Comparing Treatments to Lower Cholesterol

Low-density lipoprotein (LDL) cholesterol, the so-called bad form of cholesterol, is a major risk factor for cardiovascular disease, which is the leading cause of death in the United States. Patients with high cholesterol that requires treatment usually receive prescriptions for statin drugs, which are effective for most people.

Recently, though, the FDA approved two new medications—evolocumab and alirocumab—to treat patients with very high cholesterol, those who are at very high risk of cardiovascular disease, or those who have not responded sufficiently to statins. These medications, called proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, are given by injection and are usually added to statin therapy. Notably, the annual cost can be $14,000.

Stakeholder groups told us that they are interested in the use of PCSK9 inhibitors to treat high LDL-cholesterol, particularly for patients who are not at very high risk for cardiovascular disease (i.e., those who would not typically receive the new drugs). So PCORI convened a meeting in June 2016 that included experts in clinical trials, lipid treatment specialists, health plan medical officers, and PCORI staff. The group discussed, at a technical level, how a clinical trial could best test the use of PCSK9 inhibitors for first-line prevention of cardiovascular disease. PCORI also surveyed patients and healthcare providers to learn their concerns about use of these drugs and identify questions that a patient-centered outcomes study on this topic should address.

I invite you to review the resulting draft study protocol to learn about the many issues involved in designing and conducting such trials. This document is not intended to serve as a final protocol, nor does PCORI now plan to support such a trial. But we hope this document, the result of PCORI’s stakeholder-guided approach to patient-centered outcomes research design, will serve as a basis for discussion and planning by any organization that seeks to further the conversation or consider such a study. We welcome your feedback.

Editor's note: At the time that this blog post was published, Diane E. Bild, MD, MPH served as associate director in the Clinical Effectiveness and Decision Science program.