European Primary Care Cardiovascular Society

Cholesterol synthesis inhibitor safely lowers LDL-c in high risk patients on lipid-lowering therapy

Mar. 20, 2019

Efficacy and Safety of Bempedoic Acid Added to Maximally Tolerated Statins in Patients with Hypercholesterolemia and High Cardiovascular Risk: The CLEAR Wisdom Trial

Presented at ACC.19 by Anne Carol Goldberg (Washington University, St Louis, MO, USA)

Introduction and methods

Despite statin or other lipid-lowering therapy, many patients with high CV risk have elevated LDL-c levels. This can be due to an insufficient response to high-intensity statins, or intolerability. Therefore, additional therapies are needed to lower LDL-c in those patients with elevated LDL-c levels. Bempedoic acid is an oral, small molecule drug that inhibits synthesis of cholesterol in the liver, but unlike statins, does not inhibit production in the muscles.

The efficacy and safety of bempedoic acid was investigated in high CV risk patients who were on maximally tolerated statins and/or other lipid-modifying therapies. A phase 3, double-blind, placebo-controlled, parallel-group study was performed, in which patients were randomized in a 2:1 ratio to receive bempedoic acid (n=522) or placebo (n=257) for 52 weeks in addition to maximally tolerated statin and/or other lipid-lowering therapy. Patients had pre-existing atherosclerotic CVD (ASCVD) or heterozygous FH and baseline LDL-c ≥70 mg/dL. Primary endpoint was percent change in LDL-c from baseline to week 12.

Main results

Conclusion

Data of the CLEAR Wisdom trial showed that bempedoic acid is effective and safe and might be an additional therapeutic option to lower LDL-c in high CV risk patients with elevated LDL-c treated with maximally tolerated statins and/or other lipid-modifying therapies.

Discussion

Discussant Valentin Fuster said that he had expected a greater LDL-c reduction, based on how the drug works. It blocks cholesterol synthesis and acts proximal to how statins work. But, he makes the comparison with ezetimibe, which was found to be more beneficial when subsequent events were included in efficacy analyses. The same may be true for bempedoic acid. He thinks this was a great study and is looking forward to following what bempedoic acid will show in the future.

During the discussion, it was emphasized that bempedoic acid should be considered another add-on option, in patients already on statins and/or ezetimibe, but who still have elevated LDL-c and are at high risk. By lack of outcome data for bempedoic acid, it should not replace currently recommended therapies with demonstrated CV benefit.

- Our coverage of ACC.19 is based on the information provided during the congress –

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