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New Guidance on Managing Patients on Aspirin for Secondary Cardioprevention

  • Authors: Roxana Mehran, MD; Michael Blaha, MD, MPH; W. Schuler Jones, MD
  • CME / ABIM MOC Released: 2/18/2022
  • Valid for credit through: 2/18/2023, 11:59 PM EST
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Target Audience and Goal Statement

This activity is intended for a healthcare provider (HCP) audience of primary care physicians (PCPs)/internal medicine physicians, cardiologists, neurologists/neurosurgeons, diabetologists/endocrinologists, nurses, nurse practitioners (NPs), physician assistants (PAs), and pharmacists.

The goal of this activity is to increase clinician knowledge on the latest data and guidance of the role of aspirin in secondary cardioprevention.

Upon completion of this activity, participants will:

  • Have increased knowledge regarding the
    • Latest clinical data on the use of aspirin in the setting of secondary cardioprevention
  • Have greater competence related to
    • Tailoring antiplatelet therapy for patients with established cardiovascular (CV) disease to prevent another CV event or stroke


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  • Roxana Mehran, MD

    Professor of Medicine
    Interventional Cardiovascular Research and Clinical Trials
    Icahn School of Medicine Sinai 
    New York, New York


    Grants for clinical research from: Abbott; ABIOMED; Applied Therapeutics; Arena Pharmaceuticals, Inc.; AstraZeneca Pharmaceuticals LP; Bayer; Biosensors International Group Ltd.; Bristol Myers Squibb Company; Boston Scientific; Cardiawave; CellAegis; CERC; Chiesi; Concept Medical; CSL Behring; Daiichi Sankyo, Inc.; Insel Gruppe AG; Medtronic, Inc.; Novartis; OrbusNeich; Philips; Transverse Medical; Zoll Medical Corporation
    Advisor or consultant for: ACC; Cine-Med Research; CIRM; Janssen; SCAI
    Other: Divested Equity Claret Medical

  • Michael Blaha, MD, MPH

    Professor of Medicine
    Director of Clinical Research
    Ciccarone Center for the Prevention of Cardiovascular Disease
    Johns Hopkins University
    Baltimore, Maryland

    Participation by Dr Blaha does not constitute or imply endorsement by the Johns Hopkins University or the Johns Hopkins Hospital and Health System.


    Grants for clinical research from: Amgen, Inc.; Bayer; Novo Nordisk
    Advisor or consultant for: Amgen, Inc.; Bayer; emocha Health; Inozyme Pharma; Kaleido Biosciences; Kowa Company Ltd.; Novartis; Novo Nordisk; Regeneron Pharmaceuticals, Inc.; Roche; Sanofi; VoxelCloud; 89Bio Inc

  • W. Schuyler Jones, MD

    Associate Professor of Medicine
    Associate Professor in Population Health Sciences
    Duke University of School of Medicine
    Durham, North Carolina


    Independent contractor for: Bayer; Bristol Myers Squibb Company; Janssen
    Grants for clinical research from: Bayer; Merck

Steering Committee

  • Charles P. Vega, MD, FAAFP

    Clinical Professor of Family Medicine
    Assistant Dean
    University of California-Irvine School of Medicine
    UC Irvine Program in Medical Education for the Latino Community (PRIME-LC)
    Irvine, California


    Disclosure: Charles P. Vega, MD, FAAFP, has disclosed the following relevant financial relationships:
    Served as an advisor or consultant for: Johnson & Johnson

  • Fuad M. Baroody, MD

    Professor of Otolaryngology-Head and Neck Surgery and Pediatrics
    The University of Chicago Medicine 
    Comer Children's Hospital
    Chicago, Illinois


    Disclosure: Fuad M. Baroody, MD, has disclosed the following relevant financial relationships:
    Served as an advisor or consultant for: ALK; AstraZeneca Pharmaceuticals LP; Bayer; GlaxoSmithKline; Regeneron Pharmaceuticals, Inc.; Sanofi

  • Deepak L. Bhatt, MD, MPH

    Professor of Medicine
    Harvard Medical School
    Executive Director of Interventional Cardiovascular Programs
    Brigham and Women's Hospital Heart and Vascular Center
    Boston, Massachusetts


    Disclosure: Deepak L. Bhatt, MD, MPH, has disclosed the following relevant financial relationships:
    Served as an advisor or consultant for: Abbott; Afimmune; Amarin Corporation plc; Amgen, Inc.; AstraZeneca Pharmaceuticals LP; Bayer; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb Company; Cardax; CellProthera; Cereno Scientific; Chiesi; CSL Behring; Eisai, Inc.; Ethicon, Inc.; Ferring Pharmaceuticals; Forest Laboratories; Fractyl Laboratories, Inc.; Garmin; HLS Therapeutics; Idorsia Pharmaceuticals Ltd; Ironwood Pharmaceuticals, Inc.; Ischemix, Inc.; Janssen; Lexicon Pharmaceuticals, Inc.; Lilly; Medtronic, Inc.; MyoKardia; NirvaMed Inc; Novartis; Novo Nordisk; Owkin; Pfizer, Inc.; PhaseBio Pharmaceuticals, Inc.; PLx Pharma Inc; Regeneron Pharmaceuticals, Inc.; Roche; Sanofi; Synaptic Pharmaceutical Corporation; The Medicines Company; 89Bio Inc
    Received grants for clinical research from: Abbott; Afimmune; Amarin Corporation plc; Amgen, Inc.; AstraZeneca Pharmaceuticals LP; Bayer; Boehringer Ingelheim Pharmaceuticals, Inc.; Bristol Myers Squibb Company; Cardax; CellProthera; Cereno Scientific; Chiesi; CSL Behring; Eisai, Inc.; Ethicon, Inc.; Ferring Pharmaceuticals; Forest Laboratories; Fractyl Laboratories, Inc.; Garmin; HLS Therapeutics; Idorsia Pharmaceuticals Ltd; Ironwood Pharmaceuticals, Inc.; Ischemix, Inc.; Janssen; Lexicon Pharmaceuticals, Inc.; Lilly; Medtronic, Inc.; MyoKardia; NirvaMed Inc; Novartis; Novo Nordisk; Owkin; Pfizer, Inc.; PhaseBio Pharmaceuticals, Inc.; PLx Pharma Inc; Regeneron Pharmaceuticals, Inc.; Roche; Sanofi; Synaptic Pharmaceutical Corporation; The Medicines Company; 89Bio Inc

  • Stephen Brunton, MD, FAAFP

    Executive Vice President
    Primary Care Education Consortium
    Murrieta, California


    Disclosure: Stephen Brunton, MD, FAAFP, has disclosed the following relevant financial relationships:
    Served as an advisor or consultant for: Abbott Diabetes; Bayer Diabetes; Gelesis; Novo Nordisk; Sanofi Aventis
    Served as a speaker or a member of a speakers bureau for: AstraZeneca Pharmaceuticals LP; Bayer Diabetes; Boehringer Ingelheim Pharmaceuticals, Inc.; Lilly; Novo Nordisk
    Owns stock, stock options, or bonds from: Paracrine Cell Therapy

  • Linda Cox, MD

    Practicing Physician
    Allergy and Asthma Center 
    Ft. Lauderdale, Florida


    Disclosure: Linda Cox, MD, has disclosed no relevant financial relationships.

  • Roxana Mehran, MD

    As Seen Above


  • Kathy Merlo

    Medical Education Director, Medscape, LLC 


    Disclosure: Kathy Merlo, disclosed no relevant financial relationships.

  • Nancy Ashley, MSN, APRN, ANP-BC

    Medical Education Director, WebMD Global, LLC 


    Disclosure: Nancy Ashley, MSN, APRN, ANP-BC, has disclosed no relevant financial relationships.

Compliance Reviewer/Nurse Planner

  • Leigh Schmidt, MSN, RN, CMSRN, CNE, CHCP

    Associate Director, Accreditation and Compliance, Medscape, LLC


    Disclosure: Leigh Schmidt, MSN, RN, CMSRN, CNE, CHCP, has no relevant financial relationships.

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This activity has been peer reviewed and the reviewer has no relevant financial relationships.

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New Guidance on Managing Patients on Aspirin for Secondary Cardioprevention

Authors: Roxana Mehran, MD; Michael Blaha, MD, MPH; W. Schuler Jones, MDFaculty and Disclosures

CME / ABIM MOC Released: 2/18/2022

Valid for credit through: 2/18/2023, 11:59 PM EST


Activity Transcript

Roxana Mehran, MD: Hello, I'm Roxana Mehran, professor of medicine at Icahn School of Medicine at Mount Sinai. Welcome to this program titled, "New Guidance on Managing Patients on Aspirin for Secondary Cardioprevention."

I am so thrilled today with our panel of experts who are joining me: Dr Michael Blaha, who's professor of medicine at Ciccarone Center for the Prevention of Cardiovascular Diseases at Johns Hopkins University in Baltimore, Maryland, and Dr Schuyler Jones, who's associate professor of medicine at Duke University School of Medicine in Durham, North Carolina. Welcome to the both of you. Thanks for joining me.

Today, we will discuss the role of aspirin in secondary cardioprevention, which was solidified in meta-analyses from the Antithrombotic Trialists (ATT) Collaboration. We know this very well. Some years ago, the Lancet publication of this ATT data in 2009 definitively showed the role of aspirin in reducing ischemic events, at a small cost of bleeding. But over the last few years, there's been some confusion regarding the use of aspirin for preventing important ischemic events. Separating this primary and secondary prevention is really a very important concept that I hoped we could begin to discuss here today. We've also seen several clinical trials where novel strategies are being used in secondary prevention, including withdrawing aspirin.

I hope that this discussion is going to provide our audience with information that's factual and scientifically based, to effectively use aspirin for secondary cardioprevention in patients with known atherosclerotic cardiovascular disease (ASCVD). So, Schuyler, I'm going to come to you first. Can you define primary cardioprevention, and how it's different than secondary?

W. Schuyler Jones, MD: Sure, Roxana. In a simple way, primary prevention is treating patients without disease, and secondary prevention is treating patients with established, in this case, ASCVD. As we all know, it's never simple black and white, because patients have existing disease without presenting with things like heart attacks, but in general, primary prevention really reflects treating those patients to prevent heart attacks and to prevent disease. I think for aspirin, the big thing that really came into play is that 3 large studies showed that for at least primary prevention, aspirin really wasn't effective. Those studies came out in 2018 and caused some confusion. And as we discuss secondary prevention, it's really important to understand that we're dealing with patients with established heart disease.

Dr Mehran: And there's no question about that, right? I think that there was this very recent publication on a population-based study on the use of aspirin. Mike, you want to tell us a little bit about that study and what it showed?

Michael Blaha, MD, MPH: Yes, absolutely. Looking at the trends of aspirin use over time is very interesting. We've seen in the last 10 years a slight decrease in the use of aspirin, but what we do see when we look at those studies is a lot of aspirin use in primary prevention, sometimes in patients who may not benefit, like older patients or patients who don't have any risk factors. We also see only about 70% of patients in secondary prevention, as you've heard, who are taking aspirin, and that's where the benefit of aspirin is known. So, we're seeing a lot of use of aspirin in this country, and a lot of use in primary prevention sometimes where it shouldn't be. But we're also seeing not always consistent use of aspirin in secondary prevention, particularly in women, those with low socioeconomic status, or patients who don't have healthcare insurance. There is an incomplete use of aspirin. So it's a mixed picture of sometimes some overuse, and sometimes some underuse of aspirin, and that's where that distinction, I think, of primary and secondary prevention is so important.

Dr Mehran: Well, there's no question about that, is there? And I think I get really concerned when I hear that women are underutilizing aspirin, as are those with low socioeconomic status, who are on a drug that is effective for secondary prevention, with a small amount of cost. Isn't that right, Mike?

Dr Blaha: Yeah. The drug is very inexpensive, of course, and it should be accessible to everyone, but there's just I think confusion about its use, because it is available over the counter, you can take it in primary and secondary prevention for different reasons. I think we just need to make sure that message is very clear, that the use for secondary prevention is unquestioned as the bedrock of therapy, based on, the decades of clinical trial data supporting aspirin in secondary prevention.

Dr Mehran: So, Schuyler, I have a patient who comes in who's 60 years old. He has hypertension, prediabetes, and hypercholesterolemia, and his calcium score is 350, with a lesion in the mid-LAD. Is aspirin use primary or secondary prevention in this patient?

Dr Jones: That's a patient that kind of fits into this gray zone that we deal with in clinical practice a lot. I'd be interested in a conversation with you 2. My interpretation is that there are likely lots of patients in the primary prevention studies that had calcium score findings that signaled that they had disease, but they were still included in those studies. And therefore, without overt heart disease, without in most cases, an angiographic finding of coronary stenosis greater than 70%, a prior myocardial infarction (MI), or a prior coronary revascularization, I would include this patient in primary prevention, and probably counsel the patient to say the data does not support the use of aspirin to prevent future events.

Dr Mehran: I'm with you on this, but I can tell you probably what Mike was talking about in terms of the use of aspirin, is a lot of on these types of patients were totally scared about their score and their risk factors, and they feel like, "Well, I should be on aspirin, “and they use lots of aspirin. I'd love to hear Mike's interpretation. To me, that patient's risk factors are what we need to focus on. This includes getting the low-density lipoprotein (LDL) as low as possible, getting the hemoglobin A1C down, increasing exercise, implementing diet changes with an emphasis on a plant-based diet, smoking cessation, and then blood pressure control, which is the most important one. I think that's what we should be focusing on, rather than, "Oh, you should be on an aspirin a day." Mike, I'd love to hear what you think.

Dr Blaha: I might be a slight outlier or maybe take a middle ground here, because I think what I'm most concerned about, as we all are, is patients in primary prevention who have no risk factors and are taking aspirin -- patients who are low risk. That happens all the time. But we also know, like you said, there's a middle ground, patients who aren't really primary prevention, but they aren't really secondary prevention. They've got substantial subclinical disease, and there's some observational modeling data, which you guys have probably seen, that suggested if you've got a high calcium score, you might get a net benefit of aspirin primary prevention.

I think what they're really telling us is we need to be personalized. We can't say, "aspirin for everyone"; we need to make sure our low-risk patients don't take aspirin. We know it's overused in the population. We saw that in that population-based study, but we need to do a better job of finding those patients who are high risk,and counseling them in a discussion about whether aspirin's right for them. Some patients in primary prevention can have risk closer to secondary prevention, in fact, and really, the distinction is sometimes less clear. So, this is all very interesting and it really gets at the theme, I think, of aspirin these days, which is personalization.

Dr Mehran: I love what you just said about the risk, and certainly high risk. For someone who's diabetic, who's got all of these other risk factors, I want all their risks controlled, but I also want to prevent that first event as well. I'm with you there, but if it's a frail old lady who might bleed on aspirin, I may not do that until we have further understanding. Moving on, there's this huge issue about what's the dose of aspirin? Do we know the appropriate dose of aspirin? Let's get back to the basics, and maybe Schuyler, you can tell us about the trial that was just conducted and presented from Duke Clinical Research Institute (DCRI), ADAPTABLE, that you had a very big part of. Congratulations on your work. Can you tell us a little bit about ADAPTABLE?

Dr Jones: Sure. Thanks, Roxana. ADAPTABLE was a large pragmatic study that we ran in the United States at 40 centers in the National Patient Centered Clinical Research Network (PCORnet) network. We studied the 2 most common doses of aspirin, 81 mg and 325 mg daily. We randomized 15,076 patients to those 2 doses. This was really direct-to-participant research. While we had 40 study centers, the centers identified the patient, they sent letters or emails to the participants, and patients could really direct the research on their own. They could log onto the patient portal, enroll, and randomize themselves. They did informed consent via the internet. So, then they were randomized to the study doses for about 2 years. Over the course of 2 years, we studied those patients, looking at a primary effectiveness endpoint of all-cause mortality, hospitalization for MI, and hospitalization for stroke. We found that there was no difference between the 2 doses. And so, because most of the patients were taking 81 mg from the beginning of the study and because there wasn't a difference between the doses, we recommended with our patient partners, actually, that most patients should take 81 mg, because we tend to default to the lower dose. I don't know if that's societal or medical, but lower dose in general is probably the recommended choice for aspirin at this point.

Dr Mehran: So, in terms of now that we know the dose, probably 81 mg is perfectly fine for that indefinite use for secondary prevention, what is the appropriate dose? And especially because we see a lot of these patients on dual antiplatelet therapies, for how long? Is it really, truly forever?

Dr Jones: We default to indefinite because that's what we have frequently done over the past decades, but we don't have definitive data to suggest that it is lifelong. I think most of us believe that being on an antiplatelet medication for secondary prevention is important, and we'll probably talk about some other formulations that may be tested or work as well. But in general, I think that's an area that we can further explore. Mike, what do you think?

Dr Blaha: I think that if a patient remains high risk and hasn't accrued any new bleeding risk factors, that generally, you're going to continue the aspirin to maintain that cardiovascular benefit. But I think part of the story is we need to be reassessing always the bleeding risk of our patients too. We recognize that aspirin has clear cardiovascular benefit, but clearly increases gastrointestinal bleeding too. So, using tools to assess bleeding risk, or just looking at the risk of the patient and maybe underlying factors like age and frailty, help to personalize that decision-making, but most of the time when a patient has cardiovascular disease, that's going to be the driver of risk. So, most patients with existing cardiovascular disease are going to stay on aspirin, and stay on aspirin at least indefinitely, unless there's another change and life event to make sure they have that cardioprotection.

Dr Mehran: And it comes back to your original, sort of not one-size-fits-all, personalized medicine, assessing risks over and over again. It's not just the one-off visit with that patient, and this constant surveillance of this patient, because risks change over time. And I think what's important, and maybe we can have a little bit of a discussion, is there a tool that you actually use, like do you use the DAPT score or the PRECISE-DAPT score? What do you use? Do you use these risk calculators? Mike, let's start with you first.

Dr Blaha: That's a great question. I mean, there's certain things, of course, that aren't even in risk scores, like the patient develops a new cancer, or the patient has to go on a systemic therapy where, of course, you're going to have to reconsider the benefits of aspirin. But 1 thing we don't do as much of in clinical practice as we probably should is formally assess bleeding risk. There are lots of ways of predicting bleeding, and that's with things like the DAPT score, or PRECISE-DAPT, particularly in the setting of dual antiplatelet therapy are useful for, things like age of the patient or creatinine clearance, which show up in those risk scores as predictors of bleeding. What gets tricky is some of those same things are predictors of cardiovascular risk.

So, it gets tricky, but there are some tools out there now to help decide which patients tend to be on the higher end of the bleeding spectrum, where we're going to possibly pare back sometimes to maybe aspirin alone in certain settings. For patients who have lower bleeding risk, being more aggressive with antiplatelet therapy makes sense to give maximal cardioprotection, and I think once again, that's where we're headed -- to making individualized decisions. Sometimes we're going to add a drug to aspirin for a period of time, sometimes we're going to stick with only aspirin, based on the patient's bleeding risk. But I'm curious what you guys think.

Dr Mehran: I think there's no question that we have all of these long-term studies like DAPT, CHARISMA, PEGASUS-TIMI 54, THEMIS, all of them showing a really beneficial effect of adding a P2Y12 receptor inhibitor to our armamentarium of caring for these patients. But we know that every time you gained benefit, you also had some bleeding risk. So, I think individualizing care is going to be really important, and I think it is also very important to not just use the risk calculators as the only evaluation, but actually talking to the patient, as you said, and picking up your own clues of what's going on. So, let's get to that. I'm going to ask you guys some questions. So, Schuyler, you have a frail 82-year-old man who comes in after a myocardial infarction who had a complex PCI, a bunch of stents after their MI, but he's frail and 82 years old. What do you do? How do you treat this patient?

Dr Jones: Yes, that's a common scenario, as you know, as we do more percutaneous coronary intervention for older patients. I think that, like you say, I have a conversation with the patient about the risk, and you can guide patients to not necessarily scare them about ischemic risk, but I think most patients can hear about repeat MI or stroke. Those are definitely important outcomes, but the bleeding risk is also real in this patient. So, especially for a frail older patient, I probably will reduce my length of time that they're on DAPT. I would probably go back to aspirin, just that's my practice, and whether that's at 3 months or 6 months is probably dependent on how they're doing. I'm going to see them more carefully at early time points. I tend not to do a lot of 1 month of DAPT in my practice.

Dr Mehran: That's interesting, because for me, if I know that the PCI was done well, that they got great results, and as an interventionalist, of course, I have a lot of good feeling about that. I'd rather keep that patient on a P2Y12 monotherapy. If I'm going to go to clopidogrel, I'd probably test that patient to make sure they're responding, if I'm going to just use clopidogrel monotherapy, I will keep the P2Y12 receptor inhibitor for a while, and then switch out to aspirin monotherapy at some point. Mike, to you, the 45-year-old guy who comes in a year after their MI and has other risk factors -- what do you want to do? Do you switch to aspirin?

Dr Blaha: This is a good question. I mean, a 45-year-old with a premature event, a very-high-risk patient, of course, and generally speaking, age, of course, is one of the strongest predictors of bleeding risk. So this gentleman would be probably be on the lower end of the bleeding spectrum, as long as he doesn't have a history of Helicobacter pylori, or gastritis, or a bleeding ulcer. So, this is the kind of patient you can have a conversation about longer DAPT for, for example, especially if the PCI was complex or a multivessel small arteries, et cetera. But nonetheless, I think the most important message is that patient needs to be on some antiplatelet therapy, probably aspirin, at least, probably for life of course, who's developed a premature aggressive atherosclerosis and is likely to have more events, and thus, treated very aggressively. So I'm going to tell that patient the importance of not just discarding antiplatelet therapy after 1 year, for example, after an MI, but staying on a baseline antiplatelet therapy, probably in my practice, that's aspirin, 81 mg for life.

Dr Mehran: No, it's really great, and I think we also have other choices for this patient, like use of dual-pathway inhibition for these patients, based on the COMPASS trial. You touched on the gastrointestinal issues, and everyone always asks me, enteric- versus non-enteric-coated aspirin. Do you have any opinions about one versus the other?

Dr Blaha: Yes, I think a consensus is sort of building around this issue, that it turns out that enteric-coated just doesn't give you the gastric protection that we thought it might. It also can decrease the bioavailability of aspirin, too. You can get a little less aspirin absorbed into the system, and a less consistent effect with the enteric-coated aspirin. So if you're not going to get as much of the gastric protection and you get some changes in the bioavailability of aspirin, I think most people are favoring regular chewable aspirin in this scenario, and saying coated maybe is appropriate only for patients with severe dyspepsia or something symptomatic that you want to prevent. But, generally speaking, good old-fashioned chewable aspirin gives you the most reliable antiplatelet effect, and I think for most patients, it's probably what we choose.

Dr Mehran: No, it's a good discussion point. I'd love to hear from Schuyler. What do you think about the nonresponsiveness with enteric versus non-enteric formulations?

Dr Jones: Yeah, there's been a lot of discussion about that, and Mike mentioned some of it. It kind of brings to my mind the article that Deepak Bhatt published a couple years ago on the PL2200 compound I think when you look at different formulations, both the time to platelet blocking really is 1 facet, but also the completeness. And so, whether or not new compounds will do that and will do it reliably is a big question, and then if there is a space to have different formulations that are either prescribed or over the counter, I guess will be a second question.

Dr Mehran: Yeah. I'm really interested in the new formulation. But speaking about the gastrointestinal issues, Mike, do you recommend use of a proton pump inhibitor with aspirin therapy for everyone? And if so, based on what?

Dr Blaha: So that's a really good question, right? I mean, the concept here, of course, is that aspirin can cause mucosal damage in the stomach, mediated by, of course, the acid milieu of the stomach, and taking a PPI might reduce that acid and reduce the gastric injury. So, it makes a lot of sense, and there's some limited data that suggests that PPIs are quite effective at reducing severe gastric injury in the form of ulcers, to the tune of like a 75% reduction. Now, there isn't the highest quality randomized controlled data that we'd like to see, but some small studies really support the use of PPI, particularly in high-risk patients, patients that are more likely to have the severe dyspepsia or ulcers from an aspirin, which is based on their history, or Helicobacter pylori status, or their age.

So, while guidelines around the world kind of either are mute or variable on this issue, the European Society of Cardiology guidelines, for example, do say there's a class I indication to use a PPI in the setting of chronic aspirin therapy for those patients who are at high risk of gastric injury. So, I think that's where I come down to -- I do use a PPI in patients who I think are more likely to have gastric injury from aspirin. If you have a lower-risk patient, maybe you can get away without one, but definitely think about this issue. I think it's something that's clearly underused in the United States, and I think it'd be great to have some more consensus around this issue in future guidelines.

Dr Mehran: What about you, Schuyler? I give all my patients a PPI. A lot of them are on DAPT, so I give them PPIs. What are you doing in your practice?

Dr Jones: Yeah, I would say I don't have a consistent practice of using PPIs, and I do think a lot of patients are already on it or get discharged on it after their index hospitalization. So if they're on it, I definitely continue it, and then if there's any signal of bleeding or other things. I think examining the underlying causes and using it makes a ton of sense.

Dr Mehran: Yes, and since I'm with you and you were part one of the leaders in ADAPTABLE, we figured out dosing with 81 mg and 325 mg didn't really have a difference, no significant difference in CV events. I think that was a very important finding, even though many of the patients were on the 81 mg. For me, I still think that the 325-mg dose should be given to anyone who presents with an acute coronary syndrome (ACS), and we give the chewable aspirin in the emergency room, regardless of whether or not they were taking aspirin at home. Is that your practice? Mike, is that also your understanding of this, regarding the dosing and when we would use a 325-mg dose? Let's start with you first, Schuyler.

Dr Jones: Yes, definitely with acute presentations, I think 325 mg chewable should be given. When we looked at the data, Roxana, in the US, this is a decade ago, about 60% of patients were being discharged on aspirin 325 mg, but since then, it's changed dramatically, right -- when looking at discharged from an index hospitalization for an MI. Now I think we've seen a shift to the ESC guidelines, and I suspect the US guidelines will change as well to 81 mg. But upfront, at least the first dose during an acute event, I think should be 325 mg, and then switching to 81mg. Mike, what do you think?

Dr Blaha: Yes, I agree. I mean, it's a completely different setting when you need that rapid onset of antiplatelet effect, the dose makes sense, a larger dose to bring those levels up quickly. Now, a chronic setting is very different, where you're on a maintenance dose and you have kind of a chronic level of platelet inhibition. Then it makes sense to be more thoughtful about the dose, particularly as ADAPTABLE taught us, use that lower dose. Now, a patient, of course, who has an 81-mg dose at home who's having a chest pain, or someone around them is having chest pain, can chew 4 of those doses to get to that 324 mg dose. But yes, in the acute setting, we're still sticking with that rapid-onset 325 mg, and we're moving towards in the chronic phase where we're, once again, at that equilibrium with our platelets of an 81-mg dose, that seems to do the job.

Dr Mehran: No, that's great, thank you. Thank you so much. So now the big question. When should I take my aspirin, in the morning or at night? Schuyler, why don't we start with you? Maybe you can shed a little bit of light about the bedtime aspirin.

Dr Jones: I think there have been observational studies that have looked at improvements in blood pressure (BP) with taking aspirin at night. Certainly, I think it's a great question in general, like when should you take any of your medicines? When should you take your blood pressure medicines? When should you take your statin? I think we've oscillated over time with different things, and ultimately, there is some mechanistic information on when to take aspirin, and so, these are smaller studies suggesting that potentially taking it at night is associated with lower BP. I think that we live in a complex world, so just getting our patients to remember to take aspirin is important. So, if we're trying to get them to take a single tablet at night, whereas they take everything else in the morning, I'm not sure that that benefit is actually there. We'd probably have to, as Mike said earlier, personalize for them and just get it in their system, right? This is especially important in those patients with established heart disease.

Dr Blaha: I think what Schuyler mentioned is so critical, and I think it's true with almost any medicine, we need to give a dose and a frequency that they'll actually take, right? The drugs only work if you take them, and that's really important. Aspirin adherence is actually a really big question, because a fair number of patients can get gastritis or dyspepsia from aspirin, and discard their aspirin and stop taking it, or misunderstand why they're taking it. So I think the first step is to get them to take the drug consistently and work with their schedule, and then consider some of the interesting mechanistic data like we heard about from Schuyler. But the name of the game in chronic medical therapy is compliance and adherence with the therapy. So, working with the patient is the name of the game, I think, here.

Dr Mehran: Absolutely. And what about the cost?

Dr Blaha: Cost is an important question, and I think part of what we discussed in this program is the idea of aspirin as foundational therapy, but also, some patients need dual antiplatelet therapy, right? And of course, the P2Y12 inhibitors are more expensive than aspirin. So, the fact that aspirin is cheap and widely accessible is one of its benefits, but of course, its over-the-counter availability and cost can also lead to some of the overuse issues that we talked about earlier. In fact, there was a recent study that compared aspirin use and perceptions toward aspirin use in the United States and in Europe. There's lot less primary prevention use of aspirin in Europe, partly because the drug isn't available over the counter, like it is in the United States, whereas in both countries, there's still limitations and barriers to getting all of our patients in secondary prevention on aspirin.

Dr Blaha: So, we need to remind ourselves this is an inexpensive drug, it's widely available, particularly in those patients, that are harder to reach who have less touch points with the medical system, who need to be reminded that aspirin is widely available and cheap, and is a great option for chronic therapy and secondary prevention. Particularly when the question of DAPT comes up, in terms of their availability and a patient's access to getting those drugs, cost is an important issue, and that's why aspirin still remains kind of this topic of discussion, right? It works, and it's inexpensive. It's got some limitations, too, but it works. It's a very interesting topic, but thank goodness aspirin is amongst the cheapest drugs that we have in CV prevention.

Dr Jones: I agree. The only thing I'll add is that it's sometimes difficult to track when patients are on aspirin, because it's not a prescribed medicine. It doesn't impact cost, but it impacts how we study it, and it impacts how we think about addressing those concerns with patients, because we use our electronic health records for everything. So, not necessarily pertaining to cost, but just kind of day to day asking patients and reporting it.

Dr Mehran: I think what we heard from Mike though, and to our audience, is that for secondary prevention, it's best to prescribe it so we can follow it, and avoid the underutilization or overutilization of aspirin in the right places, and I think that's really important.

Dr Mehran: I think what we learned today is that aspirin is an essential therapeutic regimen for our patients for secondary prevention, which is preventing recurrent events in patients who have established atherosclerotic cardiovascular disease. I also think what we've learned is that the dosing of less with 81 mg for indefinite use is probably just as good as 325 mg, and it's probably best to stick with that.

Regarding enteric versus noncoating, most likely better to go with the chewable non-enteric coating, if you don't have an issue with the person's GI status. And then very important is regarding the PPI use, especially in combination with dual antiplatelet therapies. But for now, it seems that for most patients, you go to aspirin monotherapy until we get more and more data in this arena. And certainly, imagining and using a very, very good personalized approach to treating patients with aspirin is really important, assessing their ischemic and bleeding risk, not just as a one-off, but in a continuous fashion. The cost is important for many, many patients, but certainly, it's better to prescribe it for secondary prevention so we can track its use. And lastly, and importantly, I think is the timing of when you should take aspirin, and it seems like, well, it matters. Make sure that your patient actually will take it. So go back and talk to your patient about when they take their meds. The bedtime makes a lot of sense because it's associated with lower BP in the morning, and we see a lot of those events early in the morning, clustering around early in the morning. So it might be better if they take it at bedtime, but it's much more important if they take it.

I think we learned a lot from the 2 of you. Thank you so much. Did I miss anything, guys, that you wanted to add, maybe just some last-minute pearls for our audience? Let's start with you, Mike, and then we'll go to Schuyler to close this out.

Dr Blaha: Yeah, just important, once again, to take those questions that you're going to get from your patient about, "Should I stop my aspirin? I read this clinical trial; it didn't show it was beneficial." But then you remind them they had had coronary artery bypass surgery and a couple stents, and clearly, aspirin, of course, is still mandatory, or near mandatory in secondary prevention. You remind them and reassure them that they should take it. Now, if you have your patient call and say, "I've been taking aspirin because I have a family history, but I have no risk factors," then you need a personalized discussion with that patient, because that's primary prevention, not secondary prevention. So that's my key message, I think, and that's what a lot of providers are hearing nowadays: these questions from patients about, does aspirin work? It still works, but we need to be careful about when we use it.

Dr Mehran: Thank you, Mike. Schuyler?

Dr Jones: I think in addition to the primary and secondary prevention topic that Mike just brought up, I think the dose matters, and having a little bit of confidence on the 81 mg, and being a little bit more precise, I think does help because the different formulations that are out there now over the counter, really can confuse patients, and so, we get a lot of questions about that. And so if we can simplify things for patients and for clinicians, I think it's helpful.

Dr Mehran: Mike and Schuyler, thank you for this great discussion, and thank you for participating in this activity, to all of the audience here listening. Please continue on to answer the questions that follow and complete the evaluation.

This is a verbatim transcript and has not been copyedited.

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