It’s highly unfortunate, considering the level of confusion that already exists concerning COVID-19, and the amount of misinformation, scams, and deliberate lies being fed into the system, but two major papers that each received significant publicity in connection with the pandemic and medications have now been withdrawn. There’s no doubt that this action is going to raise … doubt.
In a very real way, this is a perfect illustration of the scientific review process at its best: carefully examining the data, acknowledging issues, and addressing concerns regardless of the stakes, reputations, and egos involved. Though, yes, it’s preferable to have problems spotted before articles are published in in the world’s two most prestigious medical journals.
And making everything worse, one of these involves the drug that Donald Trump keeps flogging.
The first of these studies to be pulled was published two weeks ago in the British journal The Lancet. And yes, I previously highlighted the results of this study. With emphasis on highlight. Considering where the paper was published, and that it was funded by Brigham and Women’s Hospital, this seemed like the authoritative large-scale review of hydroxychloroquine as a treatment for COVID-19. It wasn’t a randomized trial, but it was just a lot of data.
The paper took information from 96,000 patients being treated for COVID-19 at over 650 hospitals around the world, going back to the original cases in China at the end of December, 2019. It looked at overall outcomes, then it looked at a 15,000-patient subset that had received antimalarial drug hydroxychloroquine or the closely related chloroquine, as a treatment. The conclusion of that study was, as I said on May 22, “Patients given hydroxychloroquine had a significantly greater risk of dying than those who were not treated with Trump’s favorite drug.”
The authors of the paper were particularly adamant that, “There was absolutely no evidence of benefit noted” in giving hydroxychloroquine to COVID-19 patients and that there was “clear depiction of harm.” It was the kind of paper that got a lot of attention not just at Daily Kos, but also in medical circles where, despite Donald Trump announcing just days later that he was taking hydroxychloroquine as a prophylactic, the results surely scuttled some additional trials and cut down on individual off-label prescriptions.
Those results did not come out of left field. While hydroxychloroquine is used in low doses to treat inflammation in diseases like lupus and rheumatoid arthritis, the dosage levels used in treatment of malaria are known to bring a risk of heart-related issues. Considering the fact that heart problems, including high blood pressure, have been widely correlated with a higher rate of death from COVID-19, it seemed completely reasonable that taking large doses of a drug known to stress the heart might exacerbate the issue. And maybe it does. Because what happened here wasn’t that the paper was found to be wrong. It was found to be … Well, at best missing key data. At worst, fake science.
The issue comes back to one of the authors of the paper, Sapan Desai, and to a Chicago-based company named Surgisphere which is owned by Desai. The data behind the study was supposedly gathered and collated by Surgisphere. However, once the study was out there, physicians and researchers found significant problems with that underlying data. Issues such as case numbers and result outcomes that did not match information that was available to them. After publishing an open letter from a large group of doctors who reported concerns about the study, The Lancet first amended the study to acknowledge concerns over what was said to be incorrect reporting of patient numbers in some locations. Then the other authors whose names were on the study announced they were pulling the paper after Desai’s company refused to provide the raw data on which the tables in the study were based. Which is … pretty damning. Surgisphere also refused to turn over the data to the media, or to provide a full list of hospitals used in the study.
This doesn’t mean that hydroxychloroquine is effective. It certainly does mean that the results of the paper are beyond suspect.
And that brings things across the pond to The New England Journal of Medicine. That august publication had run another large-scale, data-based study earlier in May that was focused on outcomes for COVID-19 patients taking high-blood pressure medication. In particular, the concern was centered on patients taking medication that works by inhibiting the action of angiotensin-converting enzyme, also known as ACE inhibitors.
ACE inhibitors relax the walls of blood vessels, increasing flow and decreasing pressure. They’re widely used since for many patients they have a good outcome and are well tolerated with few side effects. They’re also used to manage chronic heart failure. Doctors are very reluctant to fiddle with blood pressure medications when they’re working well, because finding the right combination for any patient that is both effective and tolerated can be a challenge.
Unfortunately, ACE is involved in a complex regulatory system with another enzyme, ACE2. In a way, the two enzymes counterbalance each other, so taking ACE inhibitors can affect the expression of ACE2. And that’s where COVID-19 comes in. ACE2 is known to bind to the spike protein of the SARS-CoV-2 virus. That binding is a critical part of how the virus enters human cells.
As a result of all this, there are real concerns that those who are taking drugs which inhibit ACE might be at higher risk of infection or greater risks of developing serious illness. There have even been some worries that the connection between COVID-19 deaths and high blood pressure might really be a finger pointing straight at the ACE inhibitors taken by tens of millions around the world.
So when The New England Journal of Medicine study—courtesy of the same authors as The Lancet article—said that ACE inhibitors didn’t correlate to a higher rate of death from COVID-19, it was a great relief. Doctor’s didn’t have to weigh the risk of taking all those patients off their medications and moving them to something else, because all was good. Except now that study has also been pulled. And all is … mud. The data behind this study was also provided by Surgisphere.
Just as with the hydroxychloroquine study, this doesn’t mean that ACE inhibitors are not safe. There’s been data both suggesting that there is, and is not, a connection between these drugs and a higher rate of serious illness and death from COVID-19. What it mostly means is that we need additional studies.
Confession time: I have a personal stake in one of these studies. No, not the hydroxychloroquine one. If it’s actually helpful, which we do not know, Trump can brag all he wants.
Nope, it’s the ACE inhibitor study that I really hated to see get pulled. I’ve had high blood pressure since my late 20s. So did my father. So does my son. No treatment has been great, and on any given day my BP spikes into a range that would have many people zipping toward the ER. But ACE inhibitors help (I take generic ramipril) and don’t seem to bring some of the fun effects of other drugs (like slowing my heart rate into the 30s).
So, apologies for pushing the hydroxychloroquine paper. But at least there are a lot of other studies on the way. In the meantime, stay safe.