A New Alternative to Statins for Cholesterol Management: Bempedoic Acid
Administration of statins to lower elevated levels of low-density lipoproteins (LDL), or bad cholesterol as I was taught, has been a cornerstone of therapy for patients to reduce the risks of major cardiovascular events for decades. But statin medications, despite being a powerful tool for the treatment of high cholesterol, are also host to a great deal of unwanted side effects for some patients. Most prominently: statin-induced myopathy or muscle pain is a very common side effect among patients on this medication. It also happens to be one of the largest factors influencing adherence in these patients. After all, many patients don’t outwardly see or feel the effect their statin is having on their health, but what they do feel is the fatigue, muscle pain, tenderness, weakness, cramping, and tendon pain these medications are associated with.
However, recently a new study was published that may provide these statin-intolerant patients with another option for managing their cholesterol in the future: bempedoic acid.
What is bempedoic acid?
Bempedoic acid, brand name Nexletol or Nexlizet, is an ATP citrate lyase inhibitor that reduces low-density lipoprotein (LDL) cholesterol levels and is associated with a low incidence of muscle-related adverse events; but its effects on cardiovascular outcomes specifically were the subject of this study.
Per the study, bempedoic acid is similar to statins in terms of its ability to reduce cholesterol synthesis and raise the expression of LDL receptors, thereby increasing the clearance of LDL from circulation. But bempedoic acid is special in that it is a prodrug, which in this case means that it is activated in the liver and not in most peripheral tissues! As a result it is not activated within the skeletal muscle either, which may be the reason for its reduced incidence of myopathy, a key difference when compared to statins.
What did the study show?
The article, Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients, outlined the study. It was conducted throughout 1250 sites in 32 countries as a double-blind, randomized, placebo-controlled trial involving patients who were unable or unwilling to take statins due to unacceptable adverse effects and were also at high risk for cardiovascular disease. For this study 13,970 patients recruited and then divided into two groups with patients either being assigned 180 mg of oral bempedoic acid daily or placebo.
The median duration of follow-up was 40.6 months with a reduction in the level of LDL that was significantly greater with bempedoic acid compared to placebo. Additionally the study’s primary end point (a four-component composite of major adverse cardiovascular events), was significantly lower in the bempedoic acid group compared to placebo (819 patients [11.7%] vs. 927 [13.3%]). The study received adequate power and also included other end points that can be found within the study itself.
For the curious who are interested in the particular details I’ll provide the link to the study through NEJM here.
What conclusions can we draw?
It appears that among statin-intolerant patients, treatment with bempedoic acid was associated with a lower risk of major adverse cardiovascular events. These events included death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization as primary end points.
Among patients for whom primary or secondary prevention of cardiovascular disease is clinically indicated but were unable or unwilling to take guideline-recommended doses of statins, bempedoic acid could be a strong option for these patients!
While the concept of statin intolerance can be seen as controversial, as a pharmacist I have seen countless patients struggle with the side effects statins bring, resulting in modifying doses, changing diets, and switching from one option to the other only to still find no success. I think there is a real tangible benefit for patients in this specific group who struggle with statins and that bempedoic acid could have a place in current treatment algorithms. With the potential benefits shown in this study I believe it could certainly at the very least be another tool in the doctor’s ever expanding tool box.
But I would love to hear from anyone else in regards to this topic, do you believe it will be significant and something we’ll see in practice?
