Michael J. Blaha, MD, MPH: I am Mike Blaha from the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease. I am here in Chicago at the 2018 American Heart Association (AHA) Scientific Sessions, where there has been a roll-out of new AHA/American College of Cardiology (ACC) cholesterol guidelines.
I am joined by associate professor Salim Virani from Baylor College of Medicine, coauthor of the 2018 ACC/AHA cholesterol guidelines. We are going to talk about some of the things that are new and some of the things that are unchanged from previous guidelines.
Salim, the bedrock of what we know about cholesterol treatment is the same. Other things have changed. Let us start with some of the things that have stayed the same. What are the big messages to primary care doctors about the things we are going to continue to do from the prior guidelines?
Salim S. Virani, MD, PhD, FACC: I am glad we are talking about it, because that is an important question. The first message is that lifestyle remains the cornerstone of cardiovascular risk reduction. Even when medications are needed, lifestyle changes have to happen. That is number one.
The second is that the measurement of lipids when a patient is put on therapy remains a class 1 recommendation. It is something that should be done to both assess adherence—which we know is a big problem—as well as the efficacy of lipid-lowering therapy. Those two things have stayed the same.
Four high-risk groups were described in the 2013 ACC/AHA cholesterol guidelines:
Patients with established cardiovascular disease;
Patients with high low-density lipoprotein-cholesterol (LDL-C) levels;
Patients with diabetes; and
Patients with an elevated 10-year risk.
Primary prevention for those patients really stays the same.
The things that have changed are that we now describe a very high-risk secondary prevention group. In primary prevention, we use the same [risk calculation] tool, but now we have other strategies to further refine risk assessment. Primary care clinicians in particular will find a lot of tools to further refine risk in their patients.
Blaha: One thing that has changed is with regard to use of nonfasting lipid measurements. Tell me about that.
Virani: Yes, that has changed. That is a great point.
As you know, both fasting and nonfasting lipid panels perform the same way. We do not get any more benefit in risk assessment by having fasting lipid panels. We know that it is a big inconvenience to our patients, as well as for providers.
The guideline is saying that for risk assessment, clinicians could use either a fasting or a nonfasting lipid panel, which makes it really easy. If you have a patient who is coming to see you this afternoon, you can get it done that morning. Or you can just get it done while the patient is waiting to see you, get the result, and have that conversation right there. Otherwise, you have to wait and call the patient about the lipid panel, and that never becomes part of a live patient discussion, unless they come back for another visit.
Now both fasting and nonfasting lipids are allowed to be used for risk assessment purposes. That is a major change that is based on good science, which I think a lot of clinicians will find very useful.
Blaha: In a busy practice, it is about convenience. It makes sense. A big discussion with regards to the last guideline was, of course, the idea of LDL-C targets. Some notion of an LDL number is back to drive our decision-making. Let's talk about LDL-C thresholds. Tell us what that means.
Virani: LDL-C remains the primary treatment goal. We know that it is all about lowering echogenic lipoproteins. LDL particle is one of them. As far as the lipid parameter that we are going to target, that remains the main goal.
The prior set of guidelines did not give a treatment goal. We still do not have a goal per se. What we have is exactly as you said—thresholds where clinicians could start thinking about add-on therapies, especially in very high-risk patients, whether we are talking about very high-risk primary prevention patients or very high-risk secondary prevention patients. Clinicians have more leeway in terms of using those thresholds. They are not automatic triggers, but rather a point where clinicians and patients can start having a discussion about add-on therapies for each of those secondary and primary prevention risks.
Blaha: To be clear, by saying that the guidelines do not have an [LDL-C] goal, you are not saying you have to get to this LDL number. You are saying if you are above this threshold, consider advancing the therapy.
Virani: Correct. Advancing therapy in the highest-risk patients.
Defining High-Risk Patients
Blaha: Let us shift to this very high-risk secondary prevention group that has been identified in the guidelines and is, of course, the target of some of the most aggressive LDL-lowering that we do in clinical practice. Tell me about that group and what our clinician audience should do to start to treat those patients and get them to the low LDL that we are seeking.
Virani: There are some who are very high-risk [secondary prevention patients] and some who are not [as high]. This concept was introduced in this guideline, but it is something that you and I and all of our practicing primary care clinicians already know.
We make a judgment in our head when we are seeing a patient for secondary prevention. Secondary prevention patients who have already had a heart attack, stroke, or revascularization with a stent or bypass surgery are not all created the same way. A patient who had a stent placed 10 years back is not the same risk as a patient who had a myocardial infarction (MI) 6 months back.
What these guidelines do is to basically divide the patients who have clinical atherosclerotic cardiovascular disease (ASCVD) and are secondary prevention patients into two large groups. One is the very high-risk ASCVD group, and the other are the stable ASCVD patients who are not very high-risk.
In stable ASCVD patients, the treatment recommendations are the same that we had before: use the maximally tolerated statin therapy. Obviously in those who remain very high-risk, clinicians have the option of using those LDL-C thresholds and using add-on therapies, such as ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, which have been shown to improve cardiovascular outcomes.
It intuitively makes sense to define those very high-risk ASCVD patients using things that any clinician can assess in the clinical setting and do not require extra testing. Patients with a history of multiple major ASCVD events (MI, multiple acute coronary syndrome [ACS] events, stroke, symptomatic peripheral arterial disease) are more likely to benefit from an add-on therapy.
There are multiple risk factors to consider, all of which make sense. Secondary prevention patients who are over the age of 65, have uncontrolled hypertension, diabetes, cigarette smoking, chronic kidney disease (CKD), persistently elevated LDL-C levels, or familial hyperlipidemia (FH) are more likely to see benefit from add-on therapies. The reason for doing that is evidence-based.
The IMPROVE-IT trial examined the use of ezetimibe in post-ACS patients. Patients who had more of the nine clinical factors [considered in the trial], some of which are the same risk factors that we talked about, had a greater absolute risk reduction and more benefit from ezetimibe compared with patients who only had one of those clinical risk indicators.
Similarly, for PCSK9 inhibitors, we know that patients with peripheral artery disease, more than one MI in 4 years, an MI within the past 2 years, or multivessel coronary artery disease derived way more benefit than an average patient who was enrolled in those PCSK9 inhibitor trials.[3,4]
The ODYSSEY outcomes trial found that the subgroup of patients with LDL-C above 100 mg/dL, as well as patients with FH, seem to derive more benefit with use of PCSK9 inhibitors. We all know that these patients are very high-risk, particularly for secondary prevention.
It all makes intuitive sense and allows better clinical decision-making. I think we are all doing it anyway; what the guideline does is solidifies that concept that clinicians already use.
Blaha: I think you guys did a great job of taking what we do in clinical practice and making it simple and accessible.
The Issue of Cost
Blaha: There was a comment in the guidelines about cost of PCSK9 inhibitors. That is something that we are not used to seeing as much in guidelines. We are going to get used to seeing a lot more thinking about cost-effectiveness. Tell us a little bit about the thinking about that [cost-benefit] statement and about PCSK9 inhibitors in particular.
Virani: The guidelines now have to make a value statement if it is possible, because we all know that a lot of decisions that we make are [driven by cost]. What is the add-on value for a therapy?
For PCSK9 inhibitors, the guideline committee was tasked with creating a value statement based on a conceptual framework created by ACC and AHA, based on the cost for one quality-adjusted life-year (QALY) gained. If you look at the cost-effectiveness analyses[5,6,7,8,9,10] that have been performed in secondary prevention with PCSK9 inhibitors, six out of seven calculated an incremental cost-effectiveness ratio (ICER) of above $150,000 [cost per QALY], which would put this category of drugs in the low-value category. One trial calculated an ICER value of about $140,000 per QALY. The cost of a high-value agent should be less than $50,000/QALY. A cost of $50,000-$150,000 per QALY is intermediate.
Calculating the ICER value on the basis of the mid-2018 list price for these drugs, because that is what we had available at the time these guidelines were developed, found them to be of low value. We put [that cost calculation in the guideline] so clinicians and patients can have that discussion of this add-on therapy. But in terms of cost and value, they are definitely not there yet. We hope that the prices will come down, and that will bring [the ICER value] down.
Obviously, you are aware of the announcement [of a price cut for one PCSK9 inhibitor] that was made a couple of weeks back. We welcome that announcement, because that will help patients and clinicians with this decision. The guidelines will be updated once more analysis comes out based on the recent price structure.
Blaha: I do not want to shortchange primary prevention, so let's discuss that. The guideline mentions a group of patients that may not need to be treated as aggressively after risk assessment. Tell me about that.
Virani: A 10-year risk calculation should be performed in all patients between the ages of 40 and 75 years. Lifestyle risk and working on individual risk factors are very important.
Let us talk about that 40- to 75-year age group. Patients with a 10-year risk calculation of less than 5% generally require only lifestyle modification. Those with a risk score of 5%-7.5% generally should be treated with lifestyle unless the patients has one of the risk-enhancing factors that the guidelines discuss for primary prevention.
A risk discussion with patients in that intermediate risk category of 7.5%-20% should include those enhancers discussed in the guideline. If the patient or the clinician is still not certain about patient risk, which is not uncommon, then you have the option to use a coronary calcium score as a decider in the decision to recommend statin therapy or not. Clinicians have a lot more tools now for that intermediate-risk group.
Blaha: The coronary calcium score can allow more individualized decision-making. If the score is zero, that patient is perhaps someone for whom you could consider doubling down on lifestyle before advancing pharmacotherapy.
Blaha: Great discussion. Great guidelines. From what I am hearing, everyone is excited about them. There is very little controversy and a lot of consensus on these great topics. Thank you for the discussion.
Virani: Thank you.
© 2018 American College of Cardiology & Medscape
Cite this: ACC/AHA 2018 Cholesterol Guideline: The New and the Old - Medscape - Nov 16, 2018.