For well over 30 years, physicians have understood the role of LDL (low-density lipoprotein, or “bad”) cholesterol in the development of cardiovascular disease (CVD). LDL cholesterol levels are directly correlated with increasing CVD risk and, as summarized in a recent blog post, lowering LDL cholesterol levels, through both lifestyle changes and medications, has been shown to reduce this risk.
Statins are the first-line choice of medications for lowering LDL cholesterol. They are widely prescribed for both primary prevention (reducing CVD risk in patients without known CVD) and secondary prevention (preventing subsequent heart attacks, strokes, and other CVD events in patients with established CVD).
How do PCSK9 inhibitors work?
In 2003, researchers found a genetic mutation that caused some people to develop very high LDL cholesterol levels and CVD at a young age. This laid the groundwork for understanding the PCSK9 pathway, and ultimately the medications now known as PCSK9 inhibitors.
Our liver makes PCSK9 protein, and this protein breaks down LDL receptors, which remove LDL cholesterol from our bloodstream. So the more PCSK9 protein in our bodies, the fewer LDL receptors in our liver, and the higher our LDL cholesterol levels. PCSK9 inhibitors are monoclonal antibodies that block the PCSK9 protein from working. As a result, levels of LDL receptors increase, and LDL cholesterol levels fall. PCSK9 inhibitors work via a pathway different from statin medications, and may be used together.
The FDA approved two PCSK9 inhibitors in 2015: alirocumab (Praluent) and evolocumab (Repatha). These drugs must be given by injection, typically every two to four weeks.
Who could benefit from PCSK9 inhibitors?
The most recent cholesterol treatment guidelines, a collaborative effort from multiple professional organizations including the American Heart Association and the American College of Cardiology, were updated in 2018. These guidelines were broadened from the previous version to include LDL treatment targets, which has prompted doctors to think about adding PCSK9 inhibitors to treat select patients. In the 2018 guidelines, high-risk patients are defined as those with known CVD or with elevated cholesterol levels and diabetes. For high-risk individuals, the guidelines recommend an LDL cholesterol target of less than 70 mg/dl. This cholesterol goal can usually be achieved