Multimedialna platforma wiedzy medycznej Internetowa Księgarnia Medyczna Kalendarium Konferencji
Arterial Hypertension
MENU
Shortcuts Submit an article Author Guidelines Ahead Of Print Reviewers 2023

open access

Vol 24, No 3 (2020)
Original paper
Published online: 2020-09-21
View PDF Download PDF file Supp./Additional Files [1]
Get Citation

Severity of SARS-COV-2 infection and angiotensin converting enzyme inhibitors and angiotensin receptor blockers: a meta-analysis

Teodoro J. Oscanoa1, Xavier Vidal2, Alfonso Carvajal3, José Amado1, Roman Romero-Ortuno4
DOI: 10.5603/AH.a2020.0013
·
Arterial Hypertension 2020;24(3):106-114.
Affiliations
  1. Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Drug Safety Research Centre, Facultad de Medicina Humana, Universidad de San Martín de Porres, Hospital Almenara, ESSALUD, Lima, Perú
  2. Clinical Pharmacology Department, Vall d’Hebron Hospital, Barcelona, Spain
  3. Centro de Estudios sobre la Seguridad de los Medicamentos (CESME), Universidad de Valladolid, Valladolid, Spain
  4. Global Brain Health Institute, Trinity College Dublin, Ireland

open access

Vol 24, No 3 (2020)
ORIGINAL PAPERS
Published online: 2020-09-21

Abstract

Background: The mechanism of entry of SARS-COV-2 into the human host cell is through the ACE2 receptor. During the pandemic, a hypothesis has been proposed that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) could be risk factors for the development of severe SARS-COV-2 infection. The objective of the study was to conduct a meta-analysis of the association between ACEI or ARB use and SARS-COV-2 infection severity or mortality.

Material and methods: We searched PubMed, EMBASE, Google scholar and the Cochrane Database of Systematic Reviews for observational studies published between December 2019 and August 4, 2020 Studies were included if they contained data on ACEI or ARB use and SARS-COV-2 infection severity or mortality.

Effect statistics were pooled using random-effects models. The quality of included studies was assessed with the Newcastle–Ottawa Scale (NOS). Data on study design, study location, year of publication, number of participants, sex, age at baseline, outcome definition, exposure definition, effect estimates and 95% CIs were extracted.

Results: Twenty-six studies (21 cohort studies and 5 case-control studies) were identified for inclusion, combining to a total sample of 361467 participants. Mean age was 61.48 (SD 8.26) years and 51.63 % were men. The mean NOS score of included studies was 7.85 (range: 7–9). Results suggested that ACEI or ARB use did not increase the risk of severe disease or mortality from SARS-COV-2 infection (OR = 0.88, 95% CI: 0.75–1.02, p > 0.05).

Conclusions: At present, the evidence available does not support the hypothesis of increased SARS-COV-2 risk with
ACEI or ARB drugs.

Abstract

Background: The mechanism of entry of SARS-COV-2 into the human host cell is through the ACE2 receptor. During the pandemic, a hypothesis has been proposed that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) could be risk factors for the development of severe SARS-COV-2 infection. The objective of the study was to conduct a meta-analysis of the association between ACEI or ARB use and SARS-COV-2 infection severity or mortality.

Material and methods: We searched PubMed, EMBASE, Google scholar and the Cochrane Database of Systematic Reviews for observational studies published between December 2019 and August 4, 2020 Studies were included if they contained data on ACEI or ARB use and SARS-COV-2 infection severity or mortality.

Effect statistics were pooled using random-effects models. The quality of included studies was assessed with the Newcastle–Ottawa Scale (NOS). Data on study design, study location, year of publication, number of participants, sex, age at baseline, outcome definition, exposure definition, effect estimates and 95% CIs were extracted.

Results: Twenty-six studies (21 cohort studies and 5 case-control studies) were identified for inclusion, combining to a total sample of 361467 participants. Mean age was 61.48 (SD 8.26) years and 51.63 % were men. The mean NOS score of included studies was 7.85 (range: 7–9). Results suggested that ACEI or ARB use did not increase the risk of severe disease or mortality from SARS-COV-2 infection (OR = 0.88, 95% CI: 0.75–1.02, p > 0.05).

Conclusions: At present, the evidence available does not support the hypothesis of increased SARS-COV-2 risk with
ACEI or ARB drugs.

Full Text:

View PDF Download PDF file Supp./Additional Files [1]
Get Citation

Keywords

SARS-COV-2; COVID-19; angiotensin II receptor blockers, angiotensin-converting enzyme inhibitors; renin–angiotensin system (RAS)

Supp./Additional Files (1)
Supplementary Data
Download
13KB
About this article
Title

Severity of SARS-COV-2 infection and angiotensin converting enzyme inhibitors and angiotensin receptor blockers: a meta-analysis

Journal

Arterial Hypertension

Issue

Vol 24, No 3 (2020)

Article type

Original paper

Pages

106-114

Published online

2020-09-21

Page views

1809

Article views/downloads

817

DOI

10.5603/AH.a2020.0013

Bibliographic record

Arterial Hypertension 2020;24(3):106-114.

Keywords

SARS-COV-2
COVID-19
angiotensin II receptor blockers
angiotensin-converting enzyme inhibitors
renin–angiotensin system (RAS)

Authors

Teodoro J. Oscanoa
Xavier Vidal
Alfonso Carvajal
José Amado
Roman Romero-Ortuno

References (50)
  1. Derington CG, King JB, Herrick JS, et al. Trends in Antihypertensive Medication Monotherapy and Combination Use Among US Adults, National Health and Nutrition Examination Survey 2005-2016. Hypertension. 2020; 75(4): 973–981.
    CrossRefPubMed
  2. Hamming I, Timens W, Bulthuis MLC, et al. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004; 203(2): 631–637.
    CrossRefPubMed
  3. Serfozo P, Wysocki J, Gulua G, et al. Ang II (Angiotensin II) Conversion to Angiotensin-(1-7) in the Circulation Is POP (Prolyloligopeptidase)-Dependent and ACE2 (Angiotensin-Converting Enzyme 2)-Independent. Hypertension. 2020; 75(1): 173–182.
    CrossRefPubMed
  4. Wahba L, Jain N, Fire AZ, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 579(7798): 270–273.
    CrossRefPubMed
  5. Ge XY, Li JL, Yang XL, et al. Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Nature. 2013; 503(7477): 535–538.
    CrossRefPubMed
  6. Prabakaran P, Xiao X, Dimitrov DS. A model of the ACE2 structure and function as a SARS-CoV receptor. Biochem Biophys Res Commun. 2004; 314(1): 235–241.
    CrossRefPubMed
  7. Cheng ZJ, Shan J. 2019 Novel coronavirus: where we are and what we know. Infection. 2020; 48(2): 155–163.
    CrossRefPubMed
  8. de Wit E, van Doremalen N, Falzarano D, et al. SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol. 2016; 14(8): 523–534.
    CrossRefPubMed
  9. Ferrario CM, Jessup J, Chappell MC, et al. Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2. Circulation. 2005; 111(20): 2605–2610.
    CrossRefPubMed
  10. Sommerstein R, Kochen MM, Messerli FH, et al. Coronavirus Disease 2019 (COVID-19): Do Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers Have a Biphasic Effect? J Am Heart Assoc. 2020; 9(7): e016509.
    CrossRefPubMed
  11. Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med. 2020; 8(4): e21.
    CrossRefPubMed
  12. Bavishi C, Maddox TM, Messerli FH. Coronavirus Disease 2019 (COVID-19) Infection and Renin Angiotensin System Blockers. JAMA Cardiol. 2020 [Epub ahead of print].
    CrossRefPubMed
  13. Moher D, Liberati A, Tetzlaff J, et al. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med. 2009; 6: e1000097.
    CrossRefPubMed
  14. World Health Organization. Clinical management of severe acute respiratory infection when novel coronavirus (‎‎‎‎‎‎2019-nCoV)‎‎‎‎‎‎ infection is suspected: interim guidance, 28 January 2020. https://apps.who.int/iris/handle/10665/330893.
  15. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010; 25(9): 603–605.
    CrossRefPubMed
  16. Cumpston M, Li T, Page MJ, et al. Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Database Syst Rev. 2019; 10: ED000142.
    CrossRefPubMed
  17. DerSimonian R, Laird N. Meta-analysis in clinical trials. Contemp Clin Trials. 1986; 7(3): 177–188.
    CrossRefPubMed
  18. Guo T, Fan Y, Chen M, et al. Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020 [Epub ahead of print].
    CrossRefPubMed
  19. Liu Y, Huang F, Xu J, et al. Anti-hypertensive Angiotensin II receptor blockers associated to mitigation of disease severity in elderly COVID-19 patients. medRxiv (preprint). .
    CrossRef
  20. Zhang P, Zhu L, Cai J, et al. Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19. Circ Res. 2020; 126(12): 1671–1681.
    CrossRefPubMed
  21. Li J, Wang X, Chen J, et al. Association of Renin-Angiotensin System Inhibitors With Severity or Risk of Death in Patients With Hypertension Hospitalized for Coronavirus Disease 2019 (COVID-19) Infection in Wuhan, China. JAMA Cardiol. 2020 [Epub ahead of print].
    CrossRefPubMed
  22. Choi H, Koo HJ, Seok H, et al. ARB/ACEI use and severe COVID-19: a nationwide case-control study. MedRxiv. 2020.
    CrossRef
  23. Hu J, Zhang X, Zhang X, et al. COVID-19 patients with hypertension have more severity condition, and ACEI/ARB treatment have no infulence on the clinical severity and outcome. J Infect. 2020 [Epub ahead of print].
    CrossRefPubMed
  24. Zhou X, Zhu J, Xu T. Clinical characteristics of coronavirus disease 2019 (COVID-19) patients with hypertension on renin-angiotensin system inhibitors. Clin Exp Hypertens. 2020; 42(7): 656–660.
    CrossRefPubMed
  25. Huang Z, Cao J, Yao Y, et al. The effect of RAS blockers on the clinical characteristics of COVID-19 patients with hypertension. Ann Transl Med. 2020; 8(7): 430.
    CrossRefPubMed
  26. De Spiegeleer A, Bronselaer A, Teo JT, et al. The Effects of ARBs, ACEis, and Statins on Clinical Outcomes of COVID-19 Infection Among Nursing Home Residents. J Am Med Dir Assoc. 2020; 21(7): 909–914.e2.
    CrossRefPubMed
  27. Nicastri E, Petrosillo N, Ascoli Bartoli T, et al. National Institute for the Infectious Diseases "L. Spallanzani", IRCCS. Recommendations for COVID-19 clinical management. Infect Dis Rep. 2020; 12(1): 8543.
    CrossRefPubMed
  28. Ip A, Parikh K, Parrillo J, et al. Hypertension and Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Covid-19. MedRxiv. 2020.
    CrossRef
  29. Khera R, Clark C, Lu Y, et al. Association of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers with the Risk of Hospitalization and Death in Hypertensive Patients with Coronavirus Disease-19. medRxiv. 2020.
    CrossRefPubMed
  30. Peng YD, Meng K, Guan HQ, et al. [Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV]. Zhonghua Xin Xue Guan Bing Za Zhi. 2020; 48(6): 450–455.
    CrossRefPubMed
  31. Reynolds HR, Adhikari S, Pulgarin C, et al. Renin–Angiotensin–Aldosterone System Inhibitors and Risk of Covid-19. N Engl J Med. 2020; 382(25): 2441–2448.
    CrossRefPubMed
  32. Richardson S, Hirsch JS, Narasimhan M, et al. and the Northwell COVID-19 Research Consortium. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020 [Epub ahead of print].
    CrossRefPubMed
  33. Chaudhri I, Koraishy F, Bolotova O, et al. Outcomes Associated with the Use of Renin-Angiotensin-Aldosterone System Blockade in Hospitalized Patients with SARS-CoV-2 Infection. Kidney360. 2020; 1(8): 801–809.
    CrossRef
  34. Dublin S, Walker RL, Floyd JS, et al. Renin-angiotensin-aldosterone system inhibitors and COVID-19 infection or hospitalization: a cohort study. medRxiv. 2020.
    CrossRefPubMed
  35. Felice C, Nardin C, Di Tanna GL, et al. Use of RAAS inhibitors and risk of clinical deterioration in COVID-19: results from an Italian cohort of 133 hypertensives. Am J Hypertens. 2020 [Epub ahead of print].
    CrossRefPubMed
  36. Lam KW, Chow KW, Vo J, et al. Continued in-hospital ACE inhibitor and ARB Use in hypertensive COVID-19 patients is associated with positive clinical outcomes. J Infect Dis. 2020 [Epub ahead of print].
    CrossRefPubMed
  37. Şenkal N, Meral R, Medetalibeyoğlu A, et al. Association between chronic ACE inhibitor exposure and decreased odds of severe disease in patients with COVID-19. Anatol J Cardiol. 2020; 24(1): 21–29.
    CrossRefPubMed
  38. Meng J, Xiao G, Zhang J, et al. Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension. Emerg Microbes Infect. 2020; 9(1): 757–760.
    CrossRefPubMed
  39. Bean DM, Kraljevic Z, Searle T, et al. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are not associated with severe COVID-19 infection in a multi-site UK acute hospital trust. Eur J Heart Fail. 2020; 22(6): 967–974.
    CrossRefPubMed
  40. Yang G, Tan Z, Zhou L, et al. Angiotensin II Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors Usage is Associated with Improved Inflammatory Status and Clinical Outcomes in COVID-19 Patients With Hypertension. medRxiv. 2020.
    CrossRef
  41. Feng Y, Ling Y, Bai T, et al. COVID-19 with Different Severities: A Multicenter Study of Clinical Features. Am J Respir Crit Care Med. 2020; 201(11): 1380–1388.
    CrossRefPubMed
  42. Feng Z, Li J, Yao S, et al. The Use of Adjuvant Therapy in Preventing Progression to Severe Pneumonia in Patients with Coronavirus Disease 2019: A Multicenter Data Analysis. medRxiv. 2020.
    CrossRef
  43. Rentsch CT, Kidwai-Khan F, Tate JP, et al. Covid-19 Testing, Hospital Admission, and Intensive Care Among 2,026,227 United States Veterans Aged 54–75 Years. medRxiv. 2020.
    CrossRefPubMed
  44. Zeng Z, Sha T, Zhang Y, et al. Hypertension in patients hospitalized with COVID-19 in Wuhan, China: A single-center retrospective observational study. medRxiv. 2020.
    CrossRef
  45. Sunden-Cullberg J. Chronic Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers Is High Among Intensive Care Unit Patients With Non-COVID-19 Sepsis but Carries a Moderately Increased Risk of Death. Hypertension. 2020; 75(6): e15–e16.
    CrossRefPubMed
  46. Shinohara Y, Origasa H. Post-stroke pneumonia prevention by angiotensin-converting enzyme inhibitors: results of a meta-analysis of five studies in Asians. Adv Ther. 2012; 29(10): 900–912.
    CrossRefPubMed
  47. Sriram K, Insel PA. Risks of ACE Inhibitor and ARB Usage in COVID-19: Evaluating the Evidence. Clin Pharmacol Ther. 2020; 108(2): 236–241.
    CrossRefPubMed
  48. Gurwitz D. Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Dev Res. 2020; 81(5): 537–540.
    CrossRefPubMed
  49. Liu Y, Yang Y, Zhang C, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci. 2020; 63(3): 364–374.
    CrossRefPubMed
  50. Aronson JK, Ferner RE. Drugs and the renin-angiotensin system in covid-19. BMJ. 2020; 369: m1313.
    CrossRefPubMed

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By VM Media Group sp. z o.o., Grupa Via Medica, ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail: viamedica@viamedica.pl