Statins, a mainstay of for elevated cholesterol for many years, do not always lower cholesterol enough. For patients at risk for cardiovascular disease who have a less-than-expected response to statins or are intolerant of them, proprotein convertase subtilisin/kexin type 9 (PCSK9) serine protease inhibitors fill an important treatment gap. Access to these drugs has been challenging, however, so during a Monday session at the Asembia Specialty Pharmacy Summit 2019, experts emphasized the need for clinicians to use every available tool when patients need PCSK9 inhibitors but face access barriers. 

Joseph Saseen, PharmD, BCPS, BCACP, FNLA, FAHA, CLS, presented the first section of this discussion, focusing on the guidelines and the safe and effective management of hypercholesterolemia.

The American Heart Association (AHA), which tracks statistics associated with heart disease and stroke closely, recently issued its 2019 update on these conditions. As the audience was well aware, high cholesterol is a primary causal factor for the development of atherosclerotic cardiovascular disease (ASCVD). Approximately 28.5 million adults have total cholesterol levels that exceed 240 mg/dL, and 1 in 200 individuals is affected with more severe elevations (ie, familial hypercholesterolemia).

Using a number of colorful visuals, Saseen presented the 2018 blood cholesterol guidelines released by the AHA and American College of Cardiology in collaboration with 10 other organizations, and the studies that reflect the current evidence-based recommendations.

Saseen noted that over the years, guidelines and expert recommendations regarding primary prevention have changed. Currently, primary prevention should be initiated in individuals whose low-density lipoprotein cholesterol (LDL-C) is 190 mg/dL or more, any patient who has diabetes (type 1 or 2) and is aged 40 to 75 years, and any patient who has an increased 10-year ASCVD risk and is between ages 40 and 75 years.

Saseen carefully covered an often confusing area: determining statin intensity. He indicated that high-intensity therapy requires use of atorvastatin or rosuvastatin, whereas the other statins can be used as moderate-intensity statin therapy. He emphasized that statins have limitations.

“Clinicians often demonstrate therapeutic inertia and don’t esca- late statins appropriately,” Saseen said. “Some patients are nonadherent or just stopped taking their statins due to a variety of reasons, including statin-associated muscle symptoms. Fear of [adverse] effects can be demotivating for patients even though many of the well-known adverse events have been overexaggerated.”

Saseen noted that alirocumab and evolocumab, the 2 currently available PCSK9 inhibitors, have a proven track record in significantly reducing LDL-C and subsequently reducing major adverse cardiac events. Recent cost-effectiveness data indicate that the 2 PCSK9 inhibitors, both fully human monoclonal antibodies, have moderate value in clinical ASCVD. List prices have fallen, so their value should increase.

Rhonda Cooper-DeHoff, PharmD, MS, FAHA, FACC, continued the presentation by addressing the PCSK9 inhibitors’ potential.

Cooper-DeHo reviewed PCSK9, explaining its role in LDL degradation and recycling, and covered specific FDA-approved indications. Both of the approved biologics are administered subcutaneously every 2 weeks but can also be given once monthly. After initiation, clinicians need to check LDL within 4 to 8 weeks.

These agents’ adverse effects tend to be tolerable, with nasopharyngitis, injection-site reactions, flu-like reactions, and upper respiratory infections among the most common.

Patient counseling is essential, as these are high-cost interventions. Cooper-DeHoff noted, “Whenever we have patients who need subcutaneous injections they will self-administer, we have to review every step of the process several times. For these biologics, patients need to be reminded to take the medication out of the refrigerator 30 to 45 minutes before they inject, and they also need to be coached on all the important points of self-injection.”

Cooper-DeHoff also addressed the barriers that patients face and noted the lack of a universally accepted definition of statin intolerance. She described muscle-related symptoms specifically and stressed that the symptoms must resolve with discontinuation and reoccur on rechallenge. She also noted that clinicians need to try a variety of statins in patients.

With the drop in price from approximately $14,000 annually to less than $6000 per year for these biologics, patients should be able to access them more readily. Results from several studies have demonstrated that the PCSK9 inhibitors have value, especially at the lower price.