Anakinra to Prevent Post-infarction Remodeling

Thousands of patients die daily from early and late complications of a heart attack (acute
myocardial infarction, AMI). Patients surviving AMI remain at high risk of death from adverse
cardiac remodeling (dysfunction and enlargement of the heart) leading to heart failure
(weakening of the heart).

Current interventions proven to reduce adverse remodeling and progression to heart failure
include early reperfusion (restoring blood flow to the heart muscle) and long-term use of
medicines that block the effects of hormones (such as angiotensin II, norepinephrine and
aldosterone) involved in adverse remodeling. Despite these treatments, however, many patients
continue to develop heart failure within 1 year of AMI. These patients are at very high risk
of death.

Numerous changes occur in the hearts of patients after AMI that lead to adverse remodeling.
Ischemia (lack of oxygen) and infarction (cell damage) lead to increased interleukin-1 (IL-1)
production in the heart. IL-1 plays a critical role in adverse cardiac remodeling by
coordinating the inflammatory pathway (leading to wound healing) and apoptotic pathway
(leading to cell death).

In opposition to IL-1 activity, the human body produces a natural IL-1 receptor antagonist
that blocks the effects of IL-1. The drug form of this IL-1 receptor antagonist (anakinra) is
currently FDA approved for the treatment of rheumatoid arthritis, an inflammatory disease
characterized by excessive IL-1 activity. Experimental studies show that anakinra is able to
prevent cardiac remodeling and improve survival in mice after AMI.

We hypothesize that anakinra will show similar benefits in human patients by preventing
adverse remodeling and heart failure after AMI.