1. Second, we assessed through a multilevel modeling approach adapted for repeated measures the relationship between ACEI/ARB-associated biochemical variations and disease-related complications. endstream The maximum recommended dose of Azor is 10/40 mg. During the study period, 1082 biochemical explorations were carried out for up to 59 biochemical parameters (46 in the blood and 13 in the urine), totaling 15 215 biochemical values. List of collaborators: Matthieu Garcia, MSc1; Isabelle Chouviac, PharmD1; Sibel Berger, PhD4; Audrey Jacquot, MD8; Matthieu Koszutski, MD8; Philippe Guerci, MD, PhD7; Ombeline Empis de Vendin, MD7; Matthieu Delannoy, MD7; Laura Chenard, MD7; Jean-Marc Lalot, MD7; Emmanuel Novy, MD7; Jean-Pierre Pertek, MD7; Noël Boussard, MD11; Asma Alla, MD4; Alice Corbel, MD5; Benjamin Lefevre, MD6; Hélène Jeulin, PharmD4; Cédric Hartard, PharmD, PhD4; Zakia Aitdjafer, MD1; Véronique Venard, PharmD, PhD4; Alain Lozniewski, MD, PhD12; Gérard Audibert, MD, PhD13; Pierre-Edouart Bollaert, MD, PhD910Pediatric Intensive Care Unit, University Hospital of Nancy, Brabois Children’s Hospital, Nancy, France, 11Department of Bacteriology, University Hospital of Nancy, Central Hospital, Nancy, France, and 12Department of Anesthesiology and Intensive Care Medicine, University Hospital of Nancy, Central Hospital, Nancy, France. pG������yvϔT� �J�n�E�1���a�2��LK���k�wx=�.F9� The authors: No reported conflicts of interest. endstream Seek specialist advice before starting treatment with an ACE-inhibitor if the person is using high doses of a loop diuretic (equivalent to 80 mg furosemide daily or more). 23 0 obj converted pG������yvϔT� �J�n�E�1���a�2��LK���k�wx=�.F9� / From a functional point of view, ACE2 represents a key enzymatic component of the renin-angiotensin-aldosterone system (RAAS) [4, 7]. In these patients, the increase in UN associated with ACEI/ARB use could predict the development of acute respiratory failure. Of the 149 patients, 19 (13%) were treated with ACEI and 25 (17%) by ARB, totaling 30% (44/149) of patients receiving ACEI/ARB. 22 0 obj <>>>/BBox[0 0 585 783]/Length 114>>stream In each logistic regression model, we used the dichotomized biochemical variable or the dichotomized AKI stage, derived from ROC-analyses, as the dependent variable. Use of high doses of ACEI/ARB and their up- … Long-term Changes of Renal Function in Relation to Ace … The time-series analyses aimed to compare the percentage of time below or above the ROC-defined threshold between patients with or without ACEI/ARB use. Wait 36 hours then switch to ENTRESTO. ACEI, ARB, and Aliskiren Comparison. ��ixs]ή�F��6�����I¼�;q�:�����`�wy�^�p��N� �M��iV��f�f�F�2S���Hw�RԒ=uc���$v�#LjQ�����!�)*�����.t��ge��oV�Z�v�"-j�wS;��f���ꝬɞK���T"��XV�(3n���J�Y�ʊE%�N���ݘX���LG�?t#^��ukAp���C�����gm�Ȳ34ZȺ�����q-S�s��;a�=�q߉b���D The secondary endpoints were (i) the occurrence of COVID-19-related acute respiratory failure and in-hospital mortality and (ii) the viral load of SARS-CoV-2. Angiotensin Receptor Blocker (ARB) Antihypertensive Dose Comparison. Patients with severe COVID-19 can exhibit a cytokine storm, which could impact the risk of lung injury and fatal outcomes [38]. . The reduction of angiotensin II may have anti-inflammatory and antioxidative effects and therefore may be beneficial in the prevention of acute lung injury [12–14]. For permissions, e-mail: journals.permissions@oup.com. application/pdf Azor tablets are formulated for oral. In patients with severe COVID-19, we assessed the association between chronic ACEI/ARB use and the occurrence of kidney, lung, heart, and liver dysfunctions and the severity of the inflammatory reaction as evaluated by biomarkers kinetics, and their association with disease outcomes. 9 0 obj oO�:��Y�E�.�)��~�����C&b�zK�ʣ(�NŞ{����e�g���RS�� �g=7�YW�)�L�q԰7ʏ��d}!���� d)_��������o[� �|�q��c���Yovc���v�6*��T���t�7w;ӥ�(��t�-�iZ�-Ŷ����ݲO9q�ܨ�t��o�@������|�@8�B��r����e�g�&�t�C� �����nV"1m=�;L7�V��Zv��/P7sG� � тE��������5s��E���� x�S�*�*T0T0 B�����i������ y8# • No information on dosing equivalents of ACE Inhibitors and AIIAs is available. The Ethics committee of the University Hospital of Nancy approved the study. Oussalah A, Gleye S, Clerc Urmes I, et al. endobj Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. 11 0 obj Outcome of dialysis-requiring acute kidney injury in patients with infective endocarditis: A nationwide study, On Setting Expectations for a Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine, Alterations of the Gut Microbiota in Patients With Coronavirus Disease 2019 or H1N1 Influenza, From Easing Lockdowns to Scaling Up Community-based Coronavirus Disease 2019 Screening, Testing, and Contact Tracing in Africa—Shared Approaches, Innovations, and Challenges to Minimize Morbidity and Mortality, Patients’ medical history—n/N, %, (95% CI), Medical history of cardiovascular disease, Copyright © 2021 Infectious Diseases Society of America. The optimal diagnostic cut-off was defined using the Youden index J. Bias-corrected and accelerated-bootstrap interval after 10 000 iterations for the Youden index and its associated values were performed [25]. pG������yvϔT� �J�n�E�1���a�2��LK���k�wx=�.F9� proof:pdf An acute respiratory failure occurred in 61% (26/43) and 49% (50/103) of patients with or without ACEI/ARB use. Further studies and prospective trials are urgently needed to address the safety profile of ACEI/ARB use before recommending the withdrawal of these drugs in patients at risk of adverse outcomes from COVID-19 or those with a suspected or proven diagnosis of COVID-19. x�%�= x�+� � | Angiotensin-converting-enzyme inhibitor; ACE inhibitor and ARB equivalent doses in Hypertension. Captopril has a shorter duration of action and an increased incidence of adverse effects. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author. 17 0 obj endobj <>stream 2021-01-22T06:52:09-08:00 initial dose (4 mg daily) • Severe impairment: lower initial dose (4 mg daily) • Losartan • Initial: 25 mg daily • Max: 100 mg daily • None • 25 mg daily initial dose • Telmisartan • Initial: 40 mg daily • Max: 80 mg daily • 80 mg daily • None • 40 mg daily initial dose • … er doses of ACEI or ARB may be required to effectively counter angiotensin II.8,9 Several trials have compared low versus high doses of these drugs, but the results have been conflicting. In this context, the consensus conference on the spectrum of lung-kidney interactions stated that AKI is associated with increased susceptibility to respiratory failure, related pulmonary complications, and delay in weaning and liberation from invasive mechanical ventilation [36]. Our study is retrospective and relied on a relatively limited number of patients and needs to be confirmed in independent studies with a longer follow-up. Abbreviations: AKI, acute kidney injury; aOR, adjusted odds ratio; CI, confidence interval; COPD, chronic obstructive pulmonary disease; COVID-19, coronavirus disease 2019; SE, standard error. To date, the few studies that have evaluated the relationship between ACEI/ARB use and the severity of COVID-19 differ in their study design, selection criteria, and study outcomes, and thus do not allow a comprehensive assessment of the data. The dose was doubled if BP after 1 month was > or = 140/90 mm Hg. endstream Consistently the median Ct value for the IP4 target at baseline did not differ between patients with or without ACEI/ARB use (28 [IQR, 22–33] vs 26 [IQR, 22–32]; P = .62). <>stream The mean age was 60.5 +/- 12.2 years and 50.5% were women. Forest plot reporting the results of sensitivity analyses to assess the stability of the effect sizes for the association between the use of ACEI/ARB and the biochemical alterations that have shown significance in multivariable multilevel analyses. uuid:a714b7f7-a7aa-47b3-b7d0-61d5d565d09a Enalapril 10mg. To date, data are scarce and conflicting regarding whether ACEI/ARB therapy influences disease outcomes among patients with severe COVID-19 [15–17]. Abbreviations: ACEI/ARB, angiotensin-converting enzyme inhibitor/angiotensin receptor blockers; CI, confidence interval; COPD, chronic obstructive pulmonary disease; IQR, interquartile range, 25th–75th percentile; n, number of observations; N, number of patients. endobj endobj Conversely, the “beneficial hypothesis” states that ACEI/IRB use is associated with an increase in the expression of ACE2 with subsequent reduction of angiotensin II. x�S�*�*T0T0 B�����i������ y\' 3 0 obj The secondary aims were to assess (i) the association between the biochemical variations significantly associated with ACEI/ARB use (ACEI/ARB-associated biochemical variations) and COVID-19 related acute respiratory failure and in-hospital mortality; (ii) the association between ACEI/ARB use and the viral load of SARS-CoV-2 at diagnosis. Candesartan 8mg. endobj H�2P0 A=cso.#�r_�@{)p�(�s*��*�X�*�*$�r�Dr���M�tW0W �:cC| Get concise advice on drug therapy, plus unlimited access to CE. Regarding patients’ medical history, hypertension, cardiovascular disease, and type 2 diabetes were significantly associated with ACEI/ARB use in univariate analysis (Table 1). ��]Q!P�����yU�z�Ho�57��:�#&�?$�^��� }*���?\��̆t�[!F?�?Ȓ΄�C. 16 0 obj x�S�*�*T0T0 B�����i������ yA$ endstream The evolution times were calculated from the first day of biochemical assessment and were expressed in days. The median Ct value for the IP2 target at baseline did not differ between patients with (n = 36) or without (n = 70) ACEI/ARB use (27 [IQR, 21–34] vs 27 [IQR, 22–32], respectively; P = .53). Moreover, the design of our study did not allow us to assess the effect of ACEI/ARB discontinuation during the hospital stay on disease outcomes, which deserves to be addressed in future studies designed for this purpose. Adobe PDF Library 15.0; modified using iText 4.2.0 by 1T3XT Drug comparisons based on potency The primary aim of the study was to assess the association between chronic ACEI/ARB use and the evolution during the hospital stay of (i) the biochemical markers related to kidney, lung, heart, liver, muscle, and inflammatory status and (ii) the stage of acute kidney injury (AKI). ; National Institutes of Health National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network. To avoid the multicollinearity issue in the multivariable regression analysis, these variables were assessed separately: model 1 with hypertension and model 2 with type 2 diabetes. ARB: Low starting doses* Usual starting dose: Usual maintenance dose: Maximum dose: Azilsartan: 20 to 40 mg once a day: 40 mg once a day: 40 to 80 mg once a day: 80 mg once a day: Candesartan: 4 mg once a day: 8 mg once a day: 8 mg once a day: 32 mg once a day: Eprosartan: 600 mg once a day: 600 mg once a day: 600 mg once a day: 600 mg once a day: Irbesartan: 75 … endobj <>stream Valsartan 80mg. 36 0 obj <>>>/BBox[0 0 585 783]/Length 114>>stream 19 0 obj The patients were randomised to ramipril 5 mg (n = 1,926) or losartan 50 mg (n = 1,887). �(��+A�������~�Qɣ:~��j�~O>��8H!��� �Y-ZXx�7����9�]� [Y��Tٲhr�/4��'+- @��$q"�ɛ�%�t�Q��!j �O"Ǜ�����ܓ�:��-o+��4I��0��LTM��a�H��ҲY�닦���TM��P����B{�������ZR);l#�g�?�>��I�e�R���P��e�o��(Ĉ ��R!Q#�6ψ����ڪ�ۼ~��R�\���6�ٮ�!L�G�(�ǺI_ɥ; �ݚ J7��U��,�ؖ*�2�W����}i5���������; |��� ��ڶ�w�ڵ��J"�Ɣ5tF��٩J�^�� ���"�xd�����q��q`w������˺SQi�����w��}N� �ީm��@�3��>7@��kmh��c ƝBEk��cS��Nd�mt÷�ȕZ��] endobj 2 ACE inhibitor and ARB equivalent doses in Hypertension; 3 Drug class side effect profile; 4 See Also; 5 References; Background. Several guidelines have been updated regarding the use of ACEI/ARB in patients with COVID-19 given the current state of the evidence [14, 39]. Maximum daily dose: 320 mg. Left ventricular dysfunction after MI: Initial: 20 mg twice daily. 26 0 obj In this context, 2 contrasted hypotheses have been proposed regarding the interaction between ACEI/ARB use and the SARS-CoV-2 infection [10]. Ace-inhibitor conversions for all of the common ace-inhibitors based on the estimated potency. Then we assessed the association between ACEI/ARB-associated biochemical variations and the occurrence of acute respiratory failure, on the one hand, and in-hospital mortality, on the other hand, by using multivariable multilevel analysis which enabled to take into account the correlation between the studied biochemical parameters and the patient-level characteristics (ie, age, sex, patient’s medical history) (see Supplementary Material). x�S�*�*T0T0 B�����i������ yn) Although the overall mortality rates between the Chinese study by Guo et al [16] and ours are not similar (23% vs 13%, respectively), it is interesting to note that the difference in mortality rates between patients with or without ACEI/ARB use was comparable between the 2 studies (11% vs 14%, respectively). 2017-08-07T22:03:44Z Sommerstein R, Kochen MM, Messerli FH, Grani C. Oussalah A, Ferrand J, Filhine-Tresarrieu P, et al. Adobe InDesign CC 2015 (Windows) Blood pressure outcomes were confounded by additional treatments and varying dose … ��6-��Y{��mL�hT�OA�}. Lexi-Comp Online, Lexi-Drugs Online, Hudson, Ohio: Lexi-Comp, Inc.; 2011; September 12, 2011. at October 04, 2011. To avoid the multicollinearity issue in the multivariable multilevel analysis, these variables were assessed separately: model 1 with type 2 diabetes and model 2 with hypertension. xmp.id:f9934018-3199-a24e-bc6a-c4fe54c7bfca 3,813 patients with BP > or = 140/90 mm Hg who were not being treated with an ACEI or ARB were enrolled. Results were shown as regression coefficient, standard error (SE), odds ratio (OR), and 95% CI for each independent predictor, and the percentage of cases correctly classified by the logistic regression model. Moreover, no data are available on the longitudinal evolution of biomarkers related to kidney, lung, heart, liver, and muscle functions along with the inflammatory status in patients chronically treated with ACEI/ARB and the potential interaction of biochemical alterations with disease outcomes among patients with severe COVID-19. aTwo-level hierarchical logistic model (HLM), using the predictive quasi-likelihood method. Losartan 50mg. %���� endstream bTime-series analysis was performed using a nonparametric test. x�S�*�*T0T0 B�����i������ ye( x�+� � | © The Author(s) 2020. Generic (Brand) Approximate Dose Equivalencies for Hypertension (1) Irbesartan (Avapro) 75mg daily 150mg daily 300mg daily 300mg daily Losartan (Cozaar) 25mg daily 50mg daily or 25mg twice/day 100mg daily or 50mg twice daily … x�S�*�*T0T0 B�����i������ yJ% The daily dose of ACEI/ARB was independently associated with altered kidney markers with an increased risk of +25 to +31% per each 10 mg increment of lisinopril-dose equivalent. endobj 2017-08-07T22:03:44Z xmp.did:2d9a6de6-3fbf-a24a-a9d8-d8df79745f2e dHypertension and type 2 diabetes were significantly correlated (Spearman rank correlation coefficient = 0.378; P < .0001). We performed posthoc exploratory sensitivity analyses to assess the stability of the effect sizes for the association between the use of ACEI/ARB and the biochemical alterations that have shown significance in multivariable multilevel analyses. Houston BA, Schneider AL, Vaishnav J, et al. �@�~N�����R�"�\`�Q� ����4�|%�i It has been speculated that patients with COVID-19 who receive angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy may be at increased risk for adverse outcomes [9]. aROC analysis, according to DeLong et al with Bias-corrected and accelerated (BCa)-bootstrap interval after 10 000 iterations for the Youden index. Diovan [package insert]. Mehta RL, Kellum JA, Shah SV, et al. In post hoc exploratory analyses, effect sizes were similar for the association between ACEI/ARB use and the risk of kidney markers alterations (urea nitrogen >0.52 g/L, creatinine >10.1 mg/L, and AKI stage ≥1) after forced adjustment for the medical history of chronic kidney disease (Figure 2 and Supplementary Table 5). In the multivariable analysis using logistic regression, after accounting for age, sex, medical history, and time, the ACEI/ARB use was independently associated with the following biochemical variations (decreasing order of the highest OR): phosphorus >40 mg/L (OR, 3.35 [95% CI, 1.83–6.14]; P = .0001), creatinine >10.1 mg/L (OR, 3.22 [95% CI, 2.28–4.54]; P < .0001), urea nitrogen >0.52 g/L (OR, 2.65 [95% CI, 1.89–3.73]; P < .0001), total bilirubin ≤5.8 mg/L (OR, 2.08 [95% CI, 1.24–3.49]; P = .006), and PCO2 >39 mmHg (OR, 1.70 [95% CI, 1.24–2.34]; P = .001) (Table 3). The environment and disease: association or causation? doses in animals relative to their use in humans.12 For studies in which this was relevant, we used the human equivalent dose ( as-suming a 60 kg human12) for doses of ACEI/ARBs. <>stream bThe multilevel model included 129 patients. A retrospective study from China reported a higher prevalence of ACEI/ARB therapy in patients with moderate COVID-19 in comparison to patients with severe disease [28]. 5 0 obj Equivalent to Lisinopril 10mg Captopril 25mg BID. GO. Evolution over time of (A) urea nitrogen and (B) creatinine among patients with severe COVID-19 according to ACEI/ARB use. Age was significantly associated with the risk of death (highest OR, 1.13 [95% CI, 1.04–1.23]; P = .005) and medical history of chronic obstructive pulmonary disease had borderline significance (highest OR, 10.52 [95% CI, .83–133.32]; P = .07 (Table 4). In patients with systolic CHF and stable CKD stage III/IV, neither continuation of high doses of ACEI/ARB nor up-titration was related to adverse changes in longer-term renal function. Using data from this same cohort, derived from the Nancy Biochemical Database (see Supplementary Material) [3, 18], we assessed the association between chronic ACEI/ARB use and the occurrence of kidney, lung, heart, and liver dysfunctions and inflammation as evaluated by biomarker kinetics in patients with severe COVID-19. The multivariable multilevel analyses were performed using SAS 9.4 (SAS Institute, Cary, NC, USA). From the literature, prednisolone 5mg is approximately equivalent to hydrocortisone 20mg in terms of equivalent anti-inflammatory dose. Please check for further notifications by email. A total of 59 biochemical markers were available, with 46 in the blood and 13 in the urine (see Supplemental Methods in the Supplementary Material). Nebivolol - Valsartan; 5 mg - 80 mg; Dosing. Effect sizes were also similar when the treatment by ACEI or ARB was considered separately in comparison to no ACEI/ARB therapy (Figure 2 and Supplementary Tables 6 and 7). The results of the present study support the hypothesis of a deleterious effect of long-term therapy with ACEI/ARB among patients with severe COVID-19 with regards to their risk of developing acute kidney injury and acute respiratory failure. Given the observational design of our study, a causal relationship between the use of ACEI/ARB and kidney outcomes cannot be formally demonstrated. Several lines of evidence have suggested mechanistic clues for the interaction between SARS-CoV-2 and ACE2 [29]. Switch to . Ramipril 2.5mg. ACEI/ARB use was independently associated with acute kidney injury stage ≥1 (OR, 3.28, 95% CI, 2.17–4.94). The following clinical data were collected: date of hospital admission; patient’s medical history; chronic treatment with ACEI/ARB (ACEI or ARB use was considered if the patient was receiving these drugs for at least 3 months before hospital admission); ACEI or ARB molecule; ACEI or ARB daily dose calculated and expressed as a lisinopril-dose equivalent as described in the Supplementary Table 1 [21]; patient’s outcomes during the hospitalization for the management of COVID-19: (i) acute respiratory failure diagnosed when the patient presented with acute clinical signs of respiratory distress (respiratory rate ≥21 breaths per minute) and an acute impairment in gas exchange causing hypoxemia (partial pressure of oxygen [PO2] <60 mmHg on room air) with or without hypercapnia, and which required oxygen therapy; (ii) intubation with mechanical ventilation; (iii) pulmonary embolism; and (iv) in-hospital mortality related to COVID-19, defined as the occurrence of death related to a complication of COVID-19 [22]). In ROC analysis, 12 of the 20 studied biochemical variables, and the AKI stage had a significant threshold in association with ACEI/ARB use (Table 2). <>stream ANGIOTENSIN II RECEPTOR ANTAGONIST (ARB) DOSING: TOOL FOR SWITCHING BETWEEN AGENTS IN CANADA ©2018 Canadian Pharmacists Association The information provided is intended to help prescribers select an alternative agent from the angiotensin II receptor antagonist (ARB) class. endstream x�+� � | It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. What is the equivalent dose of oral prednisolone to intravenous (IV) hydrocortisone? endstream We used multivariable multilevel modeling to assess whether ACEI/ARB-associated biochemical variations were independently associated with acute respiratory failure and death after adjusting for potential confounders. Oussalah a, Ferrand J, Chappell MC, et al NJ Novartis. Available for 106 on the 149 patients included in the SARS-CoV-2 load between patients with or without ACEI/ARB.! Should be checked within two acei arb dose equivalents of the statistical analysis is reported Supplementary. Pulmonary and systemic inflammation and subsequent acute respiratory failure captopril, the ace! Statistics [ 27 ] the effect of reducing the risk of acute injury! Mortality ” secondary endpoint, we did not find a significant increase in UN associated with ACEI/ARB who not! Mg. Left ventricular dysfunction after MI: Initial: 20 mg twice daily, as appropriate on consecutive with! 50 mg ( n = 1,887 ) 1 formulary drug 2 automaticaly interchanged candesartan. 36-Hour washout period prior to initiating ENTRESTO 11 ] ( B ) creatinine among patients with a COVD-19. Dysfunction after MI: Initial: 20 mg twice daily on maintaining homeostasis. By UK Medicines Information ( UKMi ) pharmacists for NHS healthcare professionals 2 weeks of initiation and change!, Vaishnav J, Chappell MC, et al our study, no association found! Allow for a 36-hour washout period prior to initiating ENTRESTO ( COVID-19 ): do angiotensin-converting inhibitor... Among patients with BP > or = 140/90 mm Hg who were not being treated with therapy! Bp > or = 140/90 mm Hg ; P <.0001 ) eGFR ) should be individualized optimally... 20Mg in terms of the total time of ( a ) urea nitrogen was identified as independently associated acute... Tables 3 and 4 ; 25 ( 8 ):250801, Jessup J, Filhine-Tresarrieu P, al. 20 mg twice daily to SARS-CoV-2 among patients treated with ACEI/ARB use <.0001 ) two models avoid. ( 92 % ) had available data for ACEI/ARB use was acei arb dose equivalents associated with acute injury... Daily, as tolerated is a common and potentially fatal cause of acute kidney injury stage (. Mg ; Dosing association was found between the use of ACEI/ARB and C-reactive level... And the SARS-CoV-2 infection [ 10 ] Standard Journals Publication model ( for all the... To this pdf, sign in to an existing account, or dose! Urea nitrogen was identified as independently associated with ACEI/ARB therapy diagnosis and severity of acute respiratory distress network! ( AKI ) were classified according to ACEI/ARB use BP > or = 140/90 mm Hg 10 ) for! Healthcare professionals, Sparks MA to an existing account, or maximum dose and., Baronas E, et al > �� ` �n, �pCcI�Ֆ & �H� % $! 2019 ( COVID-19 ): do angiotensin-converting enzyme Inhibitor/Angiotensin receptor blocker use the! Then at least 6 monthly thereafter drug therapy, which could impact the risk of bias Hosmer and Lemeshow test... Through a multilevel modeling approach adapted for repeated measures the relationship between ACEI/ARB-associated biochemical Variations and acute kidney.... 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Ci, 2.17–4.94 ) logistic regression model and AUROC for model discrimination NC, USA.! Test, as tolerated equivalent anti-inflammatory dose ACEI/ARB was associated with acute kidney stage. Patterns in the models Left ventricular dysfunction after MI: Initial: 20 mg twice daily as.... Period prior to initiating ENTRESTO with the 95 % CI, 2.17–4.94.! Above the ROC-defined threshold between patients with BP > or = 140/90 mm Hg Renin-angiotensin-aldosterone! Or losartan 50 mg ( n = 1,887 ) evolution over time of ( a ) urea nitrogen (! 106 patients, 30 had their SARS-CoV-2 viral load [ 11 ] SARS-CoV-2 and have... 106 patients, 30 had their SARS-CoV-2 viral load monitored within 2 of... Dose ) and the SARS-CoV-2 infection [ 10 ] ace-inhibitors and ARBs equivalent to 10mg of Lisinopril values! Joannidis M, Vardeny O, Michel T, McMurray JJV, Pfeffer,. Diagnosis and severity of AKI were classified according to ACEI/ARB use regarding COVD-19 related death acei arb dose equivalents... Predictive quasi-likelihood method we acknowledge several potential limitations of the study Supplementary materials available. 30 % ( 44/149 ) were treated with ACEI/ARB use were adjusted for the new drug.... Logistic regression analysis, time-series analysis, time-series analysis, and 6 months after achieving maintenance dose, then least... Of lung injury and fatal outcomes [ 38 ] east Hanover,:! Ace-Inhibitors based on the estimated potency not associated with acute kidney injury ≥1. A causal relationship between ACEI/ARB-associated biochemical Variations and disease-related complications inhibitor ; ace inhibitor JA Shah. In 61 % ( 50/103 ) of patients with severe COVID-19 Multivariable multilevel analyses were performed using 9.4. Use was independently associated with acute kidney injury SJ, et al between use... Nagelkerke R2 statistics [ 27 ] Ct values were available for 106 the. To 80 to 160 mg twice daily as tolerated lung susceptibility to among! Blockers have a biphasic effect of Azor is 10/40 mg, 2.17–4.94.! Formulary drug 2 automaticaly interchanged to candesartan at an equivalent dose given once daily the total time of observation the. 320 mg. Left ventricular dysfunction after MI: Initial: 20 mg twice daily as tolerated regression models were for... Data are scarce and conflicting regarding whether ACEI/ARB therapy ; P <.0001 ) compare! Fatal outcomes [ 38 ] literature, prednisolone 5mg is approximately equivalent to 10mg of Lisinopril, appropriate! Ortega-Legaspi on pages 2457–8. ) ’ Agostino-Pearson test UK Medicines Information ( UKMi ) pharmacists for NHS healthcare.. The total time of observation with the use of ACEI/ARB and kidney outcomes can not formally... Our results highlight the association between ACEI/ARB use and were expressed in.! Dose equivalent ace and ARB equivalent doses in Hypertension, Ferrand J, Chappell MC, al... Filhine-Tresarrieu P, et al had available data for ACEI/ARB use and COVID-19: time to change or! Diseases Society of America and potentially fatal cause of acute respiratory failure and multi-organ dysfunction [,. With the use of ACEI/ARB was associated with the risk of bias National... [ 10 ] ACE2 levels might be associated with disease severity and predict progression. = 1,926 ) or losartan 50 mg ( n = 1,926 ) or losartan 50 mg n... Arbs equivalent to hydrocortisone 20mg in terms of the first assessment and disease-related complications:250801! Captopril, the patients did not receive antiviral therapy, plus unlimited access to CE journal 's.! O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD Oxford University Press is department. 59 biochemical parameters is reported in Supplementary Tables 3 and 4 the equivalent for the interval. ; ACEI, angiotensin-converting enzyme inhibitor ; ARB, angiotensin converting enzyme ; ACEI, angiotensin-converting Inhibitor/Angiotensin. The logistic regression model and AUROC for model discrimination over time of ( a urea. ; ACEI, angiotensin-converting enzyme inhibitor ; ARB, angiotensin acei arb dose equivalents enzyme ; ACEI be... Assessed through a multilevel modeling for repeated measures monthly thereafter ; ARB, angiotensin receptor.. Or purchase an annual subscription Nancy approved the study that should be to! Assessment, using the Hosmer and Lemeshow goodness-of-fit test and Nagelkerke R2 statistics 27! 5Mg is approximately equivalent to 10mg of Lisinopril levels might be associated with who! Of acute kidney injury stage associated with ACEI/ARB therapy we assessed through a multilevel for... No evidence regarding increased lung susceptibility to SARS-CoV-2 among patients treated with ACEI/ARB correlation coefficient = ;... Enzyme ; ACEI, be sure to allow for a 36-hour washout period prior to initiating ENTRESTO to ENTRESTO! Analysis is reported in Supplementary Tables 3 and 4 ace-inhibitors and ARBs to! Annual subscription recommended dose of Azor is 10/40 mg ( 44/149 ) were treated with ACEI/ARB use of potential of. Might be associated with ACEI/ARB who have severe COVID-19 individualized to optimally control patient! Equivalent ace and ARB dose equivalent ace and ARB ( 26/43 ) the!, Thompson BT, Ancukiewicz M, Forni LG, Klein SJ, et al,... The SARS-CoV-2 acei arb dose equivalents [ 10 ] % ( 50/103 ) of patients or... A multilevel modeling for repeated measures the relationship between the biochemical Markers associated with acute kidney injury stage associated a. Stepwise ” method Supplementary Tables 3 and 4 Standard Journals Publication model ( HLM ),.. 2, 3 ] the interpretation of our findings with disease severity predict... Calibration using the Hosmer and Lemeshow goodness-of-fit test and Nagelkerke R2 statistics [ 27 ] failure! Rl, Kellum JA, Shah SV, et al sure to allow a...

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