Experts Recommend Additional Cholesterol-Lowering Drugs for Adults With High LDL

The recommendations apply to individuals who are already taking the maximum dose of statins.

Additional cholesterol-lowering drugs should be offered to individuals with high levels of low-density lipoprotein (LDL) cholesterol who are also at high risk of heart disease, a panel of experts told The BMJ.1

The drugs assessed by the panel include ezetimibe and PCSK9 inhibitors, which work by reducing the absorption of cholesterol from foods and the production of cholesterol in the body.1

The recommendations, which are part of The BMJ’s “Rapid Recommendations” initiative to produce rapid and trustworthy guidance based on new evidence to help physicians make better decisions for patients, apply to adults who are already taking the maximum dose of statins or those who are intolerant to statins.1

The experts balanced the benefits against the burdens and potential harms of starting a new drug according to an individual’s level of risk, preferences, and values, and their advice represents a shift from the traditional focus on lowering cholesterol levels to a focus on reducing an individual’s overall risk for cardiovascular (CV) risk.1

The experts discussed new evidence from 14 trials that included a total of 83,600 individuals and showed that ezetimibe and PCSK9 inhibitors could reduce heart attacks and strokes in individuals with very high and high CV risks. However, individuals with low or moderate CV risk did have the same reduction.1

The relative benefits in these trials were consistent, but the absolute magnitude varied based on CV risk in individuals. For example, for 1000 individuals treated with PCSK9 inhibitors in addition to statins over 5 years, benefits ranged from 2 fewer strikes in the lower risk group to 21 fewer in the highest-risk group.1

There were no important adverse events reported. However, PCSK9 inhibitors that required injections sometimes caused injection site reactions, which the experts said is a burden and harm that could matter to individuals using the injections.1

Additionally, PCSK9 inhibitors are more expensive than ezetimibe and statins.1

The experts favored ezetimibe over PCSK9 inhibitors but said that either type of drug provides important benefits for adults in both the high-risk and very high-risk groups.1

There would be little benefit for adults in the low-risk group, they said.1

The experts acknowledged some uncertainties in the evidence that are underlying in the guidelines, and said that physicians should identify patients’ CV risks to apply the risk-stratified recommendations.1

Additionally, the experts said that their recommendation may be altered as new evidence emerges.1

LDL cholesterol, also known as “bad” cholesterol, makes up most of the body’s cholesterol, and high levels of LDL cholesterol raise an individual’s risk for CV disease and stroke, according to the CDC.2

LDL cholesterol can build up on the walls of blood vessels and cause a plaque buildup.2


1. Experts recommend additional cholesterol lowering drugs for adults at high heart disease risk. EurekAlert. News release. May 4, 2022. Accessed May 5, 2022.

2. LDL and HDL cholesterol: “bad” and “good” cholesterol. CDC. Updated January 31, 2020. Accessed May 5, 2022.