When standard therapies fail to work, a new class of cholesterol-lowering drugs is now recommended for high-risk patients with persistently high cholesterol levels, based on recent guidelines from the European Society of Cardiology and the European Atherosclerosis Society.
Published in the European Heart Journal, these guidelines addressed the use of a new class of drugs called PCSK9 inhibitors (proprotein convertase subtilisin/kexin type 9). PCSK9 inhibitors work by targeting a specific gene that regulates low-density lipoprotein (LDL), or “bad” cholesterol, in the bloodstream to reduce bad cholesterol levels and risk for life-threatening heart events.
These drugs were first approved by the U.S. Food and Drug Administration in 2015. Since then, new findings have been published on their use in high-risk patients.
As outlined in the recent guidelines, there are currently two approved PCSK9 inhibitors including alirocumab and evolocumab. Both are administered by injection and have been shown to significantly lower LDL cholesterol levels. A third type of PCSK9 inhibitor called bococizumab was also tested in clinical trials but was discontinued in 2016 because it was not working as expected.
Fortunately, evidence continues to show that the two approved drugs, alirocumab and evolocumab, are safe and effective at lowering cholesterol levels. Based on existing evidence, experts recommend PCSK9 inhibitors in three specific groups of patients.
The first includes patients with heart disease who continue to have high LDL levels despite the use of statins and other cholesterol-lowering drugs. The second includes patients with high cholesterol who can’t tolerate statins, often due to side effects like muscle pain or liver inflammation. The third group includes patients with a genetic disorder called familial hypercholesterolemia, often referred to as FH, which causes abnormally high cholesterol levels beginning at birth. In the recent guidelines, experts recommend PCSK9 inhibitors in FH patients who continue to have high LDL levels despite treatment.
In short, the drug is reserved as a second line of cholesterol-lowering treatment for patients at very high risk of heart events after standard therapies fail to work. The goal is to prioritize these high-risk patients to improve outcomes, while the drug continues to be studied in other populations.