Guideline Recommendations for Lipid Lowering

Erin D. Michos, MD, MHS, FACC, FASPC: Let’s talk about the guidelines. There are a lot of guidelines out there: the European guidelines, and in the United States we have the ACC/AHA [American College of Cardiology/American Heart Association] guidelines, NLA [National Lipid Association] guidelines, AACE [American Association of Clinical Endocrinology] guidelines. Alison can review the ACC/AHA guidelines, and then we’ll hear about the AACE guidelines from Bob. We have these new tools now; the 2018 guidelines that you’re a part of only focused on nonstatin therapies of ezetimibe and the monoclonal antibodies for PCSK9 because that’s all we had back in 2018. But now we have these new tools we just discussed, bempedoic acid and inclisiran for LDL [low-density lipoprotein] lowering, icosapent ethyl for patients with elevated triglycerides. In more of these updated decision pathways, what are the roles for these new agents? How do we think about the algorithm of who we should be starting these in?

Alison Bailey, MD, FACC: The Expert Consensus Decision Pathway just came out, looking at nonstatin therapies. We’re still looking at that ASCVD [atherosclerotic cardiovascular disease] very high-risk group. In that group we want a lipid goal of less than 55 mg/dL or more than a 50% reduction. We would still start with a maximally tolerated statin, based on all the data we’ve already discussed on the importance of statins. But we know that not all of our patients are going to tolerate that. Our next-line drug would be ezetimibe or a PCSK9 inhibitor. We still want to get to that less than 55 mg/dL goal and more than 50% reduction. If we don’t get there, then we would think about bempedoic acid and inclisiran.

The pathway does make a statement that we don’t have cardiovascular outcomes trials yet. But these are still very reasonable drugs to start because they are well tolerated, patients take them, not everybody’s going to take an injection, many of the reasons we just discussed. Inclisiran has some interesting payment pathways that may be advantageous to a lot of our patients. Then if we think about the hypertriglyceridemia and icosapent ethyl, it’s the same thing Pam has already summarized really well. Patients who have ASCVD and elevated triglycerides saw a significant risk reduction with icosapent ethyl, and it really wasn’t dependent on the level of triglyceride lowering in that trial. The consensus pathway doesn’t mention any of the other drugs or pathways at this point.

Erin D. Michos, MD, MHS, FACC, FASPC: What are the AACE guidelines, and are they different at all from the ACC/AHA, or do you have any additional comments about your approach to these newer agents?

Robert Busch, MD: As I mentioned, if you have type 2 diabetes, you’re on a statin. It’s unusual for the type 2 patient not to have other coexisting risk factors. Then it’s high risk, which means LDL below 70 mg/dL, diabetes with risk factors. If you have diabetes and an event, it’s below 55 mg/dL. Oftentimes, as Pam mentioned, our patients have high triglycerides as well. So, part of our breakfast mix is the statin, maybe a statin and ezetimibe, or bempedoic acid, and icosapent ethyl. That’s a lot of pills, but a lot of benefit. Remember, these patients are at very high risk for cardiac disease. And besides lowering microvascular disease by good diabetes control, what about their heart and strokes, and peripheral vascular disease? That’s what we review every visit. Why are they taking it, not just to take it to get to goal, but the reason they’re taking it.

Jorge Plutzky, MD: What I find helpful in these conversations, it comes back to talking to patients about these issues, is that we end up as doctors talking so much about pills and medicines. Sometimes with patients, there’s a pushback about how many pills they are taking, they don’t want to take a pill, don’t like taking pills. I find it helpful to take an approach that says independent of any pills, what the genetics tells us, that these are experiments of nature, that are informing us and have guided us and tell us as we’re sitting here together, across from one another saying, “How do we keep you from having a heart attack or a stroke?” I think that’s very motivating for patients. When you look at an experiment of nature, where someone is born, and spends their entire life with an LDL in the 30 to 50 mg/dL range, what’s wrong with them? Do they have muscle aches? Do they have brain issues? Can they not bear children? No, they’re completely normal; they just don’t have heart attacks and strokes, or at a much-reduced level.

When you go on the other side of extreme, we’re not talking about drugs, we’re talking about an experiment of nature, where someone goes through life with an LDL of 300, 400, 500, 600 mg/dL with homozygous familial hypercholesterolemia. What happens to them? Well, they can have a heart attack or stroke before puberty, even as early as age 1. As I say to patients, that’s not because of hamburgers and French fries. You see their eyes lighting up and engaging with this idea of, this really matters. In between those extremes is where so many of our patients live. I think that separating it from the medicines, and saying, “This is what we know, this is what the science is telling us. Now, let’s apply that to you,” can be very helpful in terms of creating a context for patients, so they know what we know, as we referred to.

Transcript edited for clarity