SAFETY AND EFFICACY OF BEMPEDOIC ACID AS A MONO AND COMBINED THERAPY IN STATIN HYPERLIPIDEMIC PATIENT: A SYSTEMATIC REVIEW

SAFETY AND EFFICACY OF BEMPEDOIC ACID AS A MONO AND COMBINED THERAPY IN STATIN HYPERLIPIDEMIC PATIENT: A SYSTEMATIC REVIEW

Asghar Badshah¹, Mubashira Asif¹, Emmama Jamil¹, Memoona Almas¹, Zumar Mehboob¹, Zimal Zainab¹, Muhammad Faisal¹, Muhammad Abubakar¹, Matti Ullah1

1. Faculty of Pharmacy, Hamdard University, Islamabad Campus, Pakistan

Corresponding Authors:

Asgharbadshah23@gmail.com

mattiullah@hamdard.edu.pk

ABSTRACT:

Cardiovascular diseases (CVD) are the prominent cause of death both in the United States and worldwide. Hyperlipidemia is the primary risk factor that leads to atherosclerosis and several other vascular diseases. Statin therapy has been the most prescribed therapy for hyperlipidemia for almost three decades, but the prescription comes with some adverse side effects. Bempedoic acid is a novel oral drug recently approved by the FDA for hyperlipidemia patients especially it is beneficial for those who are facing statin intolerance. The studies were collected from different databases i.e. PubMed, clinicaltrails.gov, web of Science, and Google Scholar. The selection criteria were based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The phase 2 trials showed reduced Low-density lipoproteins (LDL) by 27% at 120 mg of Bempedoic acid. When Bempedoic acid and ezetimibe are administered alone, LDL-C levels are reduced by 13-23% and 13-20%, respectively. Bempedoic acid+ atorvastatin causes a reduction of LDL to 22%, but with a placebo treatment, there will be no reduction in LDL level. Bempedoic acid 120mg plus ezetimibe 10mg LDL-C levels decreased by 43%and 48%with Bempedoic acid 180mg plus ezetimibe 10mg. Bempedoic acid has an interesting biochemical profile and presents an interesting new option for managing the complex dyslipidemia issue. The FDA has approved Bempedoic acid and Bempedoic acid plus antihyperlipidemic agents for the treatment of people with Heterozygous Familial Hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular disease (ASCVD) who need further LDL-C reduction with statin therapy that is maximally tolerable.

INTRODUCTION

Cardiovascular disease (CVD) is the prominent cause of death both in the United States and worldwide [1]. The fat-like substance is necessary for the body to function properly but too much low-density, LDL cholesterol can lead to buildup in the blood vessels [2]. Hyperlipidemia is the primary risk factor that leads to atherosclerosis and several other vascular diseases [3]. Hyperlipidemia causes increased Low-density lipoprotein cholesterol (LDL-C) which plays a key role in the development of Heart and vascular diseases [4, 5]. However, following acute cardiovascular events, women face higher mortality rates and poorer scenarios than men. These gender-specific differences in CVD exhibition and outcomes highlight the significance of personalized approaches to prevention, diagnosis, and treatment to address the unique challenges faced by each gender [6]. While several medications exist for treatment, statin therapy has been the most prescribed therapy for hyperlipidemia for almost three decades, but the prescription comes with some adverse side effects [7]. Statins are competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-COA) reductase and reduce LDL levels, Despite the effectiveness of statins, many patients do not reach optimal LDL-C levels even after taking maximum statin tolerated dose with or without the addition of non-statin agents such as ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors[8].

figure: Mechanism of action of bempedoic acid and statin in liver and muscle cells.

PCSK9 inhibitors are present in injectable form and are very expensive due to which patient compliance decreases[9]. Several studies show that patients taking statin therapy complain about muscle pain (myalgia) and diabetes mellitus which reduce patient adherence to therapy [10, 11]. it is important to note that there exists a subset of patients who are unable to tolerate appropriate or any form of statin therapy. Consequently, these individuals necessitate an alternative pharmacological approach to achieve a satisfactory lowering of low-density lipoprotein cholesterol (LDL-C) [4, 5].In this context, Bempedoic acid emerges as a novel solution. It is a pioneering, orally administered, small-molecule inhibitor of cholesterol biosynthesis [12]. Intriguingly, it operates within the same biological pathway as statins, effectively reducing LDL-C levels [13]. Currently, Bempedoic acid therapy is being increasingly favored for patients exhibiting statin intolerance and dyslipidemia. Moreover, it has demonstrated efficacy in mitigating cardiovascular events, underscoring its therapeutic potential [14]. Bempedoic acid is a pro-drug; upon activation by liver metabolism, it inhibits adenosine triphosphate-citrate lyase (ACL) in the liver as a result decreases LDL-C levels [11, 15]. A meta-analysis study (including 13 randomized control trials) reported the safety and efficacy of Bempedoic acid to lower LDL-C. However, the combination of Bempedoic acid with other lipid-lowering drugs may prove to be better than mono-therapy [16]. Further research and public health efforts are crucial to reducing the impact of CVD and promoting better cardiovascular health for all. The objective of this systemic review is to explore the safety and efficacy of Bempedoic acid as a mono and combination therapy in statin intolerance patients with hyperlipidemia and CV events.