Increasing Confidence in Prescribing PCSK9 Inhibitors



Howard Weintraub, MD: What I have found to be a problem is that a patient will come to me and we’ll recommend a PCSK9 inhibitor. Then the patient goes back to their primary care doctor, who’s a little concerned about what’s going on, and they talk to their local cardiologist, who may not be an aficionado of lipid lowering. It’s not a stretch to say that the average physician has been confused since about 2013, maybe longer. In 2013, there were no longer targets. There were statin-treatment groups, and then it took them 5 years to figure out that maybe there should be some reincorporation. They were then incorporated as thresholds. That was a new term and a new concept for doctors. As any consumer does when confused, a doctor is going to do nothing and figure, “When you guys figure it out, give me a call and I’ll do what’s appropriate.” The problem has been that a lot of the subgroup data, particularly FOURIER, are just that.

There’s a challenge in getting the information that you and I just discussed to the ears and heads of individuals like primary care physicians, internists, and those like nephrologists who see others at risk. I have always tried to empower the individuals who do not start every day looking forward to tackling a lipid problem. I look at every patient with a PCSK9 inhibitor as a possibility, rather than saying, “You know, I don’t know. What should I do,” banging my head against the wall and waiting for someone else to solve the problem.

I hope that the kind of discussion that you and I just had will allow people to feel a bit more comfortable. To summarize, these are highly effective, easy to use, every-2-week medicines. From the time they prep the skin until the time they put a Band-Aid on, it’s usually under 60 seconds. There’s no one who doesn’t have the time for that every 2 weeks. The adverse-effect profile is amazingly benign.

Between the 2 of us, with all the patients that we see and treat with PCSK9 inhibitors, we have had fewer than a handful of people who have to come off. A couple of those are through no fault of the drug but by fault of genetics. They probably had LDL [low-density lipoprotein] receptor abnormality that prevented the PCSK9 inhibitor from working, even though a statin might still work. These are very effective drugs. All doctors want to do what’s best for their patients, and as long as the financial burden is tolerable and surmountable, these are medicines that I’m surprised are not receiving better uptake. Just as a bit of trivia, we were the first office in New York City to start a patient on a PCSK9 inhibitor, which was alirocumab, back in the summer of 2015.

I’m happy to give my thoughts on this. It’s 1 extra burden on the patient to have to go see a specialist and then keep coming back for it. It’s not that I mind, because I’m very happy to see them, and I’m sure you are as well. But this is something I hope gains better traction.

Alan S. Brown, MD, FACC, FAHA, FNLA: I agree. These have a reasonable cost, very low adverse-effect profile, and no real drug interactions, and the patients have to inject only every 2 weeks. One of the barriers is that the physicians need to see how the drug is given. Many times, if they’re not comfortable explaining to the patient what they’re going to get in the pen and how to do the injection, they avoid the conversation I actually tell the reps, “Make sure you use those demonstration pens and show the doctors how to use the drug.” Once you realize how easy it is, you’re much more likely to think about prescribing it.

In our clinic, we have the ability for the patient take their first injection in the clinic. I find that extremely helpful. But in many health care systems, including ours, they don’t allow samples. That becomes a problem for demonstration. This is 1 situation in which it is worth asking your health care system to make an exception because they’ve already not been adequately controlled on generic medications. It is helpful to have the patient see how to do the injection and also realize that it’s not painful.

As we finish, I want to clarify 1 thing about thresholds vs. goals. You brought it up a couple of times, and it’s true that numbers changed with the 2018 guidelines. For the people who struggle with that, what’s the difference between a goal and a threshold? This was a way to get around the patient who comes in with an acute coronary event whose LDL is relatively low. Imagine a patient who comes in with an acute MI [myocardial infarction], or an angioplasty and a stent, whose LDL is 72 mg/dL. They have a low HDL [high-density lipoprotein] and high triglycerides, and we see more of those cases as we’re seeing more metabolic syndrome patients. If you had a goal of 70 mg/dL and you brought that patient’s LDL from 72 to 69 mg/dL, you would have achieved a goal. But you have done absolutely nothing for that patient’s risk. That’s the reason there was a resistance to the term goal, because more patients are arriving with LDLs that are not sky-high with acute coronary events.

What we know from clinical trials is that if you add a drug to that patient, it may lower LDL another 60%. If you add a drug to that patient who has been proven in a trial to get benefit on top of whatever they’re taking, you’re going to have better outcomes. You aren’t going to have better outcomes if you put them on 5 mg of pravastatin and get their LDL from 72 to 69 mg/dL. The whole idea of switching from a goal to a threshold was to give instruction on what to do in a patient whose LDL is not very high. If their LDL is 160 mg/dL, then having a goal of 70 mg/dL is probably effective. You’re going to lower their LDL at least 50%.

I want to remind everyone that in clinical trials, when they added a drug that’s been proven to work, such as a statin in high-risk patients, they lowered LDL 50%, even if the starting LDL was relatively low at 75 or 80 mg/dL. That’s where a goal would not be adequate and a threshold makes more sense. A threshold is not a number at which you’re good when you get below it. It’s a number above which you would add a potent therapy that’s been proven in a clinical trial to reduce events. That is why the guidelines say if your LDL is still above 70 mg/dL, that’s a threshold in a very high-risk patient at which you would consider adding a PCSK9 inhibitor. If they’re not on a statin, that’s a threshold at which you would add a statin or intensify therapy. It’s not about where you end up.

It’s about a call to action above that threshold. I just wanted to clarify that. If you look at it that way, we’re not far from the European guidelines. We just came at it in a slightly different way.

Transcript Edited for Clarity

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