Sergio Fazio, M.D., Ph.D.
Dr. Fazio directs the OHSU Center for Preventive Cardiology. He is professor of medicine and is board-certified in clinical lipidology. Dr. Fazio’s expertise includes genetic and acquired lipid disorders and alternative therapies for patients who cannot tolerate standard lipid-lowering drugs.
The new statin alternative — who should take it and will insurance approve it?
One of the biggest medical news stories of 2015 was FDA approval of a new class of lipid-lowering agents, PCSK-9 inhibitors. Evolocumab (Repatha) and alirocumab (Praluent) have many features we have not previously seen in medications for this purpose.
What’s so exciting about PCSK-9 inhibitors?
These are the first injectable agents for hyperlipidemia. This is a major shift from the standpoint of patient psychology. Previously, only oral agents have been available. However, patients tend to view committing to an injectable medication as a larger investment in their health. Injectables were previously available only for painful conditions such as rheumatoid arthritis and Crohn’s disease. Patients with hyperlipidemia generally feel well unless (and until) they have a myocardial infarction (MI). Using an injectable medication for prevention raises the stakes of controlling cholesterol for the patient.
PCSK-9 inhibitors are biologics. As we know, drugs are small molecules the body works hard to metabolize. If we rely on a medication, we generally take it daily, because the liver has metabolized yesterday’s pill. Biologics are large proteins (antibodies) that enter the circulation and, since the body does react against them, swiftly block the targeted protein, in this case PCSK-9, responsible for high LDL.
Just 13 years ago, the PCSK-9 protein was unknown. These agents are available after what may be the shortest period from discovery to market to date.
The PCSK-9 inhibitors are a long-awaited innovation. As you know, many patients cannot tolerate statins, but they are the standard therapy for hyperlipidemia. Most are generic and inexpensive, and thus they are the first-line agent for high cholesterol. For patients who cannot tolerate these medications, nothing else was available until 2015.
Who cannot take statins?
Approximately 15 to 20 percent of patients at high risk of MI cannot take statins. This includes patients who have already had one or more cardiac events. Symptoms of statin intolerance include debilitating fatigue, muscle pain, inability to walk or raise the arms, and severe nighttime leg cramps. The PCSK-9 inhibitors are expected to help this group of patients reduce cardiac risk.
Who can take PCSK-9 inhibitors?
You may already know that the FDA did not expressly approve the PCSK-9 inhibitors for statin intolerance. However, the indications are worded to allow use in certain patients. We recommend PCSK-9 inhibitors for two groups:
1) Patients with familial hypercholesterolemia not satisfactorily controlled with lifestyle modifications and statin therapy.
2) Patients with cardiovascular disease who have survived a heart attack and may have a stent or bypass graft. If the treating physician deems the patient’s LDL level is still not safe on maximally tolerated statin therapy, then the patient is a candidate for PCSK-9 inhibitors. If the patient is statinintolerant, then the maximally tolerated statin therapy is zero and the patient is a candidate for a PCSK-9 inhibitor.
The high cost of protection?
The PCSK-9 inhibitors cost approximately $15,000 per year. At the recommended dosage of two injections per month, the cost per injection is more than $600. Even if patients have insurance that covers prescription drugs, a 20 percent copayment on a $625 dose is still $125, or $250 per month. This is simply too expensive for some patients. Patient assistance programs may cover the copayment, provided the PCSK-9 inhibitor is not placed in the second or third tier of the formulary, out of reach for some patients.
How to cope with the high cost of a drug that may be the only effective option for certain patients? Patient selection is a provider’s main concern. Referral to a specialized center with experience in diagnosing and prescribing these agents may be helpful to the patient and primary provider. In our practice, we have refined the preauthorization and appeal processes and are experienced at working with insurers.
Other effects of PCSK-9 inhibitors
The PCSK-9 inhibitors are so powerful, we tell some patients they will not recognize their own blood test results. LDL can drop 50 to 70 percent, with some patients achieving levels of 10 to 20.
As yet, we do not know the long-term effects of ultralow LDL. The discussion is similar to early questions about whether statins induce cognitive impairment, mental deterioration and memory loss. If low LDL is responsible for these effects, PCSK-9 inhibitors lower LDL even further. If the effects are due to statins’ molecular structure, the picture is different. When prescribing PCSK-9 inhibitors, it is important to attend to any concerns about changes in memory and mental acuity. You may want to give patients a validated questionnaire for a mental status baseline before starting therapy.
The injection itself does not cause significant side effects. No patients have reported muscle pain. We know that statins may raise the risk of type 2 diabetes. As with cognitive changes, the question is whether low LDL is the cause. These suspicions should be monitored, but to date, they are clinical concerns rather than established facts.
The Center for Preventive Cardiology at the OHSU Knight Cardiovascular Institute includes specialists in hyperlipidemia and all types of conditions increasing the risk of a heart attack. We are always happy to discuss your patients. If you have questions or would like to refer a patient for consultation, please call the OHSU Physician Consult & Referral Service at 800 245-6478 or fax to 503 346-6854.Back to articles