CMHC Pulse Blog

Introduction: Addressing the Need for Improved LDL Management in the US 

There is a clear need for innovative treatments to combat cardiovascular disease (CVD). 

Heart disease remains the leading cause of death for men and women. 80% of heart attacks and strokes linked to CVD are preventable with optimal risk factor management. However, every 40 seconds, an individual in the US suffers a heart attack. 

What are we falling short? 

LDL is significantly undertreated, and while statins are the gold standard of lipid-lowering therapy, they aren’t sufficient for several reasons: 

1. High Baseline Levels of LDL-C 

2. Lack of adherence to statin regimens 

3. Discontinuation of statin therapy 

4. Side effects associated with statins (such as muscle-related symptoms and concerns regarding cognitive decline/dementia, along with the onset of new type 2 diabetes) 

5. Variability in LDL response to statin therapy 

There is an immediate need for additional therapeutic options. Providers like you require more tools in your arsenal. Many preventive cardiologists are enthusiastic about the updated label expansion of bempedoic acid tablets and combination bempedoic acid and ezetimibe tablets for reducing cardiovascular risk. 

New Addition to the Clinical Toolkit 

On March 22, 2024, the US FDA approved broad new label expansions for Esperion’s NEXLETOL® (bempedoic acid) Tablets and NEXLIZET® (bempedoic acid and ezetimibe) Tablets. This endorsement is based on positive CLEAR Outcomes data, including indications for cardiovascular risk reduction and extended LDL-C reduction in primary and secondary prevention patients. Moreover, the updated labels support the use of bempedoic acid tablets and combination bempedoic acid and ezetimibe tablets either independently or in conjunction with statins. They also introduce new indications for primary hyperlipidemia, either as standalone treatments or in combination with a statin, making them the only non-statin drugs indicated for primary prevention patients. 

Key Takeaway: This development is promising for millions of patients and physicians seeking novel treatment options to reduce cardiovascular risk. At the timing of this writing, it stands as the only LDL-lowering non-statin drug indicated for primary prevention. The recent label expansions add a cardiovascular risk reduction indication, expands to primary prevention, and removes the statin use qualifier from the indication. 

CLEAR Trial Results

The US FDA label expansions of bempedoic acid tablets and combination bempedoic acid and ezetimibe tablets for reducing cardiovascular risk and lowering LDL-C were backed by data from the CLEAR Outcomes trial, published in the New England Journal of Medicine in March 2023. This trial evaluated the impact of NEXLETOL® (bempedoic acid) Tablets on cardiovascular outcomes in nearly 14,000 patients with or at high risk of cardiovascular disease. Over a median duration of 3.4 years, bempedoic acid exhibited a generally safe and well-tolerated profile. The study demonstrated a 20% reduction in LDL-C, a 22% decrease in hsCRP, and no elevation in glucose levels compared to placebo. Patients treated with bempedoic acid experienced relative risk reductions of: 

1. 15% for MACE-3 (comprising death from a cardiovascular cause, nonfatal stroke, or nonfatal myocardial infarction) 

2. 27% for nonfatal myocardial infarction 

3. 19% for coronary revascularization 

4. 39% for MACE-3 in primary prevention patients 

According to Esperion, the pending label expansions in Europe are progressing as anticipated, marked by a favorable opinion from the Committee for Medicinal Products for Human Use (CHMP) on March 21, 2024. Esperion expects the European Medicines Agency to give a final decision in the second quarter of 2024. 

Concluding Remarks 

Despite significant advancements in our understanding of disease progression and treatment options, heart disease persists as the leading cause of death globally. While statin therapies have been groundbreaking in improving outcomes, there is a pressing need for nonstatin lipid-lowering treatments either as adjuncts or alternatives to statins. The recent updates in labeling of bempedoic acid tablets and combination bempedoic acid and ezetimibe tablets have notably expanded the eligible patient populations and introduced a new option for healthcare providers. However, it’s crucial to recognize that this isn’t a cure-all solution. 

Looking ahead, we anticipate the introduction of numerous treatments to the market, offering more therapeutic options of nonstatin therapies with distinct indications, advantages, disadvantages, and evidence base. This evolving landscape of nonstatin therapies will give patients more options for reducing cardiovascular risk.