triPle Oral thERapy With Bempedoic Acid vs uSual Care in Early Lipid Management of Patients With acUte coronAry synDromE (PERSUADE)

Heart Care Foundation

Status and phase

Begins enrollment in 3 months

Phase 3

Conditions

Lipids

Acute Coronary Syndromes

Secondary Prevention

Treatments

Drug: Triple oral lipid lowering treatment

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT07440381

G114

Details and patient eligibility

About

Early and intensive LDL-cholesterol (LDL-c) reduction is associated with improved short-term and long-term outcomes. Bempedoic acid is an oral ATP citrate lyase inhibitor that lowers LDL-c upstream of HMG-CoA reductase. When added to maximally tolerated statins, it has demonstrated significant LDL-c reduction and cardiovascular benefit, particularly in statin-intolerant or high-risk patients. However, evidence on early initiation of bempedoic acid during the index ACS hospitalization is currently lacking. The investigators therefore would like to see whether early (pre-discharge) initiation of an oral triple lipid-lowering therapy including bempedoic acid, high-intensity statin (HIS), and ezetimibe is superior to usual care in reducing LDL-c levels at 8 weeks after randomization in patients hospitalized for ACS.

Full description

Despite major improvements in the acute management of Acute Coronary Syndromes (ACS), recurrent cardiovascular events remain frequent after hospital discharge. Real-world registries consistently show suboptimal implementation of guideline-recommended lipid-lowering strategies, with more than 60% of patients failing to achieve recommended LDL-cholesterol (LDL-c) targets after ACS. Early and intensive LDL-c reduction is associated with improved short-term and long-term outcomes. While injectable lipid-lowering therapies such as PCSK9 inhibitors have demonstrated rapid LDL-c reduction when initiated early after ACS, their high cost and parenteral administration limit widespread adoption. Bempedoic acid is an oral ATP citrate lyase inhibitor that lowers LDL-c upstream of HMG-CoA reductase. When added to maximally tolerated statins, it has demonstrated significant LDL-c reduction and cardiovascular benefit, particularly in statin-intolerant or high-risk patients. However, evidence on early initiation of bempedoic acid during the index ACS hospitalization is currently lacking.

Enrollment

600 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age ≥18 years
Male and females at birth
Admitted for ACS caused by an atherothrombotic coronary event;
Calculated LDL-c: 70-140 mg/dL within 24 hours from admission for the ACS index event
Lipid lowering therapy on admission consisting of a low/moderate intensity statin or a high intensity statin (HIS); or no lipid lowering therapy (naïve patients)
Lipid-lowering therapy at discharge (at the time of randomization) consisting of HIS or HIS + ezetimibe
Scheduled home discharge
Written informed consent provided; patients who are unable to give informed consent for any reason will be excluded from the study.

Exclusion criteria

Patients already treated with HIS+Ezetimibe on admission for the ACS event,
Patients currently, previously or planned to be treated with PCSK9i or inclisiran,
Patients treated currently or in the last 3 months with bempedoic acid or in whom this treatment is planned in the following 8 weeks,
Known allergy, sensitivity or intolerance to bempedoic acid and/or study drugs' formulation ingredients (e.g. lactose intolerance),
Patients with history of documented intolerance to statins, ezetimibe or bempedoic acid
Patients with known Familial Hypercholesterolemia (FH; heterozygous or homozygous),
Patients with plasma triglycerides concentration exceeding 400 mg/dL (4.52 mmol/L),
Patients with dysbetalipoproteinemia (type III hyperlipoproteinemia),
Unstable clinical status (hemodynamic or electrical instability),
Severe renal dysfunction (eGFR <30 ml/min/1.73m2 using the CKD-EPI formula),
Active liver disease or hepatic dysfunction (AST or ALT levels > 3xUNL),
Current enrolment in another investigational device or drug study,
Current pregnancy, lactation or women of childbearing potential, unless using highly effective contraception,
Patients unlikely to comply with the protocol or unable to understand the nature, scope and possible consequences of the study.