This evidence is from (CEBM wording) as well as a “living” systematic review published and updated as new studies are published in the Annals of Internal Medicine

Main questions currently circulating

  1. Do ACEis/ARBs have any role to play in treating COVID-19?
  2. Conversely should individuals currently taking these drugs stop taking them in advance of an infection or at least when an infection occurs?

There is true equipoise (in other words there is no good basis for a choosing between these care options): Untested hypotheses of mechanism underpin both of these questions. COVID clinical trials are currently underway and will inform us more.

Summary Conclusions

1 Suggestions of potential benefit

  • We do not know whether the supposed benefits of ACE-1 inhibitors or ARBs during an episode of infection with SARS-CoV-2 outweigh the potential harms.
  • It is generally unwise to institute any pharmacological therapy on the basis of an untested mechanistic hypothesis, since unexpected harms may outweigh hoped-for benefits. Until evidence emerges, based on randomized trials or at least data-mining of patients’ records, we suggest that it would be unwise to use either conventional ACE-1 inhibitors or ARBs to treat COVID-19.

2 Suggestions of potential harm

  • Patients who are already taking ACE-1 inhibitors or ARBs have generally been advised to continue taking their medicines. There is a lack of any evidence at present to support a harmful effect of ACE-1 inhibitors and ARBs in the context of the pandemic COVID-19 outbreak;
  • Lack of evidence does not demonstrate that the supposed benefit will outweigh the potential harms in individual infected patients. Patients with cardiovascular disease diagnosed with COVID-19, individualized treatment decisions should be made according to the individual’s hemodynamic status and clinical presentation.

3 Clinical Scenarios

Continuing treatment prior to infection 

Those in whom these medications are most likely to be beneficial (i.e. those with severe hypertension or heart failure) are those in whom continued therapy is likely to be needed, and also those in whom adverse effects of COVID-19 are more likely and in whom it appears that mortality is increased in COVID-19. In the absence of more information, such patients should probably continue to take their medications.

Continuing treatment during an infection 

In the absence of clinical trials in COVID-19, it is probably best to accept the proven benefits of continuing therapy for severe cardiovascular disease, and to continue therapy with ACE inhibitors or ARBs if an acute infection occurs, even at the uncertain risk of harms.

In general if the BP falls to unacceptably low levels as part of any acute illness then it make sense to hold antihypertensives.

Other considerations

Hypertension appears to have been associated with increased mortality risk in some early COVID 19 studies, but these were not adjusted for possible confounders so it is possible that hypertension is a marker for other things (comorbidities, medications, demographics). Evidence will likely improve with more data.

Many patients with mild diabetes, CVD, or both are taking these medicines for their long-term benefits; withdrawing treatment during an acute infection will cause little harm and is reasonable.

Those who are deriving marginal benefit from these medicines, but who are at a high risk of infection because of exposure (e.g. younger healthcare workers) might reasonably stop taking these medicines during the epidemic; the adverse effects of drug withdrawal will be small and the risks of continuing therapy before and especially during an infection, albeit not quantified, may be greater

Full Text from the Centre for Evidence-Based Medicine

The update to the “living“ systematic review on 23 July 2020 stated that there continues to be  high-certainty evidence that ACEI or ARB use is not associated with more severe COVID-19 disease.

Prepared by Dee Mangin, March 31, 2020 (updated August 19, 2020)

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