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Bipedenic acid may represent a complementary oral therapeutic option to ezetimibe in statin intolerant patients who require additional low density lipoprotein (LDL-C) cholesterol reduction. The results of the "CLEAR Tranquility" study published online in "Atherosclerosis" are highlighted
Bipedolic acid may represent a complementary oral therapeutic option to ezetimibe in patients with intolerance to statins that require further lowering of low density lipoprotein cholesterol. (LDL-C). The results of the "CLEAR Tranquility" study published online in "Atherosclerosis" are highlighted.
"Patients with hyperlipidemia who do not tolerate optimal treatment with statins have an increased cardiovascular risk due to the continuous increase in LDL- Remember the authors, coordinated by Christie M. Ballantyne of the Department of Medicine, Baylor College of Medicine, Houston, USA.
CLEAR Tranquility's goal – the researchers explain – was to evaluate the efficacy and safety of bempedenic acid when it is added to a lipid-modifying treatment in patients with a history of statin intolerance requiring additional LDL-C reduction.
Inhibition of cholesterol synthesis upstream of HMG-CoA reductase
The acid Bempedoic – the researchers explain – is a small oral molecule, once a day, first in its clbad, inibi cholesterol synthesis, developed for the treatment of hyperlipidemia. "As an inhibitor of adenosine triphosphate (ATP) citrate lyase, bempedenic acid acts upstream of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase to inhibit cholesterol biosynthesis and increase LDL receptor expression "add.
In phase 2 clinical studies, bempedenic acid significantly reduced LDL-C, reduced atherogenic lipid levels, decreased C-reactive protein concentrations at high sensitivity (hsCRP) and was well tolerated. "Improvements in lipid parameters were observed when bempaic acid was administered as monotherapy or as adjunctive therapy to other therapies. lipids, "added Ballantyne and colleagues.
" These studies included a wide range of populations in primary and secondary prevention, including patients with primary hyperlipidemia or dyslipid Mixed sandwich, some of which also had a history of type 2 diabetes, coronary heart disease and / or & # 39; statin intolerance "stress.
Doses of bempedic acid ranging from 40 to 240 mg / day were evaluated in phase 2 studies. The favorable profile of efficacy and safety supported the use dose of 180 mg / day in phase clinical studies. 3.
Low Rate of Muscle Adverse Events
In the CLEAR Tranquility Phase 3 Study, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Patients with a History of Patients with Statin intolerance was recruited and a LDL-C value = 100 mg / dL while they were in stable lipid modification therapy.
After a 4-week break-in period with ezetimibe 10 mg / day, patients were randomized to a 2: 1 ratio of treatment with bipedenic acid 180 mg or a placebo unum / day at 10 mg / day ezetimibe for 12 weeks. The primary endpoint was the percentage change in LDL-C between the beginning and the 12th week. The study population consisted of 269 patients (181 treated with bempedolic acid, 88 in the placebo group).
Bipedenic acid added to lipid modification therapy – which included ezetimibe – reduced LDL-C by 28.5% more than placebo (p <0.001; -23). , 5% with bempedoico acid, + 5.0% with placebo).
Significant reductions were also observed for secondary endpoints – including high-density non-lipoprotein cholesterol (-23.6%), total cholesterol (-18.0%), apolipoprotein B ( -19.3%) and hsCRP (-31.0%) – with bempedolic acid compared with placebo (p <0.001).
Bempedoic acid was well tolerated. Rates of treatment-related adverse events, muscle-related adverse events, and discontinuations of treatment were similar in the bempedolic acid and placebo treated groups
. Clinical significance of the research
"Patients with indication The lowering of LDL-C level badociated with statin intolerance represents a population at risk that requires therapeutic alternatives that effectively reduce LDL-C and the badociated cardiovascular risk, "said Ballantyne and colleagues.
"In our study population, which included patients with a history of intolerance to at least one statin, less than one-third received a statin despite a high prevalence of risk factors. and Values of Atherosclerotic Cardiovascular Disease (ASCVD). "The ability to significantly reduce LDL-C in these patients while avoiding muscle-related symptoms supports the potential of bempaic acid as an agent. complementary lipid-lowering agent. an ezetimibe in patients who can not tolerate more than a therapy with statins at low doses and who require an additional lowering of LDL-C, "they conclude.
Key Evidence of the Study
- Biodedic acid further reduces LDL-C when added to ezetimibe
- Acid Bipedenic reduces atherogenic lipids and hsCRP in statin intolerant patients.
- Bempedic acid is well tolerated, including a low rate of adverse events related to the musculature
Giorgio Ottone
Literature reference:
Ballantyne CM , Banach M, Mancini GBJ, et al. Statin intolerant patients with hypercholesterolemia: A randomized, placebo-controlled study. Atherosclerosis, 2018 June 12. doi: 10.1016 / j.atherosclerosis.2018.06.002. [Epub ahead of print] lire
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