Cholesterol-lowering medications: PCSK9 inhibitors

In the summer of 2015, the FDA approved two new cholesterol- lowering drugs, alirocumab (Praluent) and evolocumab (Repatha). They belong to a novel category of medications called PCSK9 inhibitors.

To understand what these drugs are and how they work, it's helpful to know a little bit about PCSK9 and why you might want to inhibit it. PCSK9 is a protein that targets and breaks down a certain class of receptors in the liver. Those receptors remove LDL from the blood as it passes through the liver. By reducing the number of these receptors, PCSK9 effectively increases the level of LDL in the blood. Studies have shown that people with excess PCSK9 have higher LDL and tend to suffer early heart disease, while those who are lacking PCSK9 (either entirely or partially) have low LDL and less heart disease.

That's where the PCSK9 inhibitors come in. By hampering PCSK9's ability to work, they allow more LDL receptors to remain in the liver—and with more receptors available to sweep away LDL, a person's blood levels of LDL plummet.

What the drug trials revealed

Three trials published in The New England Journal of Medicine demonstrated the LDL lowering ability of these new drugs, which are given by injection under the skin. In all three trials, all of the participants took a statin to lower cholesterol. In addition, half were given a PCSK9 inhibitor (either evolocumab or alirocumab) by injection every two to four weeks; the other half got a dummy injection (placebo). After a year, LDL levels were 40% to 60% lower in the PCSK9- inhibitor groups. In those treated with evolocumab, the average LDL after one year of treatment was 48 milligrams per deciliter (mg/dL), the lowest LDL ever seen in the experimental arm of a cholesterol-lowering trial. Some participants' LDL levels even fell below 25 mg/dL—arguably lower than needed. But both PCSK9 inhibitors have similar effects.

To learn more about cholesterol and heart disease, read Managing Your Cholesterol, a Special Health Report from Harvard Medical School.

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