Avian Flu Diary: Study: Hypertension, Medications, and Risk of Severe COVID‐19

#15,577

Shortly after the emergence of COVID-19 we learned that the causative virus - SARS-CoV-2 - bound to ACE2 receptor cells (see ACE2 Is the SARS-CoV-2 Receptor Required for Cell Entry), which immediately raised concerns over the risks that millions of patients currently receiving ACE Inhibitor or ARB therapy for hypertension might face with this new virus.

Early on, opinions were mixed - with a number of hypothesized downsides - including:

Patients who Take ACEIs and ARBs May Be at Increased Risk of Severe COVID-19
Mar 25, 2020

At the same time, we saw this opposite take:

ACEI/ARB Treatment May Benefit Patients With COVID-19 and Hypertension

Florence Chaverneff, Ph.D.

Despite this uncertainty, a number of leading journals cautioned against halting ACE or ARB therapy, citing insufficient evidence of harm (see March AHA news release).

In May, the World Health Organization published a scientific brief (see WHO Scientific Brief: COVID-19 & The Use Of ACE Inhibitors or ARBs), that reviewed the (scant) existing literature - and while not exactly a ringing endorsement - found:

`. .. low-certainty evidence that patients on long-term therapy with ACE inhibitors or ARBs are not at higher risk of poor outcomes from COVID-19.'

Three weeks later, in Meta-Analysis: COVID-19 Mortality Among Patients Taking ACEIs & ARBs For Hypertension, we looked at a meta-analysis published in the AHA journal Hypertension, which found decreased mortality ( among patients with hypertension) who were receiving ACEI or ARB therapy.

While the news since then has been overwhelmingly supportive for the continued use of ACE inhibitors and ARBs during this pandemic, those recommendations have often been based on limited data derived from observational studies.

We've a new analysis, published two days ago in the Journal of Clinical Hypertension, which provides additional reassurance on the topic, albeit again from an observational study.

The full open-access study is available at the link below.

Hypertension, medications, and risk of severe COVID‐19: A Massachusetts community‐based observational study
Ann Z. Bauer ScD ,Rebecca Gore PhD ,Susan R. Sama ScD ,Richard Rosiello MD ,Lawrence Garber MD ,Devi Sundaresan MS ,Anne McDonald RN … See all authors
First published: 21 November 2020
https://doi.org/10.1111/jch.1410

Abstract

It remains uncertain whether the hypertension (HT) medications angiotensin‐converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) mitigate or exacerbate SARS‐CoV‐2 infection. We evaluated the association of ACEi and ARB with severe coronavirus disease 19 (COVID‐19) as defined by hospitalization or mortality among individuals diagnosed with COVID‐19. We investigated whether these associations were modified by age, the simultaneous use of the diuretic thiazide, and the health conditions associated with medication use.

In an observational study utilizing data from a Massachusetts group medical practice, we identified 1449 patients with a COVID‐19 diagnosis. In our study, pre‐infection comorbidities including HT, cardiovascular disease, and diabetes were associated with increased risk of severe COVID‐19. Risk was further elevated in patients under age 65 with these comorbidities or cancer. Twenty percent of those with severe COVID‐19 compared to 9% with less severe COVID‐19 used ACEi, 8% and 4%, respectively, used ARB.

In propensity score‐matched analyses, use of neither ACEi (OR = 1.30, 95% CI 0.93 to 1.81) nor ARB (OR = 0.94, 95% CI 0.57 to 1.55) was associated with increased risk of severe COVID‐19. Thiazide use did not modify this relationship. Beta blockers, calcium channel blockers, and anticoagulant medications were not associated with COVID‐19 severity.

In conclusion, cardiovascular‐related comorbidities were associated with severe COVID‐19 outcomes, especially among patients under age 65. We found no substantial increased risk of severe COVID‐19 among patients taking antihypertensive medications. Our findings support recommendations against discontinuing use of renin–angiotensin system (RAS) inhibitors to prevent severe COVID‐19.

(SNIP)

Discussion

In this analysis of data on COVID‐19 patients from a large group medical practice, we investigated the relationship between pre‐infection treatment with hypertension medications and severe COVID‐19, among all individuals diagnosed with COVID‐19 in a community‐based population in central Massachusetts. Our primary focus was on RAS inhibitors as they may induce elevated expression of ACE2, the cellular receptor of SAR‐CoV‐2, raising concern that these medications might increase the risk of severe sequelae of COVID‐19.

Our findings are consistent with other recent studies which have found no deleterious effect of these or any of five hypertension medication classes with regard to COVID‐19 severity.12-14, 25, 26 Further, we investigated the potential for effect modification by additional use of the diuretic thiazide on the RAS inhibitors and found no such relationship.

Collectively, these findings do not support a change to the current use of these medications in relation to COVID‐19. While this is consistent with the guidance of the professional societies’ recommendations,27 our results are based only on reported use of hypertension medications prior to COVID‐19 diagnosis. We did not have data to investigate the effect on severity of continued or discontinued use of these medications after COVID‐19 diagnosis.

(SNIP)

Our findings do not support the discontinuation of ACEi or ARB in the management of hypertension, as a preventive measure to reduce risk of severe COVID‐19 disease. Other studies should also investigate whether or not hypertension medications were continued during hospitalization. Findings should be confirmed using other populations and study designs including randomized controlled trials.

More investigation of pre‐infection risk factors such vitamin D3 level,37 anticoagulant medication use,38 diabetes control,39 blood type,40 MMR, and flu vaccine status,41 in both the general and younger populations, is warranted.