Evolocumab in Patients With Acute MI (EVACS II)

Evolocumab in Patients With Acute MI (EVACS II)

Brief Summary:
Vascular and myocardial inflammation are significantly increased in Acute Coronary Syndrome (ACS) patients, are closely correlated to LDL-C levels, and are associated with these adverse consequences in the post-ACS patient population. Serum proprotein convertase subtilisin/kerin type 9 (PCSK9) levels are also increased in ACS, may raise LDL-C, and the investigators' pre-clinical studies indicate that PCSK9 is also a potent inducer of vascular inflammation. The addition of the PCSK9 antibody evolocumab, currently approved to lower LDL-C in certain patient populations, to current medical therapies would appear to be of particular benefit in patients with an ACS by markedly reducing LDL-C, stabilizing vulnerable plaque, and limiting inflammation-associated myocardial cell loss and resultant dysfunction.

Detailed Description:
Despite aggressive early intervention and current secondary prevention strategies, many patients who survive hospitalization for an acute coronary syndrome (ACS) experience subsequent unfavorable outcomes, including recurrent ischemic events and unfavorable cardiac remodeling associated with progressive left ventricular dysfunction and congestive heart failure. Vascular and myocardial inflammation are significantly increased in ACS patients, are closely correlated with LDL-C levels, and are associated with these adverse consequences. Serum proprotein convertase subtilisin/kerin type 9 (PCSK9) levels are also increased in patients with ACS, may raise LDL-C, and the investigators' pre-clinical studies indicate that PCSK9 is also a potent inducer of vascular inflammation. The addition of evolocumab to current medical therapies may therefore be of particular benefit in these patients, by markedly reducing LDL-C, stabilizing vulnerable plaque, and limiting inflammation-associated myocardial cell loss and resultant dysfunction.

In this study, the investigators propose to test the effects of PCSK9 inhibition with evolocumab on LDL-C reduction, vascular and myocardial inflammation, cardiac function, and clinical outcomes in an ACS patient cohort.

The investigators propose a double-blind randomized study of 100 patients presenting with an ACS (ST-Elevation- and Non-ST-elevation myocardial infarction). One hundred ACS patients will be randomized to evolocumab, 420 mg or to placebo (50 in each group) during early hospitalization and will also receive current guideline-directed ACS therapy. Lipid profiles, including LDL-cholesterol levels, and traditional and novel serum markers of inflammation and endothelial function will be measured at presentation, during the index hospitalization, and at 30-day and six-month follow-up. Positron Emission Tomography (PET) scans to measure myocardial and vascular inflammation and echocardiograms will be performed during the early post-infarction period and at thirty days (PET and echocardiogram) and six-month (echocardiogram) following randomization. Clinical outcomes, such as angina class, will also be collected at the six-month follow-up visit.

The protocol and the primary and secondary lipid and inflammatory outcomes in this study are identical to those in NCT03515304 and therefore the data in the two studies may be analyzed together.


Study Type: Interventional (Clinical Trial)
Estimated Enrollment: 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Evolocumab in Patients With Acute Myocardial Infarction: A Double-blind, Prospective, Randomized Placebo-Controlled Study
Actual Study Start Date: September 1, 2019
Estimated Primary Completion Date: June 2022
Estimated Study Completion Date: June 2022

Arm:
- Experimental: Evolocumab
- Placebo Comparator: Placebo

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