A Multicenter, Prospective, Phase IV, Interventional Study to Investigate the Effectiveness and Safety of Bempedoic Acid in Patients With Primary Hypercholesterolemia or Mixed Dyslipidemia in Taiwan

Cardiovascular disease (CVD) is a chronic non-communicable disease among the most common causes of death worldwide. Substantial reductions in risks of CVD can be achieved through the management of modifiable risk factors, particularly low-density lipoprotein cholesterol (LDL-C). However, only 18.3% of high-risk primary prevention patients and 20.7% of secondary prevention patients achieved the treatment goals based on the 2019 ESC guidelines. Similar trends were reported by the latest European multinational observational SANTORINI study. These real-world evidence data indicate the suboptimal implementation of ESC/EAS 2019 guidelines on LDL-C, particularly the low use of combinational lipid-lowering therapy (LLT), leading to a substantial proportion of patients remaining at high residual risk of ASCVD events.

Bempedoic acid, a first-in-class novel nonstatin lipid-lowering agent, was approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in 2020 for the treatment of primary hypercholesterolemia. Bempedoic acid inhibits cholesterol biosynthesis through the inhibition of adenosine triphosphate-citrate lyase, an upstream enzyme of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. The unique hepatic activation of bempedoic acid results in limited exposure to skeletal muscle, which prevents musculoskeletal-related adverse events.

Phase II and III RCTs have demonstrated efficacy with adequate safety data of bempedoic acid as mono- or combination therapy with statins and ezetimibe. The CLEAR outcomes trial demonstrated the benefit of bempedoic acid in lowering the risks of major adverse cardiovascular events in statin-intolerant patients.

However, there is limited data on bempedoic acid treatment in East Asian subjects and no data in the Taiwanese population, despite modeling data from large studies indicating the potential for no ethnic differences. To investigate the effectiveness and safety of bempedoic acid in a Taiwanese population, this phase IV study is conducted to examine the treatment outcomes in approximately 180 patients using bempedoic acid in Taiwan.

This is a multicenter, prospective, phase IV, single-arm, interventional study investigating the effectiveness and safety of bempeodoic acid in Taiwanese patients with hypercholesterolemia or mixed dyslipidemia. The study will be conducted in three medical centers in Taiwan to include approximately 180 patients with hypercholesterolemia or mixed dyslipidemia.

All enrolled patients will receive bempedoic acid 180 mg once daily for 12 weeks, with a total of 3 visits as follows: Baseline, Week 4, and Week 12; and there will be one follow-up visit at 2 to 4 weeks after discontinuation for those who discontinue the study due to adverse events. Across the study period, all patients must maintain the regimen (including medication, dose, and frequency) of their background LLT that they received before initiating bempedoic acid treatment.

Aside from bempedoic acid, LLT, study visits, and assessments, other medical procedures and prescriptions will be based on physicians' judgments per real-world clinical practice. Subjects will be continually followed up from the enrollment date until Week 12, bempedoic acid discontinuation, study discontinuation, or lost to follow-up, whichever occurs first.

Eligibility Criteria:
Inclusion Criteria:

1. At least 18 years of age
2. Diagnosed with primary hypercholesterolemia (heterozygous familial and non-familial) or mixed dyslipidemia:

   * Patients who have been on statin or statin combining with other lipid-lowering therapies\* (both under the maximum tolerated dose of statin) for at least 4 weeks, but unable to reach LDL-C goals† OR
   * Patients who are statin-intolerant or contraindicated to statin, alone or have been on other non-statin lipid-lowering therapies\* for at least 4 weeks, but unable to reach LDL-C goals†

     \* Other lipid-lowering therapies: Ezetimibe, Cholesterol and/or bile acid, absorption inhibitors, PCSK9 inhibitors, Omega-3 fatty acids, Fibrates, or Niacin derivatives

     † LDL-C goals are defined as:
   * Patients with ASCVD or had conducted coronary revascularization procedures (e.g., PCI or CABG): LDL-C \< 70 mg/dL
   * Patients aside from the above population: LDL-C \< 100 mg/dL
3. The physician intends to prescribe bempedoic acid per locally approved label (the study intends no intervention in physicians' judgement on the prescription of bempedoic acid)
4. Provide written informed consent

Exclusion Criteria:

1. Concurrent participation in an interventional study (simultaneous participation in other non-interventional studies is acceptable)
2. With eGFR \< 30 mL/min/1.73 m2, end-stage renal disease (ESRD) on dialysis, severe hepatic impairment (Child-Pugh C), bempedoic acid contraindications (i.e., hypersensitivity to the active substance or any of the excipients, galactose intolerance, pregnancy, breastfeeding, concomitant use with simvastatin \> 40 mg daily)