Multifaceted Approach Can Help Patients Benefit From the Expanded Lipid-Lowering Toolbox

Am J Manag Care. 2024;30(Spec No. 10):SP771-SP774. https://doi.org/10.37765/ajmc.2024.89612

Recent years have seen a flurry of approvals and guideline updates for drugs that lower lipid levels to reduce cardiovascular risk, but there is still considerable room for improvement in implementation, according to speakers at an Institute for Value-Based Medicine event in Aurora, Colorado, on August 13, 2024. The event, held by The American Journal of Managed Care^® in partnership with the Colorado Prevention Center (CPC), featured faculty from the University of Colorado (UC) Anschutz School of Medicine in Aurora.

As introduced by event chair Marc Bonaca, MD, MPH, executive director of CPC Clinical Research and a professor of medicine, cardiology, and vascular medicine at UC School of Medicine, the evening’s agenda reflected the goal of thinking about “what we can do to better treat our patients who require lipid lowering.” The continuously expanding number of options in the therapeutic toolkit necessitates a team-based approach, so the speakers included an array of clinicians—in lipidology, interventional cardiology, and primary care—pharmacists, and a health plan leader.

Judith Hsia, MD, chief science officer at CPC Clinical Research and a research professor of medicine in the Division of Cardiology at UC School of Medicine, set the stage by explaining what current data show about lipid-lowering therapy. Ischemic heart disease is the leading cause of death worldwide, and many of those deaths are attributable to high low-density lipoprotein cholesterol (LDL-C). High-intensity statins are recommended by guidelines, but uptake in the US is disappointingly low, with GOULD registry data from 2020 revealing that just 22.5% of patients with atherosclerotic cardiovascular disease (ASCVD) are on one of these therapies.¹ Hsia cited complex and inconsistent guidelines as a persistent obstacle to achieving lower lipid levels.

Getting prescribers on the same page will be even more important as the lipid-lowering toolbox continues to grow. In addition to statins, Hsia highlighted the introduction of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors evolocumab (Repatha) and alirocumab (Praluent), as well as bempedoic acid (Nexletol). “Probably very few, if any, people in this room have prescribed” the latter yet, but it delivers a 36% LDL-C reduction when combined with ezetimibe (Nexlizet).² “This is part of the toolkit available for everybody, including statin-intolerant patients,” Hsia reminded the audience.

Next, Connie Hess, MD, MHS, an associate professor of medicine in the Division of Cardiology at UC School of Medicine and a faculty member of CPC Clinical Research, talked about bridging the gap from guidelines to the real world with a focus on patients with peripheral artery disease (PAD). These patients are at high risk of major cardiovascular and limb events; although guidelines recommend bringing down LDL-C to lower this risk, use of high-intensity statins is low in the PAD population, at just 22.0% according to her research—with 41.5% on no lipid-lowering therapy at all.³ To close this gap utilizing the principles of implementation science, she and colleagues initiated the OPTIMIZE PAD-1 trial (NCT04400409), which brings together an interprofessional vascular care team using an intensive, algorithm-based approach to lipid management.

“The clinical pharmacist is able to help with lipid checks and medication titration in a timely manner and to make sure that the patient doesn’t get lost and doesn’t fall through the cracks,” Hess said. “There’s a vascular nurse who’s also available to help coordinate all of these, and then, importantly, in this study there was an algorithm that helps the pharmacist and the physician select up-front medication to achieve the lipid goal rapidly.”

Results have been encouraging, including a significant decrease in mean LDL-C over 12 months compared with a usual-care arm.⁴ Hess said she hopes that the model can be adapted to larger health care systems and other chronic diseases such as diabetes and hypertension but that in the meantime, it serves as a powerful example of how “implementation science is needed and can be useful to increase adoption of evidence-based therapies in clinical practice.”

Jacinda Nicklas, MD, MPH, a primary care physician with UCHealth, took the stage to discuss the role of primary care in lipid management. Although some data show that primary care physicians are adapting to clinical guidelines by prescribing more medium- and high-intensity statins, PCSK9 inhibitors, and ezetimibe (Zetia), there is ample room for improvement. Primary care providers have the advantage of their patients’ trust, but stepping up lipid management can be hampered by clinical inertia, the short time slots allotted for primary care visits, and complex guidelines for not just hyperlipidemia but also the many other conditions treated in clinic. A team-based approach is crucial, as is an effort to streamline patient education tools. Overall, Nicklas said, “the goal is really to create informed and engaged patients and address barriers to taking statins and to adherence.”

The next speaker, Jeremy Wigginton, MD, MBA, chief medical officer at a regional health plan in the Northeast, concurred with the prior speakers about the need to better manage lipid levels. His presentation focused on the payer impacts on lipid management, including the variations in coverage across payer types. Whereas Medicaid and most commercial plans generally cover annual lipid screening for adults at no cost, Medicare only covers this screening once every 5 years for those with no known risk factors. Therapeutic coverage also varies, with many plans placing higher-cost therapies on higher tiers requiring prior authorization while keeping statins more easily accessible.

Wigginton mentioned coverage of other therapies to support lipid management, such as Medicare’s policy of not covering weight loss drugs, which restricts access to the new glucagon-like peptide 1 receptor agonists. He also noted that pharmacogenomic testing is a growing area and that he expects to see more conversations around coverage of these tests for identifying those likely to respond to lipid management therapy. As a clinician, he concluded that he sees the problem of therapeutic underutilization as “a combination of patient health behavior combined with the need for us to really get serious about those clinical care pathways in primary care.”

In the evening’s first panel discussion, the speakers answered audience questions, including some about the potential for scaling up the intervention in the OPTIMIZE PAD-1 trial led by Hess. To address the lack of funding for the pharmacist role in some health systems, Hsia and colleagues launched the OPTIMIZE ASCVD study, in which a nationwide pharmacy chain takes on the task of coordinating prescriptions.

“We are working toward having a system that’s self-sustaining, and this then would work very well for primary care providers like Jacinda [Nicklas], who aren’t going to have a pharmacist at their beck and call to be helping with all this activity, because the pharmacy chain pharmacists will do prior authorization support,” Hsia explained.

After a break for dinner and networking, the event resumed with a presentation by Demetria Bolden, PhD, MBA, CPTD, assistant professor of medicine at UC School of Medicine, on health equity in lipid risk management. In addition to the known modifiable risk factors, such as LDL-C level, there are numerous risk factors outside the clinic’s purview, such as cultural considerations, environmental factors, and patients’ responsibilities and familial support.

Bolden also highlighted the sex differences in statin utilization and lipid control. Women have a 22% lower likelihood of attaining LDL-C goals than men,⁵ and Black women are the group least likely to report taking statins despite having the highest proportion of individuals eligible for them.⁶

Provider awareness of these disparities is essential, Bolden said, and she advised clinicians in the audience to ask their institution for the tools and resources to close these gaps. “That doesn’t mean you’re going to get it, but it does mean that you asked for it because you’ve identified what you or your colleagues and your patients need.”

Next, Joseph Saseen, PharmD, a professor and associate dean for clinical affairs at UC Skaggs School of Pharmacy and Pharmaceutical Sciences, provided a pharmacist’s perspective on implementation of lipid-lowering therapies. Pharmacists are crucial members of the care team with an important role to play in improving adherence, initiating guideline-directed medical therapy, and prioritizing shared decision-making, he said. Their close relationships with patients enable them to address what he termed statin defiance, or resistance to and refusal to accept the therapy due to disinformation about its risks and benefits.

The pharmacist’s work is not done once a patient achieves their LDL-C target. Saseen said the communication must be ongoing, incorporating “respectful inquiry, positive verbal reinforcement, and ongoing shared decision-making to make sure people continue the commitment to stay on their path.”

Moving beyond LDL-C, the agenda turned to lipoprotein(a), or Lp(a), which is an LDL with thrombogenic and pro-inflammatory properties. Greg Schwartz, MD, PhD, professor of medicine-cardiology at UC School of Medicine, explained that Lp(a) predicts various types of cardiovascular disease and major adverse cardiovascular outcomes. Importantly, statin therapy does not negate Lp(a) as a risk factor, so new treatment strategies are emerging.

Lipoprotein apheresis is the only FDA-approved therapy for high Lp(a), but just a small number of patients are eligible for this procedure, so attention is turning to the PCSK9 inhibitors. Research has found a median 23% reduction of Lp(a) with alirocumab in patients with recent acute coronary syndrome,⁷ and other work shows that Lp(a) is an effect modifier for PCSK9 inhibitors, which reduce LDL-C as well as Lp(a).⁸

“The difference in the circulating concentration [of Lp(a)] may be small, but it identifies patients who seem to respond to this intervention, whether it’s due to the Lp(a) reduction or due to some interaction between the LDL and the Lp(a) levels,” Schwartz said. “Those are the patients who seem to get the most benefit, and maybe it identifies plaques that are amenable to further stabilization.”

Looking forward, trials of targeted Lp(a)-lowering drugs will test the hypothesis that Lp(a) reduction decreases cardiovascular risk and will also provide important safety insights, Schwartz noted.

Finally, Robert L. Page II, PharmD, MSPH, professor in the Departments of Clinical Pharmacy and Physical Medicine at the UC School of Pharmacy, presented a case study of how a population health initiative can impact cardiovascular outcomes. The Colorado Evidence-Based Drug Utilization Review Program has worked with Colorado’s Medicaid program to eliminate the need for prior authorization for certain indications—for instance, sacubitril/valsartan (Entresto) for patients with a diagnosis of heart failure with reduced ejection fraction—and lower the barriers to coverage of PCSK9 inhibitors.

“Partnerships are important,” Page concluded. “Perceptions and opinions from providers, patients, and local stakeholders are critical in terms of policy development.”

In a panel discussion to wrap up the event, the speakers identified priorities for future research, such as how to balance the targeting of Lp(a) and LDL-C in a personalized manner. Personalization will also be key to boosting participation in clinical trials so that they represent the full diversity of patients in the real world, Bolden said.

“When we’re doing a study, when we’re seeking answers, we have to include everyone at the table because everyone is in the world that’s taking the medications. Everyone is in the world that needs to follow the recommendations,” she said. “We’re all people, and so you have to say everyone needs to be represented with that.”

Author Information: Ms Mattina is an employee of MJH Life Sciences, the parent company of the publisher of Population Health, Equity & Outcomes.

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