The Safety and Long-Term Clinical Benefit of PCSK9i in STEMI Patients

• Status: Not yet recruiting
• Trial end date: 2024-10-30
• Target enrollment: 0
• Participant gender: All

Summary

Patients with acute coronary syndromes (ACS) have an increased risk of recurrent ischemic events, particularly during the first year following the index event, which is mainly due to unattended risk factors and/ or poor compliance with medications. Lowering low-density lipoprotein cholesterol (LDL-C) reduces cardiovascular morbidity and mortality in patients with atherosclerotic cardiovascular disease (ASCVD), with a magnitude of clinical benefit that is proportional to the reduction in LDL-C levels. Proprotein convertase subtilisin/ kexin type 9 (PCSK9) antibodies have emerged as a new class of drugs that rapidly and effectively lower LDL-C levels up to 77 % of the original value in combination with statins.

The primary objective of this study is to confirm the safety and the long-term clinical benefit associated with the use of PCSK9i when combined with statin in patients with ACS-STEMI.

The study is an investigator-initiated, prospective, randomized, open label study that will be the first study looking for the safety and the clinical benefit and outcome associated with the use of PCSK9i in ACS-STEMI patients specifically. Internationally, this will be the first trial studying the effect of PCSK9i on patients with acute myocardial infarction (STEMI) in terms of reduction in cholesterol level and reduction in cardiac events rate (re-infarction and cardiac death) after myocardial infarction. This trial will have a significant impact in the management of patients with STEMI, locally and internationally and it will be conducted purely in Qatar. This trial will help to improve the clinical outcome of patients in Qatar in terms of reduction of myocardial reinfarction rate and mortality.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hamad Medical Corporation
• Treatments: Evolocumab

Criteria

Inclusion Criteria:

• Inclusion and exclusion criteria:

Inclusion Criteria

• Male or female ≥ 18 years of age and less than 80 years

• Hospitalized for a recent ACS-STEMI within 12 hours of onset of symptoms.

• Successful revascularization with PCI.

• LDL-C levels defined as follows:

• LDL-C ≥1.8 mmol/L in patients who have been receiving stable treatment with high-intensity statin within ≥ 4 weeks prior to enrollment (i.e., continuous treatment that has not changed with regard to statin intensity over the past 4 weeks)

• LDL-C ≥2.3 mmol/L in patients who have been receiving stable treatment with low- or moderate-intensity statin within ≥ 4 weeks prior to enrollment (i.e., continuous treatment that has not changed with regard to statin intensity over the past 4 weeks)

• LDL-C ≥3.2 mmol/L in patients who are statin-naïve or have not been on a stable (unchanged) statin regimen for at least 4 weeks prior to enrollment.

• Ability to understand the requirements of the study and to provide informed consent

Exclusion criteria

• Unstable clinical status (hemodynamic or electrical instability)

• Uncontrolled cardiac arrhythmia, defined as recurrent and symptomatic ventricular tachycardia or atrial fibrillation or flutter with rapid ventricular response not controlled by medications in the past 3 months prior to screening

• Severe renal dysfunction, defined by estimated glomerular filtration rate <30 ml/min/1.73m2

• Active liver disease or hepatic dysfunction, either reported in patient medical record or defined by aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels > 3x the upper limit of normal.

• Patient need urgent CABG

• patients symptoms onset is more than 12 hours.

• Reported intolerance to atorvastatin (any dose) OR statin intolerance defined by the following criteria:

• inability to tolerate at least 2 different statins (one statin at the lowest starting average daily dose and the other statin at any dose).

• intolerance associated with confirmed, intolerable statin-related adverse effect(s) or significant biomarker abnormalities.

• symptom or biomarker changes resolution or significant improvement upon dose decrease or discontinuation.

• Known allergy to contrast medium, heparin, aspirin, ticagrelor or prasugrel

• Known sensitivity to any substances or medication to be administered during the trial

• Patients who previously received Evolocumab or other PCSK9 inhibitor

• Treatment with systemic steroids or systemic cyclosporine in the past 3 months.

• Known active infection or major hematologic, metabolic, or endocrine dysfunction in the judgment of the Investigator

• Patients who will not be available for study-required procedures in the judgment of the Investigator

• Current enrollment in another investigational device or drug study

• Active malignancy requiring treatment

• Pregnant women. For female of childbearing potential (age <50 years and last menstruation within the last 12 months), who did not undergo tubal ligation, ovariectomy or hysterectomy, pregnancy is excluded by a pregnancy test prior to inclusion in the study.