Efficacy Of Bempedoic Acid Research Articles

Short Commentary on “Safety and Efficacy of Bempedoic Acid among Patients with Statin Intolerance and Those Without: A Meta-Analysis and a Systematic Randomized Controlled Trial Review”

Short Commentary on “Safety and Efficacy of Bempedoic Acid among Patients with Statin Intolerance and Those Without: A Meta-Analysis and a Systematic Randomized Controlled Trial Review”

Safety and efficacy of bempedoic acid among patients with statin intolerance and those without: A meta-analysis and a systematic randomized controlled trial review.

Bempedoic acid, an innovative oral medication, has garnered significant interest in recent times due to its potential as a therapeutic intervention for hypercholesterolemia. Nonetheless, the outcomes of the initial investigations might have been more definitive and coherent. Our objective was to perform a quantitative meta-analysis in order to evaluate bempedoic acid's safety and effectiveness. A search was conducted on ClinicalTrials.gov, and PubMed from the time of inception until September 28, 2023. Randomized controlled trials comparing the safety and efficacy of bempedoic acid among patients with statin intolerance and those without were included in our analysis. The trial outcomes were summarized using a random effects model and were provided as mean differences or odds ratios (ORs) with a confidence interval of 95%. Additionally, trial heterogeneity and the possibility of bias were evaluated and investigated. Bempedoic acid treatment reduced low-density lipoprotein cholesterol levels more than placebo (mean difference -2.97%, 95% CI -5.89% to -0.05%), according to a pooled analysis of 16 eligible trials. The risk of death (OR 1.18, 95% CI 0.70 to 1.98) and muscle-associated occurrences (OR 1.00, 95% CI 0.77 to 1.31) was not impacted by bempedoic acid. In contrast, discontinuation of treatment was more frequently caused by adverse events in the bempedoic acid group (OR 1.13, 95% CI 1.01 to 1.27). In patients with statin intolerance as well as those without, bempedoic acid is a safe and efficacious lipid-lowering agent, according to findings from randomized controlled trials.

Safety and efficacy of bempedoic acid: a systematic review and meta-analysis of randomised controlled trials

Background and aimsBempedoic Acid (BA) is a novel Lipid-Lowering Therapy (LLT). We performed a systematic review and meta-analysis to assess the efficacy and safety of BA in patients with hypercholesterolemia.MethodsPubMed, Scopus, and Cochrane library databases were searched for randomised controlled trials evaluating the efficacy and/or safety of BA compared with placebo. Trials investigating dosages other than 180 mg/die were excluded. Major adverse cardiovascular events (MACE) were the primary efficacy endpoint. LDL-cholesterol reduction was the primary laboratory endpoint. Pre-specified safety endpoints included muscle-related adverse events, new-onset diabetes, and gout. The protocol was registered on PROSPERO (temporary ID:399,867).ResultsStudy search identified 275 deduplicated results. 11 studies, encompassing 18,315 patients (9854 on BA vs 8461 on placebo/no treatment) were included. BA was associated with a reduced risk of MACE (OR 0.86, 95% CI 0.79–0.95), myocardial infarction (OR 0.76, 95% CI 0.64–0.88) and unstable angina (OR 0.69, 95% CI 0.54–0.88) compared to control, over a median follow up of 87 (15–162) weeks. BA was associated with a reduction of LDL-Cholesterol (mean difference [MD]–22.42,95% CI − 24.02% to − 20.82%), total cholesterol (− 16.50%,95% − 19.21% to − 13.79%), Apo-B lipoprotein (− 19.55%, − 22.68% to − 16.42%) and high-sensitivity CRP (− 27.83%, − 31.71% to − 23.96%) at 12 weeks. BA was associated with a higher risk of gout (OR 1.55, 95% CI 1.27–1.90) as compared with placebo. Efficacy on laboratory endpoints was confirmed, with a variable extent, across patients on statin or ezetimibe background therapy.ConclusionsThe improved cholesterol control achieved with BA translates into a reduced risk of MACE, including myocardial infarction and coronary revascularisation. The drug has a satisfactory safety profile except for an increased risk of gout.

Abstract 18261: Efficacy and Safety of Bempedoic Acid for Prevention of Cardiovascular Events and Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Control Trials

Background: Bempedoic acid (BA) is considered an alternative therapy for hyperlipidemia (HLD) in statin-intolerant patients. Given the positive results from the CLEAR-OUTCOMES trial, we performed a meta-analysis pooling recently conducted randomized control trials (RCTs) to provide a comprehensive clinical evaluation of the safety and efficacy of BA. Hypothesis: Bempedoic acid therapy in HLD patients with statin intolerance may be associated with a significant reduction in LDL-C levels, and CV events. Methods: All RCTs reporting CV outcomes and/or % change in LDL-C from baseline till completion of follow-up duration in HLD patients with statin-intolerance were included in MEDLINE, Google Scholar, and Scopus databases (Inception to April 2023). The outcome measures were summary random effects risk ratio (RR) and mean differences (MD) with 95% confidence intervals. Results: Twelve RCTs were included with 18 510 patients (10,033 BA vs. 8,477 placebo). BA therapy resulted in greater significant % reduction in LDL-C levels post-treatment (mean difference from baseline: 21.73% [-26.94, -16.51], p<0.00001) with no significant impact of the male sex, age, and follow-up duration on LDL-C upon meta-regression analysis. The risk of MACE (RR, 0.86 [0.79, 0.93], p < 0.0004), coronary artery revascularization (RR, 0.81 [0.72, 0.91], p = 0.0005), and myocardial infarction (RR, 0.71 [0.51, 0.99], p= 0.04) were significantly reduced with BA ( Figure 1) . However, no significant reduction in cardiac death (RR, 1.05 [0.89, 1.24], p = 0.56) was observed. A total of 1,019 new-onset DM events (521/6027 with BA; 498/4946 with placebo) were reported, and demonstrated a non-significant lower risk of new-onset or worsening DM (RR 0.83; 95% CI [0.62, 1.13]; P = 0.24) with BA vs. placebo. Conclusion: BA was observed to be safe, efficacious, associated with improved cardiovascular outcomes, and with no effect on new-onset or worsening DM among HLD patients with statin intolerance.

New data of the treatment with bempedoic acid in clinical routine

Background and Aims : Bempedoic acid, an inhibitor of ATP citrate lyase, reduces low-density lipoprotein cholesterol (LDL-C) and since 2020 has become an additional treatment option to reach the LDL-C treatment goal. The aim of this analysis is to provide new data of side effects and efficacy of bempedoic acid in a “real-world” cohort.

†Safety and Efficacy of Bempedoic Acid in Patients with Hypertension

<h3>Lead Author's Financial Disclosures</h3> KCF has received honorarium for consultancy from Amgen, Boehringer Ingelheim, Medtronic, Novartis, and Quantum Genomics. <h3>Study Funding</h3> Esperion Therapeutics, Inc. <h3>Background/Synopsis</h3> Patients with hypercholesterolemia often have hypertension (HTN), further increasing cardiovascular disease risk. Statins may affect blood pressure (BP) due to vascular effects. Bempedoic acid (BA) is an ATP citrate lyase inhibitor that lowers LDL-C. <h3>Objective/Purpose</h3> To investigate the safety and lipid-lowering effect of BA in patients with hypercholesterolemia and comorbid HTN. <h3>Methods</h3> Data were pooled from 4 phase 3 studies; patients were randomized 2:1 to BA or placebo (PBO) for 12-52 weeks. In 2 studies, patients also received moderate- to high-intensity statin, and in 2 studies, patients with statin intolerance received low-dose or no statin. Patients were grouped based on history of HTN, which was treated pharmacologically. Percent change from baseline to week 12 of LDL-C and other lipid parameters, and vital signs and adverse events were assessed. Moreover, in a 6 week 1:1 randomized phase 2 study (NCT02178098), the safety and efficacy of BA were assessed in patients with uncontrolled HTN (BP ≥140/90 and ≤180/110 mmHg) not receiving statins or other lipid-lowering therapies. <h3>Results</h3> Of the 3,623 (2,425 BA, 1,198 PBO) patients included, 78% had a history of HTN. At week 12, the PBO-corrected least squares mean (95% CI) percent change in LDL-C was −19.2% (−20.9, −17.5; P<.0001) in patients with HTN and −20.9% (−24.2, −17.5; P<.0001) in patients without HTN (interaction P=.3697). Results were similar for ApoB levels (−13.0% [−14.5, −11.5; P<.0001] for patients with HTN and −15.3% [−18.0, −12.6; P<.0001] for patients without HTN [interaction P=.1586]). Overall, through 12-52 weeks, the BA safety profile was similar in patients with or without HTN with no clinically meaningful changes in BP. In the phase 2 study (n=143; mean baseline [SD] BP 155/96 [12/6] mmHg), the PBO-corrected LS mean (95% CI) percent change in LDL C was −24.2% (−30.3, −18.1; P<.0001) at week 6. Through 6 weeks of BA treatment, 24-hour ambulatory BP monitoring showed no change from baseline in BP; BA was generally well-tolerated with a consistent safety profile across treatment groups. <h3>Conclusions</h3> Regardless of HTN status, BA was generally well-tolerated and significantly lowered LDL-C with no clinically meaningful BP changes.

†Safety and Efficacy of Bempedoic Acid in Patients with Renal Impairment

<h3>Lead Author's Financial Disclosures</h3> PPT has received honorarium for consultancy from Amarin, AstraZeneca, Kowa, Merck, Novo-Nordisk, and Resverlogix. <h3>Study Funding</h3> Esperion Therapeutics, Inc. <h3>Background/Synopsis</h3> Patients with renal impairment and elevated levels of low-density lipoprotein cholesterol (LDL-C) are at very high risk for cardiovascular disease. Statins are safe and effective in this population but are often underutilized and underdosed; additional non-statin therapies to lower LDL-C are needed. Bempedoic acid (BA) is an ATP citrate lyase inhibitor that lowers LDL-C. <h3>Objective/Purpose</h3> To evaluate the safety and efficacy of BA in patients with Stage 2 or Stage 3a+b renal impairment. <h3>Methods</h3> Data were pooled from four phase 3 studies in which patients were randomized 2:1 to BA or placebo (PBO) for 12 to 52 weeks. All studies permitted stable background lipid-lowering therapy: in 2 studies, patients received background moderate- to high-intensity statin, and in 2 studies, patients had a history of statin intolerance and received low-dose or no statin. Patients were grouped by baseline estimated glomerular filtration rate (eGFR [mL/min/1.73m2]) into the following renal function subgroups: Stage 1 (≥90), Stage 2 (60-89) or Stage 3a+b (30-59). <h3>Results</h3> A total of 3,619 (2,422 BA; 1,197 PBO) patients were included in the analysis. Baseline Stage 2 or Stage 3a+b renal impairment was present in 63% and 15% of patients in each treatment arm, respectively; 22% of the patients had Stage 1 renal function at baseline. LDL-C lowering of BA was similar across renal function subgroups with significant reductions at week 12 from baseline in each subgroup: Stage 1-20.8%, Stage 2 -18.8% and Stage 3a+b -21.1% (P < .0001 vs PBO for each; interaction P = .4442). Significant reductions in ApoB levels were also observed with BA treatment compared with PBO regardless of renal function (P < .0001). The overall pattern of adverse events was consistent across the renal function subgroups; any differences appeared to be driven by overall BA vs PBO differences rather than by renal function at baseline. Creatinine levels were generally consistent within each renal function subgroup in both arms with arm means varying by < 7% at each assessed time point through 52 weeks. <h3>Conclusions</h3> BA was generally well-tolerated among patients with Stage 2 or Stage 3a+b renal impairment and significantly lowered LDL-C regardless of renal function status.

Meta-analysis of randomized controlled trials examining the safety and efficacy of bempedoic acid

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Bempedoic acid (BA), an inhibitor of ATP citrate lyase, has emerged as a new therapy for patients with dyslipidemia. The objective of this study was to perform a meta-analysis of BA's safety and cholesterol lowering efficacy. Methods A meta-analysis was performed using RCTs testing the safety and efficacy of BA versus placebo. The primary analysis calculated the odds ratio (OR) and 95% confidence interval (CI) of any adverse events, muscular-related AEs including myopathy, muscle weakness, and myalgias, as well as serious AEs as self-defined by the individual RCT. Additionally, we evaluated the mean difference (MD) and CI of low density lipoprotein-cholesterol (LDL-C), non-high density lipoprotein-cholesterol (non-HDL-C), total cholesterol (TC), and apolipoprotein B (ApoB) at 12 weeks, as well as LDL-C at 24 weeks of BA use as compared to placebo. Results Four RCTs were identified comparing BA to placebo. There was no increased risk of any AE [OR 1.04; 95%CI 0.89, 1.22], serious AE [OR 1.07; 95%CI 0.87, 1.34], or muscular-related AE [OR 1.25; 95%CI 0.98, 1.58] with BA use compared to placebo. BA resulted in a significant reduction in LDL-C [MD -21.06; 95%CI -24.49, -17.62], TC [MD -16.02; 95%CI -19.09, -12.93], non-HDL-C [MD -17.84; 95%CI -21.34, -14.34], and ApoB [MD -14.19; 95%CI -17.18, -11.21] at 12 weeks, and LDL-C at 24 weeks [MD -16.42; 95%CI -18.15, -14.69] compared to placebo. Conclusion In this meta-analysis testing BA versus placebo, BA significantly reduced levels of LDL-C, TC, non-HDL-C, and ApoB at 12 weeks and LDL-C at 24 weeks, and was not associated with an increased risk of any AE, muscular-related AE or serious AE. Further studies with longer time of follow up are needed to confirm the safety and long term cholesterol effects of BA.

Long-Term Safety and Efficacy of Bempedoic Acid in Patients With Atherosclerotic Cardiovascular Disease and/or Heterozygous Familial Hypercholesterolemia (from the CLEAR Harmony Open-Label Extension Study)

Limited data exist on the long-term safety and efficacy of bempedoic acid, an adenosine triphosphate-citrate lyase inhibitor, for lowering low-density lipoprotein cholesterol (LDL-C). This 78-week, phase 3, open-label extension (OLE) study followed the CLEAR Harmony phase 3 study, in which patients were randomized 2:1 to bempedoic acid or placebo for 52weeks; during the OLE, patients who received bempedoic acid continued treatment (≤130weeks) and patients who received placebo initiated bempedoic acid (≤78weeks). Safety assessments included treatment-emergent adverse events, adverse events of special interest, and clinical laboratory abnormalities. Efficacy assessments included % change from the parent study baseline in LDL-C, other lipid parameters, and high-sensitivity C-reactive protein (hsCRP). Of 1,462 patients who enrolled in the OLE study, 970 received bempedoic acid in the parent study; laboratory abnormalities and reductions in LDL-C, other lipid parameters, and hsCRP observed in the parent study remained stable through 130weeks of treatment. On initiation of bempedoic acid treatment, 492 patients who received placebo in the parent study experienced reductions in LDL-C, other lipid parameters, and hsCRP, mirroring reductions observed in patients who received bempedoic acid in the parent study who remained stable through 78weeks of therapy. During the OLE, incidence of treatment-emergent adverse events and adverse events of special interest were comparable in patients who received 130weeks (78%) versus 78weeks (78%) of bempedoic acid treatment. In conclusion, bempedoic acid was generally well tolerated and demonstrated sustained efficacy with up to 2.5years of continuous treatment. Bempedoic acid safety profiles were similar between the parent and OLE studies.

Safety and Efficacy of Bempedoic Acid in Statin-Intolerant Patients

<h3>Lead Author's Financial Disclosures</h3> Nothing to disclose. <h3>Study Funding</h3> None. <h3>Background/Synopsis</h3> Bempedoic acid is a first-in-class citrate lyase inhibitor that reduces atherogenic lipoproteins. There is limited data on the incidence of muscle-related adverse effects in statin-intolerant patients treated with bempedoic acid. <h3>Objective/Purpose</h3> To determine the effect of bempedoic acid on atherogenic lipoproteins in patients not on statins and whether statin-intolerant patients experience muscle-related adverse effects. <h3>Methods</h3> We performed a systematic review and meta-analysis of all published studies reporting the outcomes of bempedoic acid versus placebo in patients with hypercholesterolemia who were not on statins. All studies were included in the analysis of the lipoprotein effects (n=6), whereas only studies of statin-intolerant patients were included in the analysis of muscle-related adverse effects (n=4). <h3>Results</h3> The meta-analysis included 1,084 patients not on statins: 792 on bempedoic acid, and 292 on placebo. Four studies included only statin-intolerant patients (n=847): 629 on bempedoic acid and 218 on placebo. During a median follow-up of 12 weeks (range 4-24 weeks), bempedoic acid produced significant reductions in LDL-C (mean difference (MD) -25.7%, p<0.001), non-HDL cholesterol (MD -21.2%, p<0.001), and total cholesterol (MD -16.7%, p<0.001), compared to placebo with a similar risk of muscle-related adverse events (odds ratio (OR) 0.82, p=0.37), including myalgia (OR 0.71, p=0.32), muscle spasm (OR 1.08, p=0.84), weakness (OR 0.47, p=0.21), and muscle pain (OR 1.10, p=0.81). <h3>Conclusions</h3> Bempedoic acid decreases atherogenic lipoproteins in patients not taking statins and does not increase the incidence of muscle-related adverse events in statin-intolerant patients.

Bempedoic acid: A nonstatin drug for the management of hypercholesterolemia.

Bempedoic acid: A nonstatin drug for the management of hypercholesterolemia.

Bempedoic Acid for Heterozygous Familial Hypercholesterolemia: From Bench to Bedside.

Bempedoic acid is a first-in-class, oral, inhibitor of cholesterol biosynthesis that is approved for use in patients with atherosclerotic cardiovascular disease (ASCVD) and for primary prevention in individuals with heterozygous familial hypercholesterolemia (HeFH) by the United States Food and Drug Administration. Pooled data from the phase III clinical trials, CLEAR Harmony and CLEAR Wisdom, have demonstrated the safety and efficacy of bempedoic acid with regard to lowering of low-density lipoprotein cholesterol (LDL-C) in patients with HeFH as an adjunct or alternative to currently existing lipid-lowering therapies. CLEAR Outcomes is a cardiovascular outcomes trial that is currently underway that will provide additional insight as to where bempedoic acid will fit into treatment regimens among the non-statin lipid-lowering therapy options. Patients who might particularly benefit from bempedoic acid are those with HeFH and those unable to take adequate doses of statins or take any statin therapy altogether who need additional LDL-C lowering. In this review, we will discuss the profile of bempedoic acid from its design, development, and its place in therapy for the management of LDL-C for the purposes of ASCVD prevention.

Efficacy and safety of bempedoic acid alone or combining with other lipid-lowering therapies in hypercholesterolemic patients: a meta-analysis of randomized controlled trials

BackgroundBempedoic 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.MethodsRandomized 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.ResultsA 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, I2 = 0; bempedoic acid + ezetimibe vs. ezetimibe: LSM difference (%), − 18.89, 95% CI, − 29.66 to − 8.13, I2 = 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 R2 = 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, I2 = 0) when compared with statin alone.ConclusionThis 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.

Long-term safety and efficacy of bempedoic acid in patients at high risk of atherosclerotic cardiovascular disease: results from the CLEAR Harmony open-label extension study

Abstract Background Bempedoic acid (BA) is an oral first-in-class, ATP-citrate lyase inhibitor that lowers low-density lipoprotein cholesterol (LDL-C) levels in adults with hypercholesterolemia. In the phase 3 CLEAR Harmony study (NCT02666664, n=2230), BA 180 mg for 52 weeks significantly lowered LDL-C at week 12 compared with placebo and was maintained for 52 weeks in hypercholesterolemic patients with atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH) on stable, maximally tolerated statins. Purpose To report long-term safety, tolerability, and efficacy of BA from the CLEAR Harmony open-label extension (OLE) study (NCT03067441). Methods After completing the 52-week placebo-controlled CLEAR Harmony study, patients immediately entered the OLE and received BA for 78 weeks, followed by a 4-week washout period; the potential cumulative exposure to BA was 2.5 years. The primary endpoint was long-term safety of BA in the OLE. Results A total of 1462 patients enrolled in the OLE (BA n=970; placebo n=492 from CLEAR Harmony). At OLE baseline, mean (SD) age was 66.9 (8.7) years, 73.9% were male, 96.3% had ASCVD, 3.7% had HeFH with or without ASCVD, and all were receiving statins (93.5% moderate or high intensity). At baseline of CLEAR Harmony, patients had mean (SD) LDL-C of 102.9 (29.9) mg/dL (BA) and 99.0 (24.2) mg/dL (placebo). The majority of OLE patients (86.2%, n=1260) completed 78 weeks of BA treatment. At week 12 and 78 of OLE treatment, respectively, mean LDL-C lowering from CLEAR Harmony baseline was –14.9% and –14.4%. A total of 1143 patients (78.2%) reported a treatment-emergent adverse event (TEAE), and 299 (20.5%) reported a serious TEAE. TEAEs of special interest, determined by the therapeutic area or prior observations in preclinical or early clinical studies, occurred at similar rates as CLEAR Harmony (creatine kinase elevations, 1.8%; gout, 2.6%; hepatic enzyme elevations, 2.0%; hypoglycemia, 1.2%; muscular disorders, 8.5%; neurocognitive disorders, 0.9%; new onset/worsening diabetes mellitus, 5.5%; renal disorders, 2.8%) with biochemical changes that were stable over the course of the study and approached baseline levels after treatment discontinuation. Overall, 114 patients (7.8%) reported a TEAE leading to discontinuation of BA (most common: myalgia [0.6%], muscle spasm [0.5%]). Conclusion Durable lipid lowering was observed through 78 weeks of BA treatment and patient adherence to BA therapy was high (86.2%). Overall safety during the OLE was similar to results reported in the 52-week-long CLEAR Harmony study and the overall BA phase 3 clinical program, with no new safety findings. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Esperion Therapeutics, Inc., funded the research for this study and provided writing support for this abstract. Medical writing assistance was provided by Agnella Izzo Matic, PhD, CMPP, and Kelly M Cameron, PhD, CMPP, of JB Ashtin.

Bempedoic acid for the treatment of dyslipidemia

Cardiovascular disease (CVD) is the leading cause of death worldwide and one key factor associated with the increased CVD risk is dyslipidemia. Statin therapy remains the first-line treatment to manage dyslipidemia, yet many patients do not achieve optimal low-density lipoprotein-cholesterol (LDL-C) levels even after taking moderate- or high-intensity statins; therefore, additional, non-statin therapy is often needed. Bempedoic acid is a prodrug that, once activated, decreases LDL-C levels by the inhibition of adenosine triphosphate citrate lyase in the liver. Five clinical trials have demonstrated the safety and efficacy of bempedoic acid and the bempedoic acid/ezetimibe combination in lowering LDL-C in patients with atherosclerotic CVD and heterozygous familial hypercholesterolemia and also in high-risk primary prevention, and statin-intolerant patients. Bempedoic acid has been demonstrated to lower LDL-C levels by 15–25% in clinical trials and up to 38% when combined with ezetimibe. In 2020, the FDA approved bempedoic acid. Furthermore, the combination of bempedoic acid with ezetimibe is FDA approved for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic CVD who require additional LDL-C lowering after maximally tolerated statin therapy. The ongoing CLEAR OUTCOMES trial aims to evaluate whether bempedoic acid can reduce cardiovascular events in patients with statin intolerance and results will be available in the next 3 years. This outcomes trial will be pivotal for determining the role of bempedoic acid in the non-statin lipid-lowering armamentarium.

A META-ANALYSIS OF BEMPEDOIC ACID FOR DYSLIPIDEMIA IN STATIN-INTOLERANT PATIENTS

There is lack of evidence for the treatment of statin intolerant patients with dyslipidemia. We aimed to study the safety and efficacy of bempedoic acid (BPA) in this population. Pubmed, Embase, Scopus and Cochrane library were searched for randomized controlled trials in adults with dyslipidemia

ATP-citrate lyase: genetics, molecular biology and therapeutic target for dyslipidemia.

ATP-citrate lyase (ACLY) has re-emerged as a drug target for LDL cholesterol (LDL-C) lowering. We review ACLY as a therapeutic strategy, its genetics, its molecular and cellular biology, and also its inhibition. ACLY is a critical enzyme linking glucose catabolism to lipogenesis by providing acetyl-CoA from mitochondrial citrate for fatty acid and cholesterol biosynthesis. Human genetic variants have been associated with enhanced growth and survival of several cancers, and with attenuated plasma triglyceride responses to dietary fish oil. In mice, liver-specific Acly deficiency protects from hepatic steatosis and dyslipidemia, whereas adipose tissue-specific Acly deletion has no phenotype, supporting therapeutic inhibition of ACLY. A lipid-regulating compound, bempedoic acid, was discovered to potently inhibit ACLY, and in animal models, it prevents dyslipidemia and attenuates atherosclerosis. Phase 2 clinical trials revealed that bempedoic acid effectively lowers LDL-C as monotherapy, combined with ezetimibe, added to statin therapy and in statin-intolerant hypercholesterolemic patients. The efficacy of bempedoic acid as an LDL-C-lowering agent has validated ACLY inhibition as a therapeutic strategy. Positive results of phase 3 patient studies, together with long-term cardiovascular disease outcome trials, are required to establish ACLY as a major new target in cardiovascular medicine.