Feature

ACE-inhibitors, ARBs and COVID-19: What GPs need to know


Evelyn Lewin


18/03/2020 4:16:30 PM

Some are considering the role of antihypertensives in the coronavirus pandemic, but experts warn against abruptly stopping these medications.

Graphic representation of the coronavirus.
Some are considering the role of antihypertensives in the coronavirus pandemic, but experts warn against abruptly stopping these medications.

Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are in the spotlight right now, as doctors question their effect on COVID-19 and what they should accordingly advise patients to do.
 
A brief summary of salient points:

  • The COVID-19 virus enters cells via ACE-2 receptors on cells
  • Some doctors are now questioning the use of antihypertensives ACE-inhibitors and ARBs due to their effect on ACE-2, and thus potential effect on COVID-19
  • Leading experts warn that ARBs may amplify COVID-19 severity in patients
  • The role of ACE-inhibitors on COVID-19 is less clear
  • Experts warn that abruptly stopping ARBs (and ACE-inhibitors) for heart failure may lead to acute heart failure, and ceasing them for ACE-inhibitors may lead to unstable blood pressure
  • Peak international cardiology bodies strongly recommend patients stay on current antihypertensive therapies
Why are antihypertensives currently a concern for COVID-19?
The issue surrounding ACE-inhibitors and ARBs stems from the fact the COVID-19 virus binds to the ACE-2 receptor, according to Associate Professor Nathan Better, cardiologist and deputy director of nuclear medicine at Royal Melbourne Hospital and private cardiologist at Cabrini Hospital.
 
‘[COVID-19] attaches to the cell’s surface via the ACE-2 protein –  that is its sole point of entry – and what we know is that ARBs … increase the expression of the ACE-2 protein in the body as many as three to five times,’ Associate Professor Better told newsGP.
 
‘It basically works to give the virus a portal to entry; that’s what is being quoted [in the research].’
 
According to Associate Professor Better, treatment with ARBs then ‘amplifies’ the effects of COVID-19. From a ‘basic science point of view’, he said, it seems patients on these antihypertensives may fare worse than average, and that they should cease these medications.
 
‘But this has not been shown in any clinical trials,’ Associate Professor Better said, keen to note he is not advising that patients cease their medications based on that.
 
However, that has not stopped many patients from contacting Associate Professor Better about this issue, who has received ‘many calls’ about the issue in recent days.
 
The connection between ARBs and COVID-19
Professor Murray Esler is the senior director of the Baker Heart and Diabetes Institute and consultant cardiologist at the Alfred Hospital Melbourne and Adjunct Professor of Medicine at Monash University.
 
He wrote a paper on this topic, which was published in the Journal of Hypertension on 11 March.
 
Professor Esler told newsGP he first became concerned about ARBs and COVID-19 when talking to his daughter, a public health physician in the Northern Territory, a few weeks ago.
 
‘The first clue was really that severe COVID-19 infection was more common in hypertension, and hypertensive patients are really not predisposed to infection at all, so that was very odd,’ he said.
 
His interest was also piqued when he found that COVID-19 enters cells by binding to ACE-2.
 
‘That’s an enzyme that’s well known to cardiologists, so I certainly pricked my ears up when I saw that,’ he said.
 
‘I knew in particular that ARBs cause very substantial overexpression of ACE-2 in experimental animals and people.
 
‘So that suggested perhaps this predisposition to severe COVID-19 infection in hypertension could possibly be a drug effect mediated by ARBs which upregulates ACE-2, and potentially predisposes to infectivity but also in particular, severe infection.’
 
Professor Esler has been in contact with colleagues in Lombardy, Italy, who are currently exploring it further.
 
‘[They] are actually looking at their databases to try and see if our hypothesis is true,’ he said.
 
What about ACE-inhibitors?
The effect of ACE-inhibitors on COVID-19 is currently controversial.
 
Associate Professor Better has concerns about a ‘possible similar effect’ for ACE-inhibitors as per ARBs.  
 
Meanwhile, Professor Esler believes they should not be an area of concern.
 
‘There was a letter in The Lancet published a day before we published our paper, and it said ACE-2 may be also an “at risk” drug, because ACE-inhibitors upregulate ACE-2 but, in fact, that’s not true,’ Professor Esler said.
 
Should patients on ARBs or ACE-inhibitors switch to a different drug?
Associate Professor Better says his advice to GPs and patients alike is not to cease these medications at this stage.
 
‘Our feeling is, it is too premature in terms of clinical verve, with a lack of clinical testing and a lack of clinic evidence that we should change management,’ he said.
 
He is also concerned about clinical outcomes if patients cease or switch these medications without proper guidance. In the case of hypertension, he is concerned about reflex rising of blood pressure.
 
‘The control wouldn’t be quite so good, and you’d get subsequent complications of hypertension,’ he said.
 
The problem is even more concerning for heart failure.
 
Associate Professor Better explains that many patients mistakenly believe they are on these medications for hypertension, when they are actually on it to treat heart failure.
 
‘And if we stop these drugs it can precipitate acute events and it may deteriorate the patients,’ he said.
 
‘So the concern we have that the frenzy that’s brought on in the patients is they stop the drugs and come in with acute failure a day or two later.
 
‘This has been troubling us a lot.’
 
For now, Associate Professor Better said he is adhering to the advice by the European Society of Cardiology. Their statement, published on 13 March, states they ‘strongly recommend’ continuing with usual antihypertensive therapy at this stage.

The American Heart Association (AHA) issued a statement in conjunction with the Heart Failure Society of America (HFSA) and the American College of Cardiology (ACC) echoing that sentiment. The AHA ‘recommend[s] continuation of ACE-inhibitors or ARB medications for all patients already prescribed for indications such as heart failure, hypertension or ischemic heart disease’.
 
That said, Associate Professor Better said if he had a new patient present to him today with hypertension (not heart failure) and he had to decide which agent to prescribe, he would use an alternative to an ARB or ACE-inhibitor at this stage.
 
‘But I make that clear that’s purely a personal feeling, there is no guideline to say that’s what you should do,’ he said.
 
The bottom line
Professor Esler says the data is still evolving and the ‘only reason’ he would consider changing a person’s medications would be if it is ‘driven by patients’. 
 
‘Because this is a hypothesis for which there is a good logic, but it’s not proven,’ he said.
 
Meanwhile, Associate Professor Better says it is imperative to stick to current recommendations by peak cardiology bodies to keep patients on their usual therapies.
 
‘At the end of the day, they say there is no clinical evidence these agents have any harm,’ Associate Professor Better said.
 
‘At this point in time, it is strongly recommended that patients should not either stop or change this group of medications.
 
‘If I had to give GPs advice, my recommendation is that if patients ring to say that there’s no clinical evidence to change at this point in time.
 
‘We should do nothing except continue on as is, as recommended by the ESC and other guidelines and obviously [we need to] to watch this space and if things change, keep an open mind as we’re all doing on a day-by-day basis with everything with coronavirus, to go with the flow.
 
‘We all know this is a rapidly evolving field and my advice this week may be completely irrelevant next week. We just don’t know.’
 
The RACGP has more information on coronavirus available on its website.
 
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ACE-inhibitors antihypertensives ARBs coronavirus COVID-19



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Dr Ian Mark Light   19/03/2020 8:02:14 AM

ACE inhibitors produce cough in close to 1 in 10 patients .
More some contend people on ACE inhibitors get a prolonged coughing when they get a viral infection and I have seen doctors take their patients off ACE in this prolonged bronchitis situation .
Stopping the ACE or ARB is not critical in hypertension there are still CCB and diuretics and though in heart failure it is more problematic increased dose of diuretic including Spironolactone is possible acutely .
In diabetics ACE treatment is oftentimes for long term .
Certainly if a patient is well - one would hesitate if there was hypertension above 180/100 less so for BP 140/90 trying to reduce to130/80-but once the prodrome starts a swap to other classes ought occur .


Dr Brian N   19/03/2020 9:35:11 PM

A key question here is: should a real link exist between ARB use and severity of COVID-19 infection, how long does it take after cessation of ARBs for the up-regulation of ACE-2 to return to baseline? If the timeframe is many weeks it may not prove to be an effective intervention at all.


Dr Jaharlal Saha   20/03/2020 10:43:18 PM

Need more information


Dr Peter Robert Bradley   21/03/2020 11:15:23 AM

I am somewhat puzzled by the cognitive dissonance raised by the following excerpts from the above. Associate Professor Better says it is imperative to stick to current recommendations by peak cardiology bodies to keep patients on their usual therapies. ‘At the end of the day, they say there is no clinical evidence these agents have any harm,’
Is this not the typical plausible deniability stance they adopt when they can't quote a controlled trial. But there is no time for that in this situation. However, I would have thought that this comment came as close as we are likely to get to some kind of clinical evidence...‘The first clue was really that severe COVID-19 infection was more common in hypertension, and hypertensive patients are really not predisposed to infection at all, so that was very odd,’ and finally, this comment speaks volumes... "That said, Associate Professor Better said if he had a new patient present to him today with hypertension he'd choose an alternative...


Dr Peter Robert Bradley   21/03/2020 11:16:50 AM

Why the 1000 characters limit - it's just not enough - especially to sensibly discuss such an important subject as this pandemic..?


Dr Rodney Paul Jones   21/03/2020 1:53:47 PM

Could we please now include Covid 19 in the resp virus screening panel as a standard along with the other URTI viruses ? We already know it comes in from overseas. We want to know when it arrives locally in our community . Sounds like they did this in Taiwan. The sooner we know when the first cases appear the sooner we can get on top of the contact tracing and isolation


Dr Meera Joshi   4/04/2020 8:57:51 PM

In my clinical experience most of Hypertensive patients -first line ACEI if no side effects if any cough more than 30 days I switched to ARB's is there any time frame or any evidence to change to Calcium channel blockers in pt 's of age 60 and over?
This question has been troubling me since day of COVID19 started .
Can we start Covid viral screening to protect healthy community ?it should not be too late.