The Role of Specialty Pharmacists in Overcoming Barriers Associated With PCSK9 Inhibitors

Introduction

Atherosclerotic cardiovascular disease (ASCVD) is a common condition that is treated with lipid-lowering agents. Risks associated with developing or worsening ASCVD include family history, elevated cholesterol and triglycerides levels, ethnicity, and other comorbidities. Individualized pharmacotherapy plans are determined by the patient’s risk for ASCVD.¹

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According to the 2018 American Heart Association (AHA)/American College of Cardiology (ACC) Guidelines for the Management of Blood Cholesterol, β-hydroxy-β-methylglutaryl-CoA inhibitors (commonly referred to as statins) are the first-line treatment for loweringlow-density lipoprotein cholesterol (LDL-C) levels, as well as preventing ASCVD. There are 3 levels of intensity for statins based on the magnitude of LDL lowering.

Low intensity reduces LDL by less than 30%, moderate intensity by 30% to 50%, and high intensity by greater than 50%. Intensity is selected based on the patient’s calculated 10-year risk of ASCVD and goal for lowering their levels. For circumstances in which a maximally tolerated dose of a statin is ineffective in achieving LDL-C levels, additional therapy of ezetimibe may be considered.¹

Furthermore, if this combination of statin and ezetimibe therapy is ineffective, or if a patient is at very high risk for ASCVD, additional therapy may be beneficial. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are considered second- or third-line therapy for patients with hyperlipidemia. They are also considered secondary prevention of cardiovascular events.¹

While proven effective, safe, and tolerable, providers are concerned about the expense attached to these medications. In addition to the economic burden PCSK9 inhibitors can pose, patients can also be hesitant to pursue this therapy due to the self-administration component. Specialty pharmacists play a key role in overcoming these barriers for prescribers and patients.

PCSK9 Inhibitors

PCSK9 binds to an LDL receptor on hepatocytes, resulting in the breakdown of LDL receptors in the liver. PCSK9 inhibitors, alirocumab and evolocumab, prevent this from occurring.

This ultimately increases the amount of LDL receptors which are responsible for clearing LDL from the blood. This process results in a decrease in LDL-C levels. Alirocumab and evolocumab are both indicated for patients with established cardiovascular disease or primary hyperlipidemia.^2,3 

Alirocumab is indicated for adult patients only and can be self-administered by subcutaneously injecting 75 mg once every 2 weeks or 300 mg once every 4 weeks. Common adverse effects (AEs) reported in more than 5% of patients with established cardiovascular disease include nasopharyngitis, noncardiac chest pain, and myalgia. Patients with primary hyperlipidemia have commonly reported nasopharyngitis, injection-site reactions, and influenza.²

Evolocumab is indicated for adult and pediatric patients 10 years of age and older and is also self-administered by subcutaneously injecting 140 mg every 2 weeks or 420 mg every 4 weeks. More than 5% of patients with established cardiovascular disease have reported signs and symptoms of nasopharyngitis, upper respiratory tract infections, and diabetes mellitus.

Patients with primary hyperlipidemia have reported AEs while taking this medicine. These include nasopharyngitis, upper respiratory tract infections, influenza, back pain, and injection-site reactions.³

The FOURIER trial, a randomized, double-blind, placebo-controlled study, analyzed the efficacy and benefits of taking PCSK9 inhibitors. The study showed that PCSK9 inhibitors significantly reduce LDL levels and reduce the risk of cardiovascular events.⁴

Role of Specialty Pharmacists

Patients taking PCSK9 inhibitors typically discontinue use after 6 months of therapy due to difficulty obtaining the medication and keeping up with the costs and approval process.^5,6 However, the individualized care and monitoring provided by specialty pharmacists has resulted in easier access, prompt initiation of therapy, and high adherence rates in patients who take specialty medications.

Overcome Economic Barriers

A major barrier patients face while receiving PCSK9 inhibitor therapy is the extremely high cost of these medications. When they became FDA-approved in 2015, their annual cost was approximately $15,000 per year. After a few years on the market, their price dropped by 60% to an annual cost of $5850 per year in 2019.^7,8 Patients may find it difficult to simply obtain the medications they need due to their expense or lack of insurance coverage.⁹

Insurance companies require prior authorizations to be completed for patients with prescriptions for PCSK9 inhibitors. However, patients who meet the label indications for PCSK9 inhibitors are frequently denied coverage by their insurance companies.

A retrospective cohort study showed that patients who were more likely to gain coverage approval were older than 65 years of age, had a history of ASCVD, or were prescribed the medication by a cardiologist. Commercial payers and Medicaid were noted to have lower approval rates than Medicare.¹⁰

Insurance companies will typically approve access to PCSK9 inhibitors if a patient is already on a maximally tolerated statin or has not tolerated therapy. This population would benefit the most from these expensive medications.⁸

When PCSK9 inhibitors were originally introduced to the health care system, they were not cost-effective. Per results of the FOURIER trial, at the 2017 prices discussed previously, PCSK9 inhibitors needed a 71% price reduction to be considered cost-effective.⁸ In an updated cost-effectiveness analysis in 2019, the reduced annual price of PCSK9 inhibitors at $5850 per year was established to be cost-effective.¹¹

The specialty pharmacy team plays an important role in helping patients overcome this economic barrier. Pharmacists complete the proper insurance authorizations and can provide financial assistance to patients taking specialty medications.

If patients are deemed ineligible for PCSK9 inhibitors by their insurance, pharmacists can request an alternative therapy from the provider. If patients are deemed eligible, then pharmacists can inform the provider to start the prior authorization process.

Once approved by their insurance, pharmacists should rerun the claim and then finally dispense the medication.¹² There are also patient assistance programs (PAPs) sponsored by drug manufacturers that specialty pharmacists can enroll their patients in. These programs help patients gain access to brand name medications at a discounted price or completely free of charge.¹³

Provide Medication Education

It is imperative that patients are educated on pertinent information about the medications they are taking. Proper counseling on PCSK9 inhibitors by specialty pharmacists can play a major role in the patient’s commitment to their therapy plan and can help them successfully achieve their goals of therapy.

At initiation of treatment, specialty pharmacists counsel patients on the purpose of taking specialty medications, the benefits of therapy, potential AEs they may experience, explicit instructions on how to take the medication, and the importance of adherence.¹⁴ Patients should also be informed that although PCSK9 inhibitors are stored in a refrigerator, they should be taken out to reach room temperature prior to administration.

Patients should then inspect the injection device to make sure the solution is clear and not cloudy. Given that PCSK9 inhibitors are subcutaneously self-administered, it is imperative that specialty pharmacists take the time to demonstrate proper administration techniques to the thigh, abdomen, or upper arm, as well as emphasize the need to rotate the injection site for each administration.^2,3

Improve Adherence

Patients on statin therapy have reported poor adherence rates due to lack of awareness of the true long-term benefit, intolerance, and fear of AEs. With statins being the first-line therapy for ASCVD, poor adherence rates can increase morbidity and mortality.

PCSK9 inhibitors have the potential to have increased adherence rates due to their low-reported AEs, infrequent dosing, and easy self-administration. In a retrospective study comparing adherence rates for statins and PCSK9 inhibitors, a greater percentage of patients were found to be “fully adherent” to PCSK9 inhibitors (79.4%) than to statins (30.9%).¹⁵

Specialty pharmacists can play a major role in improving adherence by conducting specifically designed follow-up calls to patients taking specialty medications. Prior to communicating directly with patients, pharmacists can screen patient profiles to make the most out of their engagement with them and to be prepared for the encounter.

Through this call service, pharmacists can monitor and document AEs, missed doses, and the efficacy of the medication. Specialty pharmacists can also easily process claims and delivery services while on the call, so the patient has all this information up front and obtaining their medications is a seamless process.

If any notable issues arise, pharmacists can mitigate them in a timely manner by communicating with other health care providers via electronic medical records, as well as developing a plan to address the problem. If missed doses appear to be an issue, pharmacists can further educate their patients on the importance of taking their medications on time and the benefits associated with medication adherence.^12,14

Conclusion

PCSK9 inhibitors have been proven safe and effective in lowering LDL levels and reducing the risk of cardiovascular events. However, there are gaps in literature pertaining to the long-term safety, efficacy, and adherence rates of these injectable medications. Providers and patients can benefit from further research.

Although prices of PCSK9 inhibitors have dropped over the years since their approval in 2015, they are still costly, which poses a significant barrier to access for patients. Reductions in the cost of these medications will make them more cost-effective.

Specialty pharmacists play an important role in dispensing PCSK9 inhibitors and serve as a valuable source of assistance and education for all their patients.

References

1. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines J Am Coll Cardiol. 2019;73(24):3168-3209. doi:10.1016/j.jacc.2018.11.002 Published correction appears in J Am Coll Cardiol. 2019;73(24):3234-3237.
2. Praluent. Prescribing information. Sanofi-Aventis U.S. LLC; 2015. Accessed July 28, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125559orig1s000lbledt.pdf
3. Repatha. Prescribing information. Amgen Inc; 2015. Accessed July 28, 2023. https://www.pi.amgen.com/-/media/Project/Amgen/Repository/pi-amgen-com/Repatha/repatha_pi_hcp_english.pdf
4. Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376(18):1713-1722. doi:10.1056/NEJMoa1615664
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11. Fonarow GC, van Hout B, Villa G, Arellano J, Lindgren P. Updated cost-effectiveness analysis of evolocumab in patients with very high-risk atherosclerotic cardiovascular disease. JAMA Cardiol. 2019;4(7):691-695. doi:10.1001/jamacardio.2019.1647
12. Atanda A, Shapiro NL, Stubbings J, Groo V. Implementation of a new clinic-based, pharmacist-managed PCSK9 inhibitor consultation service. J Manag Care Spec Pharm. 2017;23(9):918-925. doi:10.18553/jmcp.2017.23.9.918
13. Choudhry NK, Lee JL, Agnew-Blais J, Corcoran C, Shrank WH. Drug company-sponsored patient assistance programs: a viable safety net? Health Aff (Millwood). 2009;28(3):827-834. doi:10.1377/hlthaff.28.3.827
14. Zuckerman AD, Carver A, Cooper K, et al. An integrated health-system specialty pharmacy model for coordinating transitions of care: specialty medication challenges and specialty pharmacist opportunities. Pharmacy (Basel). 2019;7(4):163. doi:10.3390/pharmacy7040163
15. Gragnano F, Concilio C, Cesaro A, et al. Adherence to PCSK9 inhibitors in high cardiovascular risk patients in real-world setting: results from a single-center experience and comparison with statin therapy. Eur Heart J. 2017;38(1):314. doi:10.1093/eurheartj/ehx502.P1513