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(Circulation. 1998;98:2829-2835.)
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports* |
Clinical Outcomes of Therapeutic Agents That Block the Platelet Glycoprotein IIb/IIIa Integrin in Ischemic Heart Disease
From the Duke Clinical Research Institute, Durham, NC (D.F.K., R.M.C., R.A.H., J.E.T., V.H.); the Cleveland Clinic Foundation, Cleveland, Ohio (D.P.M., D.J.M., A.M.L., E.J.T.); and Green Lane Hospital, Auckland, New Zealand (H.D.W.).
Correspondence to Robert M. Califf, MD, Duke Clinical Research Institute, 2024 W Main St, Durham, NC 27705. E-mail calif001{at}onyx.mc.duke.edu
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Abstract |
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 Top Abstract IntroductionMethodsResultsDiscussionReferences |
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Background—Several platelet glycoprotein (GP) IIb/IIIa receptor antagonists have been evaluated in clinical trials. We conducted a systematic overview (meta-analysis) to assess the effect of these compounds on death, myocardial infarction (MI), and revascularization.
Methods and Results—ORs were calculated for 16 randomized, controlled trials of GP IIb/IIIa inhibitors. An empirical Bayesian random-effects model combined the outcomes of 32 135 patients. There was a significant mortality reduction by GP IIb/IIIa inhibitors at 48 to 96 hours, with an OR of 0.70 (95% CI, 0.51 to 0.96; P<0.03), equivalent to a reduction of 1 death per 1000 patients treated. Mortality benefits at 30 days (OR, 0.87; 95% CI, 0.74 to 1.02; P=0.08) and 6 months (OR, 0.97; 95% CI, 0.86 to 1.10; P=0.67) were not statistically significant. For the combined end point of death or MI, there was a highly significant (P<0.001) benefit for GP IIb/IIIa inhibitors at each time point. The 30-day OR was 0.76 (95% CI, 0.66 to 0.87), or 20 fewer events per 1000 patients treated. For the composite end point of death, MI, or revascularization, there was also a highly significant (P<0.001) benefit for GP IIb/IIIa inhibitors. At 30 days, the OR was 0.77 (95% CI, 0.68 to 0.86), or 30 fewer events per 1000 patients treated. The risk differences for death, death or MI, and composite outcomes were similar at 6 months, indicating a sustained absolute improvement. Similar benefit was seen when trials were subgrouped by therapeutic indication (percutaneous intervention versus acute coronary syndromes).
Conclusions—Application of this new therapeutic class to clinical practice promises substantial benefit for both indications.
Key Words: platelet aggregation inhibitors • meta-analysis • myocardial infarction • mortality • revascularization
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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In 1983, Coller and colleagues1 described an antibody that blocked the platelet glycoprotein (GP) IIb/IIIa receptor. A chimeric monoclonal antibody,2 abciximab, was later developed for treatment of patients undergoing high-risk percutaneous intervention. Prompted by the benefit of abciximab in a randomized study,3 multiple peptide and nonpeptide antagonists of the IIb/IIIa receptor have been developed.4 5 Large clinical trials6 7 have evaluated these agents for unstable angina, acute myocardial infarction (MI), and percutaneous coronary intervention indications. This article provides a meta-analysis of available studies to evaluate the impact of intravenous GP IIb/IIIa antagonists on clinical outcomes.
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Methods |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Trial Selection
Randomized, blinded, controlled trials of parenteral GP IIb/IIIa antagonists were identified through a MEDLINE search. Records between 1980 and 1997 were searched for the words "platelet," "random$," and ("inhibi$" or "block$"), where $ is a wild card. Published results were included when available. Publicly presented data also represented several recent trials.
Studies were subgrouped on the basis of the indication for GP IIb/IIIa
inhibition. Trials of percutaneous coronary
intervention (Table 1
) included
any study in which the intent to perform a percutaneous
procedure was an entry criterion.3 8 9 10 11 12 13 14 15 16 Acute
coronary syndrome trials enrolled patients with symptoms of
acute coronary ischemia without ST-segment elevation on
the 12-lead ECG (Table 2).6 7 17 18 19 20 The overview
analysis evaluated the entire collection of trials as well as
each of the subgroups.
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Several of these studies had multiple dose arms, and different trials of the same agents used different dosing strategies. To capture all patients exposed to this compound class, our conservative overview included all treatment arms in the analysis. Two trials (PURSUIT, PRISM Plus) had treatment arms that terminated early. Furthermore, the placebo arm event rate increased as the trials progressed. These trials were evaluated using all patients enrolled before the arm was stopped and patients in the remaining treatment arm with contemporaneous controls after the termination of the stopped arm.
Adjunctive heparin regimens also differed among trials. All
percutaneous intervention trials permitted heparin
during the procedure to maintain an activated clotting time
between 200 and 400 seconds or an activated partial
thromboplastin time of 1.5 to 3 times the control value (Table 1
). Postprocedure heparin infusions were permitted in 5 of the
10 percutaneous intervention trials. Heparin was given
in all acute coronary syndrome trials except for PARAGON A,
PRISM, and PRISM Plus, which randomized patients to heparin or placebo
(Table 2).
Clinical End Points
Clinical outcomes studied included death, the composite of death
or MI, and the composite of death, MI, or
revascularization. Each outcome was evaluated at an
early time point (between 48 and 96 hours), at 30 days, and at 6
months. For percutaneous intervention trials, the early
end point occurred after the end of the study drug infusion. Patients
in acute coronary syndrome trials often received drug during
this period. Urgent revascularization events were
evaluated at the early and 30-day time points, and the occurrence of
any revascularization event was assessed at 6
months. The numbers of patients experiencing events at each time point
were compiled for treatment and control arms. Although limited numbers
of patients were lost to follow-up in several trials, the amount of
incomplete data was expected to be equal among randomized arms. The
event rates for each arm reflect the number of events observed divided
by the number of patients enrolled, according to intention to
treat.
Statistical Analysis
ORs summarizing the effectiveness of GP IIb/IIIa
inhibitors were calculated by use of Fast*Pro
software.21 These ORs were combined assuming an empirical
Bayesian model described by Hedges and Olkin.22 Risk
differences between control and treatment arms were also combined by
use of the same model. The empirical Bayesian random-effects model
reduces to a fixed-effects model when the studies are
homogeneous. The method accommodated
heterogeneity by assuming that the true effect differed
among studies and therefore must be represented by a
distribution of values instead of a single value. The result was a
wider range of uncertainty about the point estimate than was calculated
with fixed-effects models.
Although the random-effects model accommodated variability among
studies, the extent of heterogeneity in the trials was
examined by 2 methods. The Q statistic of DerSimonian and
Laird23 approximated a 
2
statistic to test a null hypothesis that all of the studies estimated
the same true value. To identify potential sources of
heterogeneity, Galbraith radial plots were
constructed.24 25 This method plotted the log OR divided
by the standard error against the reciprocal of the standard error.
Ninety-five percent of trials should fall within 2 units above or below
a line with slope equal to the overall log OR. Trials that exceed the
2-unit boundary deserve further exploration for
heterogeneity.
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Results |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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A total of 32 135 patients were included in the analysis (Figure 1
). A significant mortality
reduction with GP IIb/IIIa inhibitors was observed at the
early time point (48 to 96 hours), with an OR of 0.70 (95% CI,
0.51 to 0.96; P<0.03) (Figure 2). The combined risk difference of
-0.001 (95% CI, -0.0026 to 0.0003) was equivalent to a reduction of
1 death per 1000 patients treated. Trends toward mortality benefit at
30 days and 6 months were not statistically significant. At 30 days,
the OR was 0.87 (95% CI, 0.74 to 1.02; P=0.08), equivalent
to 3 fewer deaths per 1000 patients treated (-0.0032; 95% CI,
-0.0063 to -0.0001) (Figure 3). At 6
months, the OR was 0.97 (95% CI, 0.86 to 1.10; P=0.67),
equivalent to 2 fewer deaths per 1000 patients treated (-0.0015; 95%
CI, -0.0059 to 0.0029).
|
), combined
non–ST-segment elevation acute coronary syndromes trials
(
), and all collected trials (
). N indicates sample size; Dif,
risk difference. *P<0.05; 
P<0.01;
P<0.001.
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For the combined end point of death or nonfatal MI, there was a highly
significant (P<0.001) benefit for GP IIb/IIIa
inhibitors at every time point. For the early time point
(48 to 96 hours), the OR was 0.66 (95% CI, 0.56 to 0.78), equivalent
to 17 fewer events per 1000 patients treated (-0.017; 95% CI, -0.023
to -0.011). At 30 days, the OR was 0.76 (95% CI, 0.66 to 0.87), or 20
fewer events per 1000 patients treated (-0.020; 95% CI, -0.029 to
-0.012) (Figure 4). At 6 months, the OR
was 0.82 (95% CI, 0.74 to 0.91), or 20 fewer events per 1000 patients
treated (-0.020; 95% CI, -0.028 to -0.011).
|
For the composite end point of death, MI, or
revascularization, there was a highly significant
(P<0.001) benefit favoring GP IIb/IIIa
inhibitors. For the early time point (48 to 96 hours), the
OR was 0.66 (95% CI, 0.58 to 0.75), equivalent to 27 fewer events per
1000 patients treated (-0.027; 95% CI, -0.034 to -0.020). At 30
days, the OR was 0.77 (95% CI, 0.69 to 0.86), or 30 fewer events per
1000 patients treated (-0.030; 95% CI, -0.040 to -0.020) (Figure 5). At 6 months, the OR was 0.89 (95%
CI, 0.84 to 0.94), or 23 fewer events per 1000 patients treated
(-0.023; 95% CI, -0.033 to -0.012).
|
Percutaneous Intervention Trials
No significant difference in mortality was seen at any time point.
At 48 to 96 hours, the OR was 0.66 (95% CI, 0.34 to 1.31;
P=0.24). At 30 days, the OR was 0.77 (95% CI, 0.53 to 1.10;
P=0.15). At 6 months, the OR was 0.90 (95% CI, 0.70 to
1.16; P=0.41).
For the combined end point of death or nonfatal MI, there was a highly significant (P<0.001) benefit for GP IIb/IIIa inhibitors at all 3 time points. For the early time point (48 to 96 hours), the OR was 0.57 (95% CI, 0.45 to 0.71), equivalent to 27 fewer events per 1000 patients treated (-0.027; 95% CI, -0.037 to -0.017). At 30 days, the OR was 0.64 (95% CI, 0.51 to 0.80), or 27 fewer events per 1000 patients treated (-0.027; 95% CI, -0.040 to -0.014). At 6 months, the OR was 0.76 (95% CI, 0.64 to 0.91), or 23 fewer events per 1000 patients treated (-0.023; 95% CI, -0.037 to -0.009).
For the composite end point of death, MI, or
revascularization, there was also a significant
benefit favoring GP IIb/IIIa inhibitors. For the early time
point (48 to 96 hours), the OR was 0.56 (95% CI, 0.46 to 0.67;
P<0.001), equivalent to a reduction of 38 events per 1000
patients treated (-0.038; 95% CI, -0.049 to -0.028). At 30 days,
the OR was 0.65 (95% CI, 0.54 to 0.79; P<0.001), or 
37
fewer events per 1000 patients treated (-0.037; 95% CI, -0.52 to
-0.022). At 6 months, the OR was 0.87 (95% CI, 0.80 to 0.95;
P<0.003), or 28 fewer events per 1000 patients treated
(-0.028; 95% CI, -0.045 to -0.012).
Acute Coronary Syndrome Trials
No significant difference in mortality was seen at any time point.
At the early time point (48 to 96 hours), the OR was 0.71 (95% CI,
0.50 to 1.01). At 30 days, the OR was 0.90 (95% CI, 0.76 to 1.06). At
6 months, the OR was 1.00 (95% CI, 0.87 to 1.15).
For the combined end point of death or nonfatal MI, there was a significant (P<0.01) benefit for GP IIb/IIIa inhibitors early and at 30 days. At the early time point (48 to 96 hours), the OR was 0.81 (95% CI, 0.71 to 0.92), equivalent to a reduction of 10 events per 1000 patients treated (-0.010; 95% CI, -0.015 to -0.004). At 30 days, the OR was 0.88 (95% CI, 0.81 to 0.97), or 13 fewer events per 1000 patients treated (-0.013; 95% CI, -0.023 to -0.004). At 6 months, the OR was 0.88 (95% CI, 0.79 to 0.97), equal to 16 fewer events per 1000 patients treated (-0.016; 95% CI, -0.027 to -0.004).
For the composite end point of death, MI, or revascularization, there was a highly significant benefit favoring GP IIb/IIIa inhibitors. For the early time point (48 to 96 hours), the OR was 0.77 (95% CI, 0.69 to 0.86; P<0.001), equivalent to 19 fewer events per 1000 patients treated (-0.019; 95% CI, -0.027 to -0.011). At 30 days, the OR was 0.86 (95% CI, 0.80 to 0.93; P<0.001), or 22 fewer events per 1000 patients treated (-0.022; 95% CI, -0.034 to -0.010). At 6 months, the OR was 0.90 (95% CI, 0.83 to 0.97; P<0.01), or 20 fewer events per 1000 patients treated (-0.020; 95% CI, -0.036 to -0.004).
Heterogeneity Analyses
For percutaneous intervention trials, the
Q statistic revealed significant
heterogeneity for the death/MI end point at 30 days and
6 months and for death/MI/revascularization at 48
to 96 hours and 30 days. No significant heterogeneity
was detected in the acute coronary syndrome trials. The test of
heterogeneity for the entire trial collection reflected
the heterogeneity present within the
percutaneous intervention subgroup.
Galbraith plots (Figure 6) identified the
EPILOG trial's particularly pronounced effect in favor of GP IIb/IIIa
blockade. This finding corresponds to the quantitative results.
Q statistics calculated without the EPILOG trial are
consistent with homogeneity for all end points except early (48
to 96 hours) death/MI/revascularization. Thus,
EPILOG contributed substantially to the statistical
heterogeneity of the collected trials.
|
) and acute
coronary syndrome trials (
) for death (top row), death or MI
(middle row), and death, MI, or revascularization
(bottom row) 48 to 96 hours, 30 days, and 6 months after randomization
to a GP IIb/IIIa inhibitor or placebo. In a statistically
homogeneous sample, 95% of trials should fall within 2
units (dashed lines) of overall OR (solid diagonal line). |
Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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This new therapeutic class promises a substantial benefit when applied to clinical practice. Patients undergoing percutaneous coronary intervention or presenting with an acute coronary syndrome can expect a significant reduction in critical clinical events, including nonfatal MI and the need for repeat procedures. Much of the benefit occurs early in the patient's clinical course and is maintained at 6 months.
The effect of GP IIb/IIIa inhibitors on mortality is small compared with the number of patients studied. One might infer that no mortality benefit exists, simply because the 6-month result is not statistically significant. Another explanation recognizes that the absolute benefit (lives saved per 1000 patients treated) remains constant between the early phase and 6 months. In the early phase (during drug infusion), the 35% relative mortality reduction and paucity of deaths overall make this difference borderline statistically significant. Afterward, the numbers of additional deaths in the treatment and control groups are similar, suggesting no further effect on mortality after the infusion ends. Because deaths accumulate equally in both groups over time, the relative effect (ORs and P value) declines and becomes nonsignificant. In addition, although the point estimates remain relatively constant, the CIs widen because fewer patients had 6-month data than had 48- to 96-hour data. Last, the 30-day mortality rate was only 2.7% for the combined control arms. Proof of a mortality difference given this event rate requires either a monumental treatment effect or an enormous sample size (145 618 patients to detect a 10% relative reduction with 90% power, or 21 872 patients for a 25% reduction.) The probability of a detrimental effect on mortality is <3% for GP IIb/IIIa inhibitors given intravenously for 1 to 4 days. Long-term dosing of oral formulations may extend this effect to a larger, durable mortality benefit.
Definitions of nonfatal MI and reinfarction varied among trials, with different enzyme, ECG, and clinical criteria. A majority of the trials used adjudication committees in addition to (often complex) formal descriptive rules. The disparity among investigators and sponsors is a limitation of the trial designs in this area. Although a consensus end-point definition is highly desirable for future trials, there is at present no feasible way to reconstruct a uniform definition for previous studies. Despite this limitation, any MI, however defined, constitutes an undesirable event for patients, and we have reported results consistent with primary-end-point definitions.
Ten of the 16 trials used a composite of death, MI, or revascularization as the primary end point. A larger reduction in relative odds exists for combined death/MI events than for composite death/MI/revascularization events. Applied to 1000 patients similar to the overview population, GP IIb/IIIa blockade would prevent 20 of 91 deaths or nonfatal MIs in the first 30 days, a 22% relative reduction. Under the same conditions, the agents would prevent 30 of 169 deaths, MIs, or revascularization procedures (a 17% reduction). From a treatment policy perspective, the triple end point better reflects the anticipated benefit to clinical practice.
Efforts to accumulate all available information inevitably increase the
potential for heterogeneity in pooled data. Formal
tests for heterogeneity have low power. Thus,
statistical failure to reject the null hypothesis of homogeneity does
not imply equality26 but rather a lack of unacceptable
heterogeneity. In this overview, the methods used to
calculate the combined ORs accommodate
heterogeneity.21 27 The overview combines
studies of 3 agents with those of abciximab, which has a longer
duration of action and cross-reactivity with the
Vß3
receptor.28 As previously mentioned, patient
characteristics, therapeutic regimens, end-point definitions, and
adjunctive drugs (heparin and aspirin) were nonuniform across trials.
The EPILOG trial contributed strongly to the statistical
heterogeneity of the collected trials. The pronounced
power of EPILOG may stem from its early termination,29 30
the patient population, the dosing regimen, or inherent drug
effects.
Whether differences in clinical benefit exist among the different compounds is speculative. The variability present among trials precludes indirect comparisons of individual agents. These differences can produce disparity among trials included in meta-analyses31 and cause discrepancies between meta-analyses and subsequent large, controlled trials. For example, Fox32 attempted indirect comparisons between anistreplase and alteplase using a fixed-effects model. The ISIS-3 randomized trial33 later showed no significant difference between the 2 agents. Although practice guidelines should be influenced most by large randomized trials, properly conducted systematic overviews of large trials can describe overall benefit and summarize past experience better than individual studies examined separately.
The general mechanism of benefit is undoubtedly the inhibition of platelet aggregation, a critical component of thrombotic coronary occlusion. At 30 days, the trials of percutaneous intervention had a significantly larger relative reduction in combined death and MI than the acute coronary syndromes trials (95% CI, 0.51 to 0.80 versus 0.81 to 0.97, respectively), although the 95% CIs overlapped at the other 2 time points. These agents may perform better during angioplasty, when delivered at a time of arterial trauma and platelet aggregation. This difference also may represent a reduction in postprocedure myocardial enzyme elevation. The lesser benefit for acute coronary syndromes may reflect the delay between the initial intimal insult and institution of therapy. The optimal degree and duration of GP IIb/IIIa inhibition remain to be established for each indication.
The GP IIb/IIIa inhibitors clearly show a consistent, substantial, and durable benefit as a therapeutic class. Future randomized, comparative clinical trials will undoubtedly refine these results and identify optimal applications for specific agents. The completion of definitive outcome studies before regulatory approval should speed assimilation of these agents into clinical practice and transformation of these promising results into new standards of care.
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Acknowledgments |
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We recognize the following investigators who contributed data: Keaven M. Anderson, PhD (Centocor, Malvern, Pa); Manjushri Bhapkar, MS (Duke Clinical Research Institute, Durham, NC); Sorin J. Brener, MD (Cleveland Clinic Foundation, Cleveland, Ohio); Spencer B. King III, MD (Emory University Hospital, Atlanta, Ga); Cynthia M. MacAulay, MS (Duke Clinical Research Institute); Frederic L. Sax, MD (Merck Research Laboratories, West Point, Pa); Kristina N. Sigmon, MA (Duke Clinical Research Institute); and Maarten L. Simoons, MD (Thoraxcenter, Rotterdam, Netherlands). We also thank Penny Hodgson and Pat Williams for their editorial assistance.
Received June 17, 1998; revision received September 4, 1998; accepted September 15, 1998.
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References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Coller BS, Peerschke EI, Scudder LE, Sullivan CA. A murine monoclonal antibody that completely blocks the binding of fibrinogen to platelets produces a thrombasthenic-like state in normal platelets and binds to glycoproteins IIb and/or IIIa. J Clin Invest. 1983;72:325–338.
2. Knight DM, Wagner C, Jordan R, McAleer MF, DeRita R, Fass DN, Coller BS, Weisman HF, Ghrayeb J. The immunogenicity of the 7E3 murine monoclonal Fab antibody fragment variable region is dramatically reduced in humans by substitution of human for murine constant regions. Mol Immunol. 1995;32:1271–1281.[Medline] [Order article via Infotrieve]
3.
The 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.
4.
Lefkovits J, Plow EF, Topol EJ. Platelet
glycoprotein IIb/IIIa receptors in
cardiovascular medicine. N Engl J
Med. 1995;332:1553–1559.
5.
Lefkovits J, Topol EJ. Platelet
glycoprotein IIb/IIIa receptor antagonists in
coronary artery disease. Eur Heart J. 1996;17:9–18.
6. Simoons ML. PURSUIT preliminary results. Presented at the 19th Congress of the European Society of Cardiology in Stockholm, Sweden, August 25, 1997. http://www.esc.be/Press97/PCPR97simoons.htm
7.
The PRISM Study Investigators. A comparison of aspirin
plus tirofiban with aspirin plus heparin for unstable angina.
N Engl J Med. 1998;338:1498–1505.
8.
The EPILOG Investigators. Platelet
glycoprotein IIb/IIIa receptor blockade and low-dose
heparin during percutaneous coronary
revascularization. N Engl J
Med. 1997;336:1689–1696.
9.
Simoons ML, de Boer MJ, van den Brand MJBM, van
Miltenburg AJM, Hoorntje JCA, Heyndrickx GR, van der Wieken LR, De Bono
D, Rutsch W, Schaible TF, Weisman HF, Klootwijk P, Nijssen KM, Stibbe
J, de Feyter PJ, and the European Cooperative Study Group. Randomized
trial of a GPIIb/IIIa platelet receptor blocker in refractory
unstable angina. Circulation. 1994;89:596–603.
10. The 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]
11. Brener SJ, Barr LA, Burchenal J, Katz S, George BS, Jones AA, Moliterno DJ, Topol EJ. A randomized, placebo-controlled trial of abciximab with primary angioplasty for acute MI: the RAPPORT trial. Circulation. 1997;96(suppl I):I-473. Abstract.
12. Harrington RA, Kleiman NS, Kottke-Marchant K, Lincoff AM, Tcheng JE, Sigmon KN, Joseph D, Rios G, Trainor K, Rose D, Greenberg CS, Kitt MM, Topol EJ, Califf RM. Immediate and reversible platelet inhibition after intravenous administration of a peptide glycoprotein IIb/IIIa inhibitor during percutaneous coronary intervention. Am J Cardiol. 1995;76:122–127.
13.
Tcheng JE, Harrington RA, Kottke-Marchant K, Kleiman
NS, Ellis SG, Kereiakes DJ, Mick MJ, Navetta FI, Smith JE, Worley SJ,
Miller JA, Joseph DM, Sigmon KN, Kitt MM, du Mee CP, Califf RM, Topol
EJ, for the IMPACT Investigators. Multicenter randomized, double-blind,
placebo-controlled trial of the platelet integrin
glycoprotein IIb/IIIa blocker integrelin in elective
coronary intervention. Circulation. 1995;91:2151–2157.
14. The IMPACT-II Investigators. Randomised placebo-controlled trial of effect of eptifibatide on complications of percutaneous coronary intervention: IMPACT-II. Lancet. 1997;349:1422–1428.[Medline] [Order article via Infotrieve]
15. Kereiakes DJ, Kleiman NS, Ambrose J, Cohen M, Rodriguez S, Palabrica T, Herrmann HC, Sutton JM, Weaver WD, McKee DB, Fitzpatrick V, Sax FL. Randomized, double-blind, placebo controlled dose-ranging study of tirofiban (MK-383) platelet IIb/IIIa blockade in high risk patients undergoing coronary angioplasty. J Am Coll Cardiol. 1996;27:536–542.[Abstract]
16.
The RESTORE Investigators. Effect of platelet
glycoprotein IIb/IIIa blockade with tirofiban on adverse
cardiac events in patients with unstable angina or acute myocardial
infarction undergoing coronary angioplasty.
Circulation. 1997;96:1445–1453.
17.
Schulman SP, Goldschmidt PJ, Topol EJ, Califf RM,
Navetta FI, Willerson JT, Chandra NC, Guerci AS, Ferguson JJ,
Harrington RA, Lincoff AM, Yakubov SJ, Bray PF, Bahr RD, Wolfe CL, Yock
PG, Anderson HV, Nygaard TW, Mason SJ, Effron MB, Fatterpacker A,
Raskin S, Smith J, Brashears L, Gottdiener P, du Mee C, Kitt MM,
Gerstenblith G. Effects of integrelin, a platelet
glycoprotein IIb/IIIa receptor antagonist, in
unstable angina: a randomized multicenter trial.
Circulation. 1996;94:2083–2089.
18.
The PRISM-PLUS Study Investigators. Inhibition of the
platelet glycoprotein IIb/IIIa receptor with tirofiban
in unstable angina and non-Q-wave myocardial infarction. N
Engl J Med. 1998;338:1488–1497.
19.
The PARAGON Investigators. International, randomized,
controlled trial of lamifiban (a platelet glycoprotein
IIb/IIIa inhibitor), heparin, or both in unstable angina.
Circulation. 1998;97:2386–2395.
20.
Theroux P, Kouz S, Roy L, Knudtson ML, Diodati JG,
Marquis JF, Nasmith J, Fung AY, Boudrealt JR, Delage F, Dupuis R, Kells
C, Bokslag M, Steiner B, Rapold HJ. Platelet membrane receptor
glycoprotein IIb/IIIa antagonism in unstable angina: the
Canadian lamifiban study. Circulation. 1996;94:899–905.
21. Eddy DM, Hasselblad V. Fast*Pro Software for Meta-Analysis by the Confidence Profile Method. Boston, Mass: Academic Press, Inc; 1992.
22. Hedges LV, Olkin I. Statistical Methods for Meta-Analysis. Orlando, Fla: Academic Press; 1985:199–201.
23. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–188.[Medline] [Order article via Infotrieve]
24. Galbraith RF. A note on graphical presentation of estimated odds ratios from several clinical trials. Stat Med. 1988;7:889–894.[Medline] [Order article via Infotrieve]
25.
Thompson SG. Systematic review: why sources of
heterogeneity in meta-analysis should be
investigated. BMJ. 1994;309:1351–1355.
26. Furberg CD, Morgan TM. Lessons from overviews of cardiovascular trials. Stat Med. 1987;6:295–303.[Medline] [Order article via Infotrieve]
27.
Lau J, Ioannidis JPA, Schmid CH. Quantitative synthesis
in systematic reviews. Ann Intern Med. 1997;127:820–826.
28.
Yasuda T, Gold HK, Kohmura C, Guerrero L, Yaoita H,
Fallon JT, Bunting S, Collen D. Intravenous and
endobronchial administration of G4120, a cyclic Arg-Gly-Asp–containing
platelet GP IIb/IIIa receptor-blocking pentapeptide, enhances and
sustains coronary arterial
thrombolysis with rt-PA in a canine preparation.
Arterioscler Thromb. 1993;13:738–747.
29.
Ferguson JJ III. EPILOG and CAPTURE trials halted
because of positive interim results. Circulation. 1996;93:637.
30. Green SJ, Fleming TR, Emerson S. Effects on overviews of early stopping rules for clinical trials. Stat Med. 1987;6:361–367.[Medline] [Order article via Infotrieve]
31.
LeLorier J, Gregoire G, Benhaddad A, Lapierre J,
Derderian F. Discrepancies between meta-analyses and subsequent
large randomized controlled trials. N Engl J Med. 1997;337:536–542.
32. Fox KA. Comparative analysis of long-term mortality after thrombolytic therapy. Am J Cardiol. 1991;67:38E–44E.
33. ISIS-3 (Third International Study of Infarct Survival) Collaborative Group. ISIS-3: a randomised trial of streptokinase vs tissue plasminogen activator vs anistreplase and of aspirin plus heparin vs aspirin alone among 41,299 cases of suspected acute myocardial infarction. Lancet. 1992;339:753–770.A meta-analysis of 16 trials comprising 32 135 patients assessed the effects of platelet glycoprotein IIb/IIIa inhibitors on outcomes. These agents significantly reduced mortality at 48 to 96 hours (1 fewer death per 1000 patients treated) but not at 30 days or 6 months. The incidence of death or MI was significantly (P<0.001) reduced at all time points, with 20 fewer events per 1000 patients treated at 30 days. The composite of death, MI, or revascularization also was significantly (P<0.001) reduced, equivalent to 30 fewer events per 1000 patients treated at 30 days. These agents promise substantial benefit for ischemic heart disease patients.[Medline] [Order article via Infotrieve]
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  A. Y. Fung, J. Saw, A. Starovoytov, C. Densem, P. Jokhi, S. J. Walsh, R. S. Fox, K. H. Humphries, E. Aymong, D. R. Ricci, et al. Abbreviated infusion of eptifibatide after successful coronary intervention The BRIEF-PCI (Brief Infusion of Eptifibatide Following Percutaneous Coronary Intervention) randomized trial. J. Am. Coll. Cardiol., March 10, 2009; 53(10): 837 - 845. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. W. Hamm, H. Möllmann, J.-P. Bassand, and F. van de Werf CHAPTER 16 Acute Coronary Syndromes ESC Textbook of Cardiovascular Medicine, January 1, 2009; 2(1): med-9780199566990-chapter - med-9780199566990-chapter. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. G. Goodman, V. Menon, C. P. Cannon, G. Steg, E. M. Ohman, and R. A. Harrington Acute ST-Segment Elevation Myocardial Infarction: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 708S - 775S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Anderson, C. D. Adams, E. M. Antman, C. R. Bridges, R. M. Califf, D. E. Casey Jr, W. E. Chavey II, F. M. Fesmire, J. S. Hochman, T. N. Levin, et al. ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) Developed in Collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine J. Am. Coll. Cardiol., August 14, 2007; 50(7): e1 - e157. [Full Text] [PDF]
|
|
|
|
 |
|
 Authors/Task Force Members, J.-P. Bassand, C. W. Hamm, D. Ardissino, E. Boersma, A. Budaj, F. Fernandez-Aviles, K. A.A. Fox, D. Hasdai, E. M. Ohman, et al. Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: The Task Force for the Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of the European Society of Cardiology Eur. Heart J., July 1, 2007; 28(13): 1598 - 1660. [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Meadows and D. L. Bhatt Clinical Aspects of Platelet Inhibitors and Thrombus Formation Circ. Res., May 11, 2007; 100(9): 1261 - 1275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. S. Hollenbeak, J. P. Fitzgibbons, M. Rossi, D. L. Morris, and P. Stillman The Impact of Percutaneous Coronary Interventions on Outcomes for Acute Myocardial Infarction in Pennsylvania American Journal of Medical Quality, March 1, 2007; 22(2): 85 - 94. [Abstract] [PDF]
|
|
|
|
 |
|
 E. N. Deliargyris, B. Upadhya, L. G. Melton, C. Thompson, M. Fisher, D. A. Gabriel, G. J. Dehmer, and D. C. Sane Unfractionated Heparin Reduces the Anti-Platelet Effects of Abciximab but not Eptifibatide During PCI Clinical and Applied Thrombosis/Hemostasis, October 1, 2006; 12(4): 458 - 464. [Abstract] [PDF]
|
|
|
|
 |
|
 K. P. Alexander, A. Y. Chen, L. K. Newby, J. B. Schwartz, R. F. Redberg, J. S. Hochman, M. T. Roe, W. B. Gibler, E. M. Ohman, E. D. Peterson, et al. Sex Differences in Major Bleeding With Glycoprotein IIb/IIIa Inhibitors: Results From the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines) Initiative Circulation, September 26, 2006; 114(13): 1380 - 1387. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Chaer, J. A. Graham, and L. Mureebe Platelet Function and Pharmacologic Inhibition Vascular and Endovascular Surgery, August 1, 2006; 40(4): 261 - 267. [Abstract] [PDF]
|
|
|
|
 |
|
 E. Okmen, A. Sanli, H. Uyarel, S. Dayi, Z. Tartan, and N. Cam Impacts of Glycoprotein IIb/IIIa Inhibition on QT Dispersion After Successful Percutaneous Coronary Intervention Angiology, May 1, 2006; 57(3): 273 - 281. [Abstract] [PDF]
|
|
|
|
|
|
M. Jonas, G. W. Stone, R. Mehran, J. Hermiller, R. Feldman, H. C. Herrmann, D. A. Cox, R. E. Kuntz, J. J. Popma, C. Rogers, et al. Platelet glycoprotein IIb/IIIa receptor inhibition as adjunctive treatment during saphenous vein graft stenting: differential effects after randomization to occlusion or filter-based embolic protection Eur. Heart J., April 2, 2006; 27(8): 920 - 928. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Puma, L. T. Banko, K. S. Pieper, T. J. Sacchi, J. C. O'Shea, J. P. Dery, and J. E. Tcheng Clinical Characteristics Predict Benefits From Eptifibatide Therapy During Coronary Stenting: Insights From the Enhanced Suppression of the Platelet IIb/IIIa Receptor With Integrilin Therapy (ESPRIT) Trial J. Am. Coll. Cardiol., February 21, 2006; 47(4): 715 - 718. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Tricoci, R. A. Harrington, M. Valgimigli, T. M. Palabrica, P. B. Burton, G. Patti, L. Lassandro Pepe, G. Di Sciascio, G. Colonna, A. Montinaro, et al. Letters Regarding Article by Patti et al, "Randomized Trial of High Loading Dose of Clopidogrel for Reduction of Periprocedural Myocardial Infarction in Patients Undergoing Coronary Intervention: Results From the ARMYDA-2 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) Study" * Response Circulation, October 25, 2005; 112(17): e282 - e283. [Full Text] [PDF]
|
|
|
|
 |
|
 J. C Coons, A. L Seybert, M. I Saul, L. Kirisci, and S. L Kane-Gill Outcomes and Costs of Abciximab Versus Eptifibatide for Percutaneous Coronary Intervention Ann. Pharmacother., October 1, 2005; 39(10): 1621 - 1626. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. B. Gibler, C. P. Cannon, A. L. Blomkalns, D. M. Char, B. J. Drew, J. E. Hollander, A. S. Jaffe, R. L. Jesse, L. K. Newby, E. M. Ohman, et al. Practical Implementation of the Guidelines for Unstable Angina/Non-ST-Segment Elevation Myocardial Infarction in the Emergency Department: A Scientific Statement From the American Heart Association Council on Clinical Cardiology (Subcommittee on Acute Cardiac Care), Council on Cardiovascular Nursing, and Quality of Care and Outcomes Research Interdisciplinary Working Group, in Collaboration With the Society of Chest Pain Centers Circulation, May 24, 2005; 111(20): 2699 - 2710. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Mehta, P. G. Steg, C. B. Granger, J.-P. Bassand, D. P. Faxon, J. I. Weitz, R. Afzal, B. Rush, R. J.G. Peters, M. K. Natarajan, et al. Randomized, Blinded Trial Comparing Fondaparinux With Unfractionated Heparin in Patients Undergoing Contemporary Percutaneous Coronary Intervention: Arixtra Study in Percutaneous Coronary Intervention: A Randomized Evaluation (ASPIRE) Pilot Trial Circulation, March 22, 2005; 111(11): 1390 - 1397. [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]
|
|
|
|
 |
|
 B. S. Wiggins and S. Spinler Antiplatelet and Antithrombin Therapy for Early Management of Acute Coronary Syndromes Journal of Pharmacy Practice, October 1, 2004; 17(5): 347 - 369. [Abstract] [PDF]
|
|
|
|
|
|
K. A.A. Fox, S. R. Mehta, R. Peters, F. Zhao, N. Lakkis, B. J. Gersh, and S. Yusuf Benefits and Risks of the Combination of Clopidogrel and Aspirin in Patients Undergoing Surgical Revascularization for Non-ST-Elevation Acute Coronary Syndrome: The Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (CURE) Trial Circulation, September 7, 2004; 110(10): 1202 - 1208. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Menon, R. A. Harrington, J. S. Hochman, C. P. Cannon, S. D. Goodman, R. G. Wilcox, H. J. Schunemann, and E. M. Ohman Thrombolysis and Adjunctive Therapy in Acute Myocardial Infarction: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Chest, September 1, 2004; 126(3_suppl): 549S - 575S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Spinosa, D. A. Leung, A. H. Matsumoto, E. A. Bissonette, D. Cage, N. L. Harthun, J. A. Kern, J. F. Angle, K. D. Hagspiel, I. K. Crosby, et al. Percutaneous Intentional Extraluminal Recanalization in Patients with Chronic Critical Limb Ischemia Radiology, August 1, 2004; 232(2): 499 - 507. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. H Trichon and M. T Roe Acute coronary syndromes and diabetes mellitus Diabetes and Vascular Disease Research, May 1, 2004; 1(1): 23 - 32. [Abstract] [PDF]
|
|
|
|
|
|
E. D. Peterson Reply J. Am. Coll. Cardiol., March 3, 2004; 43(5): 927 - 928. [Full Text] [PDF]
|
|
|
|
|
|
R. M. Califf Supplement on Acute Coronary Syndromes: Introduction Circulation, October 21, 2003; 108(90161): III-1 - 5. [Full Text] [PDF]
|
|
|
|
|
|
B. K. Nallamothu and E. R. Bates Periprocedural myocardial infarction and mortality: Causality versus association J. Am. Coll. Cardiol., October 15, 2003; 42(8): 1412 - 1414. [Full Text] [PDF]
|
|
|
|
|
|
J. E. Tcheng and M. E. Campbell Platelet inhibition strategies in percutaneous coronary intervention: Competition or coopetition? J. Am. Coll. Cardiol., October 1, 2003; 42(7): 1196 - 1198. [Full Text] [PDF]
|
|
|
|
|
|
J. E. Tcheng, D. E. Kandzari, C. L. Grines, D. A. Cox, M. B. Effron, E. Garcia, J. J. Griffin, G. Guagliumi, T. Stuckey, M. Turco, et al. Benefits and Risks of Abciximab Use in Primary Angioplasty for Acute Myocardial Infarction: The Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) Trial Circulation, September 16, 2003; 108(11): 1316 - 1323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. B. Granger, K. W. Mahaffey, W. D. Weaver, P. Theroux, J. S. Hochman, T. G. Filloon, S. Rollins, T. G. Todaro, J. C. Nicolau, W. Ruzyllo, et al. Pexelizumab, an Anti-C5 Complement Antibody, as Adjunctive Therapy to Primary Percutaneous Coronary Intervention in Acute Myocardial Infarction: The COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) Trial Circulation, September 9, 2003; 108(10): 1184 - 1190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Topol, D. Easton, R. A. Harrington, P. Amarenco, R. M. Califf, C. Graffagnino, S. Davis, H.-C. Diener, J. Ferguson, D. Fitzgerald, et al. Randomized, Double-Blind, Placebo-Controlled, International Trial of the Oral IIb/IIIa Antagonist Lotrafiban in Coronary and Cerebrovascular Disease Circulation, July 29, 2003; 108(4): 399 - 406. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. D. Peterson, C. V. Pollack Jr, M. T. Roe, L. S. Parsons, K. A. Littrell, J. G. Canto, H. V. Barron, and National Registry of Myocardial Infarction (NRMI) Early use of glycoprotein IIb/IIIa inhibitors in non-ST-elevation acute myocardial infarction: Observations from the National Registry of Myocardial Infarction 4 J. Am. Coll. Cardiol., July 2, 2003; 42(1): 45 - 53. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. P. Cannon and A. G.G. Turpie Unstable Angina and Non-ST-Elevation Myocardial Infarction: Initial Antithrombotic Therapy and Early Invasive Strategy Circulation, June 3, 2003; 107(21): 2640 - 2645. [Full Text] [PDF]
|
|
|
|
 |
|
 D L Brown Deaths associated with platelet glycoprotein IIb/IIIa inhibitor treatment Heart, May 1, 2003; 89(5): 535 - 537. [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]
|
|
|
|
|
|
C. P. Cannon Small molecule glycoprotein IIb/IIIa receptor inhibitors as upstream therapy in acute coronary syndromes: Insights from the TACTICS TIMI-18 trial J. Am. Coll. Cardiol., February 19, 2003; 41(4_Suppl_S): 43S - 48S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Cohen The role of low-molecular-weight heparin in the management of acute coronary syndromes J. Am. Coll. Cardiol., February 19, 2003; 41(4_Suppl_S): 55S - 61S. [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]
|
|
|
|
|
|
D. J. Kereiakes Platelet Glycoprotein IIb/IIIa Inhibition and Atheroembolism During Bypass Graft Angioplasty: A Cup Half Full Circulation, December 10, 2002; 106(24): 2994 - 2996. [Full Text] [PDF]
|
|
|
|
|
|
R. K. Yarlagadda and W. E. Boden Cardioprotective effects of an early invasive strategy for non-ST-segment elevationacute coronary syndromes: Are we all becoming "interventional" cardiologists? J. Am. Coll. Cardiol., December 4, 2002; 40(11): 1915 - 1918. [Full Text] [PDF]
|
|
|
|
|
|
W.-C. Chang, R.A. Harrington, M.L. Simoons, R.M. Califf, A.M. Lincoff, and P.W. Armstrong Does eptifibatide confer a greater benefit to patients with unstable angina than with non-ST segment elevation myocardial infarction?. Insights from the PURSUIT Trial Eur. Heart J., July 2, 2002; 23(14): 1102 - 1111. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. K. Dyke, R. C. Becker, N. S. Kleiman, J. S. Hochman, E. G. Bovill, A. M. Lincoff, G. Gerstenblith, V. Dzavik, L. H. Gardner, V. Hasselblad, et al. First Experience With Direct Factor Xa Inhibition in Patients With Stable Coronary Disease: A Pharmacokinetic and Pharmacodynamic Evaluation Circulation, May 21, 2002; 105(20): 2385 - 2391. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F.W.G. Leebeek, E. Boersma, C.P. Cannon, F.J.J. van de Werf, and M.L. Simoons Oral glycoprotein IIb/IIIa receptor inhibitors in patients with cardiovascular disease: why were the results so unfavourable Eur. Heart J., March 2, 2002; 23(6): 444 - 457. [Full Text] [PDF]
|
|
|
|
|
|
J. I. Weitz and H. R. Buller Direct Thrombin Inhibitors in Acute Coronary Syndromes: Present and Future Circulation, February 26, 2002; 105(8): 1004 - 1011. [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
H. D. White and C. K. Wong Risk stratification and treatment benefits in patients with non-ST-elevation acute coronary syndromes Eur. Heart J., February 1, 2002; 23(3): 187 - 191. [Full Text] [PDF]
|
|
|
|
|
|
Randomized, Placebo-Controlled Trial of Titrated Intravenous Lamifiban for Acute Coronary Syndromes Circulation, January 22, 2002; 105(3): 316 - 321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. T. Collaboration Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients BMJ, January 12, 2002; 324(7329): 71 - 86. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.E. Tcheng, J. Strony, T.J. Lorenz, and J.C. O'Shea ESPRIT in context: pharmacology matters! Eur. Heart J., November 1, 2001; 22(21): 1965 - 1967. [PDF]
|
|
|
|
 |
|
 D. E Newby and K. A A Fox Unstable angina: the first 48 hours and later in-hospital management Br. Med. Bull., October 1, 2001; 59(1): 69 - 87. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Genoni, D. Zeller, O. Bertel, M. Maloigne, and M. Turina Tirofiban therapy does not increase the risk of hemorrhage after emergency coronary surgery J. Thorac. Cardiovasc. Surg., September 1, 2001; 122(3): 630 - 632. [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Fitzgerald Vascular biology of thrombosis: The role of platelet-vessel wall adhesion Neurology, September 1, 2001; 57(90002): S1 - 4. [Abstract] [Full Text]
|
|
|
|
|
|
J. E. Tcheng, D. J. Kereiakes, A. M. Lincoff, B. S. George, N. S. Kleiman, D. C. Sane, D. B. Cines, R. E. Jordan, M. A. Mascelli, M. A. Langrall, et al. Abciximab Readministration: Results of the ReoPro Readministration Registry Circulation, August 21, 2001; 104(8): 870 - 875. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Heidenreich, T. Alloggiamento, K. Melsop, K. M. McDonald, A. S. Go, and M. A. Hlatky The prognostic value of troponin in patients with non-ST elevation acute coronary syndromes: a meta-analysis J. Am. Coll. Cardiol., August 1, 2001; 38(2): 478 - 485. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. E. Tardiff, L. K. Jennings, R. A. Harrington, D. Gretler, R. F. Potthoff, D. A. Vorchheimer, P. R. Eisenberg, A. M. Lincoff, M. Labinaz, D. M. Joseph, et al. Pharmacodynamics and Pharmacokinetics of Eptifibatide in Patients With Acute Coronary Syndromes: Prospective Analysis From PURSUIT Circulation, July 24, 2001; 104(4): 399 - 405. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. C. Gilchrist, J. C. O'Shea, T. Kosoglou, L. K. Jennings, T. J. Lorenz, M. M. Kitt, N. S. Kleiman, D. Talley, F. Aguirre, C. Davidson, et al. Pharmacodynamics and Pharmacokinetics of Higher-Dose, Double-Bolus Eptifibatide in Percutaneous Coronary Intervention Circulation, July 24, 2001; 104(4): 406 - 411. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. P. Cannon, W. S. Weintraub, L. A. Demopoulos, R. Vicari, M. J. Frey, N. Lakkis, F.-J. Neumann, D. H. Robertson, P. T. DeLucca, P. M. DiBattiste, et al. Comparison of Early Invasive and Conservative Strategies in Patients with Unstable Coronary Syndromes Treated with the Glycoprotein IIb/IIIa Inhibitor Tirofiban N. Engl. J. Med., June 21, 2001; 344(25): 1879 - 1887. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Throckmorton Future Trials of Antiplatelet Agents in Cardiac Ischemia N. Engl. J. Med., June 21, 2001; 344(25): 1937 - 1939. [Full Text] [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]
|
|
|
|
|
|
K. K. Wu and J. T. Willerson Monitoring Platelet Function in Glycoprotein IIb/IIIa Inhibitor Therapy Circulation, May 29, 2001; 103(21): 2528 - 2530. [Full Text] [PDF]
|
|
|
|
|
|
J. C. O'Shea, G. E. Hafley, S. Greenberg, V. Hasselblad, T. J. Lorenz, M. M. Kitt, J. Strony, J. E. Tcheng, and for the ESPRIT Investigators Platelet Glycoprotein IIb/IIIa Integrin Blockade With Eptifibatide in Coronary Stent Intervention: The ESPRIT Trial: A Randomized Controlled Trial JAMA, May 16, 2001; 285(19): 2468 - 2473. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Randomized Trial of Aspirin, Sibrafiban, or Both for Secondary Prevention After Acute Coronary Syndromes Circulation, April 3, 2001; 103(13): 1727 - 1733. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
British Cardiac Society Guidelines and Medical Pra and Royal College of Physicians Clinical Effectiveness Guideline for the management of patients with acute coronary syndromes without persistent ECG ST segment elevation Heart, February 1, 2001; 85(2): 133 - 142. [Full Text]
|
|
|
|
|
|
D. P. Chew, D. L. Bhatt, S. Sapp, and E. J. Topol Increased Mortality With Oral Platelet Glycoprotein IIb/IIIa Antagonists : A Meta-Analysis of Phase III Multicenter Randomized Trials Circulation, January 16, 2001; 103(2): 201 - 206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Ohman, R. A. Harrington, C. P. Cannon, G. Agnelli, J. A. Cairns, and J.W. Kennedy Intravenous Thrombolysis in Acute Myocardial Infarction Chest, January 1, 2001; 119 (2009): 253S - 277S. [Full Text] [PDF]
|
|
|
|
|
|
R. Curtin and D.J. Fitzgerald A cold start for oral glycoprotein IIb/IIIa antagonists Eur. Heart J., December 2, 2000; 21(24): 1992 - 1994. [PDF]
|
|
|
|
|
|
P.W. Armstrong Reperfusion synergism: will it be both sustained and safe? Eur. Heart J., December 1, 2000; 21(23): 1913 - 1916. [PDF]
|
|
|
|
|
|
D. Cox, R. Smith, M. Quinn, P. Theroux, P. Crean, and D. J. Fitzgerald Evidence of platelet activation during treatment with a GPIIb/IIIa antagonist in patients presenting with acute coronary syndromes J. Am. Coll. Cardiol., November 1, 2000; 36(5): 1514 - 1519. [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]
|
|
|
|
|
|
E Ronner, H.A.M van Kesteren, P Zijnen, E Altmann, P.G Molhoek, L.R van der Wieken, C.A Cuffie-Jackson, K.L Neuhaus, and M.L Simoons Safety and efficacy of eptifibatide vs placebo in patients receiving thrombolytic therapy with streptokinase for acute myocardial infarction. A phase II dose escalation, randomized, double-blind study Eur. Heart J., September 2, 2000; 21(18): 1530 - 1536. [Abstract] [PDF]
|
|
|
|
|
|
S. G. Goodman, M. Cohen, F. Bigonzi, E. P. Gurfinkel, D. R. Radley, V. Le Iouer, G. J. Fromell, C. Demers, A. G. G. Turpie, R. M. Califf, et al. Randomized trial of low molecular weight heparin (enoxaparin) versus unfractionated heparin for unstable coronary artery disease: One-year results of the essence study J. Am. Coll. Cardiol., September 1, 2000; 36(3): 693 - 698. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
E. M. Ohman, C. B. Granger, R. A. Harrington, and K. L. Lee Risk Stratification and Therapeutic Decision Making in Acute Coronary Syndromes JAMA, August 16, 2000; 284(7): 876 - 878. [Full Text] [PDF]
|
|
|
|
|
|
R. A. Harrington, P. W. Armstrong, C. Graffagnino, F. Van de Werf, D. J. Kereiakes, K. N. Sigmon, T. Card, D. M. Joseph, R. Samuels, J. Granett, et al. Dose-Finding, Safety, and Tolerability Study of an Oral Platelet Glycoprotein IIb/IIIa Inhibitor, Lotrafiban, in Patients With Coronary or Cerebral Atherosclerotic Disease Circulation, August 15, 2000; 102(7): 728 - 735. [Abstract] [Full Text] [PDF]
|
|
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|
|
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W Kubler Treatment of cardiac diseases: evidence based or experience based medicine? Heart, August 1, 2000; 84(2): 134 - 136. [Full Text] [PDF]
|
|
|
|
|
|
W. S. Weintraub, T. D. Thompson, S. Culler, S. J. Boccuzzi, E. R. Becker, A. S. Kosinski, and E. Mahoney Targeting Patients Undergoing Angioplasty for Thrombus Inhibition : A Cost-Effectiveness and Decision Support Model Circulation, July 25, 2000; 102(4): 392 - 398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. P. Cannon, C. H. McCabe, R. G. Wilcox, A. Langer, A. Caspi, P. Berink, J. Lopez-Sendon, J. Toman, A. Charlesworth, R. J. Anders, et al. Oral Glycoprotein IIb/IIIa Inhibition With Orbofiban in Patients With Unstable Coronary Syndromes (OPUS-TIMI 16) Trial Circulation, July 11, 2000; 102(2): 149 - 156. [Abstract] [Full Text] [PDF]
|
|
|
|
|
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K. A A Fox CORONARY DISEASE: Acute coronary syndromes: presentation---clinical spectrum and management Heart, July 1, 2000; 84(1): 93 - 93. [Full Text] [PDF]
|
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|
|
|
|
E. Boersma, K. S. Pieper, E. W. Steyerberg, R. G. Wilcox, W.-C. Chang, K. L. Lee, K. M. Akkerhuis, R. A. Harrington, J. W. Deckers, P. W. Armstrong, et al. Predictors of Outcome in Patients With Acute Coronary Syndromes Without Persistent ST-Segment Elevation : Results From an International Trial of 9461 Patients Circulation, June 6, 2000; 101(22): 2557 - 2567. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Harrington Cardiac enzyme elevations after percutaneous coronary intervention: myonecrosis, the coronary microcirculation and mortality J. Am. Coll. Cardiol., April 1, 2000; 35(5): 1142 - 1144. [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]
|
|
|
|
 |
|
 A. Brodison, R. Katira, R. S More, and A. Chauhan Current practice: Antiplatelet use in interventional cardiology Postgrad. Med. J., February 1, 2000; 76(892): 70 - 79. [Abstract] [Full Text]
|
|
|
|
|
|
D. B. Mark, R. A. Harrington, A. M. Lincoff, R. M. Califf, C. L. Nelson, A. A. Tsiatis, H. Buell, K. W. Mahaffey, L. Davidson-Ray, and E. J. Topol Cost-Effectiveness of Platelet Glycoprotein IIb/IIIa Inhibition With Eptifibatide in Patients With Non-ST-Elevation Acute Coronary Syndromes Circulation, February 1, 2000; 101(4): 366 - 371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Alexander, R. A. Sparapani, K. W. Mahaffey, J. W. Deckers, L. K. Newby, E. M. Ohman, R. Corbalan, S. L. Chierchia, J. B. Boland, M. L. Simoons, et al. Association Between Minor Elevations of Creatine Kinase-MB Level and Mortality in Patients With Acute Coronary Syndromes Without ST-Segment Elevation JAMA, January 19, 2000; 283(3): 347 - 353. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Smith and J. L. Mehta Reviews: Glycoprotein IIb/IIIa Receptor Inhibitors in Acute Coronary Syndromes: Conquests and New Challenges Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 2000; 5(3): 143 - 150. [PDF]
|
|
|
|
|
|
E. Boersma, K. M. Akkerhuis, P. Theroux, R. M. Califf, E. J. Topol, and M. L. Simoons Platelet Glycoprotein IIb/IIIa Receptor Inhibition in Non-ST-Elevation Acute Coronary Syndromes : Early Benefit During Medical Treatment Only, With Additional Protection During Percutaneous Coronary Intervention Circulation, November 16, 1999; 100(20): 2045 - 2048. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.A.A. Fox Specific antithrombins in the context of current treatment for acute coronary syndromes Eur. Heart J., November 1, 1999; 20(21): 1519 - 1521. [PDF]
|
|
|
|
|
|
C. P. Cannon Overcoming thrombolytic resistance: Rationale and initial clinical experience combining thrombolytic therapy and glycoprotein IIb/IIIa receptor inhibition for acute myocardial infarction J. Am. Coll. Cardiol., November 1, 1999; 34(5): 1395 - 1402. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. W. Armstrong Unsticking platelets: the role of glycoprotein IIb/IIIa receptor blockade Can. Med. Assoc. J., November 1, 1999; 161(11): 1423 - 1424. [Full Text] [PDF]
|
|
|
|
|
|
T. J. Ryan, E. M. Antman, N. H. Brooks, R. M. Califf, L. D. Hillis, L. F. Hiratzka, E. Rapaport, B. Riegel, R. O. Russell, E. E. Smith III, et al. 1999 update: ACC/AHA guidelines for the management of patients with acute myocardial infarction: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction) J. Am. Coll. Cardiol., September 1, 1999; 34(3): 890 - 911. [Full Text] [PDF]
|
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|
|
 |
|
 C. M. Gibson Primary Angioplasty Compared with Thrombolysis: New Issues in the Era of Glycoprotein IIb/IIIa Inhibition and Intracoronary Stenting Ann Intern Med, May 18, 1999; 130(10): 841 - 847. [Abstract] [Full Text] [PDF]
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 Super Antiplatelet Agents: Proven Therapy for Acute Coronary Syndromes Journal Watch Emergency Medicine, February 1, 1999; 1999(201): 5 - 5. [Full Text]
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