A (0:00)

Foreign.

B (0:08)

In this episode, I'm going to demonstrate, I'm going to show you just how cool and how unique our podcast community actually is. Yes, we get messages from all over the state of Texas. That's not unusual. We're in Texas. But we also get messages from all over the US and even from international locations. Now, what makes us unique is our podcast family members. They're deep. I mean, they're looking at stuff. They know the data and they're good guys. They're good. So I'm going to play for you in just a minute a message that comes from my state about a recent episode where we covered an abstract from SMFM's annual pregnancy meeting. Remember that just happened at the end of the first week, beginning of the second week of February 2026. Now, I'm very partial to that, to that publication just because it's from my alma mater. So those are my colleagues. And so I got a little bit of bias. I'm just going to say it because the Authors are from UT Southwestern Parkland Hospital, and they compared 162mg of aspirin to 81mg and the results were pretty darn remarkable. Yes, it worked. It worked better than 81 milligrams without the concern for bleeding. I'm going to give you a quick recap right after the intro. However, when our podcast family members know the data, when they're involved and they know what's going on, they know the controversies, we get a message just like the one I'm about to play for you from one of our podcast family members. Now, this comes from Alex again. He's one of our podcast family members, but more importantly, I consider him a friend, man. And you talk about holding people accountable. He's like, hey man, wait, what about this other data set that just came out? What do we do with that? I'll tell you what, Michael, let's go ahead. Let's play Alex's intro. Alex's question, because he's going to set it up perfectly and then we're going to get into it right after he's done. Michael, let's go ahead and do this.

A (2:11)

Hi, Dr. Chapa. I enjoyed your podcast. More support for the 162mg low dose aspirin, universal use and OB here. You highlighted the UT Southwestern study presented at SMFM 2026 pregnancy meeting on February 11th. That suggests 162mg starting before 16 weeks of pregnancy may delay or prevent preeclampsia with severe features, which goes along with the dose dependent benefits seen in other studies. But the January 2026 RCT in the Green Journal by Dr. Kandar et al. Comparing 162 mg versus 81 mg showed no difference. How do you reconcile these findings and what factors do you think most likely explain the discrepancy?

B (2:59)

Thank you, Alex. Phenomenal. Phenomenal. Thank you for knowing the data. Thank you for holding us accountable and for asking a really deep, insightful question. There is an absolute answer to explain the discrepancy in that RCT just published January 2026. And then what our colleagues, my colleagues, did from UT Southwestern and Park Hospital and why the results are so strikingly different. I'm going to review that as soon as we come back from this intro. I think I've set it up enough. We'll be right back. This is Dr. Chapas, OBGYN Clinical Pearls, no Spin podcast. All right, so just a little recap if you didn't listen to the immediate past episode. First of all, shame on you. Don't ever miss an episode. We cover good stuff. But if you didn't, don't worry about it. I'm going to give you a very quick, super fast lightning round synopsis from this SMFM abstract that I'm sure is going to be a full publication as it goes through peer review. But let me just tell you briefly what UT Southwestern Parkland found when they used 162mg compared to 81mg, not as an RCT, but in two different cohorts in time. All right, so they call these, they call this the pre study epoch and then the post study epoch. In other words, at one point on the calendar they said, hey, going forward we're going to universally remember that, universally administer 162 milligrams of aspirin to our patients because these folks got some sickness. I mean, they're all high risk of some type. Trust me, guys, I know the parking population very well. And so we're just gonna, we're just gonna give them 162mg. So a couple of very novel things there. As we mentioned in the past episode, number one, universal, not risk factor based. Remember that? And number two, 162 milligrams. Okay, so they wanted to see if hypertensive disorders in pregnancy, mainly preeclampsia with severe features, was reduced in the higher dose universal protocol compared to before implemented. And they wanted to track adverse issues, mainly bleeding, intracranial Bleeding in the child and of course, placental abruption. Short of it is it worked super, super well. Now, it reduced the rates of hypertensive disorders in pregnancy across the spectrum, including gestational hypertension, as well as preeclampsia who have severe features. And here's the catch. Even in a subgroup analysis of women with chronic hypertension had lower risk of developing preeclampsia with severe features. That's phenomenal because other studies, including the Asprey trial, did not find that it reduced the rate of preeclampsia in patients with pre existing or chronic hypertension. Right. So this was a win. This thing worked. And so that was about a 29% reduction in the rate of preeclampsia with severe features across high risk categories. Phenomenal. As an additional bonus, they found no increase in abruption or in neonatal bleeding with the higher dose universal application. Okay, so very, very helpful in that even when you stratify based on risk factors, which they did, they looked at, it worked. They had a lower rate in every subgroup when it was universal aspirin. And the rates of all gestational hypertensive disorders were lower after this implement than the group who preceded them who did not get this protocol, even in women with chronic hypertension. They also reduced the rates of preeclampsia with severe features. And those numbers, even with the chronic hypertension, it was 27.1% in the treatment group compared to 34%. So this was a pretty remarkable thing. Now, remember, guys, I'm not about giving you just one study. In that past episode, we talked about the Cochrane review, the Asprey trial. Stephanie Robergi also has a meta analysis on this that found that there is a dose response effect. As Alex said in the intro, there is a dose response effect of aspirin and prevention of hypertensive disorder, preeclampsia. Okay, now, ideally, as I said before, 150 milligrams is the sweet spot, but we don't have 75 milligrams where they take two. We've got 81. So you double those, you get to 162. It seems to be legit. However, Alex brings up a phenomenal issue, and that is in the January 2026 Green Journal, there is an RCT that did the exact same thing. Now, let me explain. Let me give you the title here. Comparison. 162 mg and 81 mg aspirin for prevention of preeclampsia. A randomized controlled trial. Great. Folks who did this. This is out of, well, Cornell, New York, Pennsylvania, Pyramid School of Medicine, and even Miami. Notice it's Miami. When you're in Texas, you don't say Miami. It's Miami. Miami, Florida. Okay? The University of Miami at Miller School of Medicine. These are great folks putting together a great design. But here is the catch. Okay, let me just show this just quickly, because I don't want to belabor this episode because we've already discussed this kind of ad nauseam in the last one. But let me just give you their results quickly because it was disappointing. The incidence of preterm preeclampsia or preeclampsia with severe features was 14.1% in the 162 milligram group, compared with 17.1 in the 81 milligram group. Let me stop there. That did not reach clinical statistical significance. Okay? Or statistical significance, rather. The p value is 0.4. Okay? So statistically, the math wasn't there. However, if you look at the numbers, guys, the 162 milligrams was 14.1% compared to 17.1. That's a 3% reduction. I know it's not huge. I'm going to take any reduction that I can take. So clinically, perhaps there's some value, but the math wasn't mathing. Okay? So the statistical value wasn't there. And again, we've covered this many times before in other episodes. I would love it to be both clinically and statistically significant. But in cases where they're discrepant, I'll take some clinical significance, knowing that the math may have to do with the total study numbers and power calculations. And so I don't want to throw the baby out with the bathwater. All right, so short of it is 162mg had this 14.1% progression to preeclampsia was severe features compared to 17.1 in the 81mg. Not statistically significant, I would argue, maybe even though it's not a huge reduction, maybe some clinical significance, but it is what it is. So hold on, there's other things here. Quote, there were eight cases of placental abruption in participants randomized to 162 milligrams compared with zero in those randomized to 81, end quote. So now we've got two discrepancies here. Okay? So UT Southwestern found that 162 milligrams was more effective at a 29% reduction overall in hypertensive disorders in pregnancy and preeclampsia with severe features. Whereas this RCT said no statistical significance. It was a 3% actual drop. Not that big of a deal. And then in the southwestern group, no episodes of bleeding. But in this RCT, they had 8. 8 placental abruptions compared to 0 in the 81. Totally dichotomous results. Alex was onto something. He's like, what are we supposed to do with these two studies? Isn't that great? Because he's right. See, guys? And this is why medicine keeps evolving. That's why you got to keep doing the data and look at the holistic nature of. Of the evidence. So what is the holistic nature of the evidence before I give you the reasons why they likely have discrepant results in these two studies? Right. The con. The conglomerate nature of the studies show a couple of things. Number one, yes, there's definitely a dose response effect with aspirin benefit. It seems to have greater efficacy, greater acumen with a higher dose, specifically over 100. And most studies looked at 150. Not that many looked at 162. But by deduction, and the evidence that we do have, there is a benefit with the higher dose. The second thing is that the bleeding issue is very controversial. The meta analysis by Stephanie Roberti that I think we mentioned also in the previous episode found no increase in rates of bleeding at aspirin doses above 100. But some of those studies were very heterogeneous. Patient populations were different, and some of those didn't have adequate power. Okay, now, this publication here from the RCT from the Green Journal from last month showed there were eight cases of abruption. I can't explain that, and the authors can't either. Now, it would have been nice to do maybe a univariate or multivariate regression to see if. Once you stratify everything, if aspirin is a standalone risk factor. But they couldn't because they didn't have enough power to look for these rare occurrences. So they just reported it as what they saw. Like, hey, we saw 8 in this group, 0 in the lower group. And it needs further study. And that's true, but the biggest variable here. Guys, let me try to explain the abruptions here. And I'm not defending the 160 milligrams at all cost. I mean, 81 is fine. You're gonna do something, please. But 162 may be better. But the big issue with these studies that look at bleeding, when you compare a higher dose of aspirin in patients at high risk of preeclampsia is that their patients with a higher risk of preeclampsia and that pathophysiology, whether they are obese, chronic, hypertensive, have renal disease, smoking, whatever they are, already the inherent risk for abruption is there because they have a higher risk of preeclampsia. So that's a variable that offers a lot of confounding. All right, so it'd be nice to stratify everything, but it's hard to actually have a powered study for this because abruptions, thankfully, while traumatic and terrible, just don't happen all that frequently. So that's one of the issues here. It's a quinky dink, as they say themselves. I don't know. We found eight. We don't have enough power to figure it out. Needs further study. And I agree with that. I'm not minimizing that there is a potential for bleeding with a higher dose, but it has not been a consistent finding across studies, and the UT Southwestern study did not find that. If it sounds like I'm a little biased for UT Southwestern, I'm sorry. I'm trying to be evidence based here and give everybody equal opportunity because we're the no Spin podcast. But it's hard to when those are my old peeps. All right, having said that, why is there a discrepancy? Because I want this to be fast. I can answer that. I can answer that. Remember that the UT Southwestern publication was universal. Everybody got. You came into prenatal care. Hey, here are your vitamins. Hey, here are your freebie little gibbies. And here is your 162mg or 81mg. Take two of them that I'm going to give you whenever you come in here. You just got to take it. Okay, so it was universal regardless of risk factors. Meaning that if you just look at patients with high risk factors and include that into a study, you may be missing other groups in the population where the benefit may have been evident. But you didn't find it because you didn't include them. Remember that currently, ACOG's risk stratification is one or more high risk factors. They get aspirin or two or more moderate risk factors. They can also get aspirin. In this RCT from the Green Journal from January 2026, they only included patients who had, quote, high risk factors for preeclampsia. Now, that's fine. That's who you're supposed to include. But by not including patients who had moderate risk factors, two or more risk factors Perhaps they didn't find that, that that benefit which narrowed the overall results. Does that make sense? So this is obvious distinction here is that in the UT Southwestern publication, everybody got it. Whereas in this RCT it was only in patients who had the ACOG defined high risk factors, one or more. Okay, so that limits the pool, potentially limit, therefore the benefit. The second thing is that while this randomized trial used the risk factors and the other study used universal, there's a bigger capture with the universal, thereby potentially allowing more clinical significance. And that's why the two discrepancies are there. So the patient populations were different and also the selective versus universal use. Really, I'm convinced this paper shows it. You get different results because if you can eliminate those who have moderate risk factors, you're going to give much more narrow acumen or power or efficacy to your study drug. Okay, so again, I'm not getting after these authors. I'm just telling you exactly what they did. They used those patients who had high risk factors defined by ACOG's criteria, which were chronic hypertension, those who had type 1 or type 2 diabetes, autoimmune diseases, multifetal gestation or kidney disease. Those were the ones who were offered this medication, not. Not anybody who had two or more moderate risk factors which would have been captured in the Southwestern cohort. So. Fascinating. Anyway, I wanted this to be pretty quick because we really did have to do our, our due diligence here to explain this, because if Alex picked this up and kudos to him for doing so, I don't want somebody else, I picked it up going, hey man, what about that other one? Seems to be giving all the love to UT Southwestern and none to these folks. So now we've covered both of those scenarios, all right? Short of it is different populations, different design. I am a fan of 160mg. I think it works. I'm not that worried about the bleeding. I'm just not. But, but the most, the conservative media in the middle is give people 81 milligrams universally if you're going to do a universal approach like I do, and then those who have high risk factors, then err on the side of caution and give them the 162mg. Because based on not this RCT but based on other evidence, there is a dose effect or a dose response effect to this. The. The efficacy of aspirin for hypertensive disorders of pregnancy, incident reduction. Alex, great job. Great job, brother. Thank you for sending us that message. True to form, we actually pay attention to these. This was so good. I told Michael, our producer, we're going to kick out whatever we're going to cover next, and we're going to put this up here because super, super valuable. All right, podcast family, as always, we're thankful for you. We're glad you're part of our podcast community. And now that we've done all that, Michael, let's take it home. This is Dr. Chapas, obgyn clinical pearls no spin podcast.