Using Evolocumab to Lower LDL Cholesterol in Heart Attack Patients

Acute Myocardial Infarction Upbound to PCI Immediately (STEMI) or in the Next Three Days (NSTEMI), and Randomized to Subcutaneous Evolocumab or Normal Strategies to Reach Guidelines LDL Objectives in the Real-world - the AMUNDSEN-real Study

This study is testing if a new cholesterol-lowering drug called evolocumab can help heart attack patients lower their LDL cholesterol more effectively than standard treatments.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 2166 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Assistance Publique - Hôpitaux de Paris (Academic / other)
• Drugs / interventions: evolocumab
• Locations: 1 site (Paris)
• Trial ID: NCT04951856 on ClinicalTrials.gov

What this trial studies

This international, multicenter study aims to compare the effectiveness of evolocumab against standard care in reducing LDL cholesterol levels in patients diagnosed with STEMI or NSTEMI who are undergoing PCI. Participants will be randomly assigned to receive either evolocumab or standard treatment, with the goal of achieving a significant reduction in LDL-C levels within 12 months. The study employs a controlled, open-label design and utilizes central randomization to ensure unbiased results. The hypothesis is that evolocumab will provide superior LDL-C reduction compared to standard care, potentially improving cardiovascular outcomes.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with a recent diagnosis of STEMI or NSTEMI who require PCI.

Not a fit: Patients who do not have a diagnosis of STEMI or NSTEMI or those who are not eligible for PCI may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved management of cholesterol levels in heart attack patients, reducing the risk of future cardiovascular events.

How similar studies have performed: Previous studies have shown positive outcomes with high-dose statins and PCSK9 inhibitors in similar patient populations, suggesting a promising approach.

Eligibility criteria

Inclusion Criteria:

Participant meeting all of the following criteria will be considered for enrolment into the trial:

1. Male or female
2. Diagnosis of STEMI or NSTEMI

   STEMI defined as:
   * symptoms of acute MI of at least 30 min AND
   * within the previous 24 hours with new persistent ST-segment elevation ≥1 mm in ≥2 continuous ECG leads AND
   * an indication for primary PCI AND
   * \> 55 years reported by the patient

   NSTEMI defined as:
   * Age≥18
   * a history of chest discomfort or ischemic symptoms of ≥10 minutes duration at rest ≤48 hours prior to entry into the trial with no evidence of persistent ST-segment elevation and with an elevated troponin (≥ the upper limit of normal according to local laboratory norms), AND
   * indication for a coronary angiogram within 72hrs AND
   * indication for PCI AND
   * at least one the following high-risk characteristics: Diabetes Peripheral Artery Disease Multivessel (≥ 2 or LM) disease on the coronary angiogram History of MI or stroke without sequels prior to randomization eGFR: 15 to 45 mL/min/1.73 m2 calculated with MDRD formula at randomization
3. Statin at maximal tolerated dose, as part of the standard of care at randomization, means Intent to treat with statin and the patient will receive his first dose as soon as possible after admission
4. Informed consent obtained in writing at enrolment into the trial

Exclusion Criteria:

Participant presenting with any of the following will not be included in the trial:

1. Fibrinolysis treatment
2. Planned CABG
3. Ongoing hemodynamic instability defined as any of the following:

   * Killip Class III or IV
   * Sustained and/or symptomatic hypotension (systolic blood pressure \< 80 mm Hg)
   * Known left ventricular ejection fraction \< 30%
4. Evidence of severe hepatobiliary disease: current active hepatic dysfunction or active biliary obstruction, decompensated cirrhosis or infectious/inflammatory hepatitis
5. Active malignancy
6. A comorbid condition with an estimated life expectancy of ≤ 12 months
7. Previously received or receiving evolocumab or any other therapy to inhibit PCSK9
8. Known sensitivity to any of the products or components to be administered during trial
9. Female subject is pregnant, had a positive pregnancy test at inclusion, breastfeeding, or planning to become pregnant or breastfeed during treatment and for an additional 17 weeks after the last dose of IMP
10. Currently receiving treatment in any other investigational device or drug trial, or less than 30 days since ending treatment on another investigational device or drug trial.
11. Participant likely to not be available to complete all protocol-required trial visits or procedures, and/or to comply with all required trial procedures to the best of the participant and investigator's knowledge.

Where this trial is running

Paris

• ACTION Group, Institut de Cardiologie, Centre Hospitalier Universitaire Pitié Salpêtrière (APHP), UPMC — Paris, France (Recruiting)

Study contacts

• Principal investigator: Gilles MONTALESCOT, Pr — Assistance Publique - Hôpitaux de Paris
• Study coordinator: Gilles MONTALESCOT, Pr

Conditions STEMI - ST Elevation Myocardial Infarction; NSTEMI - Non-ST Segment Elevation MI; STEMI; NSTEMI; PCI; STATIN; EVOLOCUMAB; Anti-PCSK9