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#2 Aspirin for Primary Prevention of Cardiovascular Disease
47 Plays2 years ago
Is it true that "an aspirin a day keeps the doctor away?" Aspirin has long been used to prevent cardiovascular disease for those at risk, but new evidence has driven a major shift in professional guideline recommendations. Drs. Bobby Scott and Sandy Robertson review three landmark studies which have informed these practice-changing guidelines, and explore how over the past 20 years, we went from a state of confidence in its benefits to confidence in its lack of benefit for most people without established cardiovascular disease.
Additionally, in "Residents Ask the Darnedest Things," Dr. Scott attempts to answer a question about the best second-generation antihistamine to treat allergic rhinitis.
Key statistic for counseling patients: "For every 1200 persons taking aspirin for primary prevention for 5 years, there will be 4 fewer MACEs, 3 fewer ischemic strokes, 3 more intracranial hemorrhages, and 8 more major bleeding events." - Moriarty/Ebell ("A comparison of..." article linked below)
Episode outline:
- History of aspirin use for primary prevention 01:39
- Current ACC/AHA and USPSTF guidelines 06:05
- Evidence behind the changed recommendations 11:01
- How did we get here? Was this a medical reversal? 22:31
- Residents Ask The Darnedest Things 30:17
Links from this episode:
- 2019 ACC/AHA Guidelines: https://pubmed.ncbi.nlm.nih.gov/30879355/
- 2021 USPSTF Guidelines (Draft): https://www.uspreventiveservicestaskforce.org/uspstf/draft-recommendation/aspirin-use-to-prevent-cardiovascular-disease-preventive-medication
- ARRIVE: https://pubmed.ncbi.nlm.nih.gov/30158069/
- ASCEND: https://pubmed.ncbi.nlm.nih.gov/30146931/
- ASPREE: https://pubmed.ncbi.nlm.nih.gov/30221596/
- Post-hoc analysis of ASPREE and cancer mortality: https://pubmed.ncbi.nlm.nih.gov/32778876/
- A comparison of contemporary versus older studies of aspirin for primary prevention: https://pubmed.ncbi.nlm.nih.gov/31751455/
- The effectiveness of modern antihistamines for treatment of allergic rhinitis - an IPD meta-analysis of 140,853 patients: https://pubmed.ncbi.nlm.nih.gov/23524648/
If you liked the episode, please leave a positive review and subscribe! Tell your colleagues and friends!
Comments/Questions/Suggestions? Email us at whatstheproofpodcast@gmail.com or find us on Twitter @theproofpodcast!
Credits:
- Hosts: Bobby Scott, MD, FAAFP; Sandy Robertson, PharmD; Dawn Caviness, MD, BSN
- Production & Cover Art: Bobby Scott, MD, FAAFP
- Music: Twisterium, MondayHopes, Muzaproduction, and SergeQuadrado from Pixabay
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Transcript
Podcast Introduction
00:00:00
Speaker
You are listening to the What's the Proof podcast, where we seek to help doctors and other clinicians incorporate the best available evidence into their everyday clinical decision making. The content of this podcast is meant for educational purposes only and should not be construed as personalized medical advice. The views and opinions expressed are those of the host and guest, and no content on this podcast has been approved or sanctioned by Atrium Health.
Meet the Hosts
00:00:35
Speaker
Welcome everybody to the second episode of the What's The Proof podcast. My name is Bobby Scott and with me is Dr. Sandy Robertson. Sandy, I feel like we've really accomplished something. Now we are actually recording our second episode. I'll tell you what, we're experts now, right? We are. Is this another fake it till you make it?
00:00:56
Speaker
Maybe so, yeah. It is for me. We fooled a lot of people after the first one. I didn't get any hate mail, anything that was too critical. Really? Very positive. Well, that's good. I think people were too afraid to hurt my feelings, so I got some pretty positive feedback too. But we're going to do our best today, right? Yeah. So I'm really excited about today's episode.
Aspirin: Current Debates and History
00:01:16
Speaker
time we talked about statin use in the elderly. Today we're going to talk about aspirin, another topic that's been in the news. Patients are asking about it. Doctors have been confused about aspirin for probably a long time now. So I'm really excited to hear what you have to say. Okay. Well, I want to start off with a history lesson. Is that okay?
00:01:42
Speaker
Yeah, please. I love history. I know I'm a geek, but just bear with me. So aspirin was discovered in 1853 by a German chemist working for Bayer. Yes, Bayer, the company that still produces aspirin today. It was used to treat pain. Its mechanism of action was thought to be CNS related.
Aspirin in Heart Attack and Stroke Prevention
00:02:01
Speaker
And it wasn't until 1950 that a family doctor noticed severe bleeding in some of his patients chewing high amounts of Aspergum. Do you remember Aspergum, Bobby? You know, I actually had never heard of that. I had to look it up, but it's totally fascinating that there was Aspergum.
00:02:22
Speaker
You've tasted it? Oh yeah, as a kid I ate it. You ate it as a kid? Yes, don't go there. Okay, back to the facts. So chewing high amounts of Aspergon post tonsillectomy and he questioned its antiplatelet effects.
00:02:37
Speaker
The first RCT in heart attack survivors with aspirin started in 1963. And in 1971, the mechanism of action being irreversibly inhibiting cyclooxygenase, which we all learned in medical school, that was finally confirmed. By 2007, 20% of the US adult population was taking aspirin for, quote, heart health. With over 50% of adults 65 years or older taking aspirin regularly.
00:03:05
Speaker
Now, before we start into all the data for primary prevention, which means you've yet to have a heart attack or yet to have a stroke, I want to just give a quick reminder of the numbers. So, aspirin use immediately after a STEMI.
00:03:22
Speaker
Secondary prevention now. This is secondary prevention. You just had a STEMI. You chew up an aspirin. Standard of care. That has a mortality benefit of 1 in 42. The number needed to treat is 1 in 42 to prevent one death. And that is a very good number. Okay?
00:03:38
Speaker
Aspirin after a stroke, again, secondary prevention, you just had your stroke, now you're taking an aspirin. That is a 1 in 70 mortality or dependence benefit. A 1 in 140 for recurrent stroke.
00:03:55
Speaker
and a 1 in 245 for Major Bleed. These are good numbers, okay? So let's be very clear. The numbers for secondary prevention are beneficial, and we're not talking about that anymore, okay? Right. Okay. And I think you're talking about number needed to treat there, right? Yes, number needed to treat. Can you tell us a little bit about what that means?
00:04:16
Speaker
Sure, number needed to treat is what is the number of patients that need to take this therapy for a defined period of time that's consistent with the studies to see a benefit? So again, going back to our one in 42 mortality benefit for STEMI, 42 people immediately after taking a STEMI that take an aspirin, due to that aspirin alone, that will prevent one death.
00:04:44
Speaker
That's what that means. Now, I do think it's important to note that in May of 2014, the FDA actually denied a request by Bayer Pharmaceuticals to extend aspirin's approval for primary prevention of cardiovascular disease. I missed this, to be quite honest. I just jumped right over it. I'm sure it was in the news and I just didn't see it.
00:05:09
Speaker
The FDA reviewed the available data at the time and stated that the evidence does not support the general use of aspirin for primary prevention of a heart attack or stroke. In fact, the FDA noted that there are serious risks associated with use of aspirin, including the increased risk of bleeding in the stomach and brain in situations where the benefit of aspirin for primary prevention has not been established.
00:05:35
Speaker
Wow. Interesting. I know. Did you know that? No. I don't remember hearing that at all. So I think, you know, Bayer just wanted to kind of close the loop and get the FDA indication for primary prevention and they, the door was shut on that. But yet here we are talking about primary prevention in 2022. It's kind of amazing to think that the FDA would deny that when it was pretty much standard of care at the time. Right. Right.
00:05:59
Speaker
And not to say that we don't do things off label, I'm not saying that we have to follow everything, but in this case, I think we just jumped right over it. So, Bobby, do you want to take some time just to review for the audience what the current guidelines are for aspirin for primary prevention of cardiovascular disease?
Guidelines and Recommendations for Aspirin Use
00:06:15
Speaker
Sure, yeah, so there are lots of major guidelines out there, but probably the two most commonly paid attention to would be the ones by the USPSTF, as well as the AHA, ASA. Those were the most recent ones published in 2019, and they suggested that aspirin might be considered in select high-risk adults between the age of 40 and 70
00:06:43
Speaker
who are not at an increased risk of bleeding, meaning a history of GI bleed, peptic ulcer disease, any other severe bleed in their history. If they're older than 70, chronic kidney disease, thrombocytopenia, they're also taking NSAIDs or DOACs or steroids, a lot of different reasons.
00:07:05
Speaker
But interestingly, they do not give a 10-year risk percentage as a cutoff. What is defined as high risk, they don't give a percentage. And it's interesting because they were the group that introduced the risk estimator, right? Right. And I think some people are questioning that risk estimator now, correct?
00:07:26
Speaker
Yeah, yeah, there's a lot of question whether it's overestimating risk. So they give this a class 2B recommendation based on level A evidence, so high quality evidence. When was this published? In 2019. Oh, so very recent. OK. Yeah.
00:07:42
Speaker
So the USPSTF is interesting because we have the history that we've traced back regarding their recommendations on aspirin for primary prevention. So if you go back to 1996,
00:07:58
Speaker
At that time, the USPSTF suggested that the evidence was insufficient for its use for primary prevention for adults between 40 and 84 years old. Okay. And then fast forward to 2002, they've completely changed from insufficient to level A high quality evidence recommending using it in this same age group.
Recent Trials and Their Impact on Guidelines
00:08:25
Speaker
Okay.
00:08:26
Speaker
which is a very strong recommendation, good, clear evidence on that. So moving forward a little bit to 2009, you start to see that as we get more evidence, the recommendation is not quite as broad. It's starting to break down different age groups, stratifying between men and women based on age. So the lower cutoff is 45. I remember that, yeah, I remember that well.
00:08:53
Speaker
And for women, it was 55. And that was really more for stroke prevention, I believe, at that time.
00:09:00
Speaker
And then in 2016, things really got narrow. So their primary group that they recommended, gave a B grade recommendation for the use of aspirin, were for adults that were between 50 and 59. And they have at least a 10 year, or at least a 10% 10 year estimated ASCVD risk.
00:09:24
Speaker
but also have no increased risk of bleeding, they have a life expectancy of at least 10 years, and they're also willing to take aspirin for 10 years. So they're signing up, they're signing a 10-year contract. Exactly, yes, but only if you qualify.
00:09:41
Speaker
And then for the older groups, so 60 to 69 or younger people or even above 70, really there's not a strong recommendation for any of them and then insufficient for most. And then what's made headlines recently is this year they put out a new recommendation.
00:10:02
Speaker
And basically, adults 40 to 59 with a 10% 10-year risk and no increased bleeding risk, they now give that a C recommendation. So we've gone completely back to 1996 on the C. Yes, full circle here. Full circle, okay.
00:10:25
Speaker
C meaning now there's question about the risk and benefit ratio and now they're recommending having an individualized discussion with patients and deciding at that point. Shared decision making. Right. Right. That's always something that makes physicians cringe. It's all on you. You gotta spend 10 extra minutes now to do that. What about people older than 59?
00:10:49
Speaker
Yeah, so people older than 59, they now say, do not do it. Oh, it's a D? Yeah, it's a D recommendation. It's not beneficial and only harmful. Okay. All right. So Sandy, like we just said, we came a long way and basically have gone back to 30 years ago in our recommendations. So what is driving this change in both these sets of guidelines?
00:11:16
Speaker
Right, right. And I did have to look all this up and reread it. And being the nerd that I am, I really enjoyed it. So there are three large randomized trials that were all published in 2018. You have the ARRIVE, the ASPRI, and the ASCEND. And they're all in tens of thousands of patients, OK? And this is really what's driving this new evidence and the confidence or the lack thereof that the USPSDF is having with regards to the benefits and the harms of aspirin.
00:11:47
Speaker
If you'll allow me to, I do think it's interesting to go over the study populations that were in these trials, okay? We'll eventually get to the meta-analyses, but let's kind of break this down a little bit for the audience. So the ASCEND trial, they study diabetics, and that's really important because, you know, right? Diabetics, cardiovascular equivalent, correct? Yeah.
00:12:10
Speaker
Not really, but that's what we were taught. So ASCEND studied diabetics mean age of 63. They studied them for 7.4 years. 75% of those patients were on a statin and only 8% smokers. I found that interesting. That's much lower than the general population. The ARRIVE study specifically studied non-diabetics with a mean age of 63, same age, for five years.
00:12:37
Speaker
44% of them were on a statin, but 29% of them were smokers. That's different, right? Population's very different. The Asprey, or Asprey, I don't know how to say that.
00:12:53
Speaker
They studied mostly non-diabetics, so only 10% of that population had diabetes. They were a decade older. This was specifically looking at elderly, so the mean age was 74, and they studied them for five years. Only 33% of that population was on a statin, and only 4% smokers.
00:13:13
Speaker
Okay, so the study populations are different, but there's so many of them. We're talking, I think all together there's over 50,000 patients in these trials. So the study populations are very different, but I think it's enough reliable data to give us some good data for that.
00:13:28
Speaker
Yeah, that's super interesting. And one thing about the ARRIVE trial too is the mean risk estimates at baseline. So they actually use two different cardiovascular risk assessments, the old Framingham risk assessment, and the baseline mean for those people were 14%.
00:13:47
Speaker
And then when they used the ACAC AHA calculator, it was 17%. So these are pretty high-risk people that... And they were non-diabetics. Yeah, yeah. So you can't even count that. Right. Well, but I would call a heart attack waiting to happen kind of patient. Yes, exactly. A lot of doctors would be like, yeah, we're going to put this guy on statin. Interesting.
00:14:08
Speaker
And so not to go into super deep detail with these studies because we'll put everybody to sleep, but there are just some interesting things about each one. And we just talked about the ARIAID trial, but ASCEND was interesting because the results are a little different than the other two. So the ASCEND, it did find a small benefit in reduction of serious vascular events with a number needed to treat of 91.
00:14:36
Speaker
But it also found a roughly equivalent potential harm in major bleeding events with a number needed to harm of 111. So small benefit, but also roughly equivalent harm. So the ASPRE trial, like you talked about, was more in elderly patients, which was interesting.
00:14:54
Speaker
And that trial was actually stopped early, so during their interim analysis, they found there was no benefit really with aspirin, and there was actually an increased mortality. So they stopped that one after about three years. And this was the elderly, relatively healthy, four percent smokers. Right. And they were dying. Yeah. It's not good. Okay, that's not good. No, that's never a good side effect.
00:15:18
Speaker
And so the questions became, you know, what caused this mortality benefit? And there was an increased risk in major hemorrhage, but also there was increased cancer related mortality, which was very surprising because we've had a lot of studies that have suggested a potential benefit in cancer mortality, particularly around colon cancer. So that was weird. May I ask that we just table the cancer?
00:15:46
Speaker
aspirin and cancer for another day? Yes, yeah, we'll not go into that, but I will say they did do a post-hoc analysis of that. They went and looked through all the charts of all these patients that develop cancers and they found that both, at baseline, both groups, the aspirin group and the non-aspirin group, had similar cancer rates at baseline. So that's the real benefit of a large randomized trial that even these unpredicted
00:16:14
Speaker
outcomes, they should be pretty evenly balanced at the baseline. And then they tried to figure out what happened with these people and found that the group in aspirin had a higher rate of stage four metastatic cancer, which may have been what was driving the increased mortality.
00:16:35
Speaker
So maybe it has something to do with having a cancer at baseline and being on aspirin makes things worse, don't know. We don't know. But it's certainly something that needs more study. Yeah, I agree. I agree. So instead of us really trying to summarize the primary endpoints for each of these trials, would you give me permission to jump to a meta-analysis to make it a little more concise? Yes, I think everybody would appreciate that. I think they would, OK.
00:17:03
Speaker
So the one that I picked, there's actually two meta-analyses, and the one that I picked I found so interesting was published in Family Practice 2020 by Drs. Moriarty and Dr. Abel. And it was just so wonderfully written and such a good systematic review of meta-analysis. And what they wanted to do was compare the data
00:17:26
Speaker
for all the primary prevention randomized controlled studies and divide them, the data, into what was completed prior to 2005 and what was completed after 2005. And their reasoning for that was that statin use and colonoscopies were much less common in the 1990s compared to the last 15 years.
00:17:47
Speaker
So they're trying to differentiate and maybe form a hypothesis as to could this be true-true unrelated or true-false. They're trying to figure that statistical data out. So in this meta-analysis, they did include the three trials that we just talked about, and then they added a fourth trial that was a 2014 study called the JPPP.
00:18:10
Speaker
And in total, in those new studies, those four studies, there were 60,000 patients that were included. And then they compared that statistically to all the older trials, which is over 120,000 patients. So we have a lot of numbers, okay? So let me break this down for you. When you look at both groups all together, you pull all the data together,
00:18:35
Speaker
Both the studies prior to 2005 and those four studies after 2005 did show a significant reduction in the composite endpoint of MI, stroke, cardiovascular death. Again, that is known as MACE, or Major Adverse Coronary Event.
00:18:54
Speaker
And the older studies, the relative risk was 0.89. In the newer studies, the relative risk was 0.93. So that's a 7% relative risk in the newer studies. No difference in both groups compared to placebo in all-cause mortality or cardiovascular mortality. So no difference in mortality.
Communicating Risks and Benefits of Aspirin
00:19:18
Speaker
But increases in major bleeds were apparent in both groups. Okay, so now just looking at the absolute benefits and harms in these four recent trials, let me give you these numbers. The number needed to treat to prevent one of those major coronary events, MI, stroke, or cardiovascular death, one of those events was 303.
00:19:41
Speaker
So you have to treat 303 patients with an aspirin daily to prevent one of those events, okay, over five to seven years, okay, because that's how long the studies lasted. The number needed to harm in those same patients for an intracranial hemorrhage was 417. So one out of 417 will have an intracranial hemorrhage over five years. And then the number needed to harm for a major hemorrhage is 143.
00:20:11
Speaker
So you will cause a major hemorrhage in one person out of 143, an intracranial hemorrhage in one out of 417, but you will prevent an MI or stroke or cardiovascular death in one out of 303. Those are the numbers we're looking at.
00:20:29
Speaker
So how could a- How does that make you feel? Not great, to be honest. Hence why the USPSTF is now changing, has gone down to a C. That makes perfect sense, right? Yeah. And so now they're recommending having a shared decision making discussion. So how could a primary care provider
00:20:50
Speaker
translate that into something a patient could understand. Exactly. Because not this way. Okay. Right. These number needed to treats are important numbers for us as clinicians. And I think it is important to know this, but, and I'm going to give all the credit to these authors. I did not do the math on this, but put another way. This is how these authors summarized it.
00:21:10
Speaker
For every 1,200 persons taking aspirin for primary prevention for five years, there will be four fewer MACE events, meaning heart attack, stroke, cardiovascular death.
00:21:26
Speaker
three fewer ischemic strokes specifically, three more intracranial hemorrhages, and eight more major bleeds. That's the kind of information that I think if you present to a patient
00:21:45
Speaker
And you, again, go with the way you do this, Bobby. Like, if you were in Vegas and you were going to place a bet, what are the chances? This is high stakes here, though. It is high stakes. This is serious stuff. It's not something that you blow over. This is not one of those patriarchal, I think you should take aspirin, so therefore just take it. Yeah.
00:22:03
Speaker
So can you repeat that again? Because I think a lot of people want to probably memorize that and be able to talk to patients. For every 1,200 persons that take aspirin every day for five years, there will be four fewer mace events, three fewer ischemic strokes, three more intracranial hemorrhages, and eight more major bleeds.
00:22:32
Speaker
Okay, Sandy, so the last episode we talked about the concept of medical reversal. Would you consider this change to be a medical reversal? Great question. Experts might disagree with me, but I do not consider this a true medical reversal.
00:22:50
Speaker
The medical community did not jump forward too quickly based on positive results just from case control, cohort trials. We had fairly strong data back in the early 90s that aspirin was looking very positive for primary prevention.
00:23:07
Speaker
But yet now we have so much new data that we cannot ignore it. And I really applaud the organizations like the USPSDF for admitting, okay, now we have to go back. Because that is all we can do, is follow the data. But there are lots of hypotheses as to why this could be. Could this be true, true? And we just have to change what we're recommending based on our current population. And I think that's where I'm leaning.
00:23:34
Speaker
So let me just toss those out for you just to ponder. These have to be proven. But are we truly looking at a different patient population now? We know that we have fewer smokers, right? That's one major risk factor I think we can all agree on. We know that we have advances in the treatment of ACS, advances in the treatment in the cath lab.
00:23:54
Speaker
We know that time to cath lab, you know, algorithm is really, really advanced now. We have new anti platelets. We know more patients are on statins.
00:24:07
Speaker
We know that there's PCI advances, you know, STEM advances. So perhaps we are looking at just a new generation of patients. And unfortunately, even if there is a small benefit, even if you do believe those numbers, the risk unfortunately may be too high for a large portion of our patients. So my question to you, Bobby, as you sit in clinic and you talk to patients,
Criteria and Risk Factors for Aspirin Use
00:24:33
Speaker
How frustrating is this to explain, to try to explain this to our patients? Okay, because first we try to convince them to take it and now we have to explain why they shouldn't.
00:24:45
Speaker
Yeah, it's a little tough, but I've been surprised about how open patients have been. I think especially patients are eager to stop taking medicine for the most part. There are some people that are very resistant to that, but a lot of people, if I don't take another pill, I'm great with that. But when you have these kind of complete turns in the evidence, it's taught me to reword how I recommend what we
00:25:12
Speaker
do. I'm less enthusiastic about benefits. I'm not going to make big promises about how some medication is going to help. I've made that mistake many times. Yeah, for sure. So try to be a lot more numbers based. Try to give them the example you gave with number needed to treat, number needed harm. Try to give them some understandable numbers to weigh and then really listen to what their concerns are, what their hesitations are.
00:25:41
Speaker
That's where we get into that nice, shared decision-making. That's the basis of the evidence-informed decision-making, right? That's exactly right. That's right. So, Sandy, after all this, is there any patient that you would recommend aspirin for for cardiovascular prevention? I'm giving you the hard question.
00:26:05
Speaker
Maybe. Nice. So just trying to piggyback in. You did the hard work for me just explaining. So if I were a patient and I just listened to you, then I could see if my biggest fear was because I saw my mother have a heart attack at age 56. Sure.
00:26:24
Speaker
And I have a 10 year risk based on the calculation that may or may not be accurate of 17%. And I'm 51 and I have never had a GI bleed and I have no pepticals or disease and I'm not on anticoagulants. And you explain these things to me. I might say I'm going with the aspirin. And I think that you would agree with me in that situation. Yeah, especially if the patient was really worried about it.
00:26:51
Speaker
But it would have to be that narrow group of 40 to 59. You don't have any bleeding risk factors before I would really be, I guess, fully on board with that. But the patient makes the decision about their hair. Exactly. And it's over the counter. At the end of the day, we don't have a say so. Yeah, they can take it if they want to. Yes, they can. There's no more aspergum, though. I know. I wish we had that. It really was delicious.
00:27:16
Speaker
So I guess when we talk about bleeding risk then, you know, because that's I think, you know, what patients are going to know about, what would you say is the more, I guess most concerning risk factor for bleeding? Right. So I went back, I always try to go back to the original studies and see who was excluded from the trial.
00:27:35
Speaker
So when I just, we went over the intracaneal hemorrhage data and the major bleed data from the three large trials, I went back and looked at who was excluded from those trials. And honestly, I was surprised. They were pretty aggressive in who they allowed in the study. So you were excluded if you had a history of a GI bleed in the past six months or a history of active peptic ulcer disease in the last six months, okay?
00:28:01
Speaker
Recent stuff. Recent stuff. Okay, so history of GI bleed is kind of a cop-out. What does that really mean? Okay, you had a GI bleed 20 years ago, does that still apply? And I get those questions all the time, and I don't know how to answer them, okay? But in these trials, it was recent. They also excluded anyone on any anticoagulant, so warfarin, lovinox, or, you know, loamy lacquerweight heperin, or doax. And finally, they excluded active liver disease. Those were the only exclusions.
00:28:28
Speaker
So let me give you some numbers that I commonly just quote to the residents for just overall bleeding risk with aspirin. So low-dose aspirin is linked to about two GI bleeds per year per 1,000 patients. But that risk is multiplied by 10 in patients with a history of GI bleed. There is some debate as to how recent that GI bleed needs to be, and I don't always have the answer for that.
00:28:54
Speaker
Other high-risk, to me, somewhat no-brainer conditions are concomitant meds with DOACs, anti-platelets, warfarin, prednisone, daily NSAID use. When I see someone on daily meloxicam for their OA of their knee, and it's primary prevention, I cringe when they're also on low-dose aspirin. It is not to be underestimated.
00:29:15
Speaker
Although I can't, it's more difficult for me to give you absolute numbers. Those are all based on case control studies, cohort studies. It's hard to know how many NSAIDs these patients are taking. I just don't have the hard numbers. Now, let me make it also very clear to you that with regards to GI bleed, we know that PPIs are beneficial for patients who need to take aspirin or other high-risk conditions, including NSAIDs, prednisone.
00:29:41
Speaker
And certainly for secondary prevention, like let's go back to, we know that aspirin does have a net benefit. If you have that patient who really needs an aspirin, but they also have bleeding risk, that is when I'm an advocate for PPIs. And I think that, then that's a whole other discussion about the risk of PPIs. But in this situation, that's what I recommend.
00:30:03
Speaker
Yeah, I mean, with that you have a lot more. I mean, we talk about chronic PPIs and
Q&A with Residents
00:30:08
Speaker
just for treating GERD, but you know, this is a whole different risk factor, you know, staying a lot more to benefit from a PPI when you have also this risk factor, right? I think so. I think so, yes.
00:30:25
Speaker
Okay, welcome to our next segment entitled residents ask the darnedest things. And I have the luxury of just introducing Dr. Scott for this. I know that you precept a lot, Bobby. And I am sure you've had a question that you had some trouble answering. Care to
00:30:44
Speaker
Care to share with us today? Yeah, yes. This question came two days ago, so this is very recent.
Antihistamines and Patient Preferences
00:30:51
Speaker
One of my residents, one of our fabulous interns, was precepting with me and asked me the question, when you have a patient with allergic rhinitis,
00:31:01
Speaker
Do you have a preferred oral antihistamine that you recommend? Great question. It was. It is a good question, and we blow it off all the time because of allergic rhinitis. Yeah, give them whatever. Who cares? Whatever, yeah. And I told them, I don't actually know the evidence on that. There may be some comparative studies to see if one is better, but
00:31:23
Speaker
Um, typically I've just picked one and usually my, I'm personal experience from treating my own allergies. I've found Zizol or the levocytirazine to be the most effective personally, but I don't know if it truly is. So we looked it up together and I did a brief literature review and came across the only thing I could really find that was relevant to this question was.
00:31:52
Speaker
a meta-analysis done in 2013 of 10 observational studies looking at individual patient data. And so they were prospective observational studies, and so it included a lot of people, an end of about 140,000 patients, and it was done in Germany.
00:32:13
Speaker
So the outcome they were looking at were a couple of symptom scores for allergic rhinitis, and we're studying four different antihistamines, three of which we commonly use. One I'm guessing may be something that's used in Europe more, but the antihistamines they looked at were deslarotidine, fexifenidine, levocytirazine, and then the fourth one was ibastine, which I've never heard of.
00:32:39
Speaker
I've heard of it, but I think that's Europe exclusive. It's non-US for sure. Yeah, I don't think so. But interestingly, this study suggests that Levocytirizine, the one that I thought personally was... Wow, this is why you picked this topic. Yeah, it just makes me look really smart.
00:32:58
Speaker
But it was found to be the most effective of the four across these observational studies in reducing the symptom scores. So that's what we landed on. I did remind him that we have good evidence that suggests that intranasal corticosteroids are actually
00:33:19
Speaker
better overall than oral antihistamines. So that usually is going to be your first line recommendation. But if you had to choose an antihistamine based on the evidence we have now, and this is the best that I could find that maybe levocytirazine is the best. I mean, it's not a,
00:33:34
Speaker
you know, wasn't randomized controlled trials that were directly comparing head to head, but it's probably the best we got. It seems like the cost, I mean, these are all over the counter, but it seems like the cost have really come down, even for the isomer. Oh, yeah. You know, the xyzol. It's generic over the counter now. So that really makes a difference for me. Absolutely. I really, when there's a huge price difference, even if there's a statistical benefit,
00:33:58
Speaker
I have to look really hard. Is it really worth it? Because a lot of times it's not first line, given the cost difference. I love it when we can even the playing field with cost. Yes, it is great. Patients love that. Well, excellent. And for some reason, you may have a disagreement here, but I find that patients struggle with the intranasal steroid. Sometimes they just, even though we keep recommending it, they don't seem to be as compliant with actually swallowing a tablet. Is that what you're finding still? Yeah, I think
00:34:25
Speaker
You know, there's different reasons people don't like them. They don't like squirting anything up their nose or, you know, they say it tastes bad, which if they're actually tasting it, it means they're not using it correctly. And they're probably inhaling too vigorously. And, um, and you know, fluticasone propionate, you know, has the flowery smell, which I personally love, but some patients really find that repulsive. So.
00:34:51
Speaker
Right. OK. Well, excellent. And I think your your intern is lucky to have you. Oh, well, thank you. You're welcome. You're welcome. You know what? We're lucky to have a wonderful audience that is listening to our podcast and sending us nice emails. But if anybody wants to send us critical emails, we're OK with that. We have thick skin. Yeah, our skin has become thick over the years.
Closing Remarks
00:35:13
Speaker
Yes. I'll just cry a few tears. I'll get over it fast.
00:35:17
Speaker
All right. Well, thank you, Sandy. This is excellent. We have so much fun doing this. Yeah. Looking forward to our next episode, which will be out soon. Can we pick just a easier topic? Gotta pick a softball, home run topic next time. So nobody wants to listen to that. That's true. That's true. All right. Thanks so much, Bobby.
00:35:39
Speaker
And that's going to wrap up our show today. Thank you very much for listening. If you enjoyed the podcast, please leave a review and hit that subscribe follow button in your podcast app of choice. For any questions or comments about today's episode, drop us an email at whatstheproofpodcastatgmail.com. We'll see you next time.