Contemporary use of aspirin in 2024

Dr Anthony Sandre, MD, assistant professor in the Division of General Internal Medicine at McMaster University specializing in vascular medicine, discusses the contemporary role of acetylsalicylic acid (ASA) in modern cardiovascular care. He examines the indications, pharmacological properties, and recent evidence comparing aspirin with P2Y12 inhibitors.

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Outline

1. Introduction
2. ASA: When and how to use
3. ASA: When not to use
4. ASA versus P2Y12 inhibitors
5. Q&A: Rotating ASA, ASA vs non-ASA antiplatelet therapy, platelet recovery, cost

Transcript

Introduction

Roman Jaeschke, MD, MSc, DPharm: Good morning. Welcome to another edition of McMaster Perspective. The occasion is a presentation that was made during the 20th Annual McMaster Hematology and Thromboembolism Update by Dr Anthony Sandre. Anthony, maybe I will start by asking you to introduce yourself.

Anthony Sandre, MD, MSc: Thank you very much. I’m Anthony Sandre. I’m an assistant professor within the Division of General Internal Medicine. I completed additional training in vascular medicine, so I clinically work in the general internal medicine and thrombosis services within Hamilton Health Sciences and manage patients with arterial and venous thrombosis, peripheral artery disease (PAD), arteriopathies, and high-risk primary and secondary cardiovascular prevention.

Roman Jaeschke: Thank you. We’ll be talking today about a medication that is probably one of the oldest ones available to us and is used in such a big variety of clinical situations that having an internist with additional training in thromboembolism and vascular disease in general is probably most appropriate. We’ll be talking about acetylsalicylic acid (ASA), or aspirin. Anthony, the floor is yours.

ASA: When and how to use

Anthony Sandre: Thank you. I’ll share my presentation here. I’d like to talk to us about the contemporary use of aspirin in 2024.

One of the most important things is to understand when it’s commonly used and how it acts from a pharmacologic perspective. Aspirin is commonly used in coronary artery disease (CAD), including acute coronary syndrome, chronic angina, and following percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). There are nuances in patients who present with overlap with atrial fibrillation and acute venous thrombosis, which I won’t go into in this presentation today. [Other indications are] prosthetic heart valves, cerebrovascular disease, PAD, prevention of preeclampsia, and thromboprophylaxis following orthopedic surgery.

Aspirin is as commonly prescribed as Plavix (clopidogrel), and both are different and similar in their pharmacologic actions. Both are irreversible in their action but are very different in how quickly they do act and how quickly they stop acting. Aspirin has a roughly 5-minute onset, whereas Plavix (clopidogrel) is between 2 and 8 hours. Similarly, the half-life is much different: 10 to 20 minutes versus 6 hours, respectively. And the time to offset is roughly 3 days for ASA and 5 to 7 days for clopidogrel. This is important when on the inpatient service, when there’s a question of whether or not a patient would tolerate an antiplatelet therapy, or in the perioperative setting.

Looking mechanistically at how these medications work—I did mention them, but to visualize it—aspirin inhibits cyclooxygenase 1 (COX-1), which “downproduces” thromboxane A₂ and prevents platelet activation. With aspirin you will achieve platelet recovery, as new platelets are released or with aggregation of them, at ~10% per day. On the other hand, clopidogrel will inhibit P2Y12 for the entirety of the life of the platelet, which is 7 to 10 days. So again, it’s very important to consider these factors in a patient who would be considered high risk for antiplatelet therapy.

ASA: When not to use

Anthony Sandre: As much as it’s important to understand when to use aspirin, it is also important to understand when not to use it. Primary prevention of cardiovascular disease: there is robust data in the ASPREE, ASCEND, and ARRIVE trials that have shown a higher risk of bleeding without a substantial benefit from a cardiovascular perspective.

Stable PAD with full-dose anticoagulation and, similarly, stable CAD with another direct oral anticoagulant (DOAC) indication such as atrial fibrillation. In the stable CAD with other oral anticoagulant category, rivaroxaban/edoxaban monotherapy have been compared to themselves with aspirin. Edoxaban had a lower risk of bleeding and composite death, whereas rivaroxaban alone was noninferior to its combination with an antiplatelet agent.

ASA versus P2Y12 inhibitors

Anthony Sandre: In the first part of my presentation we’ll discuss aspirin versus P2Y12 inhibitors such as Plavix (clopidogrel). These medications are both very commonly prescribed, and there is new and emerging data on the safety and bleeding risks of these medications.

In order to contextualize this, a 76-year-old gentleman with the history of CAD presents on ASA monotherapy 3 weeks after being admitted for a lower gastrointestinal bleed. ASA has been restarted by the gastroenterologist and you’re wondering if there’s an alternative therapy available for this patient.

PANTHER is a large meta-analysis that came out approximately 1 year ago and compared all existing data on P2Y12 inhibitor monotherapy versus aspirin monotherapy. When we look at the composite outcome of cardiovascular death, myocardial infarction (MI), and stroke, the hazard ratio (HR) does not cross 1, so there is a small but significant preference for P2Y12 inhibitors over aspirin monotherapy and the number needed to treat to benefit was 121 patients over 2 years. When we look at bleeding, although the HR does cross 1, there is a general trend towards lower bleeding risk with P2Y12 inhibitor monotherapy versus aspirin. And finally, when we take all events together—a lot of patient-important events here, such as all-cause death, cardiovascular death, MI, stroke, hemorrhagic stroke, major bleeding, and at the very bottom net adverse clinical events—there is a general trend towards favoring P2Y12 inhibitor monotherapy over ASA.

So what does this mean? There is emerging data that P2Y12 inhibitors are associated with better patient outcomes and less bleeding versus ASA, and there may be a coming trend to rotate to clopidogrel unless otherwise advised. I would welcome any questions on this topic before we go to the next portion of my presentation.

Q&A: Rotating ASA, ASA vs non-ASA antiplatelet therapy, platelet recovery, cost

Roman Jaeschke: Thank you very much. As you were talking, I was making some notes. For the patient you presented, the one who had a bleed a few weeks ago, I guess the answer, from what I heard, would be to consider rotating from aspirin to a clopidogrel-type drug. You use clopidogrel as an example of the whole class of drugs. I guess it would still depend—because the coronary event was 3 years ago—I guess it depends on the predicted risks of bleeding as well, because would the option of not using any antiplatelet therapy be there as well? I mean that would require discussion with the patient and a cardiologist, but it probably depends on what was happening, what was causing this bleed. Would you agree with that?

Anthony Sandre: Yeah, I would agree. I think we generally feel that if a patient had a significant coronary or vascular event in the past, then they would benefit from ongoing antiplatelet therapy. If there’s a concern of bleeding, I do think that considering P2Y12 inhibitors should be on the table for the patient. But if a patient can’t tolerate antiplatelet therapy and has a clear indication for it, I agree with the multidisciplinary approach to decision-making on whether antiplatelet therapy can be discontinued or if P2Y12 inhibitors could be trialed over ASA for some new emerging data and their lower bleeding risk.

Roman Jaeschke: The general flavor of what you presented was that the non-ASA antiplatelet therapy is probably slightly more efficacious and probably less hazardous in terms of bleeding. Is there any situation in which ASA would be preferable?

Anthony Sandre: A challenging question to answer. I think because of the mechanism of action of ASA over P2Y12 inhibitor if you have a patient who’s at very high risk of bleeding but also has a very compelling indication to require an antiplatelet medication, aspirin might be preferable in the short term because you do get some recovery of platelet function, ~10% per day, whereas with Plavix (clopidogrel) you are inhibiting the platelet for the entirety of its life. So although the PANTHER data shows that P2Y12 inhibitors are lower bleeding risk, I think in the acute setting there can be some deviations from that in case-by-case, patient-by-patient setting.

Roman Jaeschke: So this would be quite a specific situation. You mentioned the recovery of platelets on aspirin in terms of 10% per day. Is it old platelets that are recovering or new platelets that are produced?

Anthony Sandre: New platelets, which are producing, and then aggregation and overcoming the mechanism that exists.

Roman Jaeschke: So why wouldn’t it apply to clopidogrel if you were to use it on one occasion and then stop? It also should have this 10%-per-day recovery.

Anthony Sandre: Correct. But I think that what happens is, as new platelets are produced in a patient who’s on aspirin, they can aggregate onto the platelets that have been inhibited and they can actually release some of that irreversible inhibition, yes.

Roman Jaeschke: OK. So the effect disappears faster. Would you know the cost comparison between those two? These McMaster Perspectives will be listened to in a number of different countries. Would you know the cost in Canada? Comparative cost?

Anthony Sandre: The rough cost of an aspirin tablet is $0.15, and the rough cost of a Plavix tablet is $0.26, so very comparable.

Roman Jaeschke: So it’s dramatically closer now than it used to be a few years ago. Thank you very much for this part of your presentation. We’ll be welcoming people to another part soon. Thank you.