[blueash]

Pre-publication and pre-peer reviewed so lots of be careful about accepting the results.

The authors using VA Hospital nationwide electronic records analyzed every patient in the system who had a positive COVID test and was hospitalized. They recorded many lab tests and vital signs from the admission record and checked the outcome of three groups. All patients were male and 65 or older. These results are specific to this demographic.

Groups:

1. Those given HCQ [hydroxychloroquine] but no AZ 97
2. Those given HCQ and AZ [azithromycin AKA Z-pack] 113
3. Those that received neither of these two drugs 158

Two outcomes were targeted for study
1 Death by the end date of the study, April 11th, just 10 days ago so rapidly reported
2 Need to go onto a ventilator

Because the patients were not randomly assigned there were some differences in the health on admission of those treated vs not treated. However many of the less ill got meds and many of the more ill did not. But more of the ill got meds overall. There were enough in each group to correct as much as statistically possible for the uneven distribution on entry. If you read the study that is the propensity score adjustment

So what was the outcome? unadjusted:

…………….. Neither Just HCQ ….Both HCQ+AZ
Death . . 11% ………….. . 28% . …………….. . 22%
Vent . . 14% . ……….. . 13% . …...………. . 7%

After adjustment for initial presentation and comorbidities :

Compared to the no HC group, there was a higher risk of death from any cause in the HC group (adjusted HR, 2.61; 95% CI, 1.10 to 6.17; P=0.03) but not in the HC+AZ group (adjusted HR, 1.14; 95% CI, 0.56 to 2.32; P=0.72) (Table 5). We did not observe a significant difference in the risk of ventilation in either the HC group (adjusted HR, 1.43; 95% CI, 0.53 to 3.79; P=0.48) or the HC+AZ group (adjusted HR, 0.43; 95% CI, 0.16 to 1.12; P=0.09), compared to the no HC group (Table 5).

We then analyzed a secondary outcome of death among patients who required mechanical ventilation (Table 1). No significant difference was observed in the risk of death after ventilation in either the HC group (adjusted HR, 4.08; 95% CI, 0.77 to 21.70; P=0.10) or the HC+AZ group (adjusted HR, 1.20; 95% CI, 0.25 to 5.77; P=0.82), compared to the no HC group (Table 5).

Conclusion:

"hydroxychloroquine use with or without co-administration of azithromycin did not improve mortality or reduce the need for mechanical ventilation in hospitalized patients. On the contrary, hydroxychloroquine use alone was associated with an increased risk of mortality compared to standard care alone."

My thoughts: Despite the early dramatic success of HCQ +/- AZ in some early reports, all the more recent papers I have seen have not been able to confirm any benefit. This is the largest reported number of patients in any study. It is retrospective. It is not random. It is in a very limited demographic, old men. But old men are the highest risk group. What it does show is that in old men there is no support found for giving either HCQ or HCQ+AZ. There is a statistically increased risk of death with HCQ even after adjustments. That is likely a statistical fluke as there is no reason why the drug alone would be risky but not in combination with AZ. The authors do not tell us whether EKG's were checked nor what doses of medications were used.

Prospective randomized studies are ongoing. Their results will be much more useful. But this study throws buckets of cold water on the HCQ enthusiasm.