Candidacy for Later-Line Cholesterol-Lowering Therapies

Peter Salgo, MD: You’re going to crank up your therapy if you’re not getting the response that you want. As I understand it, your response is either a 30% reduction early on and then to a target later on?

Howard Weintraub, MD: Right.

Peter Salgo, MD: At some point, you may get to what’s called a maximally targeted or maximally tolerated statin dose, right?

Howard Weintraub, MD: Right.

Peter Salgo, MD: So, how do you define it, and then what do you do? First of all, how would you define a maximally tolerated statin dose?

Seth J. Baum, MD: The maximally tolerated statin dose is the highest dose of a statin that a patient can tolerate, even if that dose is zero.

Peter Salgo, MD: But what is “tolerate?” In other words, some patients say, “My joints hurt” or “My muscles hurt.” Some people can’t tell you how much they hurt.

Seth J. Baum, MD: No, then they can’t tolerate it. It’s individualized. It’s a patient-dependent method.

Peter Salgo, MD: There’s no form that you fill out? There’s nothing that you can submit?

Gary L. Johnson, MD, MBA: I would say the maximally tolerated dose is that at which the patient no longer will take the drug—that could be zero.

Seth J. Baum, MD: It could be zero.

Peter Salgo, MD: Because they don’t like it because something is wrong?

Gary L. Johnson, MD, MBA: Right.

Jennifer Strohecker, PharmD, BCPS: They believe something is wrong.

Gary L. Johnson, MD, MBA: Again, it depends on the company, but I think most companies would just ask for a physician statement saying that, “My patient is at the maximally tolerated dose.”

Seth J. Baum, MD: I completely agree with you. I think you should probably speak only for your own company, only because both Howard and I have had entirely different experiences with multiple companies, where they do reject, continuously, prescriptions for PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors.

Gary L. Johnson, MD, MBA: And the question is, is that the exception or is that the rule?

Seth J. Baum, MD: It’s the rule. There are data that we now have that show that initial rejection rates are between 80% to 90% in the nation, and that overall, in the commercial population, the final approval rate is somewhere in the 30%-to-50% range, at most. And in the Medicare population, it’s between 50% and 60%—final approval after multiple appeals.

Peter Salgo, MD: Let’s get a handle on how many folks we’re talking about altogether, because under the current guidelines, if you will, or algorithms, you’re not going to start giving these new drugs to people who are already controlled on previous therapies that are sometimes generic and sometimes easy to get. So, what proportion of patients, altogether, have uncontrolled lipid levels on statins alone?

Gary L. Johnson, MD, MBA: And your definition of “uncontrolled” means what?

Peter Salgo, MD: What a good question. Why don’t you define it?

Seth J. Baum, MD: It depends on the patient population. It depends on the risk. With PCSK9 inhibitors, all we’re talking about is the high-risk patient, so all we’re talking about is the ASCVD (atherosclerotic cardiovascular disease) patient or the FH (familial hypercholesterolemia) patient. And I would say greater than 70 mg/dL would be not well controlled. So, unfortunately, the latest NHANES (National Health and Nutrition Examination Survey) data that just came out showed that only 20% of people with ASCVD are under 70 mg/dL.

Howard Weintraub, MD: Correct. There was data last year that showed that only 30% of people on a statin get to the goal that they should, and at 70, some odd million people times 30%. You do the math.

Peter Salgo, MD: Let’s parse this out. If a fair number of high-risk folks on a (we’ll use your definition) maximally tolerated statin dose. That is to say, they’ll take it, but don’t get where we need them to go. Then you go searching for some other therapy. How do you track and how do you manage those folks?

Gary L. Johnson, MD, MBA: We, as the insurance company, generally don’t, unless the company has a very active disease management program. And, again, that varies with companies. So, we don’t track it at that level. We expect the physicians to be tracking that, and monitoring it, and prescribing therapy.

Peter Salgo, MD: But surely an insurance company that’s being asked to foot the bill for new, expensive medications is tracking how many of those prescriptions are going out and how many are for reasonable reasons, right?

Jennifer Strohecker, PharmD, BCPS: Yes. I think we put considerable resources into promoting the adherence of prescribed therapies and also in making recommendations to increase the dose where it’s warranted—where the patient hasn’t complained of problems on their current dose of statin and then has the opportunity to increase it. We don’t proactively track LDL levels, but certainly, we’re working with patients every day to identify patients who may not be adherent.

Peter Salgo, MD: Let me see if I hear this correctly. Somebody comes to you and says, “I want to use this new, expensive drug.” Are you really going to go back and say, “Gee, you’re not on a maximal statin dose yet?” Is that what you’re saying?

Jennifer Strohecker, PharmD, BCPS: Yes.

Peter Salgo, MD: Is that fair?

Jennifer Strohecker, PharmD, BCPS: We may ask the question, “What have you tried in the past, and how are you taking your current medications?”

Seth J. Baum, MD: You may ask those questions?

Jennifer Strohecker, PharmD, BCPS: We will. We’re going to look at claims data.

Seth J. Baum, MD: You’re not only going to ask that question, you’re going to ask for documentation that the patient has been on more than 1 statin for a prolonged period of time. And if you can’t meet those criteria, they’re not going to get the approval.

Peter Salgo, MD: Is that what you’re talking about, the receipts?

Howard Weintraub, MD: Yes.

Seth J. Baum, MD: Or records.

Howard Weintraub, MD: Sometimes, even in notes. We will write a note that says that the patient has been on whatever statin for 2 or 3 months, and they’re going to say, “That’s not good enough. We want to see receipts that he actually bought the medicine.”

Peter Salgo, MD: Is that unfair?

Seth J. Baum, MD: Yes.

Peter Salgo, MD: If you’re going to say, “Look, the statin is not working, please give me an expensive drug,” is it unfair of them to ask, “Is he taking the drug?”

Seth J. Baum, MD: Of course it’s unfair, because the FDA has approved these drugs for that indication, and we are the doctors and we’re taking care of the patients.

Peter Salgo, MD: What indication? I’m not taking the drug?

Seth J. Baum, MD: If they’re not taking the drug, they’re not taking the drug for a reason. We, as the physicians, should have that conversation with the patient, and there needs to be some sense of our respectability that we’re actually doing the right thing.

Jennifer Strohecker, PharmD, BCPS: I appreciate that perspective, but if we were to show you pharmacy claims data that demonstrated the patient hasn’t actually been taking their statin…

Peter Salgo, MD: How do we identify patients who may need more aggressive therapy anyway? Is it simply a number or do you really drill into it and say, “Are you really taking the drug?”

Howard Weintraub, MD: Many times, when you get an unexpectedly mediocre response to a drug, you want to know, so you ask the question, “How many days a week aren’t you using the drug?” Not “Are you taking it?” And they look at it and go, “I miss it once or twice, maybe 3 times a week.” They’ll come up with that. But other patients will look at you—and after taking histories for 34 years, you get reasonably good at knowing when someone is lying—and they look at you totally honest and say, “I take it every day.”

Peter Salgo, MD: Of course, if you have to give this drug by injection, they have to come and get it. You’ve got very good records going forward.

Seth J. Baum, MD: They self-inject.

Gary L. Johnson, MD, MBA: You said you thought it was unfair to ask a physician and a patient to mutually agree to take a much more cost-effective product (all things being equal) that they could take without side effects. You thought it was unfair for us, as an insurance company, a managed care company, to ask that to be done.

Seth J. Baum, MD: No, I didn’t. I said if we say, “It’s been done,” it’s unfair for you to say, “Well, we need to see the receipts because we don’t believe you.”

Gary L. Johnson, MD, MBA: Okay, so you would agree then.

Seth J. Baum, MD: Absolutely. That’s the prescribing information (PI), though. The PI is based on maximally tolerated statin therapy, and if they haven’t been on maximally tolerated statin therapy, you’re right.

Gary L. Johnson, MD, MBA: Okay.

Peter Salgo, MD: So, basically, if I give you my word that “This is what’s happened” and then you come back and ask, “Yeah, well, where are the receipts?”, they say it’s unfair. Is it fair or not?

Jennifer Strohecker, PharmD, BCPS: I’ll say that sounds unfair. That’s incredibly strict criteria. I haven’t seen receipts from 5 years ago or prescription records. We go by prescription records or physician attestation.

Seth J. Baum, MD: We see this, I’m telling you, all day long.