New Research: Safe to Continue Commonly Used Hypertension Drugs in COVID-19 Patients

Soon after the coronavirus pandemic began, theoretical concerns were raised about the possibility that the widely prescribed angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) (see Table below) may increase the risk of contracting the coronavirus and predispose COVID-19 patients to more severe illness.[1]

These concerns were based on the known physiologic effects of ACE inhibitors and ARBs — which, depending on the drug, are used to treat hypertension (high blood pressure) and heart failure, among other disorders — and the biology of how the coronavirus infects human cells.[2]

Subsequent observational research studies helped to allay these concerns. In particular, four studies published in JAMA Cardiology, New England Journal of Medicine and Lancet found no association between ACE-inhibitor or ARB treatment and the risks of testing positive for COVID-19 or being hospitalized or dying from COVID-19.[3],[4],[5],[6] Despite being well-designed, these studies may have been subject to undetected sources of bias because they were not randomized, controlled clinical trials.[7]

Results of a new randomized, controlled trial (called the REPLACE COVID trial) published online in Lancet Respiratory Medicine in January provide new evidence that ACE inhibitors and ARBs can be safely continued in patients hospitalized with COVID-19.

List of FDA-Approved Oral ACE Inhibitors and ARBs*

*All listed drugs are designated as Limited Use by Public Citizen’s Health Research Group, EXCEPT olmesartan, which is designated as Do Not Use.
†Brand-name combination products were excluded.

The REPLACE COVID trial

The trial was conducted at 20 hospitals in the U.S., Canada, Mexico, Sweden, Peru, Bolivia and Argentina. For the trial, researchers enrolled 152 adults admitted to the hospital with COVID-19 who were taking either an ACE inhibitor or ARB before admission.[8]

The subjects were randomly assigned to either continuation (75 subjects) or discontinuation (77 subjects) of their ACE-inhibitor or ARB therapy for the duration of their hospitalization. For subjects in the discontinuation group, clinicians were encouraged to temporarily use other types of hypertension medications as needed for blood pressure control.

The trial showed no statistically significant differences between the continuation and discontinuation groups on global scores of disease severity over the course of hospitalization. There were also no significant differences in the proportion of subjects who required either transfer to an intensive care unit or mechanical ventilation or in the proportion who died.

The researchers concluded that, consistent with international medical society recommendations, health care professionals should continue to prescribe ACE inhibitors and ARBs in patients admitted to the hospital with COVID-19 who are already taking these drugs unless there is another clear medical reason for stopping the therapy.

What You Can Do

If you are taking an ACE inhibitor or ARB and are diagnosed with COVID-19, you should continue to take the drug. These medications should only be discontinued if your doctor determines that you are experiencing one of the drugs’ known serious adverse effects, such as a dangerous elevation in blood potassium levels, that requires discontinuation.

Note that we have designated one ARB, olmesartan (BENICAR), as Do Not Use because it has been shown to cause severe, life-threatening adverse gastrointestinal effects.[9] If you currently are taking olmesartan, consult with your doctor about switching to another ARB.
 

References

[1] Vaduganathan M, Vardeny O, Michel T, et al. Renin–angiotensin–aldosterone system inhibitors in patients with Covid-19. N Engl J Med. 2020;382(17):1653-1659

[2] Ibid.

[3] Mehta N, Kalra A, Nowacki AS, et al. Association of use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers with testing positive for coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020;5(9):1020-1026.

[4] Mancia G, Rea F, Ludergnani M, et al. Renin-angiotensin-aldosterone system blockers and the risk of Covid-19. N Engl J Med. 2020;382(25):2431-2440.

[5] 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.

[6] de Abajo FJ, Rodríguez-Martín S, Lerma V, et al. Use of renin-angiotensin-aldosterone system inhibitors and risk of COVID-19 requiring admission to hospital: a case-population study. Lancet. 2020;395(10238):1705-1714.

[7] Cohen JB, Hanff TC, Preethi William P, et al. Continuation versus discontinuation of renin-angiotensin system inhibitors in patients admitted to hospital with COVID-19: a prospective, randomised, open-label trial. Lancet Respir Med. 2021 Jan 7;S2213-2600(20)30558-0. doi: 10.1016/S2213-2600(20)30558-0. Online ahead of print.

[8] Ibid.

[9] Do Not Use olmesartan for high blood pressure. Worst Pills Best Pills News. January 2018. https://www.worstpills.org/member/newsletter.cfm?n_id=1170. Accessed January 14, 2021.