Clinical Updates in Myocardial

Infarction
•

Brian Lipski, Pharm.D. Candidate 2016

 Myocardial Infarction (MI)
•

Epidemiology
–

MI affects over a million Americans a year

–

One in six deaths is secondary to CHD

–

Estimated economic burden of ~$200 billion/yr

–

CHD is leading cause of premature chronic disability

 Pathophysiology of MI
•

Initial cause of most (ACS) events is an athersclerotic

plaque rupture or fissure in a coronary artery
•

Plaque rupture -> platelet aggregation, fibrin formation ->

clot stabilization -> clot occludes artery -> eliminate blood
flow to a portion of myocardium
•

Following MI, ventricular remodeling occur, causing LV

dilation and reduced pumping, leading to heart failure
•

3 classifications of ACS
–

STEMI - ST elevated myocardial infarction

–

NSTEMI - non-ST elevated myocardial infarction

–

UA - unstable angina
 STEMI
•

Transects the entire thickness of the myocardial

wall, due to a complete occlusion of a major
coronary artery
•

Formerly known as Q-wave or transmural MI

•

Myocardial necrosis from

an acute interruption of
blood supply, with elevation
of the ST segment
 NSTEMI
•

Does not transect the full thickness of the

myocardial wall.
•

Due to partial occlusion of a major coronary

artery, or complete occlusion of a minor coronary
artery
•

Myocardial necrosis that does not result in ST

segment
elevation
 UA
•

Non-occlusive thrombus obstructs coronary

blood flow partially
•

Myocardium receives inadequate blood flow

•

Severe ischemic chest pain, without myocardial

necrosis
•

Similar ECG findings as NSTEMI

2013 ACCF/AHA Guidelines for
Managment of STEMI
 MATRIX trial
•

To determine if bivalirudin (Angiomax) is more

effective than UFH ± discretionary GP 2b/3a
inhibitor in patients undergoing PCI
•

STEMI and NSTEMI patients included

•

Two bivalirudin arms: post-PCI bivalirudin and no

post-PIC bivalirudin
•

Primary outcome: composite endpoint, within 30

days, of death from any cause, MI, stroke, urgent
target-vessel revascularization, definite stent
thrombosis
 MATRIX trial

Death from any cause favors bivalirudin

–

Owing to fewer bleeding events

•

Stent thrombosis occurs more frequently with

bivalirudin
MATRIX trial
•

No difference in MACE (OR 0.94,

p=0.44)
•

No difference in net adverse clinical

events (OR 0.89, p=0.12)
–

In contrast to ACUITY and HORIZONS-

AMI studies, which showed a
statistically significant benefit for
bivalirudin
–

However, definitions of events varied,

so difficult to directly compare
MATRIX trial
•

Comparison of bivalirudin
discontinuation at the
completion of PCI vs
bivalirudin administration for
up to 4 hours after
completion of PCI
•

No statistically significant
difference in the primary
outcome on the basis of
duration (OR 0.91, p=0.34)
 MATRIX trial
•

The rates of major adverse cardiovascular

events and net adverse clinical events are similar
when comparing bivalirudin vs UFH, or
bivaliruding with or without post-PCI
administration
•

UFH ± GP 2b/3a inhibitor remains treatment of

choice in the setting of acute MI
•

Bivalirudin is treatment of choice in patients with

a history of heparin induced thrombocytopenia
(HIT)
 CIRCUS trial
•

In patients undergoing PCI, reperfusion injury

leads to additional myocardial damage
–

Can contribute up to 50% of the final infarct size

•

Thought to occur through the opening of the

mitochondrial permeability transition pore (PTP)
in the inner mitochondrial membrane
–

Allows apoptotic cytokines and ROS to leak out into

cell
–

Leads to cell death

•

Cyclosporine shown to inhibit the opening of the

mitochondrial PTP in previous trials
 CIRCUS trial

Subjects randomized to receive cyclosporine or

placebo injection prior to coronary recanalization
•

Primary outcome was, at 1 year, composite of:

–

Death from any cause

–

Worsening of heart failure during initial hospitalization

–

Rehospitalization for heart failure

–

Adverse left ventricular remodeling

CIRCUS trial
•

No difference in primary
outcome of cyclosporine
vs placebo (OR 1.04,
p=0.77)
•

No difference in any
individual measure
•

In study, 1 out of 4
patients died or were
rehospitalized for HF
–

Despite lack of positive

result in this trial,
reperfusion injury remains
an important focus for
research