PMID- 37951797
OWN - NLM
STAT- MEDLINE
DCOM- 20240325
LR  - 20240326
IS  - 1933-2874 (Print)
IS  - 1876-4789 (Linking)
VI  - 18
IP  - 1
DP  - 2024 Jan-Feb
TI  - Safety of bempedoic acid in patients at high cardiovascular risk and with statin 
      intolerance.
PG  - e59-e69
LID - S1933-2874(23)00313-6 [pii]
LID - 10.1016/j.jacl.2023.10.011 [doi]
AB  - BACKGROUND: Bempedoic acid is an oral adenosine triphosphate citrate lyase (ACL) 
      inhibitor that lowers low-density lipoprotein cholesterol (LDL-C) blood levels. 
      The Cholesterol Lowering via Bempedoic acid, an ACL-Inhibiting Regimen (CLEAR) 
      Outcomes study demonstrated that bempedoic acid reduced cardiovascular (CV) risk 
      in patients at high risk for CV events who were unwilling or unable to take 
      guideline-recommended doses of statins. OBJECTIVE: To describe detailed safety 
      information from CLEAR Outcomes, including events in the United States (US) 
      prescribing information based on previous phase 3 hyperlipidemia studies. 
      METHODS: CLEAR Outcomes was a double-blind trial conducted in 13,970 patients 
      randomized to oral bempedoic acid 180 mg daily or placebo and followed for a 
      median of 3.4 years. RESULTS: In patients who received at least one dose (7,001 
      bempedoic acid, 6,964 placebo), treatment emergent adverse events (AE) occurred 
      in 86.3 % and 85 % of patients, respectively. COVID-19 was the most frequently 
      reported AE in both groups. Changes in serum creatinine, blood urea nitrogen, 
      hemoglobin, aminotransaminases, and uric acid were consistent with the known 
      safety profile of bempedoic acid. Gout or gouty arthritis occurred in 3.2 % of 
      bempedoic acid and 2.2 % of placebo patients. AE associated with tendinopathies, 
      including tendon rupture, occurred in 2 % of patients in both treatment groups. 
      Cholelithiasis occurred in 2.2 % of bempedoic acid and 1.2 % of placebo patients; 
      AE related to gallbladder disease were similar between treatment groups. 
      CONCLUSIONS: Bempedoic acid was well-tolerated compared with placebo. Safety data 
      from the long-term CLEAR Outcomes study reinforce the positive benefit-risk 
      profile of bempedoic acid.
CI  - Copyright (c) 2023. Published by Elsevier Inc.
FAU - Bays, Harold E
AU  - Bays HE
AD  - Louisville Metabolic and Atherosclerosis Research Center, 3288 Illinois Avenue, 
      Louisville, KY 40213, USA (Dr Bays). Electronic address: hbaysmd@outlook.com.
FAU - Bloedon, LeAnne T
AU  - Bloedon LT
AD  - Esperion Therapeutics, Inc., 3891 Ranchero Drive, Suite 150, Ann Arobor, MI 
      48108, USA (Drs Bloedon, Lin, Powell and Louie).
FAU - Lin, Grace
AU  - Lin G
AD  - Esperion Therapeutics, Inc., 3891 Ranchero Drive, Suite 150, Ann Arobor, MI 
      48108, USA (Drs Bloedon, Lin, Powell and Louie).
FAU - Powell, Heather A
AU  - Powell HA
AD  - Esperion Therapeutics, Inc., 3891 Ranchero Drive, Suite 150, Ann Arobor, MI 
      48108, USA (Drs Bloedon, Lin, Powell and Louie).
FAU - Louie, Michael J
AU  - Louie MJ
AD  - Esperion Therapeutics, Inc., 3891 Ranchero Drive, Suite 150, Ann Arobor, MI 
      48108, USA (Drs Bloedon, Lin, Powell and Louie).
FAU - Nicholls, Stephen J
AU  - Nicholls SJ
AD  - Victorian Heart Institute, Monash University, 631 Blackburn Rd, Clayton VIC 3168, 
      Australia (Dr Nicholls).
FAU - Lincoff, A Michael
AU  - Lincoff AM
AD  - Cleveland Clinic, 9500 Euclid Avenue, Rm JB-820, Cleveland, OH 44195, USA (Drs 
      Lincoff and Nissen).
FAU - Nissen, Steven E
AU  - Nissen SE
AD  - Cleveland Clinic, 9500 Euclid Avenue, Rm JB-820, Cleveland, OH 44195, USA (Drs 
      Lincoff and Nissen).
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20231031
PL  - United States
TA  - J Clin Lipidol
JT  - Journal of clinical lipidology
JID - 101300157
RN  - 1EJ6Z6Q368 (8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - 0 (Dicarboxylic Acids)
RN  - 0 (Fatty Acids)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
SB  - IM
MH  - Humans
MH  - *Cardiovascular Diseases/drug therapy
MH  - Cholesterol
MH  - Dicarboxylic Acids/adverse effects
MH  - Fatty Acids/therapeutic use
MH  - Heart Disease Risk Factors
MH  - *Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
MH  - *Hypercholesterolemia/drug therapy
MH  - Risk Factors
MH  - Double-Blind Method
OTO - NOTNLM
OT  - ATP-citrate lyase inhibitor
OT  - Bempedoic acid
OT  - CLEAR Outcomes Study
OT  - Hypercholesterolemia
OT  - Low-density lipoprotein cholesterol
OT  - Safety
EDAT- 2023/11/12 00:41
MHDA- 2024/03/25 06:44
CRDT- 2023/11/11 21:57
PHST- 2023/09/07 00:00 [received]
PHST- 2023/10/23 00:00 [revised]
PHST- 2023/10/25 00:00 [accepted]
PHST- 2024/03/25 06:44 [medline]
PHST- 2023/11/12 00:41 [pubmed]
PHST- 2023/11/11 21:57 [entrez]
AID - S1933-2874(23)00313-6 [pii]
AID - 10.1016/j.jacl.2023.10.011 [doi]
PST - ppublish
SO  - J Clin Lipidol. 2024 Jan-Feb;18(1):e59-e69. doi: 10.1016/j.jacl.2023.10.011. Epub 
      2023 Oct 31.