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

Official title

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

Overview

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.

Detailed 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.

Interventions

• Drug Triple oral lipid lowering treatment
  Triple oral lipid lowering treatment including high intensity statin, ezetimibe and bembedoic acid

Primary outcome measures

• Mean percent change in LDL-c levels [Time frame: 8 weeks]

Secondary outcome measures (7)

• Percentage of patients with LDL-c level <70 mg/dL [Time frame: 8 weeks]
• Percentage of patients with LDL-c level <55 mg/dL [Time frame: 8 weeks]
• Percentage of patients with LDL-c level <40 mg/dL in those with a recurrent ACS event in the previous 48 months [Time frame: 8 weeks]
• Change in high-sensitivity CRP (hs-CRP) [Time frame: 8 weeks]
• Persistence of active treatment and discontinuation rate [Time frame: 8 weeks]
• Rate of adverse events [Time frame: 8 weeks]
• Rate of adverse events [Time frame: 3 months]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Italy · 35 centers

• Ospedale Miulli - U.O.C. CARDIOLOGIA - UTIC — Acquaviva delle Fonti
• Ospedale Della Murgia - Fabio Perinei - S.C. Cardiologia-Utic — Altamura
• Ospedale San Donato - U.O.C Cardiologia — Arezzo
• Aorn San Giuseppe Moscati - U.O. Cardiologia/Utic 'D. Rotiroti' — Avellino
• Ospedale San Paolo - Cardiologia-Utic — Bari
• Ospedale Santo Spirito - SC Cardiologia — Casale Monferrato
• Azienda Ospedaliera S. Anna E S. Sebastiano - U.O. Cardiologia D'Emergenza Con Utic — Caserta
• Azienda Ospedaliera Cannizzaro - Uoc Cardiologia — Catania
• … and 27 more centers

Identifiers

NCT: NCT07440381 · G114

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗