From the Division of Cardiology, Department of Medicine, The University
of Texas Medical School at Houston and The Hermann Heart Center, Hermann
Hospital, Houston, Tex.
Correspondence to Richard W. Smalling, MD, PhD, UT-Houston Medical School, 6431 Fannin, Room 1.246, Houston, TX 77030.
The optimal treatment
of unstable ischemic coronary syndromes has not been
settled, and little in vivo pathological information in humans has been
available to help guide the care of patients with these complicated
problems. Dr Van Belle and colleagues1 have given
us new insight into the underlying
pathophysiological substrate in patients sustaining
acute myocardial infarction who then underwent coronary
angioscopy before coronary interventions up to 1 month after
their index event. Of these patients, 98% were treated with aspirin,
66% had thrombolytic therapy, and 100% had been
treated with heparin for at least 72 hours after admission. Despite
this intense antithrombotic regimen, the residual lesions were
angiographically severe in 76%, and complete occlusions were found in
14% of the patients. By angioscopy, the majority of the
infarct-related lesions were yellow (79%), and many were ulcerated
(36%) or had visible residual thrombus (77%). Eighteen percent of the
patients had large clumps of platelets adherent to the plaque, even
late in the course after infarction. The fact that these plaques
remained "active" for up to 30 days is quite interesting and
unsettling. There was an equal prevalence of yellow ulcerated plaques
with thrombus, whether they were studied between 0 and 10 days or 10
and 30 days after admission. Furthermore, the use of
thrombolytics seemed to promote an increased incidence
of ulcerated plaques, and adherent thrombus, although smaller, was
still present. Other investigators have suggested that mechanical
restoration of infarct artery patency reduces both the incidence of
"active" plaques and the presence of thrombus several days after
intervention.2
Commentary
Several different investigators have found an increased frequency
of yellow plaques (59%), ruptured plaques (41%), and
lesion-associated thrombus (51%) in patients with unstable angina or
recent acute MI.3 4 5 6 These features have been
associated with death, reinfarction, or need for repeat
revascularization when lesions were treated within
17 days of the index event (risk ratio of 6.6 to
10.15).4 5 The presence of angioscopically
detected thrombus or ruptured plaque preceding coronary
intervention is associated with an increased rate of restenosis
(52% to 54%) as well as a higher incidence of total occlusion at
follow-up (4% to 7%).7 Van Belle et
al1 have now demonstrated that these unfavorable
lesion features persist for at least 1 month after the index event in
many patients.
Implications for Early Versus Late Events After
Thrombolysis
Angiographic trials8 9 suggested that bolus
administration of reteplase achieved earlier and more frequent
infarct-related artery patency than alteplase in patients with acute
myocardial infarction. Many of these patients, however, underwent
coronary interventions early in the course of their infarct.
Given the unstable nature of the underlying plaques, this early
intervention may have maintained the advantage achieved by early
patency with a faster-acting lytic agent. The GUSTO III mortality trial
suggested that the faster agent, reteplase, was no better than
alteplase in terms of mortality at 30 days.10 Few
patients in the GUSTO III trial underwent early (<24 hours)
angiography and rescue angioplasty. Since Van Belle and colleagues have
shown us that plaques remain active with thrombus long after
administration of thrombolytics, the early advantage of
a faster lytic may have been lost if the underlying unstable plaque was
not passivated by PTCA, stenting, and/or glycoprotein
IIb/IIIa receptor antagonists. The GUSTO I angiographic
substudy suggested that alteplase-treated patients had improved TIMI
III flow at 90 minutes compared with streptokinase, but by 24 hours
this early patency had fallen from 54% to 45%. Patients treated with
"slower lytics" (eg, streptokinase), in contrast, had progressive
increases in TIMI III patency over 24 hours.11
The GUSTO I angiographic investigators also suggested that the
angiographic characteristics of the lesion were not predictive of early
closures,12 which is consistent with the
finding by Van Belle and others that plaques are active, independent of
angiographic appearance. White et al13 showed
that late reocclusion occurs in an additional 25% of patients between
4 weeks and 1 year after thrombolytic therapy for MI,
which is consistent with Van Belle's finding that the plaques
may continue to be active for more than 1 month.
Implications for Mechanical Intervention
The PAMI investigators reported that early recurrent
ischemia was much more common after treatment with alteplase
alone than with direct PTCA (28% versus 10.3%). At
Summary
Unstable plaques causing acute ischemic syndromes have a
very high incidence of early rethrombosis in the first 48 hours. It has
now been shown that these plaques frequently remain active and are
subject to a continued increased incidence of adverse thrombotic events
for
Footnotes
The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.
References
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© 1998 American Heart Association, Inc.
Editorials
Pathophysiological Insight Into the Possible Optimal Therapies for Acute Myocardial Infarction and Unstable Angina
Key Words: myocardial infarction • thrombolysis
2 days after
admission, recurrent ischemia was much less after PTCA than
after alteplase treatment (1.1% versus
13.5%).14 Nonetheless, mechanical interventions
in acute ischemic syndromes are also associated with a
significant incidence of early reocclusion and reinfarction as well as
an excessive incidence of restenosis at 6 months. The EPIC
Trial demonstrated much better early and late outcomes in patients
treated with abciximab before coronary intervention in the
setting of acute MI and unstable angina.15 16 17
Synthesizing the EPIC results as well as the findings of Van Belle and
others suggests that abciximab, in combination with PTCA, must help
passivate the active plaque, which would otherwise continue to be
thrombogenic for at least 1 month and possibly longer. These data also
suggest that a 12-hour treatment with a very potent antiplatelet
drug may not be long enough. 30 days after the index event. New strategies must be evaluated
for plaque passivation, potentially including coated stents, local
delivery of drugs, and aggressive antiplatelet therapy for
prolonged periods (probably >1 month) in the setting of acute
myocardial infarction and unstable angina.
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