Statin therapy is the mainstay of lipid-lowering therapy for the primary prevention of atherosclerotic cardiovascular disease (ASCVD). But 5% to 10% of patients are unable to tolerate a statin at any dose or at a dose high enough to achieve patient-specific target levels of low-density lipoprotein cholesterol (LDL-C), most commonly due to muscle-related symptoms. Statin-intolerant patients have historically had few therapeutic options: ezetimibe produces only modest reductions in LDL-C levels, and proprotein convertase subtilisin/kexin type 9 inhibitors are indicated for primary prevention only if the patient is diagnosed with heterozygous familial hypercholesterolemia. Therefore, the recent approval of bempedoic acid, a new lipid-lowering agent associated with fewer muscle-related symptoms compared with statins, was an exciting development. Bempedoic acid inhibits cholesterol synthesis by blocking ATP citrate lyase, upstream of the hydroxymethylglutaryl-CoA reductase enzyme that is blocked by statins. The resulting upregulation of LDL receptors on the surface of hepatocytes enhances clearance of LDL particles from the bloodstream and lowers the level of circulating LDL-C. Bempedoic acid is associated with fewer muscle-related symptoms than statins, presumably because the enzyme responsible for activating bempedoic acid is present in hepatocytes but not in myocytes. But whether lipid lowering with bempedoic acid improves cardiovascular outcomes in statin-intolerant patients at risk of developing ASCVD was, until recently, uncertain.
Source: JAMA Online First