This will make for a hell of a rant later today about “Trump enemy statements.”

Three things about this study distinguish it from (most) other recent studies of hydroxychloroquine use by coronavirus patients. One: The sample size is enormous, involving nearly 100,000 people at 671 medical centers on six continents over four months.

Two: Researchers looked only at patients who received the drug within 48 hours of testing positive for COVID-19. That doesn’t mean that all of them were in the earliest stages of the disease when they started taking HCQ; some may not have been properly diagnosed until many days after symptoms first appeared. But anyone on a ventilator was excluded from the study so that the most dire cases wouldn’t influence the results. And the 48-hour time frame means that this should give us a sense of whether the drug is more effective taken earlier in the course of treatment.

Three, most importantly: The data suggests that HCQ might be doing more harm than good. The VA study from last month that Trump complained about this week also found that patients who took the drug were more likely to die, but the sample in that one was a tiny fraction of what it was in this new one. It’s alarming that a data set this large would end up suggesting that hydroxychloroquine is accelerating death in COVID patients.

A former FDA official who spoke to WaPo found the result so unnerving that he called on the agency to revoke HCQ’s emergency-use authorization.

“It’s one thing not to have benefit, but this shows distinct harm,” said Eric Topol, a cardiologist and director of the Scripps Research Translational Institute. “If there was ever hope for this drug, this is the death of it.”…

“I wish we had had this information at the outset,” [researcher Mandeep Mehta] said, “as there has potentially been harm to patients.”…

For those given hydroxychloroquine, there was a 34 percent increase in risk of mortality and a 137 percent increased risk of a serious heart arrhythmias. For those receiving hydroxychloroquine and an antibiotic — the cocktail endorsed by Trump — there was a 45 percent increased risk of death and a 411 percent increased risk of serious heart arrhythmias.

Here’s the breakdown from the abstract of the study itself, published at the Lancet:

96032 patients (mean age 53.8 years, 46.3% women) with COVID-19 were hospitalised during the study period and met the inclusion criteria. Of these, 14888 patients were in the treatment groups (1868 received chloroquine, 3783 received chloroquine with a macrolide, 3016 received hydroxychloroquine, and 6221 received hydroxychloroquine with a macrolide) and 81144 patients were in the control group. 10698 (11.1%) patients died in hospital. After controlling for multiple confounding factors (age, sex, race or ethnicity, body-mass index, underlying cardiovascular disease and its risk factors, diabetes, underlying lung disease, smoking, immunosuppressed condition, and baseline disease severity), when compared with mortality in the control group (9.3%), hydroxychloroquine (18.0%; hazard ratio 1·335, 95% CI 1·223–1·457), hydroxychloroquine with a macrolide (23.8%; 1·447, 1·368–1·531), chloroquine (16.4%; 1·365, 1·218–1·531), and chloroquine with a macrolide (22.2%; 1·368, 1·273–1·469) were each independently associated with an increased risk of in-hospital mortality.

“Macrolide” refers to an antibiotic like azithromycin.

The study’s not definitive, as it’s not a clinical trial. And advocates for the drug insist that it needs to be taken with zinc to be effective. WaPo notes a recent study from NYU’s health center that suggested HCQ plus zinc might mean a higher rate of survival. But that wasn’t definitive either and some experts suspect that the higher rate of survival wasn’t caused by the addition of zinc but was merely a coincidence: “They said the results also could have been due to other factors, such as the zinc being added to patients’ regimens later in the pandemic when hospital treatments and procedures had been refined.” If later studies confirm that hydroxychloroquine taken with zinc does provide some benefit, the new question will be how to square that result will the higher mortality seen in this new study. Does zinc erase all of the apparent added risk of death from taking HCQ for coronavirus patients or does it merely offset the added risk, meaning that there’s no net benefit?

Or is it patient-specific? WaPo notes that “The population infected with covid-19 in hospitals, it turned out, was already at higher risk of cardiovascular complications because many suffer from high blood pressure or other heart issues.” A well-known side effect of HCQ is cardiac arrythmia, making it riskier for people with heart problems. Maybe the drug when taken with zinc has some benefit for coronavirus patients who lack comorbidities involving the heart but is too risky for people with coronary issues to take.

There’ll be more studies. But people who’ve forgotten more about this stuff than I’ll ever know seem to think this one is highly, highly discouraging for hydroxychloroquine as a COVID-19 treatment, even though it’s not a clinical trial: “There was no evidence whatsoever of any benefit with any of these treatment regimes. There was significant evidence of harm. Here’s how it works: when something is real, you continue to see a real signal as you collect more and better data. When something is not real, it disappears. Tell me again why anyone should be advocating such treatments. But your reasons had better stand up to 14,888 patients versus 81,144 comparators. Make it good.”

Meanwhile, sales of the drug doubled in March of this year from March 2019. Prescriptions for the generic version have grown from 460,000 to 830,000.