Peer Insight: The State of Lipid Care with Kevin Maki, PhD

Need for More In-Between Therapies

Kevin Maki, PhD, chief scientist at the Midwest Biomedical Research Center for Metabolic and Cardiovascular Health, sat down with MD Magazine to discuss a multitude of topics around the state of lipid care, including the constant need for more options, the importance of balancing the cost and benefits of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and the impact of the new hypertension guidelines.“The lipid space has gone through its ups and downs,” Maki told MD Magazine. “We had a long period between 2003 and fairly recently where we had no new class of lipid-altering medication approved, [but] we’ve had a couple of additional medications approved recently. All the new medications have been relatively expensive, [though].”

In some cases, Maki said, these medications can also have a very limited indication, PCSK9 inhibitors in particular. These therapies are expensive, but they are also very effective in lowering atherogenic cholesterol, he said. Statins are one of the alternatives. In addition to being reliable, most statins are now generic, making them relatively inexpensive.

But after exhausting those options, patients are left with little else.

“If a statin isn’t enough—either the patient cannot tolerate it or, on a maximal dose, there simply is not a sufficient lowering of [low-density lipoprotein] and atherogenic cholesterol—then the options are limited,” Maki said. “We do have ezetimibe, as an example, which provides a small additional reduction in [low-density lipoprotein] cholesterol.”

Recently, ezetimibe was made available as a generic, which has helped the issue, but there is still a void. “Cost is less of an issue now with ezetimibe than it was recently, but we don’t have anything to add to that ezetimibe for a statin-treated patient right now other than a PCSK9 inhibitor,” he added.

With some new therapies in development, the future has the potential to be bright, but their ability to have an impact for patients who are statin intolerant is still far down the line.

“We have sort of the equivalent of something that gives us a small additional effect—I say a squirt gun or a bazooka—and we need some things that are in the middle,” Maki said. “We are in a situation where we have very good treatment options, and we need to figure out, ideally, additional treatment options that are less expensive than the PCSK9 inhibitors that can give an incremental reduction in atherogenic cholesterol, above and beyond what you see with a statin plus ezetimibe.

Balancing Cost and Benefit With PCSK9 Inhibitors

“I hate to speculate at this point because there are a lot of things that can prevent a drug from ultimately making it to market, but there are some reasonably promising therapies in development currently,” he added.PCSK9 inhibitors have become an increasingly popular class of medicines because of their high efficacy. But they also carry a high price tag, which limits the spectrum of patients who can afford them. Maki is not convinced that that will always be the case, though.

“We’re expecting new data from the ODYSSEY outcomes trial that’s just ending, and so the results are going to be available next year,” Maki said. “We have one trial now, FOURIER, which showed a benefit. The trial was very short, though. The follow-up period averaged only 2.2 years, and so the full benefit probably was not realized in the patients who participated in that trial. With ODYSSEY outcomes, the follow-up time will be longer.”

This longer follow-up will lead to more evidence of benefit, noted Maki, resulting in a shift in the conversation. “The question is really, Who are the appropriate patients in whom the health care system can afford to provide this very effective treatment?” he said.

Maki acknowledges that this comes with the assumption that the ODYSSEY outcomes will produce the expected results. He said, however, that he would be “very surprised” if they did not.

“We have so much evidence now that lowering atherogenic cholesterol is effective for reducing event risk,” he said. “It’s not just the amount of lowering; it is how long it stays low. So because of that, we expect favorable results with [the] ODYSSEY outcomes. If that’s the case, then I think there is going to be a much stronger argument for treating more people with PCSK9 inhibitors.”

That is when the trade-off between benefit and cost comes into play.

“I think they’re both important because, in the end, economics is the study of limited resources with alternative applications,” Maki said. “If we’re spending money on PCSK9 inhibitors, there may not be money available [for] other things. So, in patients who have high enough risk to justify the treatment, I think it’s going to make very good sense.”

The thresholds for making the decision on whom to treat with these medicines need to be identified. The real problem is not that these issues are complicated but that there are currently no existing systems to deal with them.

Some are coming into play, however. In late 2017, CVS Health, which recently acquired Aenta and its roughly 45 million members, announced that it would be providing real-time prescribing data to physicians and pharmacists—including prices of possible therapies.

“I think the CVS approach is very helpful because I know in many cases, people are prescribed a medication that’s very expensive, [and] their physician really has no idea what the cost is, and the patient doesn’t know there is an alternative that might be less expensive,” Maki said. “As one example, recently, I heard of a patient who was prescribed a medication that was something along the lines of $600 per month. It was a combination of 2 things, but if each of the things [had been] taken individually, the price would have been about one-tenth of that.”

These issues often go undiscussed. Physicians do not always know what the costs are when they are writing prescriptions for patients. Similarly, patients are often not aware of the costs when their physician recommends a therapy.

New Hypertension Guidelines

“There really isn’t that opportunity to have a discussion about, ‘Is there an alternative that might be less expensive?’” Maki said. “[As in] many places in our health care system, we don’t have good systems to manage expenses because we are ultimately going to have to manage expense versus benefit, and the current system doesn’t lend itself very well to doing that.”Like policy changes, guideline changes can carry many benefits for physicians and patients. Their impact is felt immediately and covers a broad spectrum. Since the American College of Cardiology and American Heart Association updated the hypertension guidelines for the first time since 2003, approximately half of the US adult population has been defined as having hypertension.

“I think with modifiable risk factors—the big modifiable risk factors being high cholesterol, high blood pressure, smoking, and diabetes—with those big 4 modifiable risk factors, I think it is not only the level of the risk factor [but] the length of the exposure,” Maki said. “It is really important to identify early people with elevations in modifiable risk factors and then intervene early. That does not always mean pharmacologic therapy. In certain cases, if the risk is high enough, the risk-benefit ratio favors pharmacologic therapy, but lifestyle therapies are important. They get kind of short shrift in clinical practice often.”

Lifestyle therapies are incredibly important not only because they are low in cost but also because they can be implemented early, Maki said. Even in instances when there is only a modest effect, that change can be maintained over a period of decades.

By lowering the threshold to consider therapies, the ability to treat at-risk patients sooner becomes not just a possibility but also a recommendation.

“I think we will have better ultimate results because the clinical trial data really show that for lipid-lowering, lower is better and lower is better for longer, and now with blood pressure, we are seeing that the prior targets probably were not giving us all the benefits that could be obtained with lower targets,” he said.

Watch Kevin Maki discuss more about the lipid space at www.mdmag.com/link/1766.