PMID- 33276805 OWN - NLM STAT- MEDLINE DCOM- 20210906 LR - 20210906 IS - 2050-6511 (Electronic) IS - 2050-6511 (Linking) VI - 21 IP - 1 DP - 2020 Dec 4 TI - Efficacy and safety of bempedoic acid alone or combining with other lipid-lowering therapies in hypercholesterolemic patients: a meta-analysis of randomized controlled trials. PG - 86 LID - 10.1186/s40360-020-00463-w [doi] LID - 86 AB - BACKGROUND: Bempedoic acid is a new drug that reduces cholesterol synthesis via inhibiting ATP citrate lyase. It remains unclear whether the combination of bempedoic acid and other lipid-lowering drugs is better than these drugs alone. This study systematically reviewed the efficacy and safety of bempedoic acid monotherapy or combination togethers in hypercholesterolemic patients. METHODS: Randomized controlled trials were searched across Medline, Embase, Cochrane library, web of science, etc. The net change scores [least squares mean (LSM) percentage change] in LDL-C level were meta-analyzed using weighted mean difference. The reductions in other lipids including total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein (ApoB) and high sensitivity C reactive protein (hsCRP) were also assessed. Odds ratio (OR) of the incidence of adverse events (AEs) were calculated to evaluate the safety of bempedoic acid. RESULTS: A total of 13 trials (4858 participates) were included. Pooled data showed that the combination togethers resulted in greater reductions in LDL-C level than monotherapies (bempedoic acid + statin vs. statin: LSM difference (%), - 18.37, 95% CI, - 20.16 to - 16.57, I(2) = 0; bempedoic acid + ezetimibe vs. ezetimibe: LSM difference (%), - 18.89, 95% CI, - 29.66 to - 8.13, I(2) = 87%). But the difference in efficacy between bempedoic acid and ezetimibe was not obvious. Meta-regression analysis showed the treatment duration was a source of heterogeneity (adj R(2) = 16.92, 95% CI, 0.04 to 0.72). Furthermore, the background therapy of statin before screening decreased the efficacy of bempedoic acid. In addition, bempedoic acid also resulted in a significant reduction in TC, non-HDL-C, ApoB and hsCRP level. The OR of muscle-related AEs by the combination of bempedoic acid and statin was 1.29 (95% CI, 1.00 to 1.67, I(2) = 0) when compared with statin alone. CONCLUSION: This study showed the efficacy of combination togethers were similar but stronger than these drugs alone. Of note, a trend of high risk of muscle-related AEs by the combination of bempedoic acid and statin was observed, though it is not statistically significant, such risk is needed to be confirmed by more trials, because it is important for us to determine which is the better combinative administration for statin-intolerant patients. FAU - Zhao, Xiang AU - Zhao X AD - Department of General Practice, The First People's Hospital of Huaihua, University of South China, Huaihua, 418000, People's Republic of China. AD - Evidence-based Medicine and Clinical Center, The First People's Hospital of Huaihua, University of South China, Huaihua, 418000, People's Republic of China. FAU - Ma, Xubiao AU - Ma X AD - Evidence-based Medicine and Clinical Center, The First People's Hospital of Huaihua, University of South China, Huaihua, 418000, People's Republic of China. FAU - Luo, Xing AU - Luo X AD - Evidence-based Medicine and Clinical Center, The First People's Hospital of Huaihua, University of South China, Huaihua, 418000, People's Republic of China. FAU - Shi, Zhihua AU - Shi Z AD - Evidence-based Medicine and Clinical Center, The First People's Hospital of Huaihua, University of South China, Huaihua, 418000, People's Republic of China. AD - Department of Pharmacology, The First People's Hospital of Huaihua, University of South China, Huaihua, 418000, People's Republic of China. FAU - Deng, Ziwen AU - Deng Z AD - Evidence-based Medicine and Clinical Center, The First People's Hospital of Huaihua, University of South China, Huaihua, 418000, People's Republic of China. AD - Department of Pharmacology, The First People's Hospital of Huaihua, University of South China, Huaihua, 418000, People's Republic of China. FAU - Jin, Yuanxiang AU - Jin Y AD - Evidence-based Medicine and Clinical Center, The First People's Hospital of Huaihua, University of South China, Huaihua, 418000, People's Republic of China. AD - Department of Pharmacology, The First People's Hospital of Huaihua, University of South China, Huaihua, 418000, People's Republic of China. FAU - Xiao, Zhipeng AU - Xiao Z AD - Evidence-based Medicine and Clinical Center, The First People's Hospital of Huaihua, University of South China, Huaihua, 418000, People's Republic of China. FAU - Tan, Liming AU - Tan L AD - Department of Pharmacology, The Second People's Hospital of Huaihua City, Huaihua, 418000, People's Republic of China. FAU - Liu, Pingfang AU - Liu P AD - Evidence-based Medicine and Clinical Center, The First People's Hospital of Huaihua, University of South China, Huaihua, 418000, People's Republic of China. FAU - Jiang, Shilong AU - Jiang S AD - Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China. FAU - Shu, Yuanglu AU - Shu Y AD - Evidence-based Medicine and Clinical Center, The First People's Hospital of Huaihua, University of South China, Huaihua, 418000, People's Republic of China. FAU - Tang, Bing AU - Tang B AD - Evidence-based Medicine and Clinical Center, The First People's Hospital of Huaihua, University of South China, Huaihua, 418000, People's Republic of China. FAU - Qiu, Chengfeng AU - Qiu C AUID- ORCID: 0000-0002-5984-4924 AD - Evidence-based Medicine and Clinical Center, The First People's Hospital of Huaihua, University of South China, Huaihua, 418000, People's Republic of China. qiuchengfeng0721@163.com. AD - Department of Pharmacology, The First People's Hospital of Huaihua, University of South China, Huaihua, 418000, People's Republic of China. qiuchengfeng0721@163.com. LA - eng GR - 2020JJ4072/Natural Science Foundation of Hunan Province/International GR - 2019JJ40230/Natural Science Foundation of Hunan Province/International GR - B2019034/Hunan Provincial Science and Technology Department/International GR - B2019035/Hunan Provincial Science and Technology Department/International PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20201204 PL - England TA - BMC Pharmacol Toxicol JT - BMC pharmacology & toxicology JID - 101590449 RN - 0 (Anticholesteremic Agents) RN - 0 (Dicarboxylic Acids) RN - 0 (Fatty Acids) RN - 0 (Hypolipidemic Agents) RN - 1EJ6Z6Q368 (8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid) SB - IM MH - Anticholesteremic Agents/*administration & dosage MH - Dicarboxylic Acids/*administration & dosage MH - Drug Therapy, Combination MH - Fatty Acids/*administration & dosage MH - Humans MH - Hypercholesterolemia/diagnosis/*drug therapy MH - Hypolipidemic Agents/*administration & dosage MH - Randomized Controlled Trials as Topic/*methods MH - Treatment Outcome PMC - PMC7716459 OTO - NOTNLM OT - Adverse events OT - Bempedoic acid OT - Ezetimibe OT - Low-density lipoprotein cholesterol OT - Meta-analysis OT - Statin COIS- The authors declare that they have no competing interests. EDAT- 2020/12/06 06:00 MHDA- 2021/09/07 06:00 PMCR- 2020/12/04 CRDT- 2020/12/05 05:20 PHST- 2020/03/17 00:00 [received] PHST- 2020/11/19 00:00 [accepted] PHST- 2020/12/05 05:20 [entrez] PHST- 2020/12/06 06:00 [pubmed] PHST- 2021/09/07 06:00 [medline] PHST- 2020/12/04 00:00 [pmc-release] AID - 10.1186/s40360-020-00463-w [pii] AID - 463 [pii] AID - 10.1186/s40360-020-00463-w [doi] PST - epublish SO - BMC Pharmacol Toxicol. 2020 Dec 4;21(1):86. doi: 10.1186/s40360-020-00463-w.