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Don't Stop ACE, ARB Drugs Over COVID-19 Concern, Groups Urge

— Clear potential for harm from withdrawal trumps questionable theoretical risk from continuing

MedpageToday
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There's still no reason to stop ACE inhibitors or angiotensin receptor blockers (ARBs) over COVID-19 interaction fears, several groups agreed.

The SARS-CoV-2 virus behind the pandemic illness enters human cells via angiotensin converting enzyme 2 (ACE2) receptors, so upregulation of ACE2 expression by these drugs is a concern.

Indeed, some media sources and health systems have recently called for stopping renin-angiotensin-aldosterone system (RAAS) drugs, both prophylactically and in the context of suspected COVID-19, wrote Scott Solomon, MD, of Brigham and Women's Hospital in Boston, and colleagues .

However, it's been weeks since the American College of Cardiology, American Heart Association, and Heart Failure Society of America urged patients and physicians not to dump ACE inhibitors and ARBS over weak evidence, and that evidence hasn't changed.

Hypertensive and other cardiovascular disease patients are in a high-risk category when they contract the infection, but these conditions track closely with advancing age, "which is emerging as the strongest predictor of Covid-19–related death," and studies haven't rigorously controlled for such confounders, Solomon's group noted.

Population-level , since most hypertensive patients there are not on any antihypertensive treatment and so only a fraction of those with COVID-19 have been treated with RAAS inhibitors, they added.

Animal model and human results have been mixed, and "even if RAAS inhibitors modify ACE2 levels or activity (or both) in target tissue beds, clinical data are lacking to indicate whether this would in turn facilitate greater engagement and entry of SARS-CoV-2 spike protein," they added.

Moreover, there's "clear potential for harm related to the withdrawal of RAAS inhibitors in patients in otherwise stable condition," Solomon's group wrote, noting "established benefits in protecting the kidney and myocardium, and their withdrawal may risk clinical decompensation in high-risk patients."

"Although additional data may further inform the treatment of high-risk patients with Covid-19, clinicians need to be cognizant of the unintended consequences of prematurely discontinuing proven therapies in response to hypothetical concerns that may be based on incomplete experimental evidence," they concluded.

In fact, there are actually reasons to think that RAAS drugs may help COVID-19 patients, in a viewpoint in JAMA Cardiology.

The acute lung injury and acute respiratory distress syndrome (ARDS) literature has some evidence to that effect, they noted. In a meta-analysis of 37 studies, ACE inhibitors and ARBs were associated with reduced risk of pneumonia and pneumonia-related mortality versus controls. And, an underpowered double-blind randomized clinical trial showed enalaprilat yielded numerically more ventilator-free days and days alive outside the ICU than did placebo. A retrospective study suggested ARDS patients taking ACE inhibitors or ARBs were more likely to survive.

Another by Majd AlGhatrif, MD, of the NIH, and colleagues noted age-associated decline in ACE2 expression. They stated that "older individuals, especially those with hypertension and diabetes, have reduced ACE2 expression and upregulation of angiotensin II proinflammatory signaling; the increase in ACE2 levels with ACEI/ARB treatment is more likely to be corrective to these changes."

to test as treatment for COVID-19, based on experimental and observational data suggesting that viral infection impairs ACE2 activity as a mediator of acute lung injury and possibly subsequent myocardial injury. Another in China was recently withdrawn.

"As ACEIs and ARBs are also used to retard the progression of chronic kidney disease (CKD), we suggest that these recommendations also apply to the use of these agents in CKD," a group added in .

Disclosures

Solomon disclosed relevant relationships with Alnylam, Amgen, AstraZeneca, Bellerophon, BMS, GSK, grants from Ionis, Mesoblast, MyoKardia, NIH/NHLBI, Novartis, Sanofi Pasteur, Theracos, Akros, Bayer, Merck, Roche, Quantum Genomics, Janssen, Eidos, Cytokinetics, Tenaya, Daiichi-Sankyo, Cardurion, NeuroTronik, and Respicardia.

AlGhatrif and co-authors group disclosed no relevant relationships with industry.

Messerli disclosed relevant relationships with Menarini, Medtronic, and Pfizer.

Primary Source

New England Journal of Medicine

Vaduganathan M, et al "Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19" N Engl J Med 2020; DOI: 10.1056/NEJMsr2005760.

Secondary Source

JAMA Cardiology

AlGhatrif M, et al "The Dilemma of Coronavirus Disease 2019, Aging, and Cardiovascular Disease: Insights From Cardiovascular Aging Science" JAMA Cardiol 2020; DOI: 10.1001/jamacardio.2020.1329.

Additional Source

JAMA Cardiology

Bavishi C, et al "Coronavirus Disease 2019 (COVID-19) Infection and Renin Angiotensin System Blockers" JAMA Cardiol 2020; DOI: 10.1001/jamacardio.2020.1282.