Haridarshan Patel, PharmD, PhD joins JAMA Network Open Digital Media Editor, Seth Trueger, MD, MPH, to discuss an observational cohort study comparing the odds of cardiac events among new users of azithromycin relative to new users of amoxicillin using real-world data. Read the article here:
Hello and welcome to gemma network open live i’m seth trueger digital media editor at gemini network open of course if you’re following along live please send us your questions or comments on twitter at gemma network open or in the comment box and face facebook or youtube live uh today we are talking about an interesting paper the comparison of cardiac events
Associated with zithromycin versus maxicillin and we’ve got first author dr hari patel with us welcome dr patel thank you seth thanks for having me great really glad you could join us thank um i’m really glad i worked out can you uh just start off by telling us in the audience a bit about who you are and what prompted you to do this study yeah absolutely so
I’m an outcomes researcher and a pharmacist by training i work for my own consulting company at the moment which focuses on generating real world evidence but at the time when i did this research it was actually part of my phd dissertation at the university and then the research was partly motivated by the fact that there was a lot of conflicting evidence and
Different studies that examined the same exact research question so for the longest time xetromycin was considered to be the safest drug or safest macrolide but in 2012 there was a study that showed there was an increased risk among patients were prescribed as ether myosin what this study found was that there was an increased risk of death as well and then soon
After this study the fda issued a warning which cautioned the use of the zethromyosin and then over the course of eight years like i said there’s been several observational studies that looked at this and they found either an increased risk or no risk with azithromycin so based on this what we did was we asked ourselves three questions first we asked if there was
A change in cardiac of cardiac risk factors among patients who received the zithromyosin before and after the fda warning and what we found was there was no increase there was no increase in the prevalence or decrease in the power prevalence so saying that the fda warning didn’t have any impact on the way xethromycin is prescribed uh secondly we looked at a risk
Prediction model to help us identify some of the baseline cormorate conditions and especially specific qt prolonging medications that increase the risk of cardiovascular events with azithromycin and then lastly in this third paper we examine the risk of cardiac events among azithromys and amoxicillin users and what we found was that um in a large so we what we did
Was we used a large claims database to conduct a retrospective cohort study and we use high dimensional propensity scores to control for compounding and we included almost 2 million patients who are prescribed azithromycin and match those patients against amoxicillin users and then we looked at the occurrence of cardiac events either rising from a hospitalization
An emergency room visit and we looked at this risk at a five day ten day and a 30 day period after patients are started on therapy and we looked at several subgroups we looked at patients who were elderly patients who had cardiovascular disease and then we looked at patients who had the predictors based on our prediction model from the previous analysis and so
What we find we found that there is no increased risk in the overall population but if you’re going to be prescribed as ether myosin with another qt prolonging medication then you’re going to experience at least a 40 increased risk in cardiac events yeah so great thanks that was a wonderful overview but to hit some of the key points there uh so you use the truvid
Market scan database which is which is really good database it’s got a ton of data as you said you were able to suss out uh about 2 million um moxillin uses and 2 million patients who’ve got xenomycin which you know a ton of patients 2019 2015 um you know looked at all the different outcomes of syncope palpitations long qt syndrome ventricular rhythmias cardiac
Arrest and death and then time points 5 10 30 days it’s pretty impressive i was honestly one of the things that was most impressive is even that pretty expansive definition of outcomes which includes you know just symptoms like palpitations um there were a really small rate of events it was uh less than 1500 or fewer than 1500 events which was i think if your
Math was right or if i got your math right it was um 3.4 per 10 000 which is really exactly yeah so and the the reason why that number is low so you have to keep in mind that these conditions led to a hospitalization or er visit so if you’re taking a zithromyosin you may experience palpitation and it may self-resolve um and you could have other other symptoms
That you may experience but if you haven’t gone to the doctor if you haven’t gone to see a a er doctor for instance then we wouldn’t be able to capture this so what we’re looking here is a very serious set of conditions that led to a hospitalization among exeter mice and amoxicillin users oh yes that makes a lot of sense um and i also found it interesting that you
Know not only the rates pretty similar but the uh the most common events that were that you found were were syncope and palpitations sinclair made up i think it was seven percent of the events yeah exactly so 70 of the patient has syncope 30 had uh palpitation uh out of those 1500 uh cardio cardiac events that we had measured yeah um yeah interesting and you know
As you said uh all the differences you found were not significant um the odds ratios were at five days 1.08 at 10 days 1.05 and 30 is 0.98 and they all crossed one although the five day and 10 day were pretty close to one and i think you know it would not be unfair to say to interpret this as a trend towards an increase but with two million in each group um and
Only you know 700 events in each group that seems like a a pretty low risk if there’s any there even you know being i’d say as uh i don’t know biased towards finding a difference as you can yeah no absolutely i think you make a good point in terms of the risk is definitely rare but you know among the patients who are prescribed these qt prolonging medications
That that’s a preventable risk that we want to highlight from this study is that if clinicians especially even pharmacists who can uh counsel patients or to monitor patients who are going to be taking these medications together so let’s prevent the risk that where we can yeah and looking at the table uh which unfortunately we can’t show is too big there’s too much
Data here um the uh the list of the qt prolonging drugs to me was was really fascinating it was it looks like most of them were antidepressants yep that’s right so there’s over 200 uh medications that have either known possible conditional risk of qt prolongation and majority of them are falling into the category of antidepressants so not all the antidepressants
Could be on the list but the ones that have been previously linked with qt prolongations are the ones we had included in our study right that makes sense there’s also i think a you know useful category to just kind of think about you know if i’m going to prescribe somebody azithro or amoxicillin uh you know thinking instead of what are the qt prolonging prolonged
Antidepressants look are they on an antidepressant all right now is it deeper along you want um anxiety replace difficult questions the easy questions right and then so one thing that’s interesting to me uh you know i think we all agree there’s a lot of azithromycin that’s prescribed and a lot of it is probably prescribed for uh you know some clinical reasons politely
Um but in 2019 the new pneumonia guidelines came out from the idsa and ats and basically essentially replaced a lot of the a lot of the most common indications for the horizon which was uh just for uncomplicated outpatient community acquired pneumonia with amoxicillin so i’m i think that that it’s i think could potentially provide a good natural experiment if a
Lot of people were otherwise would have gotten azithromycin are gonna be getting maxillin theoretically people actually follow the guidelines no absolutely i would love to set up that natural experiment right i mean uh we’re not gonna find a better comparison i mean we try to do the same thing in this study by using high dimensional propensity score which could
Mimic what a randomization would have done but not close to what a randomization would do yeah and i think you know burundi scores are great and you guys have a lot of data in a huge database um but you know there’s there’s so much you know potential for clinical nuance that just doesn’t get into those databases that is it’s really hard to say um absolutely yeah
I mean yeah so one of the limitations is that you know we don’t have the clinical severity of these infections or even the the conditions for which these medications are prescribed which could uh potentially uh you know result in residual compounding as you mentioned yeah and you know i would say you know from my my uh my kind of initial gut is that people who
Get azithro instead of maxillin where both would theoretically be appropriate are probably more likely to be people we think are more sick so even if they don’t take boxes that end up in a database that end up being more sick there might be some nuance there um who knows i don’t know we’ll see yeah but again i think if nothing else the low rate of events i found
Pretty reassuring here which is great yeah no overall like the message i would leave with is that it’s a safe therapy um i think the risk again it’s three to four in ten thousand prescriptions of azithromycin but what’s important is that uh one in five patients who receive the zithromyosin are on these qt prolonging medications so that’s what that’s where we want
To drive the point home is that you know let’s be careful when we’re prescribing azithromycin if we especially have another medication that’s going to prolong the qt interval yeah and of course when we say you know when you say it’s safe which i totally agree it’s that’s in the appropriate patients from this cardiac arrhythmia uh point of view you know antibiotics
Uh inappropriate antibiotic use exposes both patients and the community to all sorts of side effects uh you know someone’s between one and six and one and ten people get diarrhea one in six to one and ten women um get yeast infections i mean stuff that’s just just really unfortunate plus the more serious things like c diff and of course antibiotic resistance over
Time as we you know quickly approach the post antibiotic era yeah yep great well that brings us about to the end of the time anything else you wanted to add here no so i mean i just want to reiterate the point that you know if you’re going to be taking azithromycin more than likely you’re going to be safe but as a patient or a provider if you happen to see those
Other qt prolonging medications be careful let’s try to avoid if we can uh let’s monitor the patients who really need to be on these uh medications together that certainly sounds very reasonable so thanks again for this network and thanks for joining us today um thanks for having me great so that wraps things up for this episode of course you can get this paper
And more at jammingnetworkopen.com where everything is free and open access we’ve got new papers coming out every weekday morning at 10 a.m central time and join us again next week on september 29th 3 pm central for another episode of jno live take care and stay safe you
Transcribed from video
Cardiac Events Associated With Azithromycin vs Amoxicillin By JAMA NetworkliveBroadcastDetails{isLiveNowfalsestartTimestamp2020-09-22T200022+0000endTimestamp2020-09-22T201357+0000}
