From the NLA President: PCSK9 Inhibitors: A New Option for the Highest Risk Patients

On July 24, 2015, the United States Food and Drug Administration approved the clinical use of the PCSK9 inhibitor, alirocumab, as an adjunct to diet and maximally tolerated statin therapy for adults with heterozygous familial hypercholesterolemia (HeFH) or atherosclerotic cardiovascular disease who require additional lowering of LDL-C. On Aug. 27, 2015, evolocumab was approved for the above indications and for treatment of patients with homozygous familial hypercholesterolemia (HoFH).

In order to determine which patients require additional lowering of LDL-C, a reasonable approach is to first identify those patients who carry the highest atherosclerotic cardiovascular disease (ASCVD) risk. Patients with HoFH, recent ASCVD events, and those with HeFH or ASCVD who have diabetes mellitus and/or other poorly controlled risk factors represent the highest risk groups. Those with stable ASCVD or HeFH without additional ASCVD risk factors reside a step below the above individuals in the ASCVD risk hierarchy. There should be little argument that those in the former group, and many of those in the second group, depending upon careful clinical judgment, have the greatest need for comprehensive ASCVD risk factor modification and merit consideration for additive therapy to maximal tolerated evidence-based statins and lifestyle therapy.

In all such patients, additional emphasis on ASCVD risk factor modification is warranted. However, many will require adjunctive drug therapy to achieve desirable LDL-C and non-HDL-C levels of <70 mg/dL and 100 mg/dL, respectively. If additive therapy with second line lipid lowering therapy is not sufficient to reach these levels, many of us will be tempted to write a prescription for a PCSK9 inhibitor. As exciting as the prospect of an additional 60 percent reduction in LDL-C may seem, there are some caveats to consider.

A detailed patient-provider discussion is always the first step. Your patient should be told that your office will submit information to the pharmaceutical company to begin the process of acquiring the drug, but this does not assure that their insurance plan will cover the use of the drug. In many cases, you, as the provider, may receive additional forms or may be required to make phone calls necessary for pre-authorization. Even then, approval is not guaranteed. Patients should be reminded that co-payments will, in most cases, be required. They should be asked whether they can afford such co-payments and should be reminded that therapy will be required indefinitely. Providers are also obligated to remind patients that definitive ASCVD outcome data on PCSK9 inhibitors are not yet available.

If approval is secured, the patient must be instructed on the proper use of this subcutaneously administered drug. These medications must be refrigerated before use and taken out of the refrigerator for at least 30 minutes before injection. Those of you who do not routinely employ injectable medications should request from your pharmaceutical representative a demonstration of proper technique of medication administration so that you can instruct your staff and your patients properly. Your patients will have to be reminded of proper disposal of used injectors into a sharps container. You must remind them of the need to take injections every two weeks and should ask them how they plan to remember the dates of administration. They also must understand that periodic assessment of their lipid profile will be required.

In summary, the use of PCSK9 inhibitors should be reserved at this time for only the highest risk patients. The decision to prescribe these agents will require a significant time expenditure from you and your office staff, a long-term financial commitment from your patients, and an assurance from your patients that they understand that outcomes data for this exciting, new class of agents are still not available.