The Formulary Files

Zetia study keeps PCSK9s on approval course


Krishna Rutvij Patel, PharmD

Pharmacy directors at health plans can feel free to include ezetimibe (Zetia), the nonstatin lipid lowering medication, on their formularies thanks to results of a clinical trial unveiled by the American Heart Association. The trial looked at the effects of ezetimibe over seven years. Researchers concluded that the drug lowers LDL while simultaneously lowering the risk of cardiovascular events, though minutely. It also suggests that lower LDL is better, even if the LDL level doesn’t meet the goal.

Under the old Adult Treatment Panel-3 guidelines, providers would focus on reaching a goal for cholesterol level and would maintain the therapy once the goal was reached. Many providers still follow those guidelines. There are no goals in the new ACC/AHA guidelines other than maximum LDL lowering. For this reason, the updated ACC/AHA guidelines, published in late 2013, recommend statins as firstline therapy for LDL reduction instead of any of the nonstatin therapies.

Results of the IMPROVE-IT study were released in November. The trial compared an ezetimibe–simvastatin combination, marketed as Vytorin, with simvastatin alone. If IMPROVE-IT had failed to show that ezetimibe reduces CV events even though it lowers LDL, the FDA might have told manufacturers of PCSK9 inhibitors that their drugs would not be approved until their products actually showed a CV risk reduction, not just LDL reduction. However, with the positive, if modest, results from IMPROVE-IT, the regulatory timings of the PCSK9 will not be affected. So get ready!

Now that statins and ezetimibe have shown CV risk benefit, will payers require patients to step through statins and ezetimibe before they can be treated with the PCSK9 inhibitors? Probably not, for a couple of reasons.

First, IMPROVE-IT used subjects who had LDL ≤125 mg/dL, which is pretty low to begin with. There are many patients whose LDL level is far above this level. The second reason is that IMPROVE-IT didn’t study familial hypercholesterolemia patients, who would be treated with PCSK9 inhibitors.

IMPROVE-IT results don’t suggest that everybody should get ezetimibe. Instead, ezetimibe is now just an another addition to the armamentarium of LDL-lowering drugs showing clinical benefit. The drug probably will have little effect on health care costs.

Effect of ezetimibe–simvastatin combination on cardiovascular events

Source: IMPROVE-IT trial