Dataset Information

Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults: A Living Systematic Review.

ABSTRACT:

Background

The role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) in coronavirus disease 2019 (COVID-19) susceptibility, severity, and treatment is unclear.

Purpose

To evaluate, on an ongoing basis, whether use of ACEIs or ARBs either increases risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or is associated with worse COVID-19 disease outcomes, and to assess the efficacy of these medications for COVID-19 treatment.

Data sources

MEDLINE (Ovid) and Cochrane Database of Systematic Reviews from 2003 to 4 May 2020, with planned ongoing surveillance for 1 year; the World Health Organization database of COVID-19 publications and medRxiv.org through 17 April 2020; and ClinicalTrials.gov to 24 April 2020, with planned ongoing surveillance.

Study selection

Observational studies and trials in adults that examined associations and effects of ACEIs or ARBs on risk for SARS-CoV-2 infection and COVID-19 disease severity and mortality.

Data extraction

Single-reviewer abstraction confirmed by another reviewer, independent evaluation by 2 reviewers of study quality, and collective assessment of certainty of evidence.

Data synthesis

Two retrospective cohort studies found that ACEI and ARB use was not associated with a higher likelihood of receiving a positive SARS-CoV-2 test result, and 1 case-control study found no association with COVID-19 illness in a large community (moderate-certainty evidence). Fourteen observational studies, involving a total of 23 565 adults with COVID-19, showed consistent evidence that neither medication was associated with more severe COVID-19 illness (high-certainty evidence). Four registered randomized trials plan to evaluate ACEIs and ARBs for treatment of COVID-19.

Limitation

Half the studies were small and did not adjust for important confounding variables.

Conclusion

High-certainty evidence suggests that ACEI or ARB use is not associated with more severe COVID-19 disease, and moderate-certainty evidence suggests no association between use of these medications and positive SARS-CoV-2 test results among symptomatic patients. Whether these medications increase the risk for mild or asymptomatic disease or are beneficial in COVID-19 treatment remains uncertain.

Primary funding source

None. (PROSPERO: registration number pending).

SUBMITTER: Mackey K

PROVIDER: S-EPMC7249560 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceThe renin-angiotensin system has been implicated in mood disorders. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are among the most commonly used medications, yet their effects on mental health outcomes, particularly suicide, are poorly understood. This study examined the association between suicide and exposure to ACEIs and ARBs. Because of differences in their mode of action, it was speculated that ARBs would be associated with a higher risk of suicide than ACEIs.ObjectiveTo examine the association between suicide and exposure to ARBs compared with ACEIs.Design, setting, and participantsThis population-based nested case-control study of individuals aged 66 years and older used administrative claims databases in Ontario, Canada, from January 1, 1995, to December 31, 2015. Data analysis was performed from January to April 2019. Cases were individuals who died by suicide within 100 days of receiving an ACEI or ARB. The date of death served as the index date. For each case, 4 controls were identified and matched by age (within 1 year), sex, and presence of hypertension and diabetes. All individuals received an ACEI or ARB within 100 days before the index date.ExposuresUse of an ACEI or ARB.Main outcomes and measuresConditional logistic regression was used to estimate odds ratios for the association between suicide and exposure to ARBs compared with ACEIs.ResultsNine hundred sixty-four cases were matched to 3856 controls. The median (interquartile range) age of cases and controls was 76 (70-82) years. Most cases (768 [79.7%]) and controls (3068 [79.6%]) were men. Among cases, 260 (26.0%) were exposed to ARBs, and 704 (18.4%) were exposed to ACEIs. Among controls, 741 (74.0%) were exposed to ARBs, and 3115 (81.6%) were exposed to ACEIs. Compared with ACEI exposure, ARB exposure was associated with higher risk of death by suicide (adjusted odds ratio, 1.63; 95% CI, 1.33-2.00). The findings were consistent in a sensitivity analysis excluding individuals with a history of self-harm (odds ratio, 1.60; 95% CI, 1.29-1.98).Conclusions and relevanceThe use of ARBs may be associated with an increased risk of suicide compared with ACEIs. Preferential use of ACEIs over ARBs should be considered whenever possible, particularly in patients with severe mental health illness.