ESPEYB20 10. Type 2 Diabetes, Metabolic Syndrome and Lipid Metabolism Dyslipidemia (4 abstracts)
10.12. Bempedoic acid and cardiovascular outcomes in statin-intolerant patients
Nissen SE , Lincoff AM , Brennan D , Ray KK , Mason D , Kastelein JJP , Thompson PD , Libby P , Cho L , Plutzky J , Bays HE , Moriarty PM , Menon V , Grobbee DE , Louie MJ , Chen CF , Li N , Bloedon L , Robinson P , Horner M , Sasiela WJ , McCluskey J , Davey D , Fajardo-Campos P , Petrovic P , Fedacko J , Zmuda W , Lukyanov Y , Nicholls SJ & Nicholls CLEAR Outcomes Investigators
N Engl J Med. 2023 Apr 13;388(15):1353-1364. doi: 10.1056/NEJMoa2215024
Brief summary: In this double-blind, randomized, placebo-controlled trial, bempedoic acid (Nexletol) reduced the incidence of a composite cardiovascular.
Comment: Bempedoic acid is an ATP citrate lyase inhibitor. ATP citrate lyase catalyses the conversion of citrate to acetyl-CoA, the fundamental substrate required for the synthesis of cholesterol and fatty acids. By inhibiting the cholesterol synthesis pathway, bempedoic acid reduces intra-hepatic LDL-C.1 Bempedoic acid is a pro-drug and is converted to its active metabolite by very-long-chain acyl-CoA synthetase 1 activity. This enzyme is present mostly in the liver and is absent in skeletal muscle, which limits the theoretical possibility of myotoxicity, a common adverse effect of statin therapy.
This double-blind, randomized, placebo-controlled trial was conducted in 13 970 individuals with, or at high risk of, cardiovascular disease, and who were ‘statin-intolerant’ due to unacceptable adverse effects. The participants were assigned to oral bempedoic acid (180 mg daily) or a placebo. The primary endpoint was a four-component composite of major adverse cardiovascular events (MACE), defined as death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke or coronary revascularization, as assessed in a time-to-first-event analysis. The secondary endpoints, also assessed in a time-to-first-event, included a three-component composite of death from MACE, nonfatal stroke or nonfatal myocardial infarction; fatal or nonfatal myocardial infarction; coronary revascularization; fatal or nonfatal stroke; death from cardiovascular causes; and death from any cause.
About one third of the participants in both groups discontinued the drug. In the bempedoic acid group, compared to placebo, the risk of the primary endpoint MACE was 13% lower; and the risk of death from cardiovascular causes, nonfatal stroke or nonfatal myocardial infarction (the first key secondary endpoint) was 15% lower. The risks of fatal or nonfatal myocardial infarction and coronary revascularization were 23% lower and 19% lower, respectively. The relative reduction in MACE was slightly larger among patients without preexisting atherosclerotic vascular disease than among those with secondary-prevention.
Bempedoic acid was associated with a higher incidence of gout and cholelithiasis; and of elevated blood levels of creatinine, uric acid and hepatic enzyme. Concerns about the risks of tendinitis or tendon rupture with bempedoic acid have been reported. The FDA label advises patients to stop treatment if they experience joint pain, swelling or inflammation.
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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