Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_4011_Библиотеки_им_академика_М_И_Перельмана
.pdf
190 Part II / GPIIb/IIIa Blockade During Coronary Intervention
in the composite endpoint of death or myocardial infarction by 30 d (16.8 vs 11.8%, 30%
relative risk reduction, p = 0.01).
In PRISM PLUS, 1570 patients were treated with placebo or tirofiban (0.4 µg/kg/min
for 30 min and then 0.1 µg/kg/min infusion for 48–96 h in addition to aspirin and heparin)
(42). Catheterization and percutaneous revascularization were encouraged, but to be
deferred for 48 h, and 475 patients underwent coronary intervention while receiving study
drug. During the first 48 h (before intervention), death or myocardial infarction rates
were reduced from 2.6 to 0.9% by tirofiban in the overall 1570 patient cohort (p = 0.01);
among the 475 patients undergoing intervention, 30-d rates of death or myocardial infarc-
tion were 10.2 and 5.9% in the placebo and tirofiban groups, respectively (42% relative
risk reduction, p = 0.12). In PARAGON B, 5225 patients were randomized to receive
placebo or lamifiban, a non-peptide small molecule GPIIb/IIIa inhibitor similar to tirofi-
ban, for 72 h (43). Catheterization and revascularization were performed at the physician’s
discretion. Among the 678 patients undergoing PCI while on study drug, the composite
endpoint of death or myocardial infarction was reduced from 0.85 to 0.31% prior to PCI
and from 12.8 to 8.9% following PCI.
SYNTHESIS OF THE RANDOMIZED TRIALS
Efficacy
The consistent finding among over 25,000 patients enrolled in the trials of GPIIb/IIIa
receptor blockade during coronary intervention has been that of reduction in the risk of
important acute ischemic events by as much as 50–60%, unequivocally establishing the
clinical efficacy of this class of therapy in this setting. This treatment effect extends to each
of the components of the composite clinical endpoint (death, myocardial infarction, and
emergency revascularization), attesting to the common platelet/thrombus-mediated patho-
physiology of these events. The inhibition of acute ischemic events is achieved early,
primarily in the first 12–48 h after the revascularization procedure, and is almost invariably
maintained without attenuation thereafter. Over long-term (3-yr or more) follow-up, a
20–25% relative reduction in mortality has been convincingly demonstrated with abcixi-
mab; it is unknown whether a similar benefit is associated with eptifibatide or tirofiban.
Improved outcome with this therapy has been apparent in every subgroup of patients
tested, and no demographic, clinical, angiographic, or procedural characteristic has been
observed that will identify patients who do not benefit from GPIIb/IIIa blockade. Patients
with acute ischemic syndromes such as unstable angina, however, may derive exceptional
treatment effect from this class of therapy. Other subsets of patients who are at increased
risk for acute ischemic events, such as those requiring bailout stenting (44) or with diabetes
(45,46), also tended to experience a enhanced absolute treatment effect from GPIIb/IIIa
inhibition.
Clinical benefit is derived from GPIIb/IIIa blockade irrespective of the technique or
modality used for percutaneous coronary revascularization. The EPISTENT trial clearly
demonstrated a magnitude of treatment effect with abciximab during elective stenting
(absolute risk reduction 5.5%, relative risk reduction 51%) that was essentially identical
to that obtained with abciximab during balloon angioplasty in EPILOG (absolute risk
reduction 6.4%, relative risk reduction 56%). Similarly, subgroup analysis of patients in
EPIC and EPILOG undergoing directional atherectomy confirmed previous findings that
atherectomy patients are at substantially greater risk for ischemic complications than their
https://t.me/med1917
Chapter 8 / Overview of the GPIIb/IIIa Interventional Trials 191
counterparts treated with angioplasty and that the treatment effect of abciximab during
atherectomy tended, if anything, to be greater than that during balloon angioplasty (47).
The decision to utilize these agents during a revascularization procedure thus should not
be made contingent on whether balloon angioplasty, stent implantation, or atherectomy
is planned.
An important influence of GPIIb/IIIa blockade on restenosis following PCI is unlikely.
Although a significant reduction by abciximab in long-term target vessel revascularization
rates was observed in the EPIC trial, this treatment effect has not been definitively con-
firmed in any subsequent study of a GPIIb/IIIa inhibitor. In-stent restenosis among diabetic
patients may be somewhat favorably influenced by abciximab or tirofiban, but this find-
ing cannot be definitively confirmed.
D
IFFERENCES IN EFFICACY AMONG THE AGENTS
Although all three of the GPIIb/IIIa inhibitors reduce ischemic risk, there has been
apparent heterogeneity among the drugs since the earliest trials with regard to the magni-
tude of treatment effect. The bolus and 12-h infusion regimen of abciximab reduced 30-d
endpoints by as much as 50–60% in the EPILOG and EPISTENT trials, whereas more
modest risk reductions on the order of 15–25% were seen with eptifibatide and tirofiban
in IMPACT-II and RESTORE, respectively. It has been hypothesized that variability in
efficacy among agents, if it exists, may relate to the pharmacodynamics of receptor bind-
ing. Abciximab dissociates slowly from the GPIIb/IIIa receptor, thus providing gradu-
ally diminished inhibition of platelet aggregation for 12–24 h or more after termination
of drug infusion (6,8); in contrast, platelet aggregation following discontinuation of the
rapidly reversible agents (eptifibatide and tirofiban) is normalized within 2–4 h (9,10).
Additionally, the nonspecific blockade by abciximab of the α
v
β
3
(vitronectin) and α
m
β
2
(Mac-1) receptors in addition to platelet GPIIb/IIIa (α
Iib
β
3
) theoretically may provide
advantages over the specific agents (which bind exclusively to GPIIb/IIIa). Ex vivo expe-
rimental studies, for example, have suggested that blockade of GPIIb/IIIa and the vitro-
nectin receptors more completely suppresses platelet-mediated thrombin generation than
does inhibition of either receptor alone (48). Inhibition of Mac-1 may have additional salu-
tary effects related to suppression of inflammation or vascular smooth muscle cell death (49).
More contemporary trials of the small-molecule GPIIb/IIIa inhibitors have provided
conflicting evidence regarding the effectiveness of eptifibatide and tirofiban relative to
abciximab. The ESPRIT trial showed a substantial clinical benefit of high-dose eptifiba-
tide compared with placebo, convincingly demonstrating the importance of adequate plate-
let inhibition with these agents. The treatment effect of eptifibatide in ESPRIT can be com-
pared only indirectly with that of abciximab in EPISTENT, with all the limitations inherent
to intertrial comparisons. Nevertheless, three general observations can be made.
First, ESPRIT enrolled a lower risk group of patients than did EPISTENT, by virtue
of its exclusion of those with severe unstable angina, recent myocardial infarction, or
bypass graft disease. Second, the use of a low-dose heparin regimen (60 U/kg) in both
treatment arms raises the question of whether insufficient anticoagulation was provided
for those randomized to placebo; the median ACT was only 263 s in the placebo arm of
ESPRIT, whereas retrospective studies have suggested that an optimal ACT level for PCI
performed without GPIIb/IIIa blockade is in the range of 350–375 s (50). In contrast, the
heparin dose in EPISTENT was higher in the placebo arm (100 U/kg) than in the abciximab
arms (70 U/kg), and the median ACT among patients randomized to placebo in EPISTENT
https://t.me/med1917
192 Part II / GPIIb/IIIa Blockade During Coronary Intervention
was 346 s. Concerns regarding the adequacy of anticoagulation in ESPRIT are com-
pounded by the prohibition of thienopyridine pretreatment. These factors could have
increased the ischemic event rate in the placebo group of that trial, thereby exaggerating
the apparent treatment effect of eptifibatide. Third, the magnitude of short-term and long-
term treatment effect with eptifibatide in ESPRIT was numerically less than that of abcixi-
mab in EPISTENT at each time point (Fig. 6); although there is clearly no statistical basis
to conclude that the results of these trials are dissimilar, the trends are noteworthy.
In contrast to eptifibatide, tirofiban has been compared directly with abciximab in the
TARGET trial. Although this study was intended to show noninferiority of tirofiban, short-
term ischemic event rates were significantly lower with abciximab, reinforcing the evi-
dence for a differential treatment effect among the agents. Notably, this early difference
in ischemic complications did not translate to a significant difference between tirofiban
and abciximab treatment groups with regard to mortality at 1 yr, although TARGET was
not designed with an adequate sample size to have statistical power to assess this infre-
quent mortality endpoint.
Safety
BLEEDING
The major potential safety issue with this as well as other classes of agents directed
against platelet function or coagulation is that of bleeding. The findings of the first trial
of this class of therapy, EPIC, highlighted the potential for hemorrhagic risk with these
agents. Most bleeding with GPIIb/IIIa antagonists in this and subsequent trials was at sites
of vascular access, although spontaneous gastrointestinal and genitourinary bleeding also
occurred; long-term sequelae were infrequent. Importantly, pooled analysis of the trials
indicates that rates of intracranial hemorrhage do not appear to be increased (51). The
improvement in the safety profile of these agents subsequent to the EPIC experience
shows that modification of conjunctive anticoagulant therapy with heparin by weight
adjustment and dose reduction is a key intervention in abrogating excess bleeding risk.
Fig. 6. Comparison of EPISTENT (abciximab vs placebo) and ESPRIT (eptifibatide vs placebo) trial end-
points at 30 d, 6 mo, and 1 yr. MI, myocardial infarction; RR, risk reduction; Urg Revasc, urgent revas-
cularization. One-year mortality endpoint is treated patient analysis.
https://t.me/med1917
Chapter 8 / Overview of the GPIIb/IIIa Interventional Trials 193
Early removal of vascular sheaths and meticulous care of the access site are probably also
important means of avoiding hemorrhage. Bleeding may nevertheless be a concern in
certain groups of patients, such as those who receive GPIIb/IIIa blockade as an unplanned
or bailout intervention in the setting of full-dose heparinization or those undergoing
rescue angioplasty for failed reperfusion after full-dose thrombolysis. Partial reversal of
heparinization with protamine in the former situation and very careful heparin dose reduc-
tion and ACT monitoring in the latter will probably improve the balance between risk and
benefit in these patients.
For patients who develop refractory or life-threatening bleeding, the antiplatelet effect
of abciximab may be reversed by discontinuation of drug infusion and by platelet trans-
fusion after the approx 10–30 min required for clearance of circulating drug. After intro-
duction of new platelets into the circulation, abciximab redistributes from old to new
platelets, reducing the mean level of receptor blockade. In experimental studies, trans-
fusion of the equivalent of 10 U of platelets in primates treated with abciximab led to
prompt reduction in mean receptor blockade from 80–90% to <70%, near normalization
of bleeding times, and partial (approx 30%) recovery of platelet aggregation (52). Platelet
transfusions should rarely be necessary with the rapidly reversible agents eptifibatide and
tirofiban, but theoretically they would not be effective during the approx 2 h required for
elimination of high concentrations of these agents from the circulating plasma phase.
E
MERGENCY CORONARY BYPASS SURGERY
There has been concern about the risk of excessive perioperative bleeding if patients
require urgent coronary artery bypass surgery for failed angioplasty after administration of
a GPIIb/IIIa inhibitor. The rapidly reversible agents eptifibatide and tirofiban should pres-
ent little in the way of perioperative bleeding risk in this regard; platelet aggregation and
bleeding times return to normal following discontinuation of both of these agents within
a few hours, the time period required for coronary artery bypass to be performed. Despite its
more prolonged duration of action, however, antecedent treatment with abciximab should
not be considered a contraindication to necessary emergency surgical revascularization.
In a detailed study of surgical outcomes among 85 patients requiring urgent coronary
surgery in the EPILOG and EPISTENT trials, abciximab therapy was not associated with
a major increase in perioperative blood loss (53). Platelet transfusions were administered
more frequently (in part prophylactically) to patients who had received abciximab, but the
need for other blood products was the same in the abciximab and placebo groups. Although
surgical reexploration for bleeding tended to be more frequent in patients who had received
abciximab, surgical cross-clamp, cardiopulmonary bypass, and closure times were not pro-
longed, and the utilization of optimal mammary artery conduits was not impaired. More-
over, ischemic events tended to be less frequent in abciximab-treated patients. Thus,
hemorrhagic risk may be modestly increased by abciximab in the event of urgent coronary
bypass surgery, but it is unlikely to be associated with excess mortality or important mor-
bidity. Conventional procedures for intraoperative ACT-guided heparin dosing and selec-
tive application of platelet transfusions appear to be appropriate for the management of
these patients.
T
HROMBOCYTOPENIA
Thrombocytopenia occurs infrequently following GPIIb/IIIa inhibition, but it may be
precipitous and profound (platelet count <20,000 mm
−3
); the excess risk of profound
https://t.me/med1917
194 Part II / GPIIb/IIIa Blockade During Coronary Intervention
thrombocytopenia associated with abciximab (0.4–1.1%) appears to be higher than with
eptifibatide (0–0.2%) or tirofiban (0.1–0.3%). Thrombocytopenia in this setting is not a
benign event. In a pooled analysis of 7290 patients in the EPIC, EPILOG, and EPISTENT
trials, 178 (2.4%) developed thrombocytopenia, with an independent association observed
with abciximab therapy (odds ratio 1.75) (54). Even with the analysis confined to the 126
patients without antecedent coronary bypass surgery, those with thrombocytopenia had
significantly higher rates of major and minor hemorrhage (33% vs 9%, p < 0.001), red cell
transfusions (21% vs 5%, p < 0.001), and 30-d mortality (4.8% vs 0.6%, p < 0.001) than
did patients without thrombocytopenia. Perhaps somewhat surprisingly, however, bleed-
ing complications and mortality were less frequent if thrombocytopenia occurred in patients
who had been randomized to abciximab than if thrombocytopenia was in the context of
placebo administration.
The mechanism of thrombocytopenia associated with GPIIb/IIIa inhibitors is unknown.
Thrombocytopenia occurring after administration of a GPIIb/IIIa agent can usually be
differentiated from that caused by the heparin-induced thrombocytopenia syndrome by
the early and precipitous onset, generally within 1–24 h after administration of the GPIIb/
IIIa inhibitor (55), as well as by the absence of thrombotic complications. There is little
evidence of ongoing platelet clearance following discontinuation of the GPIIb/IIIa an-
tagonist, and most patients experience an increase in platelet count of about 20–30,000
mm
−3
/d (the rate of bone marrow production). Unlike heparin-induced thrombocytopenia,
platelet transfusions are a safe and protective therapy for profound thrombocytopenia
with or without serious bleeding induced by GPIIb/IIIa inhibitors. Platelet counts should
be measured within the first 2–4 h after administration of these agents and followed for
the duration of therapy.
R
EADMINISTRATION
Approximately 5–6% of patients will develop a human antichimeric antibody (HACA)
response to abciximab; no antibody response has been observed with eptifibatide, tiro-
fiban, or lamifiban. A prospective registry found no instances of hypersensitivity or ana-
phylactic reactions following abciximab readministration in 500 patients, and efficacy of
the agent in reducing ischemic complications appeared to be similar with readministration
as with first-time use (56). The rates of profound thrombocytopenia (platelet count <20,000
mm
−3
) following readministration were somewhat higher, however, than expected with
first-time administration. Moreover, in contrast to the typically rapid resolution of throm-
bocytopenia seen with first-time administration, a protracted time course of thrombo-
cytopenia for up to 1 wk was observed in these patients following readministration. The
presence or absence of a positive HACA titer did not appear to be predictive of a lack of
clinical effectiveness, development of thrombocytopenia, or other sequelae in patients
undergoing readministration.
RECOMMENDATIONS
Whom to Treat
Although trial data support the use of GPIIb/IIIa inhibitors in virtually all patients under-
going percutaneous coronary revascularization, these agents are not universally employed
in clinical practice, primarily because of economic considerations. Economic aspects of
GPIIb/IIIa blockade are discussed in detail in Chapter 14; it is important to recognize that
https://t.me/med1917
Chapter 8 / Overview of the GPIIb/IIIa Interventional Trials 195
cost savings derived from reduction in ischemic events offset much of the acquisition
cost of these agents. Moreover, the cost effectiveness of abciximab in reducing mortality
during coronary stenting appears quite favorable, approx $6200 per life-year saved, well
within the range of other accepted medical therapies (57). Economic considerations
aside, the benefits of this therapy should certainly be provided to patients at elevated risk
for periprocedural complications, such as those with unstable angina or acute myocardial
infarction, diabetes mellitus, complex lesion morphology, extensive myocardium at jeop-
ardy, or multivessel or multilesion interventions. Although anecdotal data suggest that
abciximab may be useful in an unplanned or bailout fashion to reverse thrombotic compli-
cations of coronary intervention (58,59), this approach has never been tested in a random-
ized fashion and must be regarded as suboptimal relative to planned use.
Which Agent to Use
Aside from the economic considerations, the available data suggest that the current
efficacy standard during and after percutaneous coronary intervention remains abciximab
administered as a bolus followed by a 12-h infusion. Aspirin, heparin, and ticlopidine or
clopidogrel (in patients receiving stents) should also be administered (60). A pretreat-
ment regimen of abciximab, as was used in CAPTURE, may be effective in stabilizing
patients prior to coronary revascularization, but it offers no clear advantage in stable
patients or even in unstable patients for whom revascularization can be immediately per-
formed. Regardless of whether or not a period of pretreatment with abciximab is used,
the 12-h postprocedural infusion appears to be necessary for optimal clinical benefit.
Even for situations in which broad use of abciximab is precluded because of economic
considerations, there is little justification for withholding the less expensive agents eptifib-
atide or tirofiban. The treatment effects of these GPIIb/IIIa inhibitors are considerable,
if not clearly equivalent to that of abciximab, and certainly justify their relatively modest
costs. A reasonable compromise between efficacy and cost might be to utilize abciximab
for those settings in which enhanced benefit has been observed with this agent relative to
the reversible inhibitors. In particular, patients with severe unstable ischemic syndromes
were excluded from inclusion in the ESPRIT trial and had a particularly inferior outcome
with tirofiban in TARGET. Abciximab is the only agent that has been tested during pri-
mary PCI for acute myocardial infarction. The robust mortality benefit of abciximab in
diabetics has also not been duplicated with the reversible agents.
For patients presenting with unstable angina or non-Q-wave myocardial infarction in
whom revascularization is not immediately planned, both eptifibatide and tirofiban have
been unequivocally shown to improve clinical outcome prior to intervention, following
intervention, or in patients treated conservatively without early intervention (see Chapter
10). Once a course of empiric therapy with eptifibatide or tirofiban has been initiated, there
are no data to suggest that patients would experience incremental benefit by conversion
to abciximab during subsequent percutaneous coronary revascularization, as the treat-
ment effects of eptifibatide and tirofiban in PURSUIT and PRISM PLUS were consider-
able in these patients.
Conjunctive Heparin and Vascular Access Site Management
A low-dose, weight-adjusted heparin regimen, using an initial bolus of 60–70 U/kg (max-
imum 6000–7000 U) adjusted to attain and maintain an ACT of ≥ 200 s, has clearly been
shown to be a safe and effective means of administering heparin when GPIIb/IIIa inhibitor
https://t.me/med1917
196 Part II / GPIIb/IIIa Blockade During Coronary Intervention
therapy is planned. There are no data to suggest that postprocedural heparin provides addi-
tional benefit in this setting, even in patients treated for acute ischemic syndromes; vascu-
lar access sheaths can typically be removed 2–6 h after the procedure, during the GPIIb/
IIIa inhibitor infusion, once the ACT is <175 s or the aPTT is <50 s. Manual or mechanical
groin compression should be maintained for at least 30 min, followed by strict bed rest with
leg immobilization for 6–8 h after sheath removal. Alternatively, vascular closure devices
may be used immediately and appear to be effective in patients who have received GPIIb/
IIIa antagonists. Other measures to help reduce bleeding risk at the vascular access site
include anterior arterial puncture only (rather than the traditional Seldinger “through-and-
through” technique), avoidance of routine venous sheath placement, and adequate patient
sedation and immobilization during periods of strict bed rest.
SUMMARY
Platelet GPIIb/IIIa receptor blockade represents one of the most significant advances
in the practice of interventional cardiology. Large-scale randomized controlled trials have
unequivocally demonstrated that these agents reduce the risk of periprocedural ischemic
complications by up to 50–60% and are efficacious in a broad spectrum of patients under-
going revascularization irrespective of risk profile, clinical indication for revasculariza-
tion, or interventional technique. This clinical benefit may be achieved without excess
major bleeding risk by modification of conjunctive heparin dosing. Issues for future study
include critical evaluation of the medicoeconomic aspects of this therapy, the effectiveness
of these agents when used in an unplanned or bailout fashion, and the potential for combin-
ing GPIIb/IIIa antagonists with novel inhibitors of thrombin or other components of the
coagulation cascade.
REFERENCES
1. Steele PM, Chesebro JH, Stanson AW, et al. Balloon angioplasty. Natural history of the pathophysio-
logical response to injury in a pig model. Circ Res 1985;57:105–112.
2. Uchida Y, Hasegawa K, Kawamura K, Shibuya I. Angioscopic observation of the coronary luminal
changes induced by percutaneous transluminal coronary angioplasty. Am Heart J 1989;117:769–776.
3. Schwartz L, Bourassa MG, Lesperance J, et al. Aspirin and dipyridamole in the prevention of restenosis
after percutaneous transluminal coronary angioplasty. N Engl J Med 1988;318:1714–1719.
4. Phillips DR, Charo IF, Parise LV, Fitzgerald LA. The platelet membrane glycoprotein IIb/IIIa complex.
Blood 1988;71:831–843.
5. Coller BS. Blockade of platelet GPIIb/IIIa receptors as an antithrombotic strategy. Circulation 1995;92:
2373–2380.
6. Tcheng JE, Ellis SG, George BS, et al. Pharmacodynamics of chimeric glycoprotein IIb/IIIa integrin
antiplatelet antibody Fab 7E3 in high-risk coronary angioplasty. Circulation 1994;90:1757–1764.
7. Kleiman NS, Raizner AE, Jordan R, et al. Differential inhibition of platelet aggregation induced by ade-
nosine diphosphate or a thrombin receptor-activating peptide in patients treated with bolus chimeric 7E3
Fab: implications for inhibition of the internal pool of GPIIb/IIIa receptors. J Am Coll Cardiol 1995;26:
1665–1671.
8. 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.
9. Harrington RA, Kleiman NS, Kottke-Marchant K, et al. Immediate and reversible platelet inhibition after
intravenous administration of a peptide glycoprotein IIb/IIIa inhibitor during percutaneous coronary inter-
vention. Am J Cardiol 1995;76:1222–1227.
10. Kereiakes DJ, Kleiman NS, Ambrose J, et al. Randomized, double-blind, placebo-controlled dose-rang-
ing study of tirofiban (MK-383) platelet IIb/IIIa blockade in high risk patients undergoing coronary
angioplasty. J Am Coll Cardiol 1996;27:536–542.
https://t.me/med1917
Chapter 8 / Overview of the GPIIb/IIIa Interventional Trials 197
11. 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.
12. Lincoff AM, Tcheng JH, Bass TA, et al. A multicenter, randomized, double-blind pilot trial of standard
versus low dose weight-adjusted heparin in patients treated with the platelet glycoprotein IIb/IIIa recep-
tor antibody 7E3 during percutaneous coronary revascularization (abstr). J Am Coll Cardiol 1995;25:
80A.
13. 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.
14. 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.
15. IMPACT II Investigators. Randomized placebo-controlled trial of effect of eptifibatide on complica-
tions of percutaneous coronary intervention: IMPACT II. Lancet 1997;349:1422–1428.
16. Phillips DR, Teng W, Arfstent A, et al. Effect of Ca
2+
on GP IIb-IIIa interactions with Integrilin.
Enhanced GP IIb-IIIa binding and inhibition of platelet aggregation by reductions in the concentration
of ionized calcium in plasma anticoagulated with citrate. Circulation 1997;96:1488–1494.
17. Tcheng JE, Talley JD, O’Shea JC, et al. Clinical pharmacology of higher-dose eptifibatide in percuta-
neous coronary intervention: results of the PRIDE study. Am J Cardiol 2001;88:1097–1102.
18. ESPRIT Investigators. Novel dosing regimen of eptifibatide in planned coronary stent implantation
(ESPRIT): a randomised, placebo-controlled trial. Lancet 2000;356:2037–2044.
19. RESTORE Investigators. Effects of platelet glycoprotein IIb/IIIa blockade with tirofiban on adverse
cardiac events in patients with unstable angina or acute myocardial infarction undergoing coronary angio-
plasty. Circulation 1997;96:1445–1453.
20. CAPTURE Investigators. Randomised placebo-controlled trial of abciximab before and during coro-
nary intervention in refractory unstable angina: the CAPTURE Study. Lancet 1997;349:1429–1435.
21. Brener SJ, Barr LA, Burchenal JEB, et al., on behalf of the ReoPro and Primary PTCA Organization and
Randomized Trial (RAPPORT) Investigators. A randomized, placebo-controlled trial of platelet glyco-
protein IIb/IIIa blockade with primary angioplasty for acute myocardial infarction. Circulation 1998;98:
734–741.
22. Neumann F, Kastrati A, Schmitt C, et al. Effect of glycoprotein IIb/IIIa receptor blockade with abciximab
on clinical and angiographic restenosis rate after the placement of coronary stents following acute
myocardial infarction. J Am Coll Cardiol 2000;35:915–921.
23. Montalescot G, Barragan P, Wittenberg O, et al., for the ADMIRAL Investigators. Platelet glycopro-
tein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction. N Engl J Med 2001;344:
1895–1903.
24. Stone GW, Grines CL, Cox DA, et al., CADILLAC Investigators. Comparison of angioplasty with
stenting, with or without abciximab, in acute myocardial infarction. N Engl J Med 2002;346:957–966.
25. Topol EJ, Moliterno DJ, Herrmann HC, et al., for the TARGET Investigators. Comparison of two plate-
let glycoprotein IIb/IIIa inhibitors, tirofiban and abciximab, for the prevention of ischemic events with
percutaneous coronary revascularization. N Engl J Med 2001;344:1888–1894.
26. Lincoff AM, Califf RM, Anderson KM, et al. Evidence for prevention of death and myocardial infarction
with platelet membrane glycoprotein IIb/IIIa receptor blockade by c7E3 Fab (abciximab) among patients
with unstable angina undergoing percutaneous coronary revascularization. J Am Coll Cardiol 1997;30:
149–156.
27. Steinhubl SR, Lauer MD, Mukherjee DP, et al. The duration of pretreatment with ticlopidine prior to stent-
ing is associated with the risk of procedure-related non-Q-wave myocardial infarctions. J Am Coll Cardiol
1998;32:1366–1370.
28. Rao AK, Pratt C, Berke A, et al., for TIMI Investigators. Thrombolysis in Myocardial Infarction (TIMI)
trial—Phase I: hemorrhagic manifestations and changes in plasma fibrinogen and the fibrinolytic system
in patients treated with recombinant tissue plasminogen activator and streptokinase. J Am Coll Cardiol
1988;11:1–11.
29. TARGET Investigators. Comparison of two platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abcixi-
mab, for the prevention of ischemic events with percutaneous coronary revascularization. N Engl J Med
2001;344:1888–1894.
30. Abdelmeguid AE, Topol EJ, Whitlow PL, Sapp SK, Ellis SG. Significance of mild transient release of crea-
tine kinase-MB fraction after percutaneous coronary intervention. Circulation 1996;94:1528–1536.
31. Kugelmass AD, Cohen CJ, Moscucci M, et al. Elevation in creatine kinase myocardial isoform following
otherwise successful directional coronary atherectomy and stenting. Am J Cardiol 1994;74:748–754.
https://t.me/med1917
198 Part II / GPIIb/IIIa Blockade During Coronary Intervention
32. Harrington RA, Lincoff AM, Califf RM, et al., for the CAVEAT investigators. Characteristics and
consequences of myocardial infarction after percutaneous coronary intervention: insights from the coro-
nary angioplasty versus excisional atherectomy trial (CAVEAT). J Am Coll Cardiol 1995;25:1693–1699.
33. 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.
34. Tardiff BE, Califf RM, Tcheng JE, et al., for the IMPACT-II Investigators. Post-intervention cardiac
enzyme elevations: prognostic significance in IMPACT II (abstr). J Am Coll Cardiol 1996;27:83A.
35. Redwood SR, Popma JJ, Kent KK, et al. Predictors of late mortality following ablative new-device
angioplasty in native coronary arteries (abstr). J Am Coll Cardiol 1996;27:167A.
36. Topol EJ, Ferguson JJ, Weisman HF, et al., for the EPIC Investigator Group. Long-term protection from
myocardial ischemic events in a randomized trial of brief integrin β3 blockade with percutaneous coro-
nary intervention. JAMA 1997;278:479–484.
37. Ellis SG, Lincoff AM, Miller D, et al., for the EPIC and EPILOG Investigators. Reduction in complica-
tions of angioplasty with abciximab occurs largely independently of baseline lesion morphology. J Am
Coll Cardiol 1998;32:1619–1623.
38. Anderson KM, Califf RM, Stone GW, et al. Long-term mortality benefit with abciximab in patients under-
going percutaneous coronary intervention. J Am Coll Cardiol 2001;37:2059–2065.
39. O’Shea JC, Buller CE, Cantor WJ, et al., for the EsPRIT Investigators. Long-term efficacy of platelet
glycoprotein IIb/IIIa integrin blockade with eptifibatide in coronary stent intervention. JAMA 2002;287:
618–621.
40. ERASER Investigators. Acute platelet inhibition with abciixmab does not reduce in-stent restenosis
(ERASER Study). Circulation 1999;100:799–806.
41. PURSUIT Trial Investigators. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with
acute coronary syndromes. N Engl J Med 1998;339:436–443.
42. 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.
43. PARAGON-B Investigators. Randomized, placebo-controlled trial of titrated intravenous lamifiban for
acute coronary syndromes. Circulation 2002;105:316–321.
44. Kereiakes DJ, Lincoff AM, Miller DP, et al., for the EPILOG Investigators. Abciximab therapy and
unplanned coronary stent deployment. Favorable effects on stent use, clinical outcomes, and bleeding
complications. Circulation 1998;97:857–864.
45. Marso S, Lincoff A, Ellis S, et al., EPISTENT Investigators. Optimizing the percutaneous interventional
outcomes for patients with diabetes mellitus. Circulation 1999;100:2477–2484.
46. Bhatt D, Marso S, Lincoff A, Wolski K, Ellis S, Topol E. Abciximab reduces mortality in diabetics fol-
lowing percutaneous intervention. JACC 2000;35:922–928.
47. Ghaffari S, Kereiakes DJ, Lincoff AM, et al., for the EPILOG Investigators. Platelet glycoprotein IIb/
IIIa receptor blockade with abciximab reduces ischemic complications in patients undergoing directional
coronary atherectomy. Am J Cardiol 1998;82:7–12.
48. Reverter JC, Beguin S, Kessels H, Kumar R, Hemker HC, Coller BS. Inhibition of platelet-mediated,
tissue factor-induced thrombin generation by the mouse/human chimeric 7E3 antibody. J Clin Invest 1996;
98:863–874.
49. Seshiah PN, Kereiakes DJ, Vasudevan SS, et al. Activated monocytes induce smooth muscle cell death.
Role of macrophage colony stimulating factor and cell contact. Circulation 2002;105:174–180.
50. Chew DP, Bhatt DL, Lincoff AM, et al. Defining the optimal activated clotting time during percutaneous
coronary intervention. Circulation 2001;103:961–966.
51. Akkerhuis KM, Deckers JW, Lincoff AM, et al. Risk of stroke associated with abciximab among patients
undergoing percutaneous coronary intervention. JAMA 2001;286:78–82.
52. Wagner CL, Cunningham MR, Wyand MS, Weisman HF, Coller BS, Jordan RE. Reversal of the anti-
platelet effects of chimeric 7E3 Fab treatment by platelet transfusion in cynomolgous monkeys (abstr).
Thromb Haemost 1995;73:1313.
53. Lincoff AM, LeNarz RA, Despotis GJ, et al., for the EPILOG and EPISTENT Investigators. Abciximab
and bleeding complications during coronary surgery: results from the EPILOG and EPISTENT trials.
Ann Thorac Surg 2000;70:516–526.
54. Kereiakes DJ, Berkowitz SD, Lincoff AM, et al. Clinical correlates and course of thrombocytopenia
during percutaneous coronary intervention in the era of abciximab glycoprotein IIb/IIIa blockade. Am
H J 2000;140:74–80.
https://t.me/med1917
Chapter 8 / Overview of the GPIIb/IIIa Interventional Trials 199
55. Berkowitz SD, Harrington RA, Rund MM, Tcheng JE. Acute profound thrombocytopenia after c7E3
Fab (abciximab) therapy. Circulation 1997;95:809–813.
56. Tcheng JE, Kereiakes DJ, Lincoff AM, et al., for the ReoPro Readminstration Registry Investigators.
Abciximab readministration. Results of the ReoPro Readministration Registry. Circulation 2001;104:
870–875.
57. Topol EJ, Mark DB, Lincoff AM, et al., on behalf of the EPISTENT Investigators. Enhanced survival
with platelet glycoprotein IIb/IIIa blockade in patients undergoing coronary stenting: one year outcomes
and health care economic implications from a multicenter, randomized trial. Lancet 1999;354:2019–2024.
58. Garbarz E, Farah B, Vuillemenot A, et al. “Rescue” abciximab for complicated percutaneous translumi-
nal coronary angioplasty. Am J Cardiol 1998;82:800–803.
59. Muhlestein JB, Karagounis LA, Treehan S, Anderson JL. “Rescue” utilization of abciximab for the dis-
solution of coronary thrombus developing as a complication of coronary angioplasty. J Am Coll Cardiol
1997;30:1729–1734.
60. Popma JJ, Weitz J, Bittl JA, et al. Antithrombotic therapy in patients undergoing coronary angioplasty.
Chest 1998;114:7288–7418.
61. Ellis SG, Vandormael MG, Cowley MJ, et al. Coronary morphologic and clinical determinants of pro-
cedural outcome with angioplasty for multivessel coronary disease. Implications for patient selection.
Circulation 1990;82:1193–1202.
https://t.me/med1917
Соседние файлы в папке Библиотека им академика М.И. Перельмана