Clinical Topics
Several new advances in the treatment of coronary artery disease are reviewed on this page.
Brachytherapy
Brachytherapy
represents a potentially powerful way to prevent restenosis. Restenosis
has been the bane of angioplasty and the delivery of local radiation
to the target site after angioplasty has now been shown to help fight
restenosis. There are several isotopes and delivery systems which are
currently under study. Recent work, however, has focused on the possibility
that the lower doses delivered to the edge of the irradiated area may
actually promote restenosis ("candy-wrapper effect"). In addition, delay
in healing may also increase the risk of late thrombosis. Until these
issues are resolved, brachytherapy remains experimental.
Growth Factors/Angiogenesis
Growth
factors represent perhaps the most promising new therapy for the treatment
of intractable coronary artery disease. Several growth factors, including
vEGF and bFGF, are currently in clinical trials. These growth factors
help promote the local formation of new blood vessels, potentially providing
a new blood supply to areas which have an inadequate blood flow. Long-term
results are currently lacking but it appears that relief from angina,
at least in the short-term, has been successful in some patients treated
with a growth factor such as vEGF and bFGF.
Percutaneous Myocardial Revascularization
(PMR)
PMR utilizes a laser to create channels within
the heart muscle itself, potentially providing relief from intractable
angina by stimulating new blood vessel formation (angiogenesis) much
like the growth factors described above, creating new channels from
blood flow, deadening the nerves to the heart, or a combination of
any or all of the above. The model for this technique comes from
the observation the reptiles do not have coronary arteries; instead,
they possess small channels which allow blood to percolate through
the heart muscle to supply it with oxygen and other nutrients. The
most recent trial, PACIFIC, was reported and found that patients
who underwent the procedure had less angina and better exercise tolerance
than those who did not.
Antiplatelet Therapy
Glycoprotein IIb/IIIa inhibitors
GPIIb/IIIa
inhibitors are a class of new drugs which inhibit the final pathway of
platelet aggregation. Platelets play an important role in clot formation
and inhibition of platelet function is critical in maintaining blood
flow to the heart. There are now three major GPIIb/IIIa inhibitors available.
Clopidogrel
Clopidogrel
is an oral antiplatelet agent which inhibits
ADP-dependent platelet aggregation. It has been demonstrated to be superior
to aspirin alone in the prevention of stroke and cardiovascular events.
It is currently under study in the prevention of subacute stent thrombosis.
Ticlopidine
Ticlopidine
is an oral antiplatelet agent which has been shown to be effetive and
superior to warfarin in the prevention of subacute stent thrombosis.
It is generally well-tolerated but may cause neutropenia and it has been
implicated in causing thrombotic thrombocytopenia purpura (TTP).
Aspirin
Aspirin is actually
a weak platelet inhibitor but has been shown to be very effective in
the primary and secondary prevention of cardiovascular events, including
myocardial infarction and death.
Antithrombotics
Low-molecular weight heparin
These
subfractions of heparin come in a variety of preparations. The best known,
enoxaparin (Lovenox), has been shown to be superior to unfractionated
heparin in the setting of an acute coronary syndrome. Several studies
are currently underway investigating the use of enoxaparin in percutaneous
coronary interventions.
Direct antithrombins
Direct
antithrombins [hirudin, hirulog (bivaluridin), argatroban] have been
extensively scrutinized in the TIMI trials as well as in other clinical
trials. They appear to be effective in preventing coronary events but
appear to be only equivalent to unfractionated heparin and cause more
bleeding events in the setting of unstable angina. Extensive clinical
studies are currently underway with the next generation of these agents.