Anakinra to Prevent Adverse Post-infarction Remodeling (2)

Acute myocardial infarction (AMI) remains a major cause of morbidity and mortality. Many
patients die early during the course, and those who survive are at risk for dying late from
adverse cardiac remodeling and heart failure.

The initial ischemic damage to the myocardium initiates an intense inflammatory response in
promoting further cardiac dysfunction and heart failure. Interleukin-1 (IL-1) is the
prototypical inflammatory cytokine involved in the tissue response to injury. In the
experimental model of large anterior wall AMI in the mouse, IL-1 blockade using anakinra, a
recombinant human IL-1 receptor antagonist ameliorates cardiac remodeling and improves
survival following AMI. Although the mouse AMI model is helpful in understanding the events
leading to adverse post-infarction cardiac remodeling and heart failure, the exact role of
IL-1 in patients with AMI has not been completely characterized. The investigators propose
to address this question by studying patients presenting with ST-segment elevation AMI
(STEMI). Such patients are at high risk for in-hospital and long-term mortality and display
several markers of inflammation. The investigators hypothesize that IL-1 blockade in
patients STEMI with will limit the acute inflammatory response and prevent adverse cardiac
remodeling, heart failure, and related morbidity.

The investigators hypothesize that treatment with anakinra will lead to more favorable
cardiac remodeling. Left ventricular end-systolic volume index (LVESVi) is the preferred
clinical marker of adverse cardiac remodeling and a strong predictor of heart
failure-related mortality in patients with STEMI, and will be used as primary endpoint of
the study. The investigators propose that anakinra will reduce the change in LVESVi from
baseline to 10-14 weeks after STEMI, and will prevent, at least in part, other changes in
cardiac function and exercise tolerance associated with adverse cardiac remodeling and heart
failure.

Inclusion Criteria:

- Patients with STEMI will be asked to enroll according to the following inclusion
criteria:

- age > 18 years,

- acute (<12 h) onset of chest pain associated with ST segment elevation (>2 mm)
in 2 or more anatomically contiguous leads at ECG,

- and successful primary percutaneous coronary intervention.

Exclusion criteria:

- inability to give informed consent,

- late presentation (>12 h),

- unsuccessful revascularization procedure,

- hemodynamic instability including hypotension,

- prior Q-wave AMI,

- end-stage congestive heart failure (AHA/ACC class C-D, New York Heart Association
IV), severe left ventricular dysfunction (EF<20%),

- severe valvular heart disease,

- pregnancy, dye allergy or contraindications to cardiac angiography and/or magnetic
resonance imaging, coagulopathy (INR>1.5 or platelet count<50000/mm3),

- recent (<14 days) use of anti-inflammatory drugs (not including NSAIDs),

- chronic inflammatory disease (including but not limited to rheumatoid arthritis,
systemic lupus erythematosus), and malignancy or any comorbidity limiting survival or
conditions predicting inability to complete the study.