When Statins Aren’t the Answer, Bempedoic Acid Could Be

Bempedoic acid has the potential to reduce major adverse cardiovascular events in at-risk patients who can’t tolerate recommended doses of statins as primary prevention, according to a study by Steven Nissen, M.D., and colleagues from Cleveland Clinic.

As many as half of patients at risk for cardiovascular events do not receive lipid-lowering therapies, the researchers note. In a registry that studied reasons why eligible patients were not taking a statin, 59% reported never being offered treatment.

Part of the problem, the researchers write, is that current recommendations are predominantly derived from clinical trials conducted decades ago during the initial development of statins to reduce low-density lipoprotein cholesterol. Moreover, recent data are limited on the effects of statins or other adjunctive treatments in patients who haven’t had a cardiovascular event, which is not surprising, when most cardiovascular outcomes trials of lipid-lowering therapies have only enrolled people who have already had a cardiovascular event.

These researchers conducted a prespecified subgroup analysis based on the CLEAR Outcomes (Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen) trial, in which 4,206 of 13,970 (30%) patients had characteristics associated with a high risk of adverse cardiovascular outcomes but who had not had a prior event.

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Statin-intolerant patients were randomly assigned to receive 180 mg bempedoic acid or placebo daily. The primary end point was time to first occurrence of a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization (4-component major adverse cardiovascular events (MACE)).

After six months of treatment, bempedoic acid, compared with placebo, reduced LDL-C levels by 30.2 mg/dL (21.3%) from a mean baseline of 142.2 mg/dL. After 12 months of treatment, it reduced high-sensitivity C-reactive protein levels by 0.56 mg/L (21.5%) from a median baseline of 2.4 mg/L.

During a median follow-up of almost 40 months, bempedoic acid reduced risk significantly for the primary end point (111 events [5.3%] versus 161 events [7.6%]). It also reduced the prespecified MACE (2.4%).

Approximately two-thirds of the participants in this study had diabetes. (Patients with diabetes have an increased risk of developing heart failure and those with heart failure are at higher risk of developing diabetes.) The findings, the researchers say, support the guideline recommendation that primary prevention patients with diabetes should be treated with statins to lower cholesterol levels.

Though prespecified, this study reports on outcomes in a subgroup within a larger clinical trial, thus the researchers advise that the results should be “interpreted as hypothesis-generating rather than definitive evidence of benefits.”