We’ve been obsessed with azithromycin’s cardiovascular effects for quite some time – with some studies showing an increase in events, and other studies using azithromycin as the active agent to decrease coronary events. Why is it such an issue? Mostly because azithromycin has become the nonsensical cure-all of eager-to-please primary care physicians for self-limited or viral conditions, let alone the mainstay of treatment for pneumonia.
This latest study comes from a retrospective cohort of Veterans Affairs patients admitted and receiving IDSA guideline-compliant treatment for community-acquired pneumonia. These authors compared a cohort of patients receiving ß-lactam + azithromycin with any other guideline-compliant therapy, typically fluoroquinolone monotherapy. They created two propensity-matched cohorts based on known confounders, resulting in comparison groups of 31,863 patients each, with a treatment period spanning 2001 to 2012.
Of these, 1,948 patients exposed to azithromycin had a myocardial infarction recorded within 90 days, compared with 1,523 in the non-azithromycin cohort, for an OR of 1.11 (95% CI 1.03-1.20). No other cardiovascular disease was increased, and no specific subgroup conferred a higher or lower risk of MI after azithromycin use. Most of the difference in MI occurred within 30 days of exposure.
However, interestingly, the overall 90-day mortality was 6,582 in the azithromycin cohort, compared with 8,152 in the non-azithromycin cohort, for an OR of 0.73 (95% CI 0.70-0.76). And, the authors happily run with this mortality advantage – concluding “azithromycin compared with other antibiotics was associated with a lower risk of 90-day mortality (number needed to treat of 21)”. But, how does a short course of a macrolide antibiotic generate such a profound survival curve that progressively widens months after exposure? The authors do not provide data on causes of death, nor do they provide much explanation for the observed survival advantage. Either short-course azithromycin provides a powerful, anti-inflammatory effect with long-term advantage – as implied by the authors – or there’s a problem with the data and the matching.
My vote is for problems with the data. Propensity matching is only as good as the prognostic importance of variables included in the algorithm, and suffers tremendously when performed on retrospective data not gathered specifically to support such analyses. Sadly, this study is probably best served to be assigned to the scrap heap of unreliable retrospective observations.
“Association of Azithromycin With Mortality and Cardiovascular Events Among Older Patients Hospitalized With Pneumonia”
May I chime in from across the pond ?
I'm happy to see you bash and trash this nonsensical study.
I have many American patients attending for colds. Yeap , that is an emergency, Sir . And most are happy to hear me tell them : "you have a virus infection that you'll overcome with tincture of time, the benevolence of the higher authorities up there, and pain/cough medication".
Yet there are some who come with a shopping list that includes "Zeepaq".
They know their body you know.
I eventually discovered that "Zeepaq" is azithromycin.
And these folks have been pavlovised by doctors I guess (yikes !) , into thinking the "Zeepaq" is the cause of their viral infection's natural cure.
Now, we had a recent miracle to help us righteous docs.
An immensely terrifying retrospective study but (I kept it secret) with no proof of causation whatsoever. Patients compared were akin to apple patients given Z-pack and orange patients given amoxicillin or something else). And that study , oh my god ! Oh my god!
It showed the odds of death were SIGNIFICANTLY increased with Zeepaq.
A miracle I tell you.
Of course , the absolute risk increase was microscopic, but OK there was a significant effect in a retrospective study that was not convincing.
But that was a great weapon !
Go figure !
"What ? Zee PAck ? You must be kidding ! Don't you know it causes sudden death ! "
"really , doctor ? "
"You bet ! "
"Holy xxxx!"
"yeap ! "
ANd now comes this new propensity thing (so trendy !) study that breaks my new Zeepaqicide weapon down to pieces ! A conspiracy !
Well anyway this new one is as unconvincing ( data look ridiculous as you point) ) as the one formerly vilifying the ZeeePaq .
Another paper anyway.
Couldn't we next bash azithromycin for long exposures to low concentrations hereby favouring resistances ?
And as for the purportedly so important sexy anti-inflammatory effects, well come on, give your patients real anti-inflammatory drugs then, guys ! The real stuff ! Prednisone ! Ketorolac !
No ? Why not ?
Well no.
Yes I'm a naughty boy. Won't do it again.