ѻý

ACEi/ARBs and COVID-19: Assessing the Strength of Evidence

<ѻý class="mpt-content-deck">— Don't take COVID-19 data about RAAS inhibitors too seriously, expert urges
Last Updated April 1, 2020
MedpageToday

A analyzed data from China on the effect of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) in patients with COVID-19 coronavirus infection. In this exclusive ѻý video, , a cardiologist at Yale University and co-founder of , critiques the study and offers a word of caution.

The following is a transcript of his remarks:

Recently there was a preprint that was posted that addressed some of the issues that people are raising about ACE inhibitors and ARBs used to treat patients from COVID-19, or to prevent the infection. The preprint appeared in medRxiv.

When we post articles or post preprints to medRxiv, they're not edited. They're not peer reviewed. They're posted as they're submitted. People are trying to get out information rapidly and trying to spread them.

This is preliminary data. It's data for discussion. What they said they were going to set out and do was, they said, "Here, we conducted a retrospective study of the effects of RAAS blockers on disease severity and COVID-19 patients. We also performed an updated meta-analysis of ACEi and ARB effects in reducing the risk of pneumonia and on pneumonia-related outcomes."

Now remember in the title, they're asserting a benefit essentially, saying that ARBs mitigate the effects of COVID-19 infections. Here they're telling you what they're doing is taking a look at their experience within their hospital. And in addition, trying to distill information from the literature.

Now what they did was they took medical records of three cohorts from Shenzhen Third People's Hospital, the Renmin Hospital of Wuhan University, and the Fifth Medical Center of the People's Liberation Army General Hospital in Beijing. And they looked at patients who are admitted from the end of December to the end of February.

Now what's important, if you look at their first figure, is that they had these three cohorts from the three hospitals, when they looked at the patients, they get down to the bottom, they had only 78 patients that were included with hypertension.

So, so this is a really important point. A lot of times people will pick up on the fact that a preprint came out, is asserting some relationships and benefits and it's important to recognize again, these preprints are pre-peer-reviewed and you've got to look and see what's the level of evidence for these studies. And how strong is it. In this case you're talking about 78 COVID-19 patients with hypertension.

And first conclusion they made was that, "There is no statistical difference in disease severity between any of the five different types of anti-hypertensive drugs (CCB, ARB, ACEi, thiazide or BB) compared to no drugs taken by all COVID-19 patients with hypertension."

I mean, I think by all rights we would say this is pretty weak information. Look, I salute the investigators for pushing forward information that they're generating, but it's up to readers to recognize that this is not information upon which to make clinical decisions.

Then what they did was they analyzed data from the 46 elderly COVID-19 patients. Those that were over 65, and here they find the patients that took ARB drugs before entering the hospital had a reduced risk of disease severity associated with the infection.

So they're not saying it prevented infection, they're not saying it improved outcomes. Again, salute the investigators for taking the time to write up their experience, but this would represent extraordinarily weak evidence upon which to make decisions.

They also did look at the literature. They were saying that ARBs are found to be associated with a reduced risk of pneumonia morbidity in a total of 70,000 people that were in studies that were looked at. But even in a subgroup, it's not clear to me it was pre-specified as one of the things that they wanted to look at. They also looked at ACE inhibitors and they said that it's been known previously that ACE inhibitors reduce morbidity and mortality in pneumonia patients. And so I think we have to be careful about these inferences and they're not here talking about COVID-19. In any case, this is all comers in studies that have been presented with pneumonia.

They come out in the discussion saying, "In this retrospective study, we report that ARB anti-hypertensive drugs significantly reduced the risk of severe pneumonia in elderly COVID-19 patients with hypertension comorbidity." I certainly hope that there are no news organizations that pick up on this and would suggests that this is any kind of evidence upon which clinical decisions should be made. I think it's a good example of a preprint server.

This issue of the ACE inhibitors and the ARBs and their role in COVID-19 prevention and treatment and whether they make things better or worse is still very active. We're eager for evidence and information. We just have to be thoughtful about the way in which we interpret the information that is presented in and particularly on preprint servers. I think it's a wonderful way to disseminate what people are thinking about and what they're doing. We just have to be careful in our interpretation.