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From Baylor College of Medicine and the Methodist Hospital, Houston, Tex
(N.S.K.); The Carl and Edith Lindner Center for Clinical Cardiovascular
Research and the University of Cincinnati (Ohio) College of Medicine (D.J.K.),
Ischemia Research and Education Foundation, San Francisco, Calif (D.P.M.);
Cleveland (Ohio) Clinic Foundation (A.M.L., E.J.T.); St. Louis (Mo) University
Medical Center (F.V.A.); Centocor Inc, Malvern, Pa (K.M.A., H.F.W.); and Duke
Clinical Research Institute, Durham, NC (R.M.C.).
Methods and Results—Of 2792 patients enrolled, 638 (23%) were
diabetic. Diabetic patients were older, shorter, and heavier; more
likely to be female and have three-vessel disease, prior
coronary artery bypass graft surgery, a history of
hypertension, or a recent myocardial infarction; and less likely to be
current smokers than their nondiabetic counterparts. During
hospitalization, death, myocardial infarction, or urgent
revascularization occurred in 7.1% of diabetics
and 7.5% of nondiabetics. By 6 months, the composite of death and
myocardial infarction had occurred in 8.8% of diabetic patients and
7.4% of nondiabetics, whereas death, myocardial infarction, or
revascularization had occurred in 27.2% and
22.6%, respectively. Abciximab treatment reduced death or myocardial
infarction among diabetic and nondiabetic patients (hazard ratios, 0.28
[95% confidence interval (CI), 0.13 to 0.57] and 0.47 [95% CI,
0.33 to 0.70] at 30 days for diabetics and nondiabetics, respectively,
and 0.36 [95% CI, 0.21 to 0.61] and 0.60 [95% CI, 0.44 to 0.82]
at 6 months for diabetics and nondiabetics, respectively). Abciximab
reduced target vessel revascularization among
nondiabetic patients (hazard ratio, 0.78 [95% CI, 0.63 to 0.96]) but
not among diabetics (hazard ratio, 1.4 [95% CI, 0.94 to 2.08]). When
standard- and low-dose heparin adjuncts were compared, diabetics
receiving abciximab with standard-dose heparin had marginally greater
reductions in the composite of death and myocardial infarction and in
target vessel revascularization than diabetics
assigned to abciximab with low-dose heparin.
Conclusions—Abciximab treatment in diabetic patients led to a
reduction in the composite of death and myocardial infarction, which
was at least as great as that seen in nondiabetic patients. However,
target vessel revascularization was reduced in
nondiabetic but not diabetic patients. This effect may be associated in
part with lower doses of heparin. These differences may be related to
differences in the platelet and coagulation systems between
diabetics and nondiabetics, the greater extent of coronary
artery disease in diabetics, or patient selection and management
factors.
Inhibition of platelet aggregation with abciximab, a monoclonal
antibody directed against the glycoprotein (GP) IIb/IIIa
receptor on the platelet surface, has been demonstrated to reduce
the risk of ischemic complications in patients with high-risk
characteristics undergoing PTCA5 and to reduce
the combined risk of death, myocardial infarction, or
revascularization of the target vessel at 6
months.6 A second study, EPILOG, recently
indicated that this risk reduction could be extended to patients
undergoing routine elective angioplasty, while the safety profile could
be improved when the dose of heparin given with abciximab was
reduced.7 Because a variety of reports have
suggested that markers of the soluble coagulation cascade are altered
and that levels of platelet activation may be higher in diabetics
than nondiabetics,8 9 10 11 we decided to examine the
clinical outcome of diabetic and nondiabetic patients undergoing PTCA
in the EPILOG study.
The primary end point of the study was the composite of death,
myocardial infarction, or urgent revascularization
at 30 days. The 6-month end point was the composite of death,
myocardial infarction, or any revascularization
procedure. Myocardial infarction was defined as the development of
pathological Q waves on the ECG or elevation of the creatine kinase
beyond three times normal with an accompanying elevation in the MB
isoenzyme. Target vessel revascularization included
repeated PTCA of any segment in the vessel dilated at the time of
enrollment in EPILOG or surgical bypass of that vessel.
Information concerning diabetic status was obtained from the case
report form. Patients were classified as diabetic on the basis of a
history of pathological elevations in the blood sugar. Diabetic
patients were further subcategorized on the basis of the presence or
absence of insulin dependence and a history of diabetic
retinopathy.
Statistical Methods
Early Treatment Efficacy
Outcomes at 6 Months
Target Vessel Revascularization at 6
Months
The hazard for the composite primary end point of death, myocardial
infarction, and revascularization was reduced
equivalently in both diabetics and nondiabetics treated with abciximab
and standard-dose heparin. However, in patients assigned to abciximab
and low-dose heparin, this hazard was reduced only in nondiabetics.
Examination of the components of the 6-month end point reveals that
target vessel revascularization was more common
among diabetics who received abciximab than placebo, particularly among
those receiving low-dose heparin (Table 6
These findings deserve several comments. First, it is clear that
treatment with abciximab produced a robust reduction in catastrophic
events, namely the composite of death and myocardial infarction, among
both diabetic and nondiabetic patients. The differing outcome responses
to heparin dose regimen among the two subgroups are puzzling. Although
the confidence limits are broad, the greater beneficial effect of
standard-dose heparin for diabetics is present in all outcome
measures examined. Some speculation on potential mechanisms therefore
seems indicated. It is unlikely that this effect is explained by gross
differences in heparin metabolism because the ACT responses
indicate that similar levels of anticoagulation were achieved with
similar doses of heparin in diabetics and nondiabetics. A variety of
other perturbations have been reported in the coagulation systems of
diabetic patients that might affect platelet function, including
larger platelets,8 greater expression of
P-selectin,14 higher platelet surface density
of GP IIb/IIIa,8 9 altered
thromboxane metabolism,15
and higher levels of circulating fibrinogen,10
vitronectin,16 17 and
thrombin–antithrombin III complexes,18 as well
as more extensive endothelial
dysfunction.19 20 Diabetic patients also have
higher mortality in the acute coronary
syndromes21 and in general have more extensive
coronary artery disease than do nondiabetics. These differences
may be reflected in the makeup of the target coronary
arterial lesions. For example, Silva and
colleagues22 reported that when subjected to
angioscopy before PTCA, diabetic patients were more likely than
nondiabetic patients to have plaque ulceration and evidence of red or
fibrin-rich thrombus. Thus, it is conceivable that bona fide
differences exist in the coagulation systems of both patient groups and
that the lesions in patients with diabetes may be more likely to be
include fibrin-rich thrombi and thus require a higher dose of thrombin
inhibitor. A higher level of platelet activation
manifest by greater surface expression of GP IIb/IIIa might have led to
lower levels of receptor occupancy in patients treated with the same
dose of abciximab. In the setting of incomplete GP IIb/IIIa receptor
blockade coupled with a greater likelihood of a fibrin-rich thrombus,
there may be a greater requirement for a thrombin inhibitor
to prevent thrombotic complications of PTCA.
Other clinical features of diabetic patients enrolled in EPILOG may
have also contributed to the observed differences. Diabetic patients in
this trial were more likely than nondiabetics to have had a recent
infarction or to have received heparin within the prior week and may
therefore have had diminished levels of antithrombin III resulting, in
a higher heparin requirement. In addition, patient selection bias may
have played an important role. Although the intent of the trial was to
encourage the enrollment of low-risk rather than high-risk patients,
the clinical threshold for referring diabetic patients for PTCA may
have been higher; thus, more acutely ill patients among the diabetics
may have been selected.
The findings concerning target vessel
revascularization are also unexpected. To
understand them better, it is helpful to compare event rates in EPILOG
with those previously reported. In the second NHLBI registry, higher
rates of death and myocardial infarction were evident in diabetic
patients during and after the initial hospitalization. The rates of
revascularization did not begin to diverge until 6
months after the index angioplasty, when the rate of repeated
angioplasty was 13.8% in nondiabetics and 16.7% in diabetics and the
respective rates of coronary artery bypass were 10.4% and
12%. Thus, 29% of diabetics and 24% of nondiabetics had a repeated
procedure by the end of 6 months.3 Within a study
of a novel pharmacological agent, the most appropriate comparator would
be the placebo-treated group. In the first large study of abciximab,
EPIC, the rates of target vessel revascularization
at 6 months were 22% and 18% for diabetic and nondiabetic patients,
respectively, whereas in EPILOG the respective rates were 15.5% and
18.9%. The rate in nondiabetic patients in EPILOG therefore appears to
be lower than in earlier studies of PTCA and more in line with the
concurrent BENESTENT-2 trial in which repeated PTCA rates of 19.5%
were reported in patients treated with standard
angioplasty,23 whereas the rate in diabetics in
EPILOG is even lower. The results of both of these studies suggest that
advances in the performance of PTCA, probably because of better
imaging, better dilation catheters, and provisional stent implantation,
have reduced the complications and recurrence rates after PTCA.
In particular, the rate of target vessel
revascularization in diabetic patients in EPILOG
was considerably lower than those seen previously in diabetics. This
low rate may be a chance finding and may in part explain the failure of
abciximab to further lower the rate of
revascularization in diabetics. It is also possible
that the enhanced early protection afforded by abciximab against the
composite of death and myocardial infarction may have led to a
paradoxical increase in revascularization
procedures by providing a larger pool of survivors with viable
myocardium. Other potential explanations include patient
selection or different methods of ascertainment.
The pathophysiological point of view offers another
potential explanation. Abciximab is able to antagonize the
Study Limitations
Clinical Implications
Guest editor for this article was David O. Williams, MD, Rhode Island Hospital, Providence.
Received June 13, 1997;
revision received December 29, 1997;
accepted January 14, 1998.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Diabetes Mellitus, Glycoprotein IIb/IIIa Blockade, and Heparin
Evidence for a Complex Interaction in a Multicenter Trial
Abstract
Top
Abstract
Introduction
Methods
Results
Discussion
References
Background—After angioplasty, major
complications and ischemic events occur more frequently in
diabetic than nondiabetic patients. To determine whether treatment with
abciximab is effective in reducing these events in diabetics, we
analyzed characteristics and outcomes of diabetic patients
enrolled in a large multicenter study (EPILOG).
Key Words: angioplasty • abciximab • diabetes mellitus • revascularization • platelets
Introduction
Top
Abstract
Introduction
Methods
Results
Discussion
References
Diabetes mellitus is
not only a critical risk factor for coronary artery
disease1 but also an important predictor of
prognosis in patients undergoing percutaneous
transluminal coronary angioplasty (PTCA). Diabetic patients
have been reported to be at increased risk to develop complications of
the procedure during hospitalization and to have higher rates of
recurrence and decreased infarct-free survival after hospital
discharge.2 3 4 In long-term follow-up, diabetic
patients undergoing percutaneous rather than surgical
revascularization had nearly a threefold increase
in late mortality.2
Methods
Top
Abstract
Introduction
Methods
Results
Discussion
References
Details of the main trial have been published
previously.7 Briefly, patients undergoing
elective coronary angioplasty or directional atherectomy were
eligible for enrollment if they did not have a contraindication to
treatment with abciximab and were not undergoing planned stent
placement or rotational atherectomy. All patients received 325 mg of
oral aspirin before the procedure. Patients were randomized to receive
one of three treatments: standard-dose heparin and a placebo for
abciximab, weight-adjusted standard-dose heparin and abciximab, or
weight-adjusted low-dose heparin and abciximab. Abciximab was
administered as a bolus of 0.25 mg/kg followed by an infusion of 0.07
mg · kg-1 ·
h-1 for 12 hours. Patients assigned to
weight-adjusted standard-dose heparin received an initial dose of 100
U/kg. An activated clotting time (ACT) was then determined, and
subsequent doses were given as needed to maintain an ACT >300 seconds.
Patients assigned to receive weight-adjusted low-dose heparin were
given an initial bolus of 70 U/kg. The resultant ACT was recorded,
but further bolus doses were not given unless the ACT was <200
seconds. Treatment assignment was blinded. To keep the study blind, all
heparin doses were administered and ACTs were recorded by an
unblinded observer who was not involved in the management of the
patient or subsequent data recording. All patients had a
12-lead ECG performed on enrollment in the study, at hospital
discharge, at 30 days, and at 6 months. In addition, blood was drawn
for determination of creatine kinase and its MB isoenzymes immediately
after the PTCA was begun and every 8 hours thereafter for the first 24
hours. Myocardial infarctions and urgent
revascularizations were reviewed individually by a
blinded adjudication committee. Six-month status was ascertained by
telephone contact.
The statistical design of the trial has been described
previously.7 Time-to-event analyses used
Kaplan-Meier product limit estimates, reference bounds for
equality,12 Cox proportional-hazards models, and
the log-rank statistic. Multiple regression analyses did not
identify any confounding variables associated with the relationship
of diabetes, abciximab, heparin dosing, and the study end points, so
all presented estimates are unadjusted. Categorical
variables are described as a percentage of nonmissing data.
Continuous variables are presented as mean±SD or as median
and interquartile range.
Results
Top
Abstract
Introduction
Methods
Results
Discussion
References
Baseline Characteristics and In-Hospital Events
Of the 2792 patients enrolled in EPILOG, 638 (23%) were diabetic.
Demographic characteristics of diabetic and nondiabetic patients are
displayed in Table 1
. In general,
diabetic patients tended to be older, shorter, and heavier; more likely
to be female, have three-vessel coronary artery disease, and
have a history of prior CABG, hypertension, or a recent myocardial
infarction; and were less likely to be current smokers than their
nondiabetic counterparts. Among diabetics, baseline clinical
characteristics were evenly distributed among all three treatment
allocations (data not shown). There were no differences in angiographic
lesion morphology of the target lesions in diabetic and nondiabetic
patients (Table 2). Diabetics tended to
receive higher heparin doses than nondiabetics; however, when the
heparin doses were corrected for body weight, the doses were nearly
identical, yielding procedural ACTs that were similar in both groups
(Table 3). Two hundred fourteen diabetics
(23%) and 424 nondiabetics (23%) were discharged on lipid-lowering
agents. Clinical outcomes during hospitalization are shown in Table 4. There were no differences in any
elements of the composite primary outcome between diabetics and
nondiabetics. Insulin-dependent diabetics and those with diabetic
retinopathy did not appear to fare worse than
non–insulin-dependent diabetics (data not shown). The peak creatine
kinase enzyme ratios were also similar between diabetics and
nondiabetics, indicating that the infarctions that did occur were
roughly of similar size. Unplanned or "bailout" stenting was
performed in 12% of nondiabetics and 11% of diabetics.
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Table 1. Baseline Clinical Characteristics by Diabetic Status
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Table 2. Overall Target Lesion Morphology by Diabetic Status
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Table 3. Heparin Dose and Activated Clotting Time
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Table 4. In-Hospital Outcome by Diabetic Status
Beginning the first day after angioplasty, abciximab produced a
marked reduction in the composite rates of death and myocardial
infarction in both diabetic and nondiabetic patients. Events at 30 days
are shown in Table 5. The composite end
point occurred slightly more frequently in diabetics than nondiabetics.
Q-wave myocardial infarction occurred in 0.4% of diabetics receiving
placebo and 0.5% of diabetics receiving abciximab (P=.9)
and in 0.9% and 0.4% (P=.21) in nondiabetics assigned to
placebo and abciximab, respectively. In contrast, abciximab reduced
rates of non–Q-wave infarction from 8.0% to 2.9% in diabetics
(P<.001) and from 7.9% to 3.6% in nondiabetics
(P<.001). In each of these four groups, more than two
thirds of the non–Q-wave infarctions were classified as "large"
(ie, creatinine kinase more than five times the upper limit
of normal). The early effect of abciximab with low-dose heparin,
reflected in the hazard ratio, was nearly identical between diabetics
and nondiabetics. However, diabetics appeared to have a greater
reduction in the hazard than nondiabetics when treated with abciximab
combined with standard-dose heparin. These findings were true of both
the primary end-point cluster and the secondary composite of death or
myocardial infarction.
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Table 5. Thirty-Day Efficacy by Diabetic Status
Death or Myocardial Infarction
By 6 months, the primary composite was more frequent among
diabetic than nondiabetic patients (Fig 1), and there was a trend toward more
frequent occurrence of the composite of death and myocardial infarction
among diabetics (Table 6). At the 6-month
point, the hazard of the composite of death and myocardial infarction
was still reduced by abciximab in both diabetics and nondiabetics (Fig 2A). The rate of Q-wave infarction was
reduced from 2.3% to 1.7% in diabetics (P=.62) and 1.4%
to 1.3% in nondiabetics (P=.77), while non–Q-wave
infarction was reduced from 9.9% to 2.9% (P<.001) and
8.0% to 4.2% (P<.001) in diabetics and nondiabetics,
respectively. Among diabetics receiving abciximab, the composite rate
of death and myocardial infarction tended to be lower in patients
assigned to standard-dose heparin (Fig 2B). Diabetics treated with
abciximab and standard-dose heparin had a greater reduction in the
composite risk of death or myocardial infarction than did nondiabetics
treated with the same regimen.
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Figure 1. A, Kaplan-Meier survival estimates for the
composite of death, myocardial infarction (MI), or
revascularization according to diabetic status. In
this and subsequent figures, the shaded area represents the
reference bounds for equivalence (P>.05) between the
two groups. B, Kaplan-Meier survival estimates for the composite end
point according to diabetic status and treatment assignment among
nondiabetics. The curves diverge sharply after 1 month, whereas among
diabetics, the curves do not change. DM indicates diabetes
mellitus.
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[in a new window]
Table 6. Six-Month Efficacy by Diabetic Status
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Figure 2. A, Kaplan-Meier survival estimates for death or
myocardial infarction (MI) among diabetic patients and nondiabetic
patients in the placebo and combined abciximab groups. Abciximab
reduced the event rates in diabetics to levels equivalent to those in
nondiabetics. B, Kaplan-Meier survival estimates for death or
myocardial infarction among diabetic patients assigned to abciximab,
according to heparin dose assignment. DM indicates diabetes mellitus;
Std, standard.
Repeated percutaneous
revascularization was performed in 368 patients;
87% of these procedures were performed on the target vessel in
nondiabetics and 87% in diabetics. Among diabetic patients, 35% of
target vessel revascularizations were
coronary artery bypass operations regardless of the treatment
assignment, whereas among nondiabetics, the respective proportions were
35% in the placebo group, 29% in the group receiving abciximab and
low-dose heparin, and 28% among patients assigned to abciximab and
high-dose heparin. Target vessel revascularization
was more common among diabetics than nondiabetics in all treatment
groups except those assigned to placebo. 
). In contradistinction, in
nondiabetic patients, the frequency of target vessel
revascularization was reduced by abciximab,
especially in combination with low-dose heparin. Among diabetic
patients, there was a relatively steep increase in the frequency of
target vessel revascularization between 2 and 4
months after the index procedure. This rise was due primarily to an
increase in repeated PTCA and appeared particularly dramatic in
diabetic patients treated with abciximab but was less pronounced in
diabetic patients assigned to placebo (Fig 3). There was a trend toward more
frequent target vessel revascularization in
diabetic patients treated with abciximab and low-dose heparin compared
with diabetics receiving abciximab and standard-dose heparin (23.5%
versus 19.1%, P=.29; Fig 4).
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[in a new window]
Figure 3. A, Kaplan-Meier survival estimates for target
vessel revascularization in placebo-treated
patients according to diabetic status. In this group, the rate of
revascularization was not higher among diabetics.
B, Kaplan-Meier survival estimates for target vessel
revascularization in abciximab-treated patients
according to diabetic status. The rate of
revascularization among diabetics was higher than
in nondiabetics.
View larger version (35K):
[in a new window]
Figure 4. Kaplan-Meier survival estimates of target vessel
revascularization in diabetic patients receiving
abciximab according to heparin treatment assignment. Std indicates
standard.
Discussion
Top
Abstract
Introduction
Methods
Results
Discussion
References
As the population ages, it is likely that the number of diabetic
patients undergoing PTCA will increase. In the first NHLBI-sponsored
PTCA registry, 9% of patients had diabetes
mellitus13; in the second registry, this
proportion had risen to 12%,3 and in the Bypass
Angioplasty Revascularization Investigation, 19%
of patients were diabetic.2 In contrast, 23% of
patients in EPILOG had diabetes. The principal findings of the
present analysis are threefold. First, we have determined
that with current angioplasty techniques, the in-hospital event rates
for diabetic patients are comparable to those for nondiabetic patients,
whereas longer-term rates of death, myocardial infarction, or
revascularization are increased in diabetic
patients. Second, and perhaps most important, we found that treatment
of diabetic patients with a bolus and infusion of abciximab produced a
reduction in the risk of death or myocardial infarction that began soon
after angioplasty, was maintained at 6 months, and was at least as
great as that seen in nondiabetic patients. Although the composite rate
of death and myocardial infarction was greater in diabetics than
nondiabetics, treatment with abciximab reduced these events to levels
comparable to the rates in nondiabetics. The third important finding of
this study is the observation that diabetic patients treated with
abciximab may have a greater heparin requirement than their nondiabetic
counterparts, as reflected in rates of death or myocardial infarction
at both 30 days and 6 months and in target vessel
revascularization at 6 months. 
Vß3
(vitronectin) receptor on platelets and smooth muscle
cells in addition to its ability to inhibit ligand binding to the
platelet IIß3 (GP
IIb/IIIa) receptor. The former receptor modulates phenotypic
alterations and migration in smooth muscle cells and has been theorized
to permit the contribution of smooth muscle cells to the process of
restenosis after angioplasty.24 25 The
plasma half-life of abciximab is extremely
brief26 since it is believed to be adsorbed
rapidly onto the platelet surface. Conceivably, then, a higher
density of GP IIb/IIIa receptor density expressed on the surface of
platelets in diabetic patients might leave less abciximab available
to binding to smooth muscle vitronectin receptors.
The principal limitation of this analysis lies in its
size. Although diabetic patients made up 23% of patients enrolled in
EPILOG, comparison between the event rates in three treatment groups is
still limited by the relatively wide confidence limits imposed by
dividing patients into multiple groups. In addition, ascertainment of
the duration of diabetes and adequacy of diabetic control would have
been helpful but was not possible. Finally, the current
analysis was not prespecified at the time of protocol design
and thus, in the absence of truly dramatic differences between groups,
should be viewed as resulting in a variety of new hypotheses to be
tested rather than in novel therapeutic recommendations.
The higher long-term event rates in diabetic patients mandate an
increased level of vigilance after coronary angioplasty, even
when the procedure is successful. Although the more common current use
of intracoronary stents may contribute to lowering
revascularization rates among diabetics, more
frequent follow-up and perhaps exercise testing nonetheless appear to
be indicated. The evidence presented in this analysis
strongly supports the use of abciximab for the prevention of
ischemic events in both diabetic and nondiabetic patients,
particularly with respect to the prevention of death and myocardial
infarction. Nevertheless, despite the low event rates in the placebo
group, the difference in outcomes, particularly target vessel
revascularization with regard to heparin dosing,
should raise a note of caution concerning heparin dosing in diabetics.
The marginally higher rate of revascularization in
patients receiving low-dose heparin, combined with the lower composite
rate of death and myocardial infarction in patients assigned to
standard dose heparin, led to a 6-month composite event rate that was
statistically lower in diabetic patients assigned to abciximab with
standard-dose heparin compared with abciximab with low-dose heparin. A
definitive recommendation concerning heparin dosing in diabetics
receiving abciximab will have to await confirmation from a second trial
of abciximab in diabetic patients and longer-term follow-up in the
current patient population.
Footnotes
Reprint requests to Neal S. Kleiman, MD, 6565 Fannin, MS F-1090, Houston, TX 77030.
References
Top
Abstract
Introduction
Methods
Results
Discussion
References
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K.-H. Mak and D. P. Faxon Clinical studies on coronary revascularization in patients with type 2 diabetes Eur. Heart J., June 2, 2003; 24(12): 1087 - 1103. [Abstract] [Full Text] [PDF]
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A. M. Lincoff Important Triad in Cardiovascular Medicine: Diabetes, Coronary Intervention, and Platelet Glycoprotein IIb/IIIa Receptor Blockade Circulation, March 25, 2003; 107(11): 1556 - 1559. [Full Text] [PDF]
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L F Hsu, K H Mak, K W Lau, L L Sim, C Chan, T H Koh, S C Chuah, R Kam, Z P Ding, W S Teo, et al. Clinical outcomes of patients with diabetes mellitus and acute myocardial infarction treated with primary angioplasty or fibrinolysis Heart, September 1, 2002; 88(3): 260 - 265. [Abstract] [Full Text] [PDF]
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E. Van Belle, M. Perie, D. Braune, A. Chmait, T. Meurice, K. Abolmaali, E. P. McFadden, C. Bauters, J.-M. Lablanche, and M. E. Bertrand effects of coronary stenting on vessel patency and long-term clinical outcome after percutaneous coronary revascularization in diabetic patients J. Am. Coll. Cardiol., August 7, 2002; 40(3): 410 - 417. [Abstract] [Full Text] [PDF]
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V. Mathew and D. R. Holmes Outcomes in diabetics undergoing revascularization: The long and the short of it J. Am. Coll. Cardiol., August 7, 2002; 40(3): 424 - 427. [Full Text] [PDF]
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A Kapur and I S Malik Is surgery still the preferred option for coronary revascularisation in diabetics with multivessel coronary disease? Heart, May 1, 2002; 87(5): 407 - 409. [Full Text] [PDF]
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 J. C. O'Shea, C. E. Buller, W. J. Cantor, A. B. Chandler, E. A. Cohen, D. J. Cohen, I. C. Gilchrist, N. S. Kleiman, M. Labinaz, M. Madan, et al. Long-term Efficacy of Platelet Glycoprotein IIb/IIIa Integrin Blockade With Eptifibatide in Coronary Stent Intervention JAMA, February 6, 2002; 287(5): 618 - 621. [Abstract] [Full Text] [PDF]
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D. P. Chew, D. L. Bhatt, A. M. Lincoff, D. J. Moliterno, S. J. Brener, K. E. Wolski, and E. J. Topol Defining the Optimal Activated Clotting Time During Percutaneous Coronary Intervention : Aggregate Results From 6 Randomized, Controlled Trials Circulation, February 20, 2001; 103(7): 961 - 966. [Abstract] [Full Text] [PDF]
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P. Theroux, J. Alexander Jr, C. Pharand, E. Barr, S. Snapinn, A. F. Ghannam, and F. L. Sax Glycoprotein IIb/IIIa Receptor Blockade Improves Outcomes in Diabetic Patients Presenting With Unstable Angina/Non-ST-Elevation Myocardial Infarction : Results From the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) Study Circulation, November 14, 2000; 102(20): 2466 - 2472. [Abstract] [Full Text] [PDF]
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E. Braunwald, E. M. Antman, J. W. Beasley, R. M. Califf, M. D. Cheitlin, J. S. Hochman, R. H. Jones, D. Kereiakes, J. Kupersmith, T. N. Levin, et al. ACC/AHA guidelines for the management of patients with unstable angina and non-st-segment elevation myocardial infarction: A report of the american college of cardiology/ american heart association task force on practice guidelines (committee on the management of patients with unstable angina) J. Am. Coll. Cardiol., September 1, 2000; 36(3): 970 - 1062. [Full Text] [PDF]
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S. R. Steinhubl, K. Kottke-Marchant, D. J. Moliterno, M. L. Rosenthal, N. K. Godfrey, B. S. Coller, E. J. Topol, and A. M. Lincoff Attainment and Maintenance of Platelet Inhibition Through Standard Dosing of Abciximab in Diabetic and Nondiabetic Patients Undergoing Percutaneous Coronary Intervention Circulation, November 9, 1999; 100(19): 1977 - 1982. [Abstract] [Full Text] [PDF]
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E. Van Belle, K. Abolmaali, C. Bauters, E. P. McFadden, J.-M. Lablanche, and M. E. Bertrand Restenosis, late vessel occlusion and left ventricular function six months after balloon angioplasty in diabetic patients J. Am. Coll. Cardiol., August 1, 1999; 34(2): 476 - 485. [Abstract] [Full Text] [PDF]
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