Breaking down barriers: How to optimize access, use of PCSK9 inhibitors
Key takeaways:
- PCSK9 inhibitors lower cholesterol and risk for heart disease, but barriers to access exist.
- A pharmacist-managed cholesterol service can optimize PCSK9 inhibitor access, use and effectiveness.
Over the years, there have been significant changes to the dyslipidemia medication management guidelines, alongside increasing evidence for novel cholesterol-lowering medications, including PCSK9 inhibitors.
All dyslipidemia management decisions begin with determining primary or secondary prevention of atherosclerotic CVD. The focus of primary prevention is to reduce ASCVD risk by targeting an LDL cholesterol level of 100 mg/dL or less. For secondary prevention, the focus is to reduce risk for ASCVD progression and future events.
The 2022 American College of Cardiology Expert Consensus Decision Pathway focused on ways to address the gaps in lowering LDL with nonstatin therapies to reduce ASCVD risk. The decision pathway highlights the importance of targeting at least a 50% reduction of LDL.
Role of nonstatin therapies
For patients on statin therapy who require additional LDL lowering or are unable to tolerate statins, ezetimibe and/or a PCSK9 inhibitor is recommended as the initial nonstatin therapy. When considering initiation of ezetimibe or a PCSK9 inhibitor, shared decision-making between the patient and health care professional is essential.
The main points to consider are desired percentage of LDL lowering, risk for recurrent ASCVD events, medication formulation and affordability. For patients classified as secondary prevention high risk, an LDL goal of 70 mg/dL or less is recommended. In those classified as very high risk — for example, a patient with two forms of ASCVD, like stroke and MI, or one type of ASCVD plus multiple risk factors like hypertension or diabetes — an LDL goal of 55 mg/dL or less or even 40 mg/dL or less may be recommended.
The extent of LDL lowering from baseline that some patients require may not be achievable with traditional statin and/or ezetimibe therapy. Ezetimibe, an oral, once-daily, generic medication, lowers LDL by 25% when added to maximally tolerated statin therapy and by 18% when used as initial therapy in patients who are statin-intolerant. PCSK9 inhibitors are brand-name, refrigerated, subcutaneous injections given every 14 days and lower LDL by 45% to 58% when added to maximally tolerated statin therapy and 58% to 64% when used as initial therapy in patients intolerant of statins.
In the current U.S. guidelines, use of a PCSK9 inhibitor could be considered over ezetimibe as the addition to maximum-intensity statin for patients requiring more than a 25% reduction in LDL. Additionally, some patients are unable to tolerate statin therapy due to adverse drug reactions (eg, myalgias, elevated liver enzymes, rhabdomyolysis). In both cases, either ezetimibe or a PCSK9 inhibitor would be an appropriate therapeutic choice, depending on the extent of LDL lowering required to reach the target. Involving patients in the decision-making process is expected to enhance medication adherence and lead to improved CV outcomes.
Barriers to PCSK9 inhibitor use
Prescriptions for evolocumab (Repatha, Amgen) and alirocumab (Praluent, Sanofi/Regeneron) have high costs and require prior authorizations, which are often a barrier to use. PCSK9 inhibitor prescriptions have a high rejection rate, with close to four of five prior authorizations being denied. In a 2016 study, Jalpa A. Doshi, PhD, the Leon Hess Professor of Internal Medicine at the Perelman School of Medicine at the University of Pennsylvania, and colleagues found that complexity of the prior authorization form increases likelihood of rejection. Some insurers had as many as 11 criteria to be addressed, with often two data entry lines per criterion, Additionally, those with Medicare insurance or a prescription written by a cardiologist have been reported to increase likelihood of prior authorization acceptance. To improve the likelihood of prior authorization approval, PCSK9 inhibitors should be reserved for patients who have had adverse reactions to multiple statins, or with LDL above goal on maximally tolerated statin therapy.
Despite prior authorization approval, high medication copays remain a barrier for many patients. Data have shown that nearly one of six patients with an approved prior authorization for either PCSK9 inhibitor did not fill the prescription due to high cost. For both medications, there are patient assistance programs, copay cards and grant funds available to assist with cost lowering for specific patient populations and financial situations. Another strategy to improve PCSK9 inhibitor access is a pharmacist-managed cholesterol service.
Pharmacist-led approaches
A standardized approach to prior authorization, often involving physician assistants, nurse practitioners and pharmacists, has been found to improve successful prior authorization acceptance. Pharmacists can have a pivotal role by optimizing drug therapy to reduce the risk for CV events, provide patient education, monitor for adverse drug effects and drug-drug interactions and promote patient adherence.
Multiple studies of pharmacist-led cholesterol management have demonstrated positive outcomes. In one study, patients with cholesterol managed by a pharmacist had an average LDL decrease of 16.5% (30 mg/dL) compared with a decrease of 6.5% (16.8 mg/dL) for patients managed by a physician. A similar study found that pharmacist management of cholesterol increased the percentage of patients achieving goal LDL levels (69%) compared with physician management (50%). These two studies highlight the value of pharmacists in successful cholesterol management and achieving lipid goals.
Pharmacists can also play an important role in PCSK9 inhibitor medication access and patient education. Pharmacists can assess a patient’s insurance and financial situation to determine eligibility for patient assistance. Patients with commercial insurance can utilize copay cards to help lower the monthly cost of the medication. For those with Medicare meeting required income criteria, manufacturer assistance programs can provide the medication for free, and third-party foundations offer grants to cover medication copays.
In regard to patient education, it is important to review the administration technique, dosing schedule and storage/disposal requirements. Valuable education tools include medication administration videos on the manufacturer websites and demonstration pens, which may be provided by the manufacturer and local pharmaceutical representatives. Patients should be made aware that PCSK9 inhibitors are required to be stored in the refrigerator and should be pulled out 30 minutes prior to injection. Once out of the refrigerator, they are stable at room temperature for up to 30 days.
Since PCSK9 inhibitors are given every 14 days, it is helpful to provide patients with medication adherence strategies. Suggestions include calendar reminders, phone alarms or mobile apps, and scheduling tips (eg, taking the medication on the 1st and 15th of each month, every other Friday, etc). After initiating a PCSK9 inhibitor, a repeat lipid panel should be completed 4 to 12 weeks later to assess efficacy. Once a patient is stable and at goal levels, lipids should be monitored every 3 to 12 months to ensure medication therapy does not need to be adjusted.
Harnessing the effectiveness of PCSK9 inhibitors
The prescribing of PCSK9 inhibitors will likely continue to increase in the coming years. These medications are extremely effective at lowering LDL and help reduce ASCVD. Given the complexity of prior authorizations and high copays, pharmacists play an important role in medication access and patient education. And in some cases, they are directly involved in helping patients achieve goal lipid levels.
References:
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- Praluent package insert; Sanofi-Aventis LLC, 2015. https://www.regeneron.com/downloads/praluent_pi.pdf. Accessed March 5, 2025.
- Repatha package insert; Amgen Inc., 2015. https://www.pi.amgen.com/-/media/Project/Amgen/Repository/pi-amgen-com/Repatha/repatha_pi_hcp_english_current.pdf. Accessed March 5, 2025.
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For more information:
Kaitlyn P. Coggsdale, PharmD, CPP, is a PGY2 Ambulatory Care Pharmacy resident at UNC Health Rex North Carolina Heart and Vascular in Raleigh, North Carolina.
Anne Rodino, PharmD, BCCP, CPP, is a clinical pharmacist practitioner at UNC Health Rex North Carolina Heart and Vascular.
Sarah L.E. Russell, PharmD, BCACP, CPP, is a clinical pharmacist practitioner at UNC Health Rex North Carolina Heart and Vascular.
Kristin D. Bradley, PharmD, BCPS, CPP, is a clinical pharmacist practitioner at UNC Health Rex North Carolina Heart and Vascular.
Sarah A. Spinler, PharmD, FCCP, FAHA, FASHP, AACC, BCPS (AQ Cardiology), is the Healio | Cardiology Today Pharmacology Consult column editor. Spinler is professor and chair of the department of pharmacy services in the School of Pharmacy and Pharmaceutical Sciences at Binghamton University. Spinler can be reached at sspinler@binghamton.edu.
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