Peter Salgo, MD: Let’s talk about the PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors. We’ve talked around them. We discussed them. We talked about the research. Now, let’s talk about them out there in the real world. You’ve had experience using them, yes?
 
Seth J. Baum, MD: Absolutely.
 
Peter Salgo, MD: Tell me about your experience.
 
Seth J. Baum, MD: Medically, they’re incredible drugs. They do exactly what FOURIER showed. They lower LDL 60%, 70%, on top of maximally tolerated statin therapies. They’re incredibly well tolerated. From an injection site-reaction standpoint, it’s really rare to have somebody with a problem. They’re a wonderful solution.
 
Gary L. Johnson, MD, MBA: I have a question from something you said earlier. You, kind of, picked 70 mg/dL as your target goal in secondary prevention.
 
Seth J. Baum, MD: Yes, but I think it should be much lower than that. That’s just the most commonly utilized number across the board.
 
Peter Salgo, MD: Is that number out there because that’s all you can get?
 
Gary L. Johnson, MD, MBA: The reason I asked that is, I think the evidence shows that this is a linear relationship.
 
Seth J. Baum, MD: Yes, it is.
 
Gary L. Johnson, MD, MBA: Why not 20 mg/dL? Why not 30 mg/dL? Why not 40 mg/dL?
 
Seth J. Baum, MD: It should be 30 mg/dL. I agree with you.
 
Howard Weintraub, MD: It was stepwise. People did arbitrary numbers, and that was about where we could go. And so, in proving a few other studies, they’ve looked at 70 mg/dL versus 100 mg/dL, but in that study as well, they looked at 50 mg/dL versus 70 mg/dL. And that was the first time 50 mg/dL reared its head. Then, from then on, we were really looking to do the best we could: 70 mg/dL is yesterday, 50 mg/dL is where we’re going, and now 30 mg/dL is the number. Actually, that’s what you’re born with, so we’re retreating to natal cholesterol levels.
 
Peter Salgo, MD: See, I told you 30 mg/dL would come back up. That being said, right now, who are the appropriate patients for these PCSK9 inhibitors?
 
Seth J. Baum, MD: I think it should be on-label. I think it should be people with clinical ASCVD (atherosclerotic cardiovascular disease) or heterozygous FH (familial hypercholesterolemia), on maximally tolerated statin therapies, who require a greater reduction in LDL cholesterol, or in the case of evolocumab, homozygous FH as well. If you follow the prescribing information, that’s who should be on the drugs.
 
Howard Weintraub, MD: What problems do you have in people with ASCVD? I know with us, we have people who say, “Wait, 90 mg/dL isn’t too high because all you’ve got to do is be below 100 mg/dL.” And one of the companies, who will go nameless, wants it to be up over 130 mg/dL.
 
Seth J. Baum, MD: Yes, I’ve seen that as well.
 
Peter Salgo, MD: But 130 mg/dL was 8 years ago.
 
Howard Weintraub, MD: Exactly. One-hundred and thirty mg/dL is a number that’s okay if you have no coronary disease and just have 1 risk factor.
 
Peter Salgo, MD: By the way, is it okay?
 
Howard Weintraub, MD: No. It was okay, then. No, as far as I’m concerned, it never was, but good question. I think they will use that as a number, and that’s most infuriating in that you don’t know what they want. And in your mind, because the FDA says, “We’ll let you guys slug it out,” what’s not done is the industry should have come up with an agreement that says, “We’re not going to go with 70 mg/dL, but we’re going to give you 80 mg/dL or 85 mg/dL. Then, we have dialogues after that. Instead, each company has its own number, which says that, “You guys are making up your own rules.”
 
Seth J. Baum, MD: I would disagree with you because I think that they shouldn’t have agreed upon a number higher than 70 mg/dL with all the data we have. We should be able to treat our patients, according to the prescribing information, in their best interest.
 
Howard Weintraub, MD: Okay.
 
Peter Salgo, MD: Let me ask a couple of provocative questions, and then I want to go on to some payer questions. Just in terms of medicine, if everybody should be 70 mg/dL, and now you can get down to 30 mg/dL, and all-comers come into your office and you know that there’s no threshold (I’m not at high risk by lifestyle or family history and my LDL cholesterol is 90 mg/dL), why not put me on a statin? Why not put me on a PCSK9 inhibitor and get me down to 20 mg/dL right now? There’s an indication.
 
Seth J. Baum, MD: First of all, it depends.
 
Peter Salgo, MD: And that’s going to break his bank.
 
Seth J. Baum, MD: It depends who you are, how old you are, what your family history is, and then some of us do subclinical testing. We do coronary CT scans and see whether you have disease. If you have no disease and you’re 67 years old and you’re a man and your LDL is 90 mg/dL, I would not put you on a statin.
 
Howard Weintraub, MD: It’s a get-out-of-jail-free card.
 
Seth J. Baum, MD: Yes.
 
Peter Salgo, MD: Okay. And one last question. You all were extraordinarily happy with the side effect profile of these drugs. How much experience do we really have to know that 10 or 15 years down the line, there’s not going to be side effects?
.
 
Howard Weintraub, MD: We don’t know that.
 
Peter Salgo, MD: It’s just fair to put that out there.
 
Seth J. Baum, MD: You could never know that, but from an LDL standpoint, I would say that with an LDL of 30 mg/dL, there is enough evidence from Mendelian Randomization Studies with PCSK9 loss-of-function mutations that these people have LDLs of 14 mg/dL or 15 mg/dL for their entire lives and they don’t have any problems—and other groups as well.
 
Peter Salgo, MD: That being said, that’s a little tricky to do because there may be other random mutations in there as well.
 
Seth J. Baum, MD: The PCSK9 inhibitor is mimicking, in a sense, the absence of PCSK9.
 
Howard Weintraub, MD: But what he’s saying is there may be other genetic abnormalities that protect them from the PCSK9, which I could understand.
 
Peter Salgo, MD: Let’s talk about coverage criteria. Now that we’ve put this down, we can establish the following truths. We hold these truths to be self-evident.
 
Seth J. Baum, MD: Self-evident, yes.
 
Peter Salgo, MD: And these truths are, you can get the LDL cholesterol down. Lower LDL cholesterols are associated with lower heart disease risk and other cardiovascular risks, and the drugs have a good side effect profile (that is to say, virtually none other than injection site issues). We’ll put that on the table. Everybody will accept this? We can move forward? What are the coverage criteria? How are you going to cover this drug?
 
Gary L. Johnson, MD, MBA: The coverage criteria is basically to the FDA label, despite what experiences you may have had.
 
Seth J. Baum, MD: Well, it’s great to hear you say that.
 
Howard Weintraub, MD: Can I ask you a question? Have you guys evolved your policy on this?
 
Jennifer Strohecker, PharmD, BCPS: Not yet.
 
Howard Weintraub, MD: Have you evolved? Has this changed, even in the last year-and-a-half that the drugs have been available?
 
Gary L. Johnson, MD, MBA: I think we’ve always covered it to label.
 
Howard Weintraub, MD: Because some of the companies came out very strict and they relaxed a little bit over the year-and-a-half they’ve been out. That’s the reason I was asking.
 
Peter Salgo, MD: Now, what about step therapy and prior authorization for these drugs? Do you require step therapy first?
 
Jennifer Strohecker, PharmD, BCPS: Yes.
 
Peter Salgo, MD: What is it like, and why?
 
Jennifer Strohecker, PharmD, BCPS: Consistent with, I think, what we see, first of all, for FH, it’s genetic testing. It’s consistent with the label for that.
 
Seth J. Baum, MD: No, it’s not. There’s no genetic testing in the label.
 
Jennifer Strohecker, PharmD, BCPS: Genetic testing physician attestation is required.
 
Peter Salgo, MD: So, there is genetic testing?
 
Jennifer Strohecker, PharmD, BCPS: This is different than step therapy or prior authorization approval. Step therapy would say, first of all, “Our approvals are consistent with the FDA label,” okay? As far as coverage criteria, we do require that patients have had done their attempts with lifestyle modifications as well as statin therapy, and we would like them to try 2 different statins before considering it a statin failure.
 
Peter Salgo, MD: That’s a fairly rigorous requirement.
 
Seth J. Baum, MD: What if they have tried Crestor (rosuvastatin) and their start point is 200 mg/dL, and they’re down to 100 mg/dL, and they have FH and vascular disease, do you require the use of a different statin even though rosuvastatin is the best, most effective statin?
 
Jennifer Strohecker, PharmD, BCPS: No. At that point, I think there is some request to see what the opportunities would be around ezetimibe therapy.
 
Seth J. Baum, MD: Which is not in the label, by the way.
 
Jennifer Strohecker, PharmD, BCPS: Yes.
 
Peter Salgo, MD: You’re going to go for step therapy. I just heard this “genetic testing” word, which somebody, earlier in the broadcast, said they didn’t require. Suddenly it pops up?
 
Jennifer Strohecker, PharmD, BCPS: It’s not required, it’s requested. Has there been genetic testing done to confirm?
 
Peter Salgo, MD: What’s the difference between requested and required?
 
Seth J. Baum, MD: And what if the answer is “No” to that? Do you then ask, “We would like genetic testing?”
 
Jennifer Strohecker, PharmD, BCPS: No, there’s a request for LDL levels where we’re looking at LDL levels to look at the fact that they haven’t achieved their goals.
 
Seth J. Baum, MD: By the way, while you’re asking these questions of us, time is going forward and time is plaque in these individuals. And so, they’re at risk for having an infarct, or stroke, or dying while this entire process is occurring.
 
Howard Weintraub, MD: You know why that’s cogent? Because the curve separated in the first 6 months in the study. So, while we’re waiting and having a back-and-forth, we could be doing something to reduce the likelihood of an event, statistically. I think this is something to be said.

Clinical Experience With PCSK9 Inhibitors

Seth J. Baum, MD; Gary L. Johnson, MD, MBA; Peter Salgo, MD; Jennifer Strohecker, PharmD, BCPS; and Howard Weintraub, MD, debate the appropriateness of step therapy in instances where a more aggressive approach is needed to manage cholesterol.
Published Online: May 18, 2017


Peter Salgo, MD: Let’s talk about the PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors. We’ve talked around them. We discussed them. We talked about the research. Now, let’s talk about them out there in the real world. You’ve had experience using them, yes?
 
Seth J. Baum, MD: Absolutely.
 
Peter Salgo, MD: Tell me about your experience.
 
Seth J. Baum, MD: Medically, they’re incredible drugs. They do exactly what FOURIER showed. They lower LDL 60%, 70%, on top of maximally tolerated statin therapies. They’re incredibly well tolerated. From an injection site-reaction standpoint, it’s really rare to have somebody with a problem. They’re a wonderful solution.
 
Gary L. Johnson, MD, MBA: I have a question from something you said earlier. You, kind of, picked 70 mg/dL as your target goal in secondary prevention.
 
Seth J. Baum, MD: Yes, but I think it should be much lower than that. That’s just the most commonly utilized number across the board.
 
Peter Salgo, MD: Is that number out there because that’s all you can get?
 
Gary L. Johnson, MD, MBA: The reason I asked that is, I think the evidence shows that this is a linear relationship.
 
Seth J. Baum, MD: Yes, it is.
 
Gary L. Johnson, MD, MBA: Why not 20 mg/dL? Why not 30 mg/dL? Why not 40 mg/dL?
 
Seth J. Baum, MD: It should be 30 mg/dL. I agree with you.
 
Howard Weintraub, MD: It was stepwise. People did arbitrary numbers, and that was about where we could go. And so, in proving a few other studies, they’ve looked at 70 mg/dL versus 100 mg/dL, but in that study as well, they looked at 50 mg/dL versus 70 mg/dL. And that was the first time 50 mg/dL reared its head. Then, from then on, we were really looking to do the best we could: 70 mg/dL is yesterday, 50 mg/dL is where we’re going, and now 30 mg/dL is the number. Actually, that’s what you’re born with, so we’re retreating to natal cholesterol levels.
 
Peter Salgo, MD: See, I told you 30 mg/dL would come back up. That being said, right now, who are the appropriate patients for these PCSK9 inhibitors?
 
Seth J. Baum, MD: I think it should be on-label. I think it should be people with clinical ASCVD (atherosclerotic cardiovascular disease) or heterozygous FH (familial hypercholesterolemia), on maximally tolerated statin therapies, who require a greater reduction in LDL cholesterol, or in the case of evolocumab, homozygous FH as well. If you follow the prescribing information, that’s who should be on the drugs.
 
Howard Weintraub, MD: What problems do you have in people with ASCVD? I know with us, we have people who say, “Wait, 90 mg/dL isn’t too high because all you’ve got to do is be below 100 mg/dL.” And one of the companies, who will go nameless, wants it to be up over 130 mg/dL.
 
Seth J. Baum, MD: Yes, I’ve seen that as well.
 
Peter Salgo, MD: But 130 mg/dL was 8 years ago.
 
Howard Weintraub, MD: Exactly. One-hundred and thirty mg/dL is a number that’s okay if you have no coronary disease and just have 1 risk factor.
 
Peter Salgo, MD: By the way, is it okay?
 
Howard Weintraub, MD: No. It was okay, then. No, as far as I’m concerned, it never was, but good question. I think they will use that as a number, and that’s most infuriating in that you don’t know what they want. And in your mind, because the FDA says, “We’ll let you guys slug it out,” what’s not done is the industry should have come up with an agreement that says, “We’re not going to go with 70 mg/dL, but we’re going to give you 80 mg/dL or 85 mg/dL. Then, we have dialogues after that. Instead, each company has its own number, which says that, “You guys are making up your own rules.”
 
Seth J. Baum, MD: I would disagree with you because I think that they shouldn’t have agreed upon a number higher than 70 mg/dL with all the data we have. We should be able to treat our patients, according to the prescribing information, in their best interest.
 
Howard Weintraub, MD: Okay.
 
Peter Salgo, MD: Let me ask a couple of provocative questions, and then I want to go on to some payer questions. Just in terms of medicine, if everybody should be 70 mg/dL, and now you can get down to 30 mg/dL, and all-comers come into your office and you know that there’s no threshold (I’m not at high risk by lifestyle or family history and my LDL cholesterol is 90 mg/dL), why not put me on a statin? Why not put me on a PCSK9 inhibitor and get me down to 20 mg/dL right now? There’s an indication.
 
Seth J. Baum, MD: First of all, it depends.
 
Peter Salgo, MD: And that’s going to break his bank.
 
Seth J. Baum, MD: It depends who you are, how old you are, what your family history is, and then some of us do subclinical testing. We do coronary CT scans and see whether you have disease. If you have no disease and you’re 67 years old and you’re a man and your LDL is 90 mg/dL, I would not put you on a statin.
 
Howard Weintraub, MD: It’s a get-out-of-jail-free card.
 
Seth J. Baum, MD: Yes.
 
Peter Salgo, MD: Okay. And one last question. You all were extraordinarily happy with the side effect profile of these drugs. How much experience do we really have to know that 10 or 15 years down the line, there’s not going to be side effects?
.
 
Howard Weintraub, MD: We don’t know that.
 
Peter Salgo, MD: It’s just fair to put that out there.
 
Seth J. Baum, MD: You could never know that, but from an LDL standpoint, I would say that with an LDL of 30 mg/dL, there is enough evidence from Mendelian Randomization Studies with PCSK9 loss-of-function mutations that these people have LDLs of 14 mg/dL or 15 mg/dL for their entire lives and they don’t have any problems—and other groups as well.
 
Peter Salgo, MD: That being said, that’s a little tricky to do because there may be other random mutations in there as well.
 
Seth J. Baum, MD: The PCSK9 inhibitor is mimicking, in a sense, the absence of PCSK9.
 
Howard Weintraub, MD: But what he’s saying is there may be other genetic abnormalities that protect them from the PCSK9, which I could understand.
 
Peter Salgo, MD: Let’s talk about coverage criteria. Now that we’ve put this down, we can establish the following truths. We hold these truths to be self-evident.
 
Seth J. Baum, MD: Self-evident, yes.
 
Peter Salgo, MD: And these truths are, you can get the LDL cholesterol down. Lower LDL cholesterols are associated with lower heart disease risk and other cardiovascular risks, and the drugs have a good side effect profile (that is to say, virtually none other than injection site issues). We’ll put that on the table. Everybody will accept this? We can move forward? What are the coverage criteria? How are you going to cover this drug?
 
Gary L. Johnson, MD, MBA: The coverage criteria is basically to the FDA label, despite what experiences you may have had.
 
Seth J. Baum, MD: Well, it’s great to hear you say that.
 
Howard Weintraub, MD: Can I ask you a question? Have you guys evolved your policy on this?
 
Jennifer Strohecker, PharmD, BCPS: Not yet.
 
Howard Weintraub, MD: Have you evolved? Has this changed, even in the last year-and-a-half that the drugs have been available?
 
Gary L. Johnson, MD, MBA: I think we’ve always covered it to label.
 
Howard Weintraub, MD: Because some of the companies came out very strict and they relaxed a little bit over the year-and-a-half they’ve been out. That’s the reason I was asking.
 
Peter Salgo, MD: Now, what about step therapy and prior authorization for these drugs? Do you require step therapy first?
 
Jennifer Strohecker, PharmD, BCPS: Yes.
 
Peter Salgo, MD: What is it like, and why?
 
Jennifer Strohecker, PharmD, BCPS: Consistent with, I think, what we see, first of all, for FH, it’s genetic testing. It’s consistent with the label for that.
 
Seth J. Baum, MD: No, it’s not. There’s no genetic testing in the label.
 
Jennifer Strohecker, PharmD, BCPS: Genetic testing physician attestation is required.
 
Peter Salgo, MD: So, there is genetic testing?
 
Jennifer Strohecker, PharmD, BCPS: This is different than step therapy or prior authorization approval. Step therapy would say, first of all, “Our approvals are consistent with the FDA label,” okay? As far as coverage criteria, we do require that patients have had done their attempts with lifestyle modifications as well as statin therapy, and we would like them to try 2 different statins before considering it a statin failure.
 
Peter Salgo, MD: That’s a fairly rigorous requirement.
 
Seth J. Baum, MD: What if they have tried Crestor (rosuvastatin) and their start point is 200 mg/dL, and they’re down to 100 mg/dL, and they have FH and vascular disease, do you require the use of a different statin even though rosuvastatin is the best, most effective statin?
 
Jennifer Strohecker, PharmD, BCPS: No. At that point, I think there is some request to see what the opportunities would be around ezetimibe therapy.
 
Seth J. Baum, MD: Which is not in the label, by the way.
 
Jennifer Strohecker, PharmD, BCPS: Yes.
 
Peter Salgo, MD: You’re going to go for step therapy. I just heard this “genetic testing” word, which somebody, earlier in the broadcast, said they didn’t require. Suddenly it pops up?
 
Jennifer Strohecker, PharmD, BCPS: It’s not required, it’s requested. Has there been genetic testing done to confirm?
 
Peter Salgo, MD: What’s the difference between requested and required?
 
Seth J. Baum, MD: And what if the answer is “No” to that? Do you then ask, “We would like genetic testing?”
 
Jennifer Strohecker, PharmD, BCPS: No, there’s a request for LDL levels where we’re looking at LDL levels to look at the fact that they haven’t achieved their goals.
 
Seth J. Baum, MD: By the way, while you’re asking these questions of us, time is going forward and time is plaque in these individuals. And so, they’re at risk for having an infarct, or stroke, or dying while this entire process is occurring.
 
Howard Weintraub, MD: You know why that’s cogent? Because the curve separated in the first 6 months in the study. So, while we’re waiting and having a back-and-forth, we could be doing something to reduce the likelihood of an event, statistically. I think this is something to be said.
View More From This Discussion
Episode 1 Current CVD Prevention and Management Challenges
Episode 2 Managed Care Decision Making in CVD and Lipid Control
Episode 3 Early Detection of Risk and Familial Hypercholesterolemia
Episode 4 Cholesterol Goals in Primary Cardiovascular Disease Prevention
Episode 5 Coverage of Statins/Nonstatins in Lipid Management
Episode 6 Lipid Management: Coverage Criteria vs FDA Labeling
Episode 7 Efficacy and Safety of PCSK9 Inhibitors
Episode 8 Management of High-Risk Populations With Hyperlipidemia
Episode 9 Candidacy for Later-Line Cholesterol-Lowering Therapies
Episode 10 Alternate Mechanisms of Action for Cholesterol Management
Episode 11 Clinical Experience With PCSK9 Inhibitors
Episode 12 PCSK9 Inhibitors: Cost Concerns and Access
Episode 13 Cholesterol Management and Long-Term Cardiovascular Disease Prevention
Episode 14 The Future of Lipid Management
Episode 15 Unmet Needs in Cholesterol Management
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