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Treatment with ACE inhibitors or ARBs and risk of severe/lethal COVID-19: a meta-analysis
  1. Maria Elena Flacco1,
  2. Cecilia Acuti Martellucci2,
  3. Francesca Bravi3,
  4. Giustino Parruti4,
  5. Rosaria Cappadona1,
  6. Alfonso Mascitelli5,
  7. Roberto Manfredini6,
  8. Lorenzo G Mantovani7,8,
  9. Lamberto Manzoli1
  1. 1 Department of Medical Sciences, University of Ferrara, Ferrara, Emilia-Romagna, Italy
  2. 2 Polytechnic University of Marche School of Medicine and Surgery, Ancona, Marche, Italy
  3. 3 University Hospital of Ferrara Arcispedale Sant'Anna Medical Department, Cona, Emilia-Romagna, Italy
  4. 4 Infectious Diseases Unit, Local Health Unit of Pescara, Pescara, Italy
  5. 5 Regional Healthcare Agency of Abruzzo, Pescara, Italy
  6. 6 Dipartimento di Scienze Mediche, Universita degli Studi di Ferrara, Ferrara, Italy
  7. 7 Center for Public Health Research, University of Milan–Bicocca, Milano, Lombardia, Italy
  8. 8 IRCCS MultiMedica, Sesto San Giovanni, Lombardia, Italy
  1. Correspondence to Professor Lamberto Manzoli, Medical Sciences, University of Ferrara, Ferrara 44121, Italy; lmanzoli{at}


Objective It has been hypothesised that the use of ACE inhibitors and angiotensin receptor blockers (ARBs) might either increase or reduce the risk of severe or lethal COVID-19. The findings from the available observational studies varied, and summary estimates are urgently needed to elucidate whether these drugs should be suspended during the pandemic, or patients and physicians should be definitely reassured. This meta-analysis of adjusted observational data aimed to summarise the existing evidence on the association between these medications and severe/lethal COVID-19.

Methods We searched MedLine, Scopus and preprint repositories up to 8 June 2020 to retrieve cohort or case–control studies comparing the risk of severe/fatal COVID-19 (either mechanical ventilation, intensive care unit admission or death), among hypertensive subjects treated with: (1) ACE inhibitors, (2) ARBs and (3) both, versus untreated subjects. Data were combined using a random-effect generic inverse variance approach.

Results Ten studies, enrolling 9890 hypertensive subjects were included in the analyses. Compared with untreated subjects, those using either ACE inhibitors or ARBs showed a similar risk of severe or lethal COVID-19 (summary OR: 0.90; 95% CI 0.65 to 1.26 for ACE inhibitors; 0.92; 95% CI 0.75 to 1.12 for ARBs). The results did not change when both drugs were considered together, when death was the outcome and excluding the studies with significant, divergent results.

Conclusion The present meta-analysis strongly supports the recommendation of several scientific societies to continue ARBs or ACE inhibitors for all patients, unless otherwise advised by their physicians who should thus be reassured.

  • cardiac risk factors and prevention
  • hypertension
  • meta-analysis

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  • MEF and CAM contributed equally.

  • Contributors The following authors have contributed to the planning (MEF, CAM, RC, LGM and LaM), conduct (MEF, CAM, FB, GP, RC, AM, RM, LGM) and reporting (MEF, FB, GP, AM, RM, LGM and LM) of the present work.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Ethics approval The study complies with the Declaration of Helsinki. As a meta-analysis, the protocol and study did not require the approval from Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request. All data are available from the corresponding author on request.

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