Individualizing Aspirin Therapy in Preventive Cardiology

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Luke J. Laffin, MD:

Welcome to the Cardiac Consult Podcast. My name's Luke Laffin. I'm a preventive cardiologist at Cleveland Clinic. I'm joined by my colleague, Dr. Vikas Sunder, also a preventive cardiologist. We're going to talk about something that we deal out like candy. It's aspirin, okay? Really, we want to talk about changing recommendations, how we should be thinking about the use of aspirin amongst our patients, particularly those primary prevention patients, because I think most of us are aligned that secondary prevention patients should be on an antiplatelet. I'm going to start the discussion by posing you a question, Dr. Sunder. How should clinicians interpret the balance between atherosclerotic cardiovascular disease risk reduction and bleeding risk?

Vikas Sunder, MD:

I think it's a great question, Dr. Laffin. I think it should be individualized, and I think that's the takeaway, especially from the primary prevention perspective. Yes, you are going to see the patient in the office, you're going to take a history, learn about their family history and their individual risk factors. We often incorporate risk prediction tools like the ASCVD (atherosclerotic cardiovascular disease) risk prevention tools, like the PREVENT calculator, in the office setting that has come out in recent years. We're also going to look at other parameters such as if that patient's had any prior imaging. Do they have a history of atherosclerosis? Do they have an elevated lipoprotein(a)? We're going to take all of those factors and make an individualized recommendation for the patient based on other issues that they may have, such as concomitant chronic kidney disease, a history of either major bleeding events in the past, intracranial hemorrhage and things like that.

Luke J. Laffin, MD:

Now, at what risk threshold does aspirin really provide net benefits? Do we have any guidelines to really help guide us a little bit there?

Vikas Sunder, MD:

Yeah. The United States Preventive Services Task Force, the USPSTF, the United States Preventive Services Task Force, they have come out with this threshold of 10% in certain patients, up to age 40 to 60, about whether or not they should be on a primary prevention aspirin. That may be appropriate. It's not necessarily a strong recommendation, but it may be appropriate for those patients.

Luke J. Laffin, MD:

Got it. All these risk calculators, they're changing, right?

We had the Pooled Cohort Equation. We obviously had Framingham first, then Pooled Cohort Equation, now PREVENT. All those numbers are coming down. Are there any other things that you look at in your clinic population to say, for primary prevention, "Oh, this person should be on aspirin," or understanding that we've got to individualize it a little bit?

Vikas Sunder, MD:

Yeah. There is some data from the Women's Health Study as well as MESA (Multi-Ethnic Study of Atherosclerosis), those trials that showed that there are certain patients who have an elevated lipoprotein(a), especially certain subtypes of it, certain variants of it who may benefit more from being on an 81 milligram aspirin.

Luke J. Laffin, MD:

What about calcium scores? How do you think about those and aspirin?

Vikas Sunder, MD:

We know that calcium scores predict risk differently at different thresholds. At zero, those are the patients who have a low risk, versus the patients who have a calcium score of 100 or greater, versus those who have a calcium score of 400 and greater. We know that patients who have a calcium score of 400 or greater, that's a higher risk group. There is even a higher risk group than that where their scores are over 1000. We really want to look at that group and manage them somewhat similarly to those at a secondary prevention level who have established cardiovascular disease, maybe a history of myocardial infarction or stroke. I think that would be, in that group who has a calcium score over 400 Agatston units, a stronger recommendation than those who have a calcium score of zero. Then you have this gray area where certain studies have shown a small net benefit of baby aspirin in those patients who have a calcium score greater than 100.

Luke J. Laffin, MD:

Got it. Okay. I think that's really helpful information. I mean, you and I have colleagues who any spec of atherosclerosis, they'll put someone on an 81 milligram of aspirin. That may or may not be appropriate, based on the age and other factors. I think this idea about lipoprotein(a), Lp(a) and aspirin dosing is pretty interesting, understanding that Lp(a) is a little bit more of an atherogenic lipoprotein.

So, there are some data to support 81 to 162, but not in everyone. I mean, the European Atherosclerosis Society statement is now a couple years old, but it's really our most contemporary understanding of Lp(a). It doesn't recommend aspirin for everyone with high Lp(a), but it says it might be something to consider.

Vikas Sunder, MD:

Correct. Our previous cardiology guidelines did not recommend aspirin, especially for patients above the age of 70 years old, our ACC guidelines, in which case they may have an increased risk of bleeding that outweighs the net benefit gleaned from the aspirin.

Luke J. Laffin, MD:

So, how do you think about adding aspirin to other dual antiplatelet therapies? How do you think about that?

Vikas Sunder, MD:

If somebody has a history of a recent coronary stent to establish cardiovascular disease, they're typically prescribed a course of dual antiplatelet therapy for a certain duration of time based on a number of characteristics, as we know. But typically after that time, in certain cases it can be a consideration whether to continue it maybe beyond a year or longer, a consideration in certain high risk patients. But generally that patient will come down to a single antiplatelet therapy strategy long term and indefinitely. But in terms of patients who are already on other medications, you have to be very careful, especially other antiplatelet medications, if they do not have established cardiovascular disease, especially oral anticoagulants. Those other stronger types of anticoagulants, combined with antiplatelet therapy, are going to increase the risk of bleeding, especially those that can increase the risk of GI upset, gastrointestinal upset, and especially with preexisting peptic ulcer disease.

Luke J. Laffin, MD:

Yeah. It's interesting when we think about dual antiplatelet therapy, some data within the past year, I believe it was a meta-analysis, or they combined data from individuals from trials, suggesting that maybe even in those secondary or chronic coronary disease patients, once you're past a year, that maybe something like clopidogrel is better than aspirin as your sole antiplatelet agent. What do you think about that?

Vikas Sunder, MD:

We used to think all of these patients with established cardiovascular disease should be on a baby aspirin indefinitely, but now we're having newer data come out where clopidogrel may be that option or a different type of antiplatelet medication indefinitely for stable coronary heart disease.

Luke J. Laffin, MD:

Now, what do you think about some unique considerations to our highest risk patients with different comorbidities? For example, chronic kidney disease, diabetes, does that change the arithmetic in your head?

Vikas Sunder, MD:

Those patients with comorbidities such as chronic kidney disease, for example, where they could have uremia, they could have platelet dysfunction that we see in chronic kidney disease, they're going to have that propensity for bleeding. We really need to be careful with concomitant use of antiplatelet therapy and make sure they have a strong indication for it and balance that risk and benefit. As well as you always want to review your patient's history and see if they've had a history of intracranial hemorrhage, for example, where an antiplatelet agent may not be the best idea or contraindicated in some cases.

Luke J. Laffin, MD:

Yeah. Then, how do you have those conversations with patients that maybe they've been on aspirin for 15 years and they're coming to see you, they're 73, and you think maybe they don't need it? Because I mean, patients are sometimes really attached. If it ain't broke, don't fix it. How do you think about that?

Vikas Sunder, MD:

You bring up a very good point, Dr. Laffin. We see this every day where we have patients who have been on a low dose aspirin for decades and they want to know, "Should I still be on it?" I think the age is important, right? If they're above the age of 70, and have risk factors for bleeding, it may not be the best idea for them to continue that aspirin. That being said, it always should be an individualized discussion and an individualized recommendation, I believe. That's looking at their whole profile, their family history, their individual lab work, as well as their imaging, and making a decision on that.

Luke J. Laffin, MD:

Yeah. I think that's such a good point. We like to pick these binary thresholds for, "Oh, you're above or under 70. We should do antiplatelet therapy." But we know that's not biology works.

Vikas Sunder, MD:

Correct. Yeah.

Luke J. Laffin, MD:

There's some 75-year-olds that could beat me in a race and out-work me in the gym.

Vikas Sunder, MD:

Right. Exactly.

Luke J. Laffin, MD:

So, we should understand that yes, life expectancy plays a little bit of a role, but we have lots of patients living into their 90s.

Vikas Sunder, MD:

Correct.

Luke J. Laffin, MD:

So, we want to give them the benefit of the data that we do have to support a long, healthy lives.

Vikas Sunder, MD:

Yeah. I think that's why having umbrella risk thresholds and age thresholds may not be the best for day-to-day clinical practice. We really need to review all the data and provide individual recommendations.

Luke J. Laffin, MD:

And the nice part is that there are ongoing studies in higher-risk elderly cohorts about aspirin and their use. Maybe it's beneficial, maybe it's not. We'll see.

Vikas Sunder, MD:

Yeah, exactly. Good point.

Luke J. Laffin, MD:

Any other take-home messages that you might have for our listeners out there thinking about their patients, particularly their higher-risk primary prevention patients that we should really help relay to the audience?

Vikas Sunder, MD:

Yeah. I think first and foremost, try to optimize other factors first. American Heart Association has their essential eight related to cholesterol, related to sleep and related to the heart-healthy diet, everything like that. Blood pressure, weight, exercise. We want to optimize all those factors first, which we know gives patients the best opportunity to prevent that first heart attack or stroke, that primary prevention patient. Then we want to get a little bit more nuanced, maybe looking at some of the other data, like have they had a lipoprotein(a) level checked? Have they had a calcium score? We want to incorporate all that data into making a guided decision about low-dose aspirin also considering comorbidities and other risk factors.

Luke J. Laffin, MD:

Yeah. I'm always surprised when patients come to me, and they say, "Oh, I've been on aspirin for 25 years, but oh, I'm never going to take a statin. That's bad for you, right?” Understanding that probably the side effects of statins are much less than any potential risk with aspirin.

Vikas Sunder, MD:

Correct. Yeah. The side effects with statins overall are pretty uncommon. But with aspirin, we know there's a risk of bleeding in some cases.

Luke J. Laffin, MD:

Well, I really appreciate your insight and your expertise, Dr. Sunder. We appreciate our listeners for listening and thank you for listening to Cardiac Consult.

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