The Role of Factor Xa Inhibitors in the Management of CAD/PAD - Episode 2
Manesh Patel, MD: Actually, I think one of the things that’s being highlighted is that continuum. It’s not just the injury, which I think was nice to highlight. It’s the continuous process of our response to injury. Biology is always a continuous yin and yang of trying to keep the homeostatic state. And so as atherosclerosis is happening or thrombosis is happening, it’s happening all the time. And part of why I think we’ve had this, as I called it, medical school description is we’re always prisoners of what we learned as therapeutics at that time. So one might imagine that with aspirin or early antiplatelet therapy, we focused a lot on antiplatelets. And then with vitamin K antagonists like warfarin, we focused a lot on broad, nonspecific anticoagulants. So the new era of other therapeutics has now started to teach us to think broader. I would say we think the same about cholesterol, lipids, and inflammation. And we’re starting to learn that about other disease processes.
Deepak L. Bhatt, MD, MPH: Along those lines, maybe you can review for our audience what the guidelines are in general for atherosclerosis. We’ll focus quite a bit on antithrombotic therapy here in a bit. But other than that, if someone has got atherosclerosis, what are you doing?
Manesh Patel, MD: We’ve been describing atherosclerosis together, and I think about this a fair bit because my wife is a primary care physician, and she spends a lot of time saying, “Can you distill all that fancy stuff down into what do I need to do in clinic?” And so one way of thinking about that is do they have known clinical atherosclerotic disease? There are a lot of people at risk. Do they have known clinical atherosclerotic disease? One caveat is we’re thinking more and more that the diabetic patient should be considered to have known clinical atherosclerotic disease.
But aside from that, there’s primary prevention and then there’s secondary prevention. I’ll start with let’s say the easier group, the secondary prevention group, people who have had a heart attack, people who have had a stroke. For people who have peripheral artery disease, we can come back to how strong the guidelines there are. For those patients, in addition to antiplatelet or antithrombotic therapy, which we’re going to talk about in a second, there are cholesterol or what I’ll call lipid guidelines. And those lipid guidelines have continued to show us that in fact, the LDL [low-density lipoprotein] hypothesis says that if you can get the LDL down as low as possible, and the current guidelines are less than 70 mg/dL, those patients have fewer cardiovascular events. The American Heart Association scientific sessions are also going to be presenting some data for stroke patients as that LDL goes down. Is it a linear relationship?
So the first message for at least primary care physicians is, if they have known cardiovascular disease, get the cholesterol LDL level down below 70 mg/dL, usually with a statin but there are a variety of therapies. And then there are some newer therapies certainly you can think about in addition to statin therapy, not just for the LDL. You’ve led some of those studies, so you can tell us about the triglyceride or other AIM studies. But I think the first message is known or not known disease. If it’s known, get the LDL less than 70 mg/dL.
Deepak L. Bhatt, MD, MPH: John, I’m just curious about the diabetes there. It certainly does raise the risk of atherosclerosis. What does it do with respect to blood clotting? There’s a fair amount that’s been written about platelets and how maybe they’re angrier in diabetic patients. What about the blood, is it angry too?
John Eikelboom, MBBS, MSc, FRCPC: Well, absolutely. And I think this speaks to the atherothrombosis concept because with diabetes, dysglycemia, we know we get coagulation activation. We know we get platelet activation. We get enhanced platelet turnover. There is the story of aspirin resistance where because of more rapid platelet turnover, the platelets are not blocked effectively in the 24-hour aspirin dosing interval. And we know that platelets, for example, produce more thromboxane; the higher the HbA1c [hemoglobin A1C], the more thromboxane is produced. I think it’s very clear with diabetes that it’s not just a metabolic process, but it’s also a prothrombotic process.
Deepak L. Bhatt, MD, MPH: It’s an interesting concept, Vamsi, this primary prevention, secondary prevention. I think you are really doing more on the secondary prevention. But it is a bit of a continuum, right? What if somebody has got stable angina but then they had a catheterization and they have no coronary disease or a stress test and no ischemia, is that really secondary prevention? Or let’s say someone is in the primary prevention camp, but for some reason either rightly or wrongly, they get a CT [computed tomography] angiogram that shows a bunch of plaque in their coronary arteries, but they’re totally asymptomatic. It’s a little bit of a continuum really of risk, and the terms are a little murkier than they appear. How do you deal with that in real life?
Vamsi Krishna, MD: I completely agree with you. I get a lot of referrals for let’s say a coronary calcium score that’s positive or greater than 400. How do you manage that type of patient? And there are some guidelines, but they are currently unable to do a stress test. We use events to determine if someone has a primary or a secondary end point, but as we know when we do IVUS [intravascular ultrasound] or OCT [optical coherence tomography], we see the thin-cap fibroatheromas. We see distal embolization even when we do angiograms. Patients can be subclinical, and so to your point, why are we waiting for a heart endpoint to determine if it’s primary or secondary? And the reality is I think as more biomarkers are becoming easily available for us to test, we’re able to be more specific on the type of therapies that we’re able to offer these patients.
I think what I have noticed in the clinic is being able to use appropriate guideline-based therapy. And the 2019 ACC [American College of Cardiology] guidelines have done a pretty good job of including LPa [lipoprotein-little-a] and hs-CRP [high-sensitivity C-reactive protein] based on some of the data out there, including a CAC [coronary artery calcium] score. So I tell my primary care providers, I’m utilizing the guidelines we have available with the recent datasets to help make a more informed decision, not necessarily waiting for the patient to have an outcome before deciding on lowering their cholesterol or treating their blood pressure, etc.
Transcript edited for clarity.