Over the past few weeks, President Trump has been promoting the malaria drug hydroxychloroquine as a treatment for Covid-19, despite the lack of benefit to patients and serious potental harms.
A physician in pulmonary medicine at Mount Sinai hospital in New York City recently told the Associated Press about his decision to give tissue plasminogen activator (tPA), a clot-busting drug often used to treat strokes, to five patients who appeared to be suffering from Covid-related blood clots.
What do these two cases have in common? In promoting the use of these therapies for Covid-19, both used the logic, “What do we have to lose?” When people are dying and we have something that could help them get better, why not try it?
For those who have been fighting against the use of unproven treatments in medicine for years, it is clear that we have a lot to lose. The most obvious potential loss is additional loss of life through side effects of these unproven medications. In the largest study of hydroxychloroquine for Covid-19 to date, not only did the drug not save more lives, it actually increased the risk of dying for these patients from 11% to 28%. The U.S. Food and Drug administration subsequently warned against using the drug outside of the hospital setting because the drug increases the risk of heart rhythm problems.
Use of the blood clot-busting drug tPA for Covid-19 is similarly unfounded and risky. The role of blood clots in Covid-19 deaths is becoming more apparent to doctors treating the virus, which has led to some using tPA to try and break up blood clots in the lungs. However, there is no proof yet that tPA helps Covid-19 patients. In fact, the benefit of tPA for patients with strokes (and not Covid) is still debated to this day, as many studies have shown that stroke patients given tPA are more likely to suffer a serious brain bleed than they are to recover. And a recent study found that giving tPA to Covid-19 patients with suspected artery clots was ineffective because many patients turned out not to have blockages at all, just symptoms that mimicked blockages.
The AP article reports that doctors at Mount Sinai gave tPA to five patients, one who died of a blood clot anyway, one who died of a different unnamed complication, and three who remained on ventilators but appeared to be “doing better.” Not quite a resounding success– yet people who see the just headline could be convinced that tPA is our best chance of saving Covid-19 patients.
“what do we have to lose?”. The patient lives but with a brain bleed and permanent severe disability. The patient dies but would have lived with supportive care alone. How is this ethical?
— Todd Lee (@DrToddLee) April 13, 2020
Doctors should trust their clinical judgement and give the treatment they believe is best for the patient–in times like this, that may include therapies with unknown benefit. However, giving some Covid-19 patients an experimental therapy is much different than telling the media, “What did I have to lose?” Given the lack of evidence for this therapy, this is not the message doctors should be sending.
The second important loss from touting unproven treatments is the chance to research them and find out if they actually work. Once President Trump started hyping hydroxychloroquine, he instantly made it more difficult for researchers to conduct a clinical trial of the drug, because it is harder to recruit patients to be randomized if they already believe that the drug is effective.
The same problem may impact trials for tPA, if people are convinced that it is the solution to Covid-related blood clots. Fortunately, many doctors noticing blood clots in Covid-19 patients are eager to test tPA before hyping it. For example, Dr. Christopher Barrett, a surgeon at Beth Israel Deaconess Medical Center who published a case report about blood clots in Covid-19 patients, said in STAT News, “I can’t stress enough that it is important to have a controlled study to demonstrate that people who get this either do or don’t do better.” Barrett hits on a key point–that until we do the right studies, we don’t know if new Covid-19 treatments will help or hurt patients, and it could go either way.
Lastly, the drive to do something to cure Covid-19 may prevent physicians from providing supportive care that could actually help patients live longer. As Harvard Medical School student Ivry Zagury-Orly and professor Dr. Richard M. Schwartzstein write in the New England Journal of Medicine, “The intense desire to try new, unproven remedies may distract health care providers from offering patients the best-quality supportive care possible.” That means being focused on the basics of care: closely monitoring patients, helping them breathe, preventing dehydration, and keeping their fever down.
Front-line health care workers are learning more about Covid-19 and how to treat it every day. But distinguishing between a good theory and an actually effective treatment will take more–and better–research. It’s up to researchers, policymakers, and the media to convey what we know and what we don’t know about new Covid-19 treatments and approach new treatments with healthy skepticism. If we don’t do this, we have a lot to lose.