Drug Manufacturer Coupon Use; Cholesterol Targets for Secondary Prevention

TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine in Baltimore, and Rick Lange, MD, president of Texas Tech Health El Paso, look at the top medical stories of the week.

This week’s topics include deprescribing levothyroxine, drug manufacturer coupon use, how low should cholesterol be targeted in those with heart disease, and hypertension in low-income patients

Program notes:

0:36 How low should cholesterol be targeted in secondary prevention?

1:40 33% reduction with target to 55

2:36 Able to do it with statin and other drugs

3:03 Deprescribing levothyroxine

4:06 Were able to discontinue in many

5:05 Thyroid not as responsive with aging

6:05 Barriers to deprescribing?

6:31 Treatment of hypertension in low-income patients

7:31 75% unemployed

8:31 Patient participates

9:06 Manufacturer coupon use

10:10 Annual patient use of coupons

11:18 Used to drive people to use drugs that are expensive

12:33 End

Transcript:

Elizabeth: Can we discontinue levothyroxine in adults with thyroid disease?

Rick: Addressing hypertension in low-income patients.

Elizabeth: What’s the state of coupons issued by drug manufacturers to help patients afford their medicines?

Rick: And with LDL cholesterol, how low should you go in people with cardiovascular disease?

Elizabeth: That’s what we’re talking about this week on TTHealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a Baltimore-based medical journalist.

Rick: And I’m Rick Lange, president of Texas Tech Health El Paso.

Elizabeth: I like the “how low will you go,” so let’s turn to the New England Journal of Medicine.

Rick: This has been an evolving story. First of all, the Framingham study showed that cholesterol was associated with cardiovascular disease, in particular LDL cholesterol, and different medications to lower it. The guidelines have been ever-changing about how low we should get LDL cholesterol, with some people concerned that if you get it too low, it causes side effects that may be undesirable and may not have any beneficial cardiovascular effects.

To address that, this is a study conducted in South Korea where they decided to target LDL cholesterol in people that had known cardiovascular disease. In half of these individuals, we’re going to target an LDL cholesterol of 70, in the other half, an LDL cholesterol of 55. Is there any benefit to lowering it even lower?

Over 3,000 patients enrolled, followed for 3 years, all of them on high-intensity statins. And then if that didn’t lower the cholesterol, they usually added ezetimibe [Zetia]. In those that had their LDL cholesterol lowered to 70, their risk of having the composite of death, heart attack, stroke, any revascularization or hospitalization for unstable angina, their incidence was 9.7%. Those that got it down to 55, it was 6.6%. There was a 33% reduction. What were the side effects? No additional side effects as such with lowering the LDL cholesterol.

Elizabeth: OK. So in this secondary prevention capacity then, that’s one thing. I’d like to hear your speculation on primary prevention and whether it would be worth targeting a lower LDL in that group also.

Rick: I think the answer to that is probably going to be yes. In terms of primary prevention, it depends upon the number of risk factors you have. People with known elevated cholesterol, hypertension, cigarette smoking, obesity, metabolic syndrome, and family history, I think we’re likely to get a bigger bang for our buck.

Elizabeth: And would you suggest that as we’re looking at these PCSK9 inhibitors that are going to be oral, that’s going to be an indication for them?

Rick: It will. Here’s the interesting thing is, in the vast majority of patients that were able to lower cholesterol to 55 by just using a statin and Zetia, about 60% to 70% — there were still some that didn’t get there — and in those patients, using a PCSK9 inhibitor should be beneficial. As you know, it’s more costly. There are some additional side effects associated with it, not with the others. But you’re right. I would start with the things that we’ve had around for 10 or 20 years, relatively inexpensive. And then if not successful, then using some of the newer agents.

Elizabeth: Let’s turn to JAMA while we’re talking about medicines. And let’s look at this issue of levothyroxine in adults aged 60 years and older.

Many, many, many of those folks, because there has been this perceived reduction in their thyroid hormone, are taking this medicine. This study looked at community-dwelling adults aged 60 years and older who were taking levothyroxine at a stable dosage for at least 1 year and had a TSH [thyrotropin] level of less than 10 mIU/L. It was conducted at 58 general practices in the Netherlands. They were looking for this primary outcome, was the proportion of participants who discontinued levothyroxine and had both a thyrotropin level of less than 10 mIU/L and a free thyroxine level within the reference range at 1 year after the start of discontinuation.

Three hundred and sixty-six participants who completed their final follow-up at 1 year. They had 95 of them who successfully stopped taking levo during that time period and were within those ranges that they wanted. Among 88 participants who had originally been taking a lower dose of levo, almost 64% of them were able to successfully discontinue this treatment.

So basically what they’re showing is that 26% of these adults who were taking this medicine over this long period of time, but fell within these reference ranges that they determined, were able to cease taking the medicine. So they say, hey, we really need to develop an algorithm for deprescribing this medicine. There are some potential problems, iatrogenic thyrotoxicosis, because of persistent use of it. So why not deprescribe?

Rick: For our listeners that may not be familiar, the brain secretes thyrotropin or TSH, and it stimulates the thyroid to put out the hormones that we need. In individuals as they age, oftentimes the thyroid isn’t quite as responsive, so the TSH level goes up to make the thyroid produce enough thyroid hormone to meet the metabolic needs. That has been called subclinical hypothyroidism. If you repeat the measurements in 60% of the individuals, those measurements come back to normal.

The second thing is there’s not really any good evidence that treating subclinical hypothyroidism actually helps individuals. So we got a large number of older individuals that are being treated for subclinical hypothyroidism who probably didn’t need it if they would have had repeat testing and aren’t benefiting from it. And so this is the first deprescribing study that shows, yeah, there’s a large number of individuals in whom it can be stopped. Was gradually reduced about every 6 weeks, and there was no change in quality of life. Measurements in the blood appeared to be fine, especially if they were receiving low levels of thyroid hormone as a replacement. So this is a really interesting study, and it should get a lot of individuals off thyroid medication that don’t really need it and don’t benefit from it.

Elizabeth: Well, I’m wondering what the barriers are to the adoption of that practice for one. And then the other thing is, it just reminds me of so many studies that we’ve discussed where the question for me is, has anybody ever looked at what happens to the levels of all of these things as we age?

Rick: Clearly, the TSH goes up as we age. This is a great example of treating a lab test instead of treating a patient. That’s why they call it subclinical hypothyroidism because the patient has no symptoms. Treating it doesn’t make the person feel any better and it doesn’t reduce the risk of other chronic diseases. So probably not needed.

Elizabeth: Back to the New England Journal.

Rick: Treatment of hypertension in low-income patients. That population is particularly interesting because the prevalence is higher. They have very low control rates of hypertension. And what we learned, if you look at the Kaiser Permanente system and the Veterans Affairs system, they’ve been actually able to achieve high rates of blood pressure control through the use of what’s called a multicomponent, system-level intervention. It’s usually team-based. It’s a physician, nurse, medical assistants, front office individuals, getting the patient involved with their care, health coaches talking about lifestyle changes, and sending the patient home with a blood pressure cuff so they can monitor it. And this whole team has been successful.

Let’s take it to the community and see if it’s just as effective. And where it should be tested are what are called federally qualified health centers. These are centers that treat individuals that are low income. And in fact, in this particular study, 36 clinics in Louisiana and Mississippi, where the individuals were about 60 years of age, about two-thirds were Black, 75% were unemployed, and about the same amount had a family income of less than $25,000 per year. They randomized them to this multifaceted strategy for hypertension control that I mentioned, or just the usual care.

As they followed these individuals over the 3 years, what they discovered was that the individuals that received the multifaceted care, their blood pressure decreased by about 15 to 16 mm Hg, and in the control group, only about 9. And they looked at were there any serious adverse events. They occurred in about 21% of individuals in the intervention group and 21% of people in the control group.

Elizabeth: What’s the lift going to look like in order to implement teams such as this in all these folks who need it?

Rick: The provider provides the initial consultation. All the blood pressure medication changes are managed by protocols, so the medical assistants, nurses, and staff that are trained can help the person manage their blood pressure. The patient takes their blood pressure at home and provides those measurements on a routine basis either by a visit or by telephone. So that’s the team.

Elizabeth: It’s been my observation that when an approach is taken that integrates, first of all, the patient’s voice, and second of all, some acknowledgement that this person has a life and that there are precluding factors that might be interfering in their compliance with their regimens, I think that those things really do help.

Rick: And you described a vulnerable population, and this represents it. Three-fourths of them unemployed and three-fourths of them below the poverty level. To have a team care about them and to have them involved in their care, you can see the results. They were actually pretty amazing.

Elizabeth: I think so.

Finally, let’s turn back to JAMA, and this is a research letter that’s taking a look at manufacturer-sponsored coupon use and brand-name drug costs among patients, and in this case, it’s patients with insurance. I think that a very apt question, and the authors even pointed out, is, yes, and what happens in those folks who don’t have insurance, an increasing population here in the United States? Coupons, of course, we know lower patient costs at the point of sale. However, they may weaken the formulary incentives of insurers and distort their competition of manufacturers by encouraging the use of high-cost therapies.

So they took a look at a 10% person-level sample of pharmacy claims from the IQVIA Formulary Impact Analyzer. And interestingly — I didn’t know about this particular database — it captures almost 60% of U.S. retail pharmacy transactions. Patients with commercial insurance who had at least one claim for a brand-name drug without generic competition. And they were looking at annual patient-level coupon use. And their secondary outcomes were coupon amount per claim and patient out-of-pocket spending.

Basically, they show that there’s a decline in patient-level coupon use from 18% in 2017 to just shy of 14% in 2024. The percentage of pharmacy claims covered by coupons per patient declined from almost 14% in 2017 to 7.6% in 2024. Specifically, the coupon use declined markedly for obesity therapies, but increased for immunomodulators. We know that those are really expensive. Interestingly, patient out-of-pocket spending remains stable throughout this study period. So I think what this shows is a really interesting snapshot of what’s going on with these coupons and something that I kind of regard as an obfuscation of the central problems with our pharmaceutical industry.

Rick: They’re certainly using it to drive people towards certain medications and types of medications. And as more medications become available, there’s less coupon use. For example, the obesity drugs that you mentioned. When there were just one or two on the market and they were expensive, and they’re trying to drive people to use them. Now that there are many on the market and they’re less expensive and oftentimes insurance covers them, then less use. Immunomodulatory medications, you mentioned, coupon use up substantially, and the amount saved per coupon up. That’s because they’re expensive. It’s a way for the manufacturers, as you described, to try to drive business for certain medications.

Elizabeth: I think this population of folks who have commercial insurance is also a skewed population if we were going to try to capture the entire picture.

Rick: Absolutely. And thank goodness that for some of these medications, the expensive ones, they’ve provided gratis to individuals that can’t afford it. Not always, and I don’t want to say the pharmaceutical companies are altogether altruistic, but they do realize that there is a social contract. And as physicians and healthcare providers, we need to make these available to some individuals that can’t afford them.

Elizabeth: On that note then, that’s a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.

Rick: And I’m Rick Lange. Y’all listen up and make healthy choices.