Efficacy of Evolocumab Versus Standard Care in LDL-C Reduction for Acute Myocardial Infarction Patients Undergoing Percutaneous Coronary Intervention

The primary objective of the study is to demonstrate the **superiority** of evolocumab compared to the standard of care in achieving a reduction in LDL-C levels of ≥ 50% from baseline and reaching an LDL-C target of <1.4 mmol/L (<55 mg/dL) at a 12-month follow-up in the overall population. This is clinically relevant as achieving these LDL-C levels is crucial in reducing the risk of cardiovascular events in patients with **acute myocardial infarction**.

The secondary objective is to demonstrate the superiority of evolocumab over standard care in achieving the same LDL-C reduction and target levels at 12 months, evaluated on a country-by-country basis. This objective aims to assess the consistency of evolocumab's efficacy across different healthcare settings and populations.

The clinical trial involves a total of **433 participants** diagnosed with **acute myocardial infarction**. The study population includes both male and female subjects, with an age range of over 55 years. Participants were selected based on specific criteria, including a diagnosis of either ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI), with additional risk factors such as diabetes, peripheral arterial disease, or a history of previous myocardial infarction or stroke. All participants are required to be on a statin at the maximum tolerated dose as part of their standard management. The trial does not include a vulnerable population, and informed consent was obtained from all participants. The study aims to evaluate the efficacy of evolocumab in achieving significant reductions in LDL-C levels compared to standard care over a 12-month follow-up period.

The clinical trial is designed to evaluate the efficacy of **evolocumab** in achieving a significant reduction in LDL-C levels in patients with **acute myocardial infarction**. This is a randomized, double-blind, controlled trial with a primary objective to demonstrate the superiority of evolocumab over standard care in reducing LDL-C by ≥ 50% from baseline and achieving an LDL-C goal of <1.4 mmol/L at 12 months follow-up. The trial is expected to last until September 2026, with participant recruitment having commenced in September 2021.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis of STEMI or NSTEMI, and other risk factors. Following randomization, participants will receive either evolocumab or standard care. Follow-up visits are scheduled at 6 and 22 weeks, and at 12 months post-randomization, to assess LDL-C levels and other lipid parameters. Additional assessments may occur at 38 weeks, 16, 20, 28, and 32 months if data is available. The end-of-study visit will mark the conclusion of the participant's involvement, which is anticipated to last up to 36 months.

Participants may be withdrawn from the study early if they experience adverse events, withdraw consent, or if the investigator deems it necessary for safety reasons. The trial's design ensures rigorous monitoring and data collection to evaluate both primary and secondary endpoints, including percentage changes in LDL-C and other lipid parameters over the study duration. The trial is conducted in accordance with ethical standards and regulatory requirements, ensuring the integrity and reliability of the data collected.

The clinical trial involves the administration of **Repatha**, a 140 mg solution for injection in a pre-filled pen, containing the active substance **evolocumab**. Evolocumab is a monoclonal antibody classified under the ATC code C10AX13, and it is derived from a protein of other origin. The pharmaceutical form of Repatha is a solution for injection, specifically designed for subcutaneous use. The medication is administered at a dosage of 140 mg, with a maximum daily dose of 140 mg and a total maximum dose of 11,060 mg over the course of the study. The treatment period extends up to 36 months, with the frequency of administration determined by the study protocol. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment regimen.

In addition to the experimental treatment with Repatha, the study includes a comparator group receiving standard-of-care therapy. This standard-of-care therapy serves as a control to evaluate the efficacy of evolocumab in achieving a reduction in LDL-C levels by ≥ 50% from baseline and reaching an LDL-C goal of <1.4 mmol/L (<55 mg/dL) at 12 months follow-up. The trial does not utilize a placebo, and the standard-of-care therapy is administered according to current clinical guidelines for the management of patients with acute myocardial infarction. The study design ensures that all participants receive appropriate medical care while assessing the potential benefits of the investigational treatment.

Efficacy in the clinical trial titled "AMUNDSEN-real trial" will be assessed primarily through the measurement of **LDL-C** (low-density lipoprotein cholesterol) levels. The primary endpoint is defined as a reduction in **LDL-C** levels of at least 50% from baseline and achieving an **LDL-C** level of less than 1.4 mmol/L at 12 months follow-up. **LDL-C** levels will be evaluated at follow-up visits scheduled at 6 and 22 weeks, and at 12 months post-randomization. Additional assessments may occur at 38 weeks, and at 16, 20, 28, and 32 months if data are available.

Secondary endpoints include achieving a 50% reduction in **LDL-C** from baseline and a final **LDL-C** level of less than 1.4 mmol/L at 12 months, analyzed country by country. Other secondary measures involve the percentage change in **LDL-C** from baseline to various timepoints, including 6, 22 weeks, 12, and 24 months, and at the end of follow-up. The time to reach the target **LDL-C** level, mean change in **LDL-C** over 12 and 24 months, and changes in other lipid parameters such as total cholesterol, HDL-C, triglycerides, non-HDL-C, and Lipoprotein(a) at specified intervals will also be evaluated.