(Circulation. 1999;99:1951-1958.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Sustained Suppression of Ischemic Complications of Coronary Intervention by Platelet GP IIb/IIIa Blockade With Abciximab
One-Year Outcome in the EPILOG Trial
From the Departments of Cardiology or Biostatistics and Epidemiology, The Cleveland Clinic Foundation, Cleveland, Ohio (A.M.L., J.E.B., C.B., E.J.T.); the Department of Medicine, Duke Clinical Research Institute, Duke University, Durham, NC (J.E.T., R.M.C.); Christ Hospital, Cincinnati, Ohio (D.J.K.); Moses Cone Memorial Hospital, Greensboro, NC (T.A.K.); William Beaumont Hospital, Royal Oak, Mich (G.C.T.); Baylor College of Medicine and the Methodist Hospital, Houston, Tex (N.S.K.); and Centocor, Malvern, Pa (C.F.C., K.M.A., H.F.W.).
Correspondence to A. Michael Lincoff, MD, Department of Cardiology, Desk F25, The Cleveland Clinic Foundation, Cleveland, OH 44195.
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background—Blockade of the platelet glycoprotein IIb/IIIa receptor with the monoclonal antibody fragment abciximab was shown in a placebo-controlled randomized trial to reduce the incidence of acute ischemic complications within 30 days among a broad spectrum of patients undergoing percutaneous coronary revascularization. The durability of clinical benefit in this setting has not been established.
Methods and Results—A total of 2792 patients enrolled in the Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade (EPILOG) trial were followed with maintenance of double-blinding for 1 year. Patients had been assigned at the time of their index coronary interventional procedure to receive placebo with standard-dose, weight-adjusted heparin (100 U/kg initial bolus), abciximab with standard-dose, weight-adjusted heparin, or abciximab with low-dose, weight-adjusted heparin (70 U/kg initial bolus). The primary outcome was the composite of death, myocardial infarction, or urgent repeat revascularization by 30 days; this composite end point and its individual components were also assessed at 6 months and 1 year. Rates of any repeat revascularization (urgent or elective), target vessel revascularization, and a composite of death, myocardial infarction, or any repeat revascularization were also reported. Follow-up at 1 year was 99% complete for survival status and 97% complete for other end points. By 1 year, the incidence of the primary composite end point was 16.1% in the placebo group, 9.6% in the abciximab with low-dose heparin group (P<0.001), and 9.5% in the abciximab with standard-dose heparin group (P<0.001). Each of the components of this composite end point was reduced to a similar extent. Nonurgent or target vessel repeat revascularization rates were not significantly decreased by abciximab therapy. Mortality rates over 1 year increased with increasing levels of periprocedural creatine kinase MB fraction elevation.
Conclusions—Acute reductions in ischemic events after percutaneous coronary intervention by abciximab are sustained over follow-up to at least 1 year. Early periprocedural myocardial infarctions suppressed by this therapy are associated with long-term mortality rates.
Key Words: angioplasty • glycoproteins • receptors • revascularization • thrombosis • platelets
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Blockade of the platelet surface membrane glycoprotein IIb/IIIa complex with abciximab (c7E3 Fab, ReoPro, Centocor, Malvern, Pa), a human-murine chimeric antibody Fab fragment, has been demonstrated in 4 large-scale placebo-controlled trials to markedly reduce the incidence of acute ischemic complications in the setting of percutaneous coronary revascularization.1 2 3 4 In the EPILOG (Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade) trial, the 30-day composite end point of death, myocardial infarction, or emergency repeat revascularization among patients undergoing elective or urgent coronary intervention was reduced by 56% relative to placebo by a bolus and 12-hour infusion of abciximab.2 By 6 months of follow-up, the reduction in acute ischemic end points appeared to have been maintained, although no differences were present among the treatment groups with respect to the need for elective target vessel revascularization procedures.
To determine whether the marked acute benefit of abciximab therapy observed in EPILOG was preserved over the long term, double-blind status was maintained and 1-year follow-up was performed among patients enrolled in the trial. Moreover, the relation between suppression of periprocedural myocardial infarction by GP IIb/IIIa blockade and late cardiovascular events was assessed.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Patient Population
The details of the EPILOG trial have been previously described.2 In brief, 2792 patients undergoing elective or urgent percutaneous coronary revascularization were enrolled at 69 investigational sites in the United States and Canada. Patients with acute myocardial infarction or unstable angina with associated ECG changes during the previous 24 hours were excluded. Other exclusion criteria included planned stent implantation or rotational atherectomy, percutaneous coronary intervention performed within the prior 3 months, or conditions that would be associated with excessive bleeding risk.2 The protocol was approved by the Institutional Review Board at each clinical site, and patients gave informed consent for participation in the trial and follow-up at 1 year.
Study Protocol
All patients were treated with oral aspirin at least 2 hours
before the index procedure and for at least 6 months thereafter.
Randomization was done by means of a central telephone hotline in a
double-blind fashion to 1 of 3 treatment groups: placebo with
standard-dose, weight-adjusted heparin; abciximab with standard-dose,
weight-adjusted heparin; or abciximab with low-dose, weight-adjusted
heparin. Abciximab was administered as a 0.25 mg/kg bolus 10 to 60
minutes before balloon inflation or device activation, followed by a
0.125 µg/kg per minute (maximum 10 µg/min) infusion for 12 hours.
The standard-dose weight-adjusted heparin regimen consisted of an
initial heparin bolus before the interventional procedure of 100 U/kg
(maximum 10 000 U), with additional weight-adjusted boluses according
to an algorithm intended to achieve and maintain an activated
clotting time 
300 seconds over the duration of the procedure. The
low-dose weight-adjusted heparin group received an initial bolus of 70
U/kg (maximum 7000 U), with additional boluses as necessary to achieve
and maintain an activated clotting time 200 seconds. To
preserve blinding of all investigators and personnel involved in
patient management, a "heparin coordinator" at each clinical site
performed all activated clotting time measurements and directed
heparin administration. Postprocedural use of heparin was discouraged,
and vascular sheaths were to be removed within 2 to 6 hours (during
abciximab infusion). Specific guidelines or algorithms were provided
for management of vascular access sites, uncontrolled bleeding, urgent
coronary artery bypass surgery, thrombocytopenia, or blood
transfusions. Stents were used in 13% of patients to maintain patency
after manifest or threatened abrupt closure.
Study End Points
The primary efficacy end point was a composite of death from any
cause, myocardial infarction, or severe myocardial ischemia
requiring urgent surgical or repeat percutaneous
coronary revascularization within 30 days
of randomization. A secondary end point was the composite of death,
myocardial infarction, or any repeat percutaneous or
surgical revascularization within 6 months of
randomization. Both of these end points, as well as their individual
components, were assessed at 1-year follow-up. End point
classifications at all time points were made by a clinical events
committee, which was blinded to study group allocation.
An end point in-hospital myocardial infarction was defined by 1 of 2
criteria2 : (1) new significant Q waves in 2 contiguous
ECG leads or (2) elevation in creatine kinase (CK) or its MB isoenzyme
3 times the upper limit of local normal, representing an
increase of 50% over the previous nadir level, in 2 samples
collected at different times. After hospital discharge, myocardial
infarction was defined by the development of new significant Q waves or
MB isoenzyme elevation to >2 times the upper limit of normal. The MB
isoenzyme value was used unless unavailable, in which case total CK was
used.
Data Collection and Statistical Analysis
All patients were contacted by the study sites by telephone or
written questionnaire between 366 and 428 days after randomization for
assessment of 1-year outcomes. Survival status and the occurrence of
cardiac events, including myocardial infarction,
revascularization, cardiac
catheterization, and rehospitalization were
ascertained. Relevant hospital records were obtained for source
documentation of any rehospitalization, outpatient
catheterization, or outpatient
revascularization procedure; death certificates and
autopsy reports, if available, were obtained for any patients who died
during the follow-up period. Data were collected on case report forms
by study coordinators at the clinical sites. Investigators and study
coordinators remained blinded to treatment allocations of individual
patients until 1-year follow-up, database entry, and clinical events
committee review were finalized.
Differences among patients with regard to efficacy were examined according to an intention-to-treat analysis. To be considered complete, the 1-year follow-up was required to have occurred at least 335 days after randomization. Survival analysis methods were used at 1 year in the same fashion as for the 30-day and 6-month analyses.2 Pairwise comparisons between the 2 abciximab treatments and the placebo treatment were made with the use of the log-rank test, with event rates calculated by the Kaplan-Meier method. Two-sided probability values are reported. Hazard ratios and 95% CIs were calculated to assess consistency of treatment effect across subgroups.
For the purpose of assessing correlation of periprocedural or early myocardial infarction with long-term clinical outcome, late clinical event rates (death, myocardial reinfarction, or repeat revascularization) were calculated by the Kaplan-Meier method and analyzed as a function of the ratio of peak periprocedural CK-MB over the upper limit of normal. Two separate analyses were performed: the first correlated periprocedural CK-MB elevations within 24 hours of randomization with subsequent end point events occurring between 24 hours and 1 year (excluding events occurring within the first 24 hours), and the second correlated early CK-MB elevations within the primary efficacy end point period of 30 days of randomization with end point events occurring between 30 days and 1 year (excluding events within the first 30 days). Results are expressed as risk ratios and 95% CIs.
Primary 30-Day Efficacy Analysis and Completeness of
Follow-Up
Enrollment took place between February 28 and December 14, 1995.
The trial had been terminated early on the recommendation of the Data
and Safety Monitoring Committee, after the first interim
analysis on December 11, 1995, demonstrated an unexpectedly
strong 30-day treatment effect among the first 1500 patients. The
results of the primary efficacy end point analysis at 30 days
have been previously reported in detail.2 In brief, the
incidence of the composite end point of death, myocardial infarction,
or urgent revascularization for severe myocardial
ischemia at 30 days was 11.7% in the placebo group, 5.2% in
the abciximab with low-dose heparin group (P<0.0001), and
5.4% in the abciximab with standard-dose heparin group
(P<0.0001).
The 1-year follow-up database was locked in April 1997. Of the 2792 patients enrolled, survival status at 335 days was unknown in 27 patients (1.0%), for whom the median follow-up was 207 days. For assessment of events other than death, a total of 75 (2.7%) patients had fewer than 335 days of follow-up with no death, myocardial infarction, or repeat revascularization reported before their last follow-up. Rates of completeness of follow-up were similar among the 3 treatment groups.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Efficacy Analysis at 1 Year
The incidence of the primary composite end point of death, myocardial infarction, or urgent revascularization (the composite used as the primary efficacy end point at 30 days) was 16.1% in the placebo group, 9.6% in the abciximab with low-dose heparin group (hazard ratio 0.56; 95% CI, 0.43 to 0.73, P<0.001), and 9.5% in the abciximab with standard-dose heparin group (hazard ratio 0.57; 95% CI, 0.43 to 0.74, P<0.001) by 1-year follow-up (Figure 1
). Each of the components of this
composite end point was reduced to a similar extent (Table 1). The treatment effect of the
combined abciximab groups relative to placebo with regard to this end
point was homogeneous across patient groups defined by age,
sex, body weight, or indication for
revascularization (Figure 2).
|
|
|
A composite end point of death, myocardial infarction, or any
revascularization (urgent or elective) was also
assessed. By 1 year, this end point had occurred in 32.4% of patients
randomized to placebo, 29.4% of patients randomized to abciximab with
low-dose heparin (P=0.093), and 29.2% of patients
randomized to abciximab with standard-dose heparin
(P=0.077). The types and circumstances of
revascularization procedures by 1 year are detailed
in Table 2. Overall
revascularization rates were not different among
the 3 treatment groups; a significant treatment effect of abciximab was
observed only for urgent revascularization.
|
Event rates for the primary composite and selected individual end
points at 30 days, 6 months, and 1 year are illustrated in Table 3. In the placebo group, the timing of
acute ischemic complications was clustered early in the course
after coronary intervention: 72% of the primary composite end
point events had accrued during the first 30 days (54% within 24
hours), with an additional 19% occurring between 30 days and 6 months
and 9% between 6 months and 1 year. Therapy with abciximab resulted in
a marked reduction in the risk of complications during the first 30-day
period, after which time incremental event rates were essentially equal
among the 3 treatment arms. Thus for the primary composite efficacy end
point, the treatment effect achieved by abciximab early (at 30 days)
was maintained without attenuation throughout the 1-year follow-up
period (Figures 1
and 3): the
absolute reduction in events (number of events prevented per 100
patients treated) in the combined abciximab groups versus placebo was
6.40 at 30 days, 6.35 at 6 months, and 6.55 at 1 year. Similarly, the
absolute treatment benefit for the individual components of this
primary composite end point was preserved to 1 year (Figure 3),
although there was a trend toward increased abciximab treatment effect
in preventing death over long-term follow-up (events prevented per 100
patients treated=0.45 at 30 days and 0.85 at 1 year). In contrast,
rates of repeat target vessel revascularization
converged somewhat after 30 days (Figure 3 and Table 3),
with no incremental benefit out to 6 months and 1 year, indicating that
abciximab had no effect on the incidence of "clinical
restenosis."
|
|
Periprocedural or Early CK-MB Elevation and 1-Year Outcome
The relation between early myocardial infarction and long-term
mortality rates, reinfarction, and repeat
revascularization was evaluated as a function of
the magnitude of CK-MB elevation above the upper limit of normal. Table 4 and Figures 4A and 5A
correlate periprocedural myocardial infarctions occurring within the
first 24 hours after randomization with subsequent events after 24
hours; Table 5 and Figures 4B and 5B correlate early myocardial infarctions occurring within 30 days
after randomization with subsequent ischemic events after 30
days. Of the 533 patients experiencing CK-MB elevations within the
first 30 days and surviving beyond 30 days, 478 (89.7%) had such
elevations occur within the periprocedural 24-hour period.
|
|
|
CK-MB<3, 3
|
The risk of death by 1 year was significantly increased among patients
who experienced CK-MB elevation during either the periprocedural (first
24 hours, Figures 4A and 5A) or early follow-up (first 30 days,
Figures 4B and 5B) period. Although the magnitude of increased
risk of death was proportional to the extent of CK-MB elevation above
the upper limit of normal, there was a significant hazard associated
even with mild rises in CK-MB. The largest periprocedural or early
myocardial infarctions (CK-MB 10 times control) were predictive of an
8-fold increased risk in death after the first 24 hours and an
approximately 3-fold increased risk of death after the first 30
days.
Periprocedural or early CK-MB elevation was also associated with the
risk of subsequent myocardial reinfarction (Tables 4 and 5),
although the hazard ratios tended to be lower than those for late death
and the gradient of reinfarction risk with increasing periprocedural
CK-MB levels was less distinct. There was no significant association
between periprocedural or early CK-MB elevations and subsequent repeat
revascularization procedures; a nonsignificant
trend was observed, however, toward fewer
revascularization procedures with increasing early
CK-MB levels (Table 5).
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The acute efficacy of platelet GP IIb/IIIa receptor blockade with abciximab among patients undergoing percutaneous coronary revascularization has been unequivocally demonstrated among almost 9000 patients.1 2 3 4 In EPILOG, rates of important ischemic end points among a broad spectrum of patients undergoing intervention were reduced by >50% in the first 30 days after the procedure.2 The current analysis demonstrates that the acute efficacy of this agent is durable over the long term. An absolute treatment effect of 6.4 acute ischemic events (death, myocardial infarction, or urgent repeat revascularization) prevented per 100 patients treated with abciximab was observed early in their clinical course and was maintained without attenuation over 1-year follow-up. All patient subgroups appeared to derive similar long-term benefit. Nonurgent revascularization procedures, however, were not prevented by abciximab, and there were no differences by 1 year among the treatment groups with regard to the overall need for surgical or repeat percutaneous revascularization procedures.
The mechanism by which a relatively brief period of intense GP IIb/IIIa receptor blockade by abciximab leads to sustained clinical benefit can be inferred from the time course of ischemic complications in EPILOG. Ischemic events tended to take place early after the interventional procedure, with nearly three quarters of the events that would ultimately occur over 1 year in the placebo group clustered within the first 30 days. During this early postprocedural time period, abciximab exerted its protective effect, reducing the incidence of ischemic end points by 56%. After 30 days, ischemic events occurred relatively infrequently and at rates that were essentially equivalent in the placebo and abciximab treatment groups; incremental benefit of abciximab in preventing these later events or elective target vessel revascularization (the clinical sequelae of restenosis) was not observed. This lack of influence of abciximab on complications after the acute phase is not surprising; despite the high avidity of abciximab binding to the GP IIb/IIIa receptor, with receptor occupancy observed by flow cytometry for over 15 days,5 inhibition of platelet aggregation by this agent is measurable for only 72 to 96 hours after the end of infusion.5 6 Thus clinical benefit is derived from abciximab therapy because the period of maximal risk is relatively short after coronary intervention, during which time this agent exerts a potent inhibitory effect on coronary platelet thrombus formation. Long-term durability of the clinical benefit suggests that the injured coronary plaque is largely passivated after this early period, reducing the stimulus for new thrombus formation and a rebound or "catch-up" phenomenon of late ischemic events. Nevertheless, it is notable that event rates nearly doubled between 1 month and 1 year in the abciximab therapy groups (composite end point increasing from 5.3% to 9.6%), demonstrating some degree of continued vulnerability of the coronary plaque even after the periprocedural period of intense platelet inhibition; this finding suggests a potential role for chronic therapy with oral GP IIb/IIIa receptor blockers to suppress late adverse events in these patients.
The long-term preservation of clinical benefit in EPILOG is concordant with the sustained reduction of ischemic events over 3 years in the first trial of abciximab during coronary intervention, EPIC (Evaluation of c7E3 for Prevention of Ischemic Complications).7 In EPIC, therapy with abciximab was also associated with a reduction in the need for target vessel revascularization procedures ("clinical restenosis"), a finding that was not reproduced in EPILOG. Reasons for the disparate effects of abciximab on nonurgent revascularization rates in the EPIC and EPILOG trials are unknown. It may be relevant, however, that placebo group rates of late repeat revascularization were considerably lower in EPILOG than in EPIC (19.4% vs 29.4%, respectively, at 6 months and 26.0% vs 32.6%, respectively, at 1 year), perhaps related to underlying differences in patient populations or improvements in interventional practice or postprocedural care. This improvement in baseline outcome in EPILOG relative to EPIC may have diminished the potential for abciximab to further prevent late revascularization events among patients in the EPILOG trial.
Notably, death was the only clinical end point in EPILOG for which the
treatment effect of abciximab trended toward incremental improvement
over 1-year follow-up. The mortality rate difference between placebo
and abciximab groups nearly doubled between 30 days and 1 year, from
0.45% to 0.85% (Figure 3); this change in the magnitude of the
treatment effect of abciximab did not reach statistical significance,
perhaps because of the low frequency of death over the relatively short
period of follow-up in this population of patients undergoing
coronary intervention. The apparent augmentation in mortality
benefit over the long term in EPILOG is consistent with that
observed in the 3-year follow-up of the EPIC trial7 :
although death rates in EPIC were identical at 30 days in the placebo
and abciximab bolus and infusion groups, an absolute mortality rate
difference of 1.8% was present at 3 years. When the mortality
rates among treated patients at 1 year in EPILOG are pooled with those
at 3 years in EPIC, the hazard ratio for death in the patients
randomized to abciximab compared with placebo is 0.73
(P=0.049).
Given that any antiplatelet effect of the 12-hour periprocedural abciximab infusion persists for no longer than 2 to 3 weeks, the apparent increasing mortality benefit with this agent would not be expected to be due to a direct effect of abciximab on the vascular wall during the year after coronary intervention. Instead, it might be postulated that late mortality rate reduction is a downstream consequence of suppression of early ischemic events. The findings of this analysis support that hypothesis. The most frequent major ischemic complication in the first 30 days after revascularization in EPILOG was myocardial infarction, prospectively classified as Q-wave, large non–Q-wave (CK-MB >5 times the control value), or small non–Q-wave (CK-MB=3 to 5 times control). Treatment with abciximab markedly reduced the incidence of all myocardial infarctions by 30 days, with the predominant effect (in terms of absolute number of events prevented) on the large infarctions (Q-wave from 0.8% to 0.45%, large non–Q-wave from 5.6% to 2.3%, and small non–Q-wave from 1.9% to 1.1%). The 1-year analysis presented here demonstrates that the occurrence of periprocedural myocardial infarction significantly increased the risk for later death and that the magnitude of increased risk was proportional to the degree of early CK-MB enzyme elevation. Peak CK-MB levels that qualified as large non–Q-wave infarctions (CK-MB >5 times control), the predominant event inhibited by abciximab therapy in EPILOG, were associated with a 5-fold increase in the risk of death after the first 24 hours and a nearly 3-fold increase in late death after 30 days. Importantly, however, no safe threshold of enzyme elevation was apparent, with adverse late outcome observed even among patients with myocardial necrosis producing levels of CK-MB just over normal values.
The clinical importance of periprocedural non–Q-wave myocardial infarctions after percutaneous coronary revascularization has been controversial. Early small reports with limited or no long-term follow-up suggested that these events were not associated with clinical sequelae.8 Subsequently, however, virtually every study that has examined the impact of periprocedural enzyme release over an adequate follow-up period has demonstrated that patients who have myocardial infarction during or after coronary intervention are at significantly greater risk for late cardiac death than those who do not.7 9 10 11 12 13 14 Some studies have suggested that late consequences of periprocedural CK elevation are not fully manifest until after 1 year.7 9 10 12 In the 3-year follow-up report of the EPIC trial, for example, an association between periprocedural myocardial infarction and subsequent death was clearly observed, but survival curves for patients treated with placebo or abciximab did not begin to diverge until after the first year.7 The apparent divergence of mortality rates among treatment groups in EPILOG within the first year may reflect the fact that infarctions were suppressed to a greater extent in EPILOG than in EPIC (57% vs 40% relative risk reductions, respectively). Taken together, the findings over long-term follow-up of patients in the EPIC and EPILOG trials provide compelling evidence that CK-MB enzyme release after coronary intervention is a clinically relevant event and suggest that prevention of periprocedural myocardial necrosis may be linked to long-term reduction in cardiac mortality rates.
The association between early CK-MB elevations and late ischemic events other than death is less clear. In EPILOG, only an inconsistent trend was observed toward a greater risk of reinfarction with increasing levels of periprocedural CK-MB, a finding that suggests that the mechanism of late death in patients with periprocedural infarction is not mediated by recurrent infarction. An interesting inverse relation was noted between the occurrence and severity of early CK-MB elevations and subsequent revascularization procedures, however, in that patients with periprocedural infarction less frequently underwent repeat revascularization. It is probable that patients with CK-MB elevations during their index procedure had less viable myocardium in the distribution of their treated vessels, were therefore less likely to develop signs or symptoms of recurrent ischemia if restenosis occurred, and were thus less frequently treated by repeat revascularization. This type of reverse interaction between early ischemic events and late revascularization procedures must be considered in the evaluation of new therapies for ischemic heart disease, as interventions such as GP IIb/IIIa blockade that diminish the likelihood of early myocardial infarction may appear to increase the late risk of "restenosis," whereas in fact only increasing the clinical perception of restenosis and the impetus for treatment.
Conclusions
Blockade of the platelet GP IIb/IIIa receptor with abciximab
during urgent or elective coronary intervention in the EPILOG
trial markedly diminished the risk of early ischemic
complications, with sustained suppression of these events over at least
1-year follow-up. Incremental treatment effect in terms of reduction in
the need for elective repeat revascularization
procedures was not observed. Early clinical benefit imparted by this
agent may be augmented over the long term, as the periprocedural
myocardial infarctions that are prevented by therapy with abciximab are
clearly correlated with subsequent late death.
|
Acknowledgments |
|---|
This study was supported by Centocor, Inc (Malvern, Pa), and Eli Lilly and Co (Indianapolis, Ind).
|
Footnotes |
|---|
1 A complete list of the principal investigators and study coordinators of the EPILOG (Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade) Study Group can be found in N Engl J Med 1997;336:1689–1696.
Received August 6, 1998; revision received December 30, 1998; accepted January 15, 1999.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. EPIC Investigators. Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. N Engl J Med. 1994;330:956–961.
2.
EPILOG Investigators. Platelet
glycoprotein IIb/IIIa blockade with abciximab with low-dose
heparin during percutaneous coronary
revascularization. N Engl J
Med. 1997;336:1689–1696.
3. CAPTURE Investigators. Randomised placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE Study. Lancet. 1997;349:1429–1435.[Medline] [Order article via Infotrieve]
4. EPISTENT Investigators. Randomised placebo-controlled and balloon-angioplasty-controlled trial to assess safety of coronary stenting with use of platelet glycoprotein IIb/IIIa blockade. Lancet. 1998;352:87–92.[Medline] [Order article via Infotrieve]
5.
Mascelli MA, Lance ET, Damaraju L, Wagner CL, Weisman
HF, Jordan RE. Pharmacodynamic profile of short-term abciximab
treatment demonstrates prolonged platelet inhibition with gradual
recovery from GP IIb/IIIa receptor blockade. Circulation. 1998;97:1680–1688.
6.
Tcheng JE, Ellis SG, George BS, Kereiakes DJ, Kleiman
NS, Talley JD, Wang AL, Weisman HF, Califf RM, Topol EJ.
Pharmacodynamics of chimeric glycoprotein IIb/IIIa integrin
antiplatelet antibody Fab 7E3 in high-risk coronary
angioplasty. Circulation. 1994;90:1757–1764.
7.
Topol EJ, Ferguson JJ, Weisman HF, Tcheng JE, Ellis
SG, Kleiman NS, Ivanhoe RJ, Wang AL, Miller DP, Anderson KM, Califf RM,
for the EPIC Investigator Group. Long-term protection from myocardial
ischemic events in a randomized trial of brief integrin
ß3 blockade with percutaneous coronary
intervention. JAMA. 1997;278:479–484.
8. Klein LW, Kramer BL, Howard E, Lesch M. Incidence and clinical significance of transient creatine kinase elevations and the diagnosis of non-Q wave myocardial infarction associated with coronary angioplasty. J Am Coll Cardiol. 1991;17:621–626.[Abstract]
9.
Abdelmeguid AE, Topol EJ, Whitlow PL, Sapp SK, Ellis
SG. Significance of mild transient release of creatine kinase-MB
fraction after percutaneous coronary
intervention. Circulation. 1996;94:1528–1536.
10. Kugelmass AD, Cohen CJ, Moscucci M, Piana RN, Senerchia C, Kuntz RE, Baim DS. Elevation in creatine kinase myocardial isoform following otherwise successful directional coronary atherectomy and stenting. Am J Cardiol. 1994;74:748–754.[Medline] [Order article via Infotrieve]
11. Harrington RA, Lincoff AM, Califf RM, Holmes DR, Berdan LG, O'Hanesian MA, Keeler GP, Garratt KN, Ohman EM, Mark DB, Jacobs AK, Topol EJ, for the CAVEAT investigators. Characteristics and consequences of myocardial infarction after percutaneous coronary intervention: insights from the coronary angioplasty versus excisional atherectomy trial (CAVEAT). J Am Coll Cardiol. 1995;25:1693–1699.[Abstract]
12.
Kong TQ, Davidson CJ, Meyers SN, Tauke JT, Parker MA,
Bonow RO. Prognostic implication of creatine kinase elevation following
elective coronary artery interventions. JAMA. 1997;277:461–466.
13. Tardiff BE, Califf RM, Tcheng JE, Lincoff AM, Sigmon KN, Harrington RA, Mahaffey KW, Teirstein P, Heinsimer J, Topol EJ, for the IMPACT-II Investigators. Post-intervention cardiac enzyme elevations: prognostic significance in IMPACT II. J Am Coll Cardiol. 1996;27:83A. Abstract.
14. Redwood SR, Popma JJ, Kent KK, Pichard AD, Satler LF, Mintz GS, Hong MK, Bucher TA, Merritt AJ, Leon MB. Predictors of late mortality following ablative new-device angioplasty in native coronary arteries. J Am Coll Cardiol. 1996;27:167A. Abstract.
This article has been cited by other articles:
 |
|
 |
|
  G. Ndrepepa, A. Kastrati, J. Mehilli, F.-J. Neumann, J. ten Berg, O. Bruskina, F. Dotzer, M. Seyfarth, J. Pache, J. Dirschinger, et al. One-year clinical outcomes with abciximab vs. placebo in patients with non-ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention after pre-treatment with clopidogrel: results of the ISAR-REACT 2 randomized trial Eur. Heart J., February 2, 2008; 29(4): 455 - 461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. L. Miller, K. N. Garratt, M. F. Burritt, R. J. Lennon, G. S. Reeder, and A. S. Jaffe Baseline troponin level: key to understanding the importance of post-PCI troponin elevations Eur. Heart J., May 1, 2006; 27(9): 1061 - 1069. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Herrmann Peri-procedural myocardial injury: 2005 update Eur. Heart J., December 1, 2005; 26(23): 2493 - 2519. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Lansky, J. S. Hochman, P. A. Ward, G. S. Mintz, R. Fabunmi, P. B. Berger, G. New, C. L. Grines, C. G. Pietras, M. J. Kern, et al. Percutaneous Coronary Intervention and Adjunctive Pharmacotherapy in Women: A Statement for Healthcare Professionals From the American Heart Association Circulation, February 22, 2005; 111(7): 940 - 953. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Lincoff, N. S. Kleiman, D. J. Kereiakes, F. Feit, J. A. Bittl, J. D. Jackman, I. J. Sarembock, D. J. Cohen, D. Spriggs, R. Ebrahimi, et al. Long-term Efficacy of Bivalirudin and Provisional Glycoprotein IIb/IIIa Blockade vs Heparin and Planned Glycoprotein IIb/IIIa Blockade During Percutaneous Coronary Revascularization: REPLACE-2 Randomized Trial JAMA, August 11, 2004; 292(6): 696 - 703. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. L. Miller, K. N. Garratt, M. F. Burritt, G. S. Reeder, and A. S. Jaffe Timing of Peak Troponin T and Creatine Kinase-MB Elevations After Percutaneous Coronary Intervention Chest, January 1, 2004; 125(1): 275 - 280. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bakhai, G. W. Stone, C. L. Grines, S. A. Murphy, L. Githiora, R. H. Berezin, D. A. Cox, T. Stuckey, J. J. Griffin, J. E. Tcheng, et al. Cost-Effectiveness of Coronary Stenting and Abciximab for Patients With Acute Myocardial Infarction: Results From the CADILLAC (Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications) Trial Circulation, December 9, 2003; 108(23): 2857 - 2863. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. O. Williams A twist in our understanding of enzyme elevation after coronary intervention J. Am. Coll. Cardiol., December 3, 2003; 42(11): 1906 - 1908. [Full Text] [PDF]
|
|
|
|
|
|
J. P. A. Ioannidis, E. Karvouni, and D. G. Katritsis Mortality risk conferred by small elevations of creatine kinase-MB isoenzyme after percutaneous coronary intervention J. Am. Coll. Cardiol., October 15, 2003; 42(8): 1406 - 1411. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. P Dobesh, S. L Lanfear, J. R Abu-Shanab, J. E Lakamp, S. Gowda, and M. Y Haikal Outcomes with Changes in Prescribing of Glycoprotein IIb/IIIa Inhibitors in PCI Ann. Pharmacother., October 1, 2003; 37(10): 1375 - 1380. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Mehta and G. M. Chertow Acute Renal Failure Definitions and Classification: Time for Change? J. Am. Soc. Nephrol., August 1, 2003; 14(8): 2178 - 2187. [Full Text] [PDF]
|
|
|
|
|
|
M. A Crouch, J. M Nappi, and K. I Cheang Glycoprotein IIb/IIIa Receptor Inhibitors in Percutaneous Coronary Intervention and Acute Coronary Syndrome Ann. Pharmacother., June 1, 2003; 37(6): 860 - 875. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Gorchakova, W. Koch, N. von Beckerath, J. Mehilli, A. Schomig, and A. Kastrati Association of a genetic variant of endothelial nitric oxide synthase with the 1 year clinical outcome after coronary stent placement Eur. Heart J., May 1, 2003; 24(9): 820 - 827. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Brener, S. G. Ellis, J. Schneider, C. Apperson-Hansen, and E. J. Topol Abciximab-facilitated percutaneous coronary intervention and long-term survival--a prospective single-center registry Eur. Heart J., April 1, 2003; 24(7): 630 - 638. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Lincoff, J. A. Bittl, R. A. Harrington, F. Feit, N. S. Kleiman, J. D. Jackman, I. J. Sarembock, D. J. Cohen, D. Spriggs, R. Ebrahimi, et al. Bivalirudin and Provisional Glycoprotein IIb/IIIa Blockade Compared With Heparin and Planned Glycoprotein IIb/IIIa Blockade During Percutaneous Coronary Intervention: REPLACE-2 Randomized Trial JAMA, February 19, 2003; 289(7): 853 - 863. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T Lenderink, E Boersma, C Heeschen, A Vahanian, M.-J de Boer, V Umans, M.J.B.M van den Brand, C.W Hamm, M.L Simoons, and for the CAPTURE investigators Elevated troponin T and C-reactive protein predict impaired outcome for 4 years in patients with refractory unstable angina, and troponin T predicts benefit of treatment with abciximab in combination with PTCA Eur. Heart J., January 1, 2003; 24(1): 77 - 85. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Karvouni, D. G. Katritsis, and J. P. A. Ioannidis Intravenous glycoprotein IIb/IIIa receptor antagonists reduce mortality after percutaneous coronary interventions J. Am. Coll. Cardiol., January 1, 2003; 41(1): 26 - 32. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Brener, B. W. Lytle, J. P. Schneider, S. G. Ellis, and E. J. Topol Association between CK-MB elevation after percutaneous or surgical revascularization and three-year mortality J. Am. Coll. Cardiol., December 4, 2002; 40(11): 1961 - 1967. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M G Gunning, I L Williams, D E Jewitt, A M Shah, R J Wainwright, and M R Thomas Coronary artery perforation during percutaneous intervention: incidence and outcome Heart, December 1, 2002; 88(5): 495 - 498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.J. Brener, S.G. Ellis, J. Schneider, and E.J. Topol Frequency and long-term impact of myonecrosis after coronary stenting Eur. Heart J., June 1, 2002; 23(11): 869 - 876. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E Drewe and R J Powell Clinically useful monoclonal antibodies in treatment J. Clin. Pathol., February 1, 2002; 55(2): 81 - 85. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Buller and R. G. Carere New advances in the management of acute coronary syndromes: 3. The role of catheter-based procedures Can. Med. Assoc. J., January 1, 2002; 166(1): 51 - 61. [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Kapadia, C. T. Bajzer, K. M. Ziada, D. L. Bhatt, O. M. Wazni, M. J. Silver, E. G. Beven, K. Ouriel, and J. S. Yadav Initial Experience of Platelet Glycoprotein IIb/IIIa Inhibition With Abciximab During Carotid Stenting: A Safe and Effective Adjunctive Therapy Stroke, October 1, 2001; 32(10): 2328 - 2332. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. McCune, J. P. Gockerman, and D. A. Rizzieri Monoclonal Antibody Therapy in the Treatment of Non-Hodgkin Lymphoma JAMA, September 12, 2001; 286(10): 1149 - 1152. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Bogousslavsky and J. R. Leclerc Platelet glycoprotein IIb/IIIa antagonists for acute ischemic stroke Neurology, September 1, 2001; 57(90002): S53 - 57. [Abstract] [Full Text]
|
|
|
|
|
|
G. W. Stone, R. Mehran, G. Dangas, A. J. Lansky, R. Kornowski, and M. B. Leon Differential Impact on Survival of Electrocardiographic Q-Wave Versus Enzymatic Myocardial Infarction After Percutaneous Intervention: A Device-Specific Analysis of 7147 Patients Circulation, August 7, 2001; 104(6): 642 - 647. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Zvara Treatment of Perioperative Myocardial Ischemia Seminars in Cardiothoracic and Vascular Anesthesia, July 1, 2001; 5(2): 166 - 183. [Abstract] [PDF]
|
|
|
|
|
|
K. M. Anderson, R. M. Califf, G. W. Stone, F.-J. Neumann, G. Montalescot, D. P. Miller, J. J. Ferguson III, J. T. Willerson, H. F. Weisman, and E. J. Topol Long-term mortality benefit with abciximab in patients undergoing percutaneous coronary intervention J. Am. Coll. Cardiol., June 15, 2001; 37(8): 2059 - 2065. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. I. Lev, J. I. Osende, M. F. Richard, J. A. Robbins, J. A. Delfin, O. Rodriguez, S. K. Sharma, T. Jayasundera, J. J. Badimon, and J. D. Marmur Administration of abciximab to patients receiving tirofiban or eptifibatide: effect on platelet function J. Am. Coll. Cardiol., March 1, 2001; 37(3): 847 - 855. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Lincoff, D. B. Mark, J. E. Tcheng, R. M. Califf, M. V. Bala, K. M. Anderson, L. Davidson-Ray, J. D. Knight, C. F. Cabot, and E. J. Topol Economic Assessment of Platelet Glycoprotein IIb/IIIa Receptor Blockade With Abciximab and Low-Dose Heparin During Percutaneous Coronary Revascularization : Results From the EPILOG Randomized Trial Circulation, December 12, 2000; 102(24): 2923 - 2929. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Bhatt and E. J. Topol Current Role of Platelet Glycoprotein IIb/IIIa Inhibitors in Acute Coronary Syndromes JAMA, September 27, 2000; 284(12): 1549 - 1558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.M. Lincoff and E.J. Topol Platelet glycoprotein IIb/IIIa inhibition during percutaneous coronary revascularization: what more needs to be proven? Eur. Heart J., June 1, 2000; 21(11): 863 - 867. [PDF]
|
|
|
|
|
|
C. Heeschen, C. W. Hamm, J. Bruemmer, M. L. Simoons, and for the CAPTURE Investigators Predictive value of C-reactive protein and troponin T in patients with unstable angina: a comparative analysis J. Am. Coll. Cardiol., May 1, 2000; 35(6): 1535 - 1542. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Lincoff, R. M. Califf, and E. J. Topol Platelet glycoprotein IIb/IIIa receptor blockade in coronary artery disease J. Am. Coll. Cardiol., April 1, 2000; 35(5): 1103 - 1115. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Topol and J. S. Yadav Recognition of the Importance of Embolization in Atherosclerotic Vascular Disease Circulation, February 8, 2000; 101(5): 570 - 580. [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Yeghiazarians, J. B. Braunstein, A. Askari, and P. H. Stone Unstable Angina Pectoris N. Engl. J. Med., January 13, 2000; 342(2): 101 - 114. [Full Text] [PDF]
|
|
|
|
|
|
A. M. Lincoff, R. M. Califf, D. J. Moliterno, S. G. Ellis, J. Ducas, J. H. Kramer, N. S. Kleiman, E. A. Cohen, J. E. Booth, S. K. Sapp, et al. Complementary Clinical Benefits of Coronary-Artery Stenting and Blockade of Platelet Glycoprotein IIb/IIIa Receptors N. Engl. J. Med., July 29, 1999; 341(5): 319 - 327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Sustained Benefit of Abciximab at One Year Journal Watch Cardiology, June 3, 1999; 1999(603): 1 - 1. [Full Text]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||