{"id":61644,"date":"2023-12-16T05:49:08","date_gmt":"2023-12-16T00:19:08","guid":{"rendered":"https:\/\/johnsonfrancis.org\/professional\/?p=61644"},"modified":"2024-02-03T06:03:47","modified_gmt":"2024-02-03T00:33:47","slug":"clear-trial-of-bempedoic-acid","status":"publish","type":"post","link":"https:\/\/johnsonfrancis.org\/professional\/clear-trial-of-bempedoic-acid\/","title":{"rendered":"CLEAR Trial of Bempedoic Acid"},"content":{"rendered":"

CLEAR Trial of Bempedoic Acid
\n<\/span><\/h2>\n

Bempedoic acid is an ATP citrate lyase inhibitor, acting upstream of HMGCoA reductase targeted by statins, and reduces LDL cholesterol levels. It is associated with low incidence of muscle related adverse events compared to statins. US FDA had a prerequisite that patients should be already on maximally tolerated stating therapy before considering bempedoic acid and had noted that their effect on cardiovascular morbidity and mortality were considered as indeterminate. The manufacturers have reported that these clauses have been removed<\/a>.<\/p>\n

The CLEAR (Cholesterol Lowering via Bempedoic Acid [ECT1002], an ACL-Inhibiting Regimen) trial published in\u00a0NEJM\u00a0<\/em>in April 2023 concluded that among statin intolerant patients, treament with bempedoic acid was associated lower risk of major adverse cardiovascular events which was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke and coronary revascularization [1].<\/p>\n

CLEAR trial was a double blind, randomized, placebo controlled trial of patients who were unable or unwilling to take statins due to unacceptable adverse effects and had or were at high risk for cardiovascular disease. 6992 patients were assigned to bempedoic acid and 6978 to placebo group. Median follow up was for 40.6 months. There was 29.2 mg\/dL more reduction of LDL with bempedoic acid compared with placebo after 6 months. Primary composite endpoint occurred in 819 patients in the bempedoic acid group and 927 patients in the placebo group (P = 0.004).<\/p>\n

There were no significant effects on fatal or nonfatal stroke, death from cardiovascular causes and death from any cause. There was a higher incidence of gout and cholelithiasis with bempedoic acid. Small increases in serum creatinine, uric acid and hepatic enzyme levels were also noted in the bempedoic acid group. Bempedoic acid is a prodrug which is activated in liver and not in skeletal muscle, which could explain the reduced potential for adverse effect on muscles [2]. Treatment discontinuation was similar to placebo. There was no increase in new onset diabetes mellitus or worsening of diabetes mellitus.<\/p>\n

Another interesting aspect is that bempedoic acid treament reduced hsCRP levels by 21.6% at 6 months compared to placebo. Though this effect has also been documented with statin therapy,\u00a0 monotherapy using PCSK9 inhibitors or ezetimibe have not been associated with similar reduction in biomarkers of inflammation. CLEAR trial had patients for both primary and secondary prevention of cardiovascular disease.<\/p>\n

An important limitation of the CLEAR trial was that it enrolled patients who were unwilling or unable to take statins and had high mean LDL cholesterol of 130 mg\/dL at baseline. Thus the effect of bempedoic acid on cardiovascular events in those with lower LDL cholesterol levels and those on therapeutic doses of statins were not evaluated.<\/p>\n

References<\/span><\/strong><\/p>\n

    \n
  1. 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; CLEAR Outcomes Investigators. Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients<\/a>. N Engl J Med. 2023 Apr 13;388(15):1353-1364. doi: 10.1056\/NEJMoa2215024. Epub 2023 Mar 4. PMID: 36876740.<\/li>\n
  2. Pinkosky SL, Newton RS, Day EA, Ford RJ, Lhotak S, Austin RC, Birch CM, Smith BK, Filippov S, Groot PHE, Steinberg GR, Lalwani ND. Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis<\/a>. Nat Commun. 2016 Nov 28;7:13457. doi: 10.1038\/ncomms13457. PMID: 27892461; PMCID: PMC5133702.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    CLEAR Trial of Bempedoic Acid Bempedoic acid is an ATP citrate lyase inhibitor, acting upstream of HMGCoA reductase targeted by statins, and reduces LDL cholesterol levels. It is associated with low incidence of muscle related adverse events compared to statins. 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