Acute Coronary Syndromes, Lipids, Secondary Prevention
Conditions
Keywords
ACS, Lipid-lowering therapy, atherothrombotic coronary event, secondary prevention, triple oral lipid lowering therapy
Brief summary
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
DRUGTriple oral lipid lowering treatment
Triple oral lipid lowering treatment including high intensity statin, ezetimibe and bembedoic acid
Sponsors
Heart Care Foundation
Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean percent change in LDL-c levels | 8 weeks | the difference in the mean percent change in LDL-c levels from baseline at 8 weeks between triple combo therapy and usual care. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of patients with LDL-c level <70 mg/dL | 8 weeks | Difference in percentage of patients with LDL-c level \<70 mg/dL at 8 weeks |
| Percentage of patients with LDL-c level <55 mg/dL | 8 weeks | Difference in percentage of patients with LDL-c level \<55 mg/dL at 8 weeks |
| Percentage of patients with LDL-c level <40 mg/dL in those with a recurrent ACS event in the previous 48 months | 8 weeks | Difference in percentage of patients with LDL-c level \<40 mg/dL at 8 weeks in those with a recurrent ACS event in the previous 48 months |
| Change in high-sensitivity CRP (hs-CRP) | 8 weeks | Change in high-sensitivity CRP (hs-CRP) at 8 weeks |
| Persistence of active treatment and discontinuation rate | 8 weeks | Rate of persistence of active treatment and discontinuation rate of allocated treatment |
| Rate of adverse events | 8 weeks | Safety of the investigational study drug by adverse event recording |
Countries
Italy
Contacts
CONTACTFrancesco Orso, MD
STUDY_CHAIRFurio Colivicchi, MD
San Filippo neri Hospital - Rome
STUDY_CHAIRAldo P Maggioni, MD
Fondazione per il Tuo cuore
STUDY_CHAIRPietro Scicchitano, MD
Ospedale Miulli - Bari
Outcome results
None listed