II. Indications

  1. Hyperlipidemia
    1. Statin Intolerant (e.g. Statin-Induced Myopathy)
    2. Second or third-line adjunct to Statin therapy if LDL not at goal

III. Contraindications

IV. Mechanism

  1. Class prototype, Bempedoic Acid, inhibits the enzyme ATP-Citrate Lyase
    1. ATP-Citrate Lyase is an enzyme key to Fatty Acid biosynthesis
    2. ATP-Citrate Lyase cleaves citrate into oxaloacetate (and acetyl CoA, ADP and orthophosphate)
  2. Lowers LDL Cholesterol as a Statin adjunct or alternative
  3. Does NOT effect Triglycerides or HDL

V. Efficacy

  1. Limited data on longterm cardiovascular outcomes
  2. Lowers LDL Cholesterol 20%
  3. NNT 63 for high Cardiovascular Risk patients to prevent 1 cardiovascular event in 3 years

VI. Dosing

  1. Bempedoic Acid (Nexletol)
    1. Take 180 mg orally daily (typically in combination with a Statin)
  2. Bempedoic Acid 180 and Ezetimibe 10 mg (Nexlizet)
    1. Take one tablet orally daily

VII. Precautions

  1. Bempedoic Acid (Nexletol) costs $400/month in 2023

VIII. Adverse Effects

  1. Increased Uric Acid
    1. Gout flare in up to 10% of patients with gout history on Bempedoic Acid (Nexletol)
  2. Gallstones
    1. Occurs in 1% of patients on Bempedoic Acid (Nexletol)

IX. Drug Interactions

  1. Pravastatin or Simvastatin
    1. Risk of Statin-Induced Myopathy when used with Bempedoic Acid (Nexletol)
    2. Limit Simvastatin doses to 20 mg orally daily when using Bempedoic Acid
    3. Limit Pravastatin doses to 40 mg orally daily when using Bempedoic Acid

XI. References

Images: Related links to external sites (from Bing)

Related Studies

Cost: Medications

nexletol (on 1/1/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
NEXLETOL 180 MG TABLET $12.27 each
nexlizet (on 1/1/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
NEXLIZET 180-10 MG TABLET $12.30 each

Ontology: ATP Citrate (pro-S)-Lyase (C0004199)

Definition (MSH) An enzyme that, in the presence of ATP and COENZYME A, catalyzes the cleavage of citrate to yield acetyl CoA, oxaloacetate, ADP, and ORTHOPHOSPHATE. This reaction represents an important step in fatty acid biosynthesis. This enzyme was formerly listed as EC 4.1.3.8.
Concepts Amino Acid, Peptide, or Protein (T116) , Enzyme (T126)
MSH D001275
SnomedCT 15297009
English ATP Citrate Lyase, ATP-Dependent Citrate Lyase, Citrate Cleavage Enzyme, Citrate Lyase, ATP, Citrate Lyase, ATP-Dependent, Cleavage Enzyme, Citrate, Lyase, ATP Citrate, Lyase, ATP-Dependent Citrate, ATP citrate (pro3s) lyase, ATP:citrate oxaloacetate-lyase ((pro-S)-CH2COO(-)--acetyl-CoA) (ATP-dephosphorylating), ATP Citrate (pro-3S)-Lyase, ATP Dependent Citrate Lyase, ATP citrate (pro-3S)-lyase (substance), Adenosine triphosphate (ATP) citrate (pro-3S)-lyase, citrate (pro3s) lyase, ATP CITRATE LYASE PRO S, ATP Citrate (pro-S)-Lyase [Chemical/Ingredient], ATP citrate pro3s lyase, citrate pro3s lyase, Adenosine triphosphate citrate (pro-3S)-lyase, Adenosine triphosphate (ATP) citrate (pro-3S)-lyase (substance), Adenosine triphosphate citrate (pro-3S)-lyase (substance), ATP citrate (pro-3S)-lyase, Citrate cleavage enzyme, ATP Citrate (pro-S)-Lyase, Citrate Synthase, ATP, Synthase, ATP Citrate, ATP Citrate Synthase
Spanish adenosina trifosfato (ATP) citrato (pro-3S)-liasa, ATP citrato (pro - 3S) - liasa (sustancia), ATP citrato (pro - 3S) - liasa, Enzima Ruptora del Citrato, adenosina trifosfato citrato (pro-3S)-liasa, adenosina trifosfato (ATP) citrato (pro-3S)-liasa (sustancia), adenosina trifosfato citrato (pro-3S)-liasa (sustancia), ATP citrato (pro-3S)-liasa, enzima divisora de citrato, ATP Citrato Liasa, ATP Citrato (pro-S)-Liasa, ATP Citrato Sintasa
Swedish ATP citrat(pro-S)-lyas
Czech ATP-citrátlyasa, ATP-citrát-(pro-S)-lyasa
Finnish ATP-sitraatti-(pro-S)-lyaasi
Italian Taglio dell'enzima citrato, ATP citrato (pro-3S)-liasi, ATP citrato liasi dipendente, ATP citrato sintasi, ATP citrato liasi, ATP citrato (pro-S)-liasi
Russian TSITRAT-RASSHCHEPLIAIUSHCHII FERMENT, ATF-TSITRAT(PRO-S)-LIAZA, ATF-TSITRAT-LIAZA, АТФ-ЦИТРАТ-ЛИАЗА, АТФ-ЦИТРАТ(ПРО-S)-ЛИАЗА, ЦИТРАТ-РАСЩЕПЛЯЮЩИЙ ФЕРМЕНТ
German ATP CITRAT LYASE PRO 3S, ATP-Citrat-(pro-3S)-Lyase, ATP-Citrat-Lyase, Citratspaltendes Enzym
Polish Enzym rozszczepiający cytrynian, Liaza (pro-S) ATP-cytrynianowa, Liaza ATP cytrynianowa
Japanese ATP-クエン酸(pro-S)-リアーゼ, ATP-クエン酸(pro-3S)-リアーゼ, ATP-クエン酸リアーゼ, ATP-シトレートリアーゼ, くえん酸開裂酵素, クエン酸開裂酵素
Portuguese ATP Citroliase, ATP Citrato (pro-S)-Liase, Enzima de Clivagem do Citrato, ATP Citrato Liase, ATP Citrato Sintase
French ATP citrate (pro-S)-lyase, Citrate cleavage enzyme, ATP citrate (pro-3S)-lyase, ATP citrate lyase, ATP citrate synthase, ATP-citrate lyase, ATP-citrate synthase, Enzyme de clivage du citrate