New Option Emerges for Statin-intolerant Patients

Cardiovascular disease remains the leading killer of Americans despite modern advancements in primary prevention. Current measures for primary prevention of clinical atherosclerotic cardiovascular disease (ASCVD) revolve around risk factor reduction, such as smoking cessation, control of hypertension, and prescription of statins when the LDL is elevated.

Unfortunately, a significant number of patients cannot tolerate statins due to side effects like myalgias and liver injury. Indeed, a recent study author has experienced issues with statins related to elevations in liver function tests. These limitations prevent a significant number of patients from experiencing the full benefits of statins for primary prevention.

Bempedoic acid, an ATP citrate lyase inhibitor, can reduce LDL levels and was shown in a randomized trial to reduce rates of major adverse cardiovascular events in statin-intolerant patients. The benefits of this agent in patients without an established history of clinical ASCVD are not well described.

Point 1: Signal for benefit with bempedoic acid

In this new sub-group analysis, patients without clinical ASCVD were evaluated based on their randomization to bempedoic acid versus placebo. All patients were either statin intolerant or could only tolerate minimal statin doses. Use of other lipid lowering agents like ezetimibe was allowed. The primary endpoint was the time from randomization to the first occurrence of any component of a composite of cardiovascular death, nonfatal myocardial infarction (MI), nonfatal stroke, or coronary revascularization.

Treatment with bempedoic acid provided a significant risk reduction for the primary end point (111 events [5.3%] vs 161 events [7.6%]; adjusted hazard ratio [HR], 0.70 [95% CI, 0.55-0.89]; P = .002). This difference was driven by lower rates of cardiovascular death and MI, while rates of stroke and coronary revascularization were not impacted. Patients taking bemedoic acid had higher rates of gout (2.6% vs 2.0%) and cholelithiasis (2.5% vs 1.1%).

Point 2: Bempedoic acid moves up the treatment ladder

Patients with statin intolerance have several options to lower LDL, including PCSK9 inhibitors, ezetimibe, and bile acid resins. Resins aren’t used today due to lack of efficacy and side effects. Both PCSK9 inhibitors and ezetimibe have impressive data when combined with high-intensity statins but are not as well studied when used as monotherapy for primary prevention in statin-intolerant patients. The PSCK9 inhibitors are further limited by parenteral administration and high drug costs.

Given these limitations, bempedoic acid is well poised to establish a key niche for primary prevention in statin-intolerant patients.