There is now overwhelming evidence to support lowering LDL-c (low-density lipoprotein cholesterol) to reduce cardiovascular morbidity and mortality. Statins are a class of drugs frequently prescribed to lower cholesterol. However, in spite of their widespread use, discontinuation and nonadherence remains a major gap in both the primary and secondary prevention of atherosclerotic cardiovascular disease. The major reason for statin discontinuation is because of the development of statin-associated muscle symptoms, but a range of other statin-induced side effects also exist. Although the mechanisms behind these side effects have not been fully elucidated, there is an urgent need to identify those at increased risk of developing side effects as well as provide alternative treatment strategies.

Bempedoic acid, an ATP citrate lyase inhibitor, reduces low-density lipoprotein (LDL) cholesterol levels and is associated with a low incidence of muscle-related adverse events; its effects on cardiovascular outcomes remain uncertain. A double-blind, randomized, placebo-controlled trial involving patients who were unable or unwilling to take statins owing to unacceptable adverse effects (“statin-intolerant” patients) is reported in the NEJM. The patients were assigned to receive oral bempedoic acid, 180 mg daily, or placebo. The primary endpoint was a four-component composite of major adverse cardiovascular events, defined as death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization. Results indicate that among statin-intolerant patients, treatment with bempedoic acid was associated with a lower risk of major adverse cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization).

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References

  1. Nissen, S. E., Lincoff, A. M., Brennan, D., Ray, K. K., Mason, D., Kastelein, J. J., Thompson, P. D., Libby, P., Cho, L., Plutzky, J., Bays, H. E., Moriarty, P. M., Menon, V., Grobbee, D. E., Louie, M. J., Chen, C., Li, N., Bloedon, L., Robinson, P., . . . Nicholls, S. J. (2023). Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients. The New England Journal of Medicine, 388(15), 1353–1364. https://doi.org/10.1056/nejmoa2215024

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