ライフサイエンスコーパス: GP IIb

1 GP IIb/IIIa antagonist potency is variably enhanced by c

2 GP IIb/IIIa inhibitor dose was defined as excessive if n

3 GP IIb/IIIa receptor blockade was 57+/-7%.

4 GP IIb/IIIa receptor blockade was 67+/-8%.

5 GP IIb/IIIa receptor blockade, impedance (5 microg/mL co

6 GP IIb/IIIa receptor inhibition during coronary interven

7 P IIb/IIIa receptor blockade) and 13300 (13% GP IIb/IIIa receptor blockade) abciximab molecules bound

8 escence intensity corresponded to 29100 (29% GP IIb/IIIa receptor blockade) and 13300 (13% GP IIb/III

9 alpha IIb beta 3-(GP IIb IIIa) is the most abundant integrin expressed on

10 coronary stent placement with aspirin and a GP IIb/IIIa inhibitor, clopidogrel pretreatment is assoc

11 d to surface-immobilized microparticles in a GP IIb/IIIa-dependent mechanism.

12 intervention regardless of whether or not a GP IIb/IIIa inhibitor is used.

13 The use of a GP IIb/IIIa inhibitor does not accentuate the relative r

14 s undergoing a PCI with the planned use of a GP IIb/IIIa inhibitor had platelet inhibition measured a

15 The use of a GP IIb/IIIa inhibitor was at the physician's discretion.

16 d at 30 days and were stratified by use of a GP IIb/IIIa inhibitor.

17 interval: 0.64 to 0.90) or did not receive a GP IIb/IIIa inhibitor (hazard ratio: 0.78; 95% confidenc

18 A total of 7,414 subjects (54.5%) received a GP IIb/IIIa inhibitor during their index hospitalization

19 Although subjects treated with a GP IIb/IIIa inhibitor had greater rates of bleeding, the

20 that inhibition of platelet function with a GP IIb/IIIa receptor antagonist would increase the effic

21 to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade (EPILOG) trial were followed with m

22 to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade), abciximab administered with weigh

23 GP IIb/IIIa-bound fibrinogen, and activated GP IIb/IIIa in response to low-dose ADP.

24 may further enhance expression of activated GP IIb-IIIa complexes.

25 Fibrinogen binding to activated GP IIb/IIIa and expression of P-selectin, GP Ib, and GP

26 erates after fibrinogen binding to activated GP IIb/IIIa.

27 reduction in platelet aggregation and active GP IIb/IIIa expression (p < or = 0.001) with clopidogrel

28 greater platelet inhibition and lower active GP IIb/IIIa expression compared with NS (p < or = 0.05).

29 nged receptor blockade with an orally active GP IIb/IIIa antagonist are not known.

30 Orally active GP IIb/IIIa blockers are being developed to allow more s

31 Orally active GP IIb/IIIa blockers may allow more sustained receptor a

32 ificantly lower PA and ADP-stimulated active GP IIb/IIIa expression compared with NS (p < or = 0.0008

33 In addition, GP IIb-IIIa antagonists unexpectedly block release of sC

34 tion Assay (RPFA) on platelet function after GP IIb/IIIa inhibition.

35 cterized inhibition of platelet aggregation, GP IIb/IIIa antagonists may obviate the proinflammatory

36 Although GP IIb/IIIa antagonist use in patients with ACS and rena

37 Although GP IIb/IIIa inhibition has been shown to reduce ischemic

38 oronary stents (76% versus 1%, P<0.001), and GP IIb/IIIa receptor antagonist (24% versus 0%, P<0.001)

39 hibition of ex vivo platelet aggregation and GP IIb/IIIa receptor blockade) were measured in 41 indiv

40 nary interventions using anticoagulation and GP IIb/IIIa inhibitor therapy can be safely and effectiv

41 ith comparable affinity to alpha(v)beta3 and GP IIb/IIIa, (2) inhibit alpha(v)beta3 and GP IIb/IIIa-m

42 d GP IIb/IIIa, (2) inhibit alpha(v)beta3 and GP IIb/IIIa-mediated cell adhesion in vitro with IC50 va

43 arction were similar for the bivalirudin and GP IIb/IIIa groups, but bivalirudin resulted in lower ra

44 ts received anticoagulation with heparin and GP IIb/IIIa inhibitor therapy with abciximab.

45 IIa and expression of P-selectin, GP Ib, and GP IIb/IIIa on the platelet surface were measured.

46 This pathway is insensitive to RGDS and anti-GP IIb/IIIa antibodies but reactive with a mutant fibrin

47 nt, (2) 6D1 (anti-GP Ib), (3) c7E3 Fab (anti-GP IIb/IIIa+alpha(v)beta3), and (4) c7E3 Fab+6D1.

48 aggregating effect of EDTA, whereas the anti-GP IIb/IIIa antibody abciximab had no effect.

49 We assessed GP IIb/IIIa activation prospectively to determine whethe

50 Because GP IIb/IIIa is essential in platelet aggregation and thr

51 formed in PRP indicated that this is because GP IIb/IIIa antagonists are more potent inhibitors of in

52 ding KD values, and (3) redistribute between GP IIb/IIIa and alpha(v)beta3 integrins in vitro.

53 eveloped because of its efficacy in blocking GP IIb/IIIa (alphaIIb/beta3) receptors on platelets, abc

54 ciximab may have the ability to inhibit both GP IIb/IIIa and alpha(v)beta3 for extended periods.

55 gimens exhibited equivalent blockade of both GP IIb/IIIa receptors and platelet aggregation throughou

56 ximab binds with equivalent affinity to both GP IIb/IIIa and alphavss3 and redistributes between the

57 face of activated platelets was inhibited by GP IIb/IIIa antagonists in a dose-dependent manner, in c

58 to the platelet surface was not inhibited by GP IIb/IIIa antagonists.

59 h a thrombin receptor agonist, inhibition by GP IIb/IIIa antagonists occurred without affecting the r

60 Platelet aggregation, a process mediated by GP IIb-IIIa, is responsible for the occlusive events in

61 platelets is regulated, at least in part, by GP IIb/IIIa, actin polymerization, and an MMP inhibitor-

62 ere was a significant mortality reduction by GP IIb/IIIa inhibitors at 48 to 96 hours, with an OR of

63 of PTCA to Improve Long-Term Outcome by c7E3 GP IIb/IIIa Receptor Blockade (EPILOG) and the Evaluatio

64 40L, thereby interrupting the platelet CD40L/GP IIb-IIIa axis.

65 The efficacy of oral agents for chronic GP IIb/IIIa receptor antagonism has not been sufficientl

66 Under physiological conditions, GP IIb/IIIa antagonists currently in clinical use do not

67 oncerning the relative efficacy of different GP IIb/IIIa antagonists, the accurate use of platelet fu

68 Although several different GP IIb/IIIa antagonists have convincingly demonstrated t

69 f whole-blood samples treated with different GP IIb/IIIa antagonists correlated well with both conven

70 intrinsic prothrombotic property of low-dose GP IIb/IIIa antagonists.

71 Hospitals that adopted early GP IIb/IIIa inhibition more rapidly also had lower adjus

72 Only 25% of eligible patients received early GP IIb/IIIa therapy.

73 ts provide evidence to physicians that early GP IIb/IIIa inhibition in combination with a prompt inva

74 study was designed to determine what effect GP IIb/IIIa antagonists have on the release of sCD40L.

75 d inhibitory activity was caused by enhanced GP IIb-IIIa occupancy by Integrilin.

76 omen were also more likely to receive excess GP IIb/IIIa doses than men (46.4% versus 17.2%, P<0.0001

77 The risk for bleeding attributable to excess GP IIb/IIIa dose was determined by sex using prevalence

78 it in ACS, but abciximab, the more expensive GP IIb/IIIa inhibitor, may be more effective during PCI.

79 s a highly significant (P<0.001) benefit for GP IIb/IIIa inhibitors at each time point.

80 o a highly significant (P<0.001) benefit for GP IIb/IIIa inhibitors.

81 erence in measurements between RPFA and free GP IIb/IIIa receptors was -2% (+/-6% SD).

82 egation (r2=0.95) and the percentage of free GP IIb/IIIa molecules in the sample (r2=0.96).

83 etter correlated with the percentage of free GP IIb/IIIa receptors than was aggregometry or the RPFA.

84 at citrate anticoagulation removes Ca2+ from GP IIb-IIIa and enhances the apparent inhibitory activit

85 atelet inhibition with gradual recovery from GP IIb/IIIa receptor blockade in the first week after ab

86 .7% vs. 1.7 +/- 2.3%, p < 0.001) and greater GP IIb/IIIa (5.7 +/- 3.1 vs. 2.1 +/- 1.2, p < 0.001) and

87 (PPCI), treated with bivalirudin or heparin+GP IIb/IIIa receptor inhibitor (heparin+GPI).

88 ithrombotics--low-molecular-weight heparins, GP IIb/IIIa inhibitors, and thienopyridines--along with

89 test: 1) if platelet glycoprotein IIb/IIIa (GP IIb/IIIa) blockade with abciximab bolus plus 12-h inf

90 The glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors abciximab and eptifibatide (Inte

91 istration of platelet glycoprotein IIb/IIIa (GP IIb/IIIa) receptor blockers can reduce ischemic compl

92 inylated fibrinogen to purified, immobilized GP IIb-IIIa.

93 reduced in Glanzmann platelets (deficient in GP IIb/IIIa).

94 DDABs appear to bind to neoepitopes in GP IIb/IIIa elicited on antagonist binding.

95 ion of the assay, correlating with increased GP IIb/IIIa receptor blockade.

96 the occlusive events in thrombosis: indeed, GP IIb-IIIa antagonists are effective in blocking arteri

97 ent from PSGL-1 or GP Ib, stabilizes initial GP IIb/IIIa-fibrinogen interactions, allowing the format

98 RAGON-B to receive lamifiban, an intravenous GP IIb/IIIa antagonist, or placebo.

99 ated a reanalysis of the role of intravenous GP IIb/IIIa inhibitors.

100 ntrolled clinical trials testing intravenous GP IIb/IIIa receptor antagonists and having more than 50

101 Previous studies investigating GP IIb/IIIa antagonist use have excluded patients with r

102 During abciximab administration, mean GP IIb/IIIa receptor blockade was > 91%, and both impeda

103 Upstream use of small molecule GP IIb/IIIa inhibition in ACS patients with moderate or

104 ACS patients upstream with a small molecule GP IIb/IIIa inhibitor and continue through medical manag

105 strategy of upstream use of a small molecule GP IIb/IIIa inhibitor was superior to selective use, and

106 Small molecule GP IIb/IIIa inhibitors have shown benefit in ACS, but ab

107 re are no rapid and simple assays to monitor GP IIb/IIIa receptor blockade.

108 study of xemilofiban, a new oral nonpeptide GP IIb/IIIa antagonist, after elective intracoronary ste

109 Neither stents nor GP IIb/IIIa inhibitors significantly enhance myocardial

110 oups on the basis of extent of activation of GP IIb/IIIa in response to 0.2 micromol/L ADP.

111 et activation, whereas maximal activation of GP IIb/IIIa occurred within the first 10 seconds, sugges

112 agen, an affect augmented by the addition of GP IIb/IIIa antagonists.

113 receiving routine upstream administration of GP IIb/IIIa inhibitors vs deferring their use for patien

114 Small-molecule antagonists of GP IIb/IIIa based on the Arg-Gly-Asp (RGD) sequence show

115 servations suggest that long-term benefit of GP IIb-IIIa antagonists treatment could be due not only

116 sms responsible for the clinical benefits of GP IIb/IIIa antagonists (at doses that optimally inhibit

117 Potential benefits of GP IIb/IIIa inhibitor use must be weighed against an inc

118 ntial therapeutic index of the oral class of GP IIb/IIIa antagonists.

119 try, we demonstrate that (1) dissociation of GP IIb/IIIa antagonists (abciximab, tirofiban, eptifibat

120 ide a mechanism by which suboptimal doses of GP IIb/IIIa antagonists may be proinflammatory.

121 The effects of GP IIb/IIIa blockade on platelet function should be exam

122 Other issues are related to the effects of GP IIb/IIIa receptor availability, neoepitopes induced b

123 ontrolled trials, and current evaluations of GP IIb-IIIa inhibitors are summarized in this review.

124 /- 8.7%, p < 0.05) and greater expression of GP IIb/IIIa (4.7 +/- 1.8% vs. 3.1 +/- 2.2%, p < 0.001).

125 Surface expression of GP IIb/IIIa was similar in resting platelets of all 3 ge

126 ibitor of the fibrinogen binding function of GP IIb-llla, has been shown to reduce the thrombotic com

127 zation, and stent thrombosis irrespective of GP IIb/IIIa inhibitor use.

128 sCD40L is also a ligand of GP IIb-IIIa and is involved in thrombus stabilization an

129 ermined differences in binding properties of GP IIb/IIIa might result in changes in platelet activati

130 s a reliable test to monitor a wide range of GP IIb/IIIa inhibition.

131 The rate of GP IIb/IIIa inhibitor use was much the same between grou

132 ng may be employed to increase the safety of GP IIb/IIIa antagonists.

133 n and myocardial necrosis with a strategy of GP IIb/IIIa inhibition warrant further investigation.

134 n platelet aggregation distinct from that of GP IIb/IIIa, which may be of importance in the initiatio

135 ated for 16 randomized, controlled trials of GP IIb/IIIa inhibitors.

136 of death and MI irrespective of the type of GP IIb/IIIa inhibitor used.

137 imilar results were obtained with the use of GP IIb/IIIa antagonists based on the arginine-glycine-as

138 Although the use of GP IIb/IIIa antagonists was associated with an increase

139 Deferred upstream use of GP IIb/IIIa inhibitors for selective administration to p

140 As an antagonist of not only GP IIb/IIIa but also alpha(v)beta3, abciximab may provid

141 developed that may be helpful in optimizing GP IIb/IIIa antagonist therapy.

142 a-thrombin pathway is observed when PAR-1 or GP IIb/IIIa is inhibited.

143 c effect of xemilofiban (SC-54684A), an oral GP IIb/IIIa antagonist, administered alone or with aspir

144 The optimal duration of oral GP IIb/IIIa blockade to effectively suppress recurrent i

145 y and efficacy of sequential parenteral-oral GP IIb/IIIa blockade therapy and may be useful in derivi

146 reated with roxifiban and, by analogy, other GP IIb/IIIa antagonists.

147 proved as an antithrombotic agent, and other GP IIb/IIIa antagonists, including oral agents, are unde

148 platelet aggregation more closely paralleled GP IIb/IIIa receptor blockade and indicated a slower rec

149 f care" exists for measuring pharmacological GP IIb/IIIa blockade.

150 ent assay (ELISA) for DDAB using solid-phase GP IIb/IIIa.

151 Platelet GP IIb/IIIa antibody eluting from polymer-coated stents

152 Platelet GP IIb/IIIa is believed to play a central role in MI, bi

153 Abciximab, a platelet GP IIb/IIIa receptor inhibitor, has consistently reduced

154 The interaction between platelet GP IIb/IIIa inhibition and diabetic status was statistic

155 ale trial experience of intravenous platelet GP IIb/IIIa inhibitors for the medical management of non

156 Inhibitors of platelet GP IIb-IIIa, the final common pathway of platelet aggreg

157 Prospective assessment of platelet GP IIb/IIIa activation permits stratification of patient

158 Therefore, the use of platelet GP IIb/IIIa inhibitors should be strongly considered in

159 elets in the absence or presence of platelet GP IIb/IIIa receptor blockade with abciximab.

160 , a potent nonpeptide antagonist of platelet GP IIb/IIIa.

161 mized trial of xemilofiban, an oral platelet GP IIb/IIIa blocking agent, administered to patients aft

162 olled trial of xemilofiban, an oral platelet GP IIb/IIIa receptor antagonist, administered to patient

163 Among 6458 diabetic patients, platelet GP IIb/IIIa inhibition was associated with a significant

164 tions enrolled in the 6 large-scale platelet GP IIb/IIIa inhibitor ACS trials: PRISM, PRISM-PLUS, PAR

165 correlate with the severity of the platelet GP IIb-IIIa abnormality.

166 on 33 of the GP IIIa subunit of the platelet GP IIb/IIIa receptor (integrin alpha(IIb)beta(3)).

167 in the Enhanced Suppression of the Platelet GP IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) tr

168 itors and 16.0% assigned to bivalirudin plus GP IIb/IIIa inhibitors (compared with heparin plus GP II

169 nhibitors, 3.9% assigned to bivalirudin plus GP IIb/IIIa inhibitors (HR, 0.99; 95% CI, 0.80-1.22; P =

170 IIIa inhibitors (n = 4603), bivalirudin plus GP IIb/IIIa inhibitors (n = 4604), or bivalirudin monoth

171 efficacy of bivalirudin versus heparin plus GP IIb/IIIa blockade for PCI.

172 Patients were assigned to heparin plus GP IIb/IIIa inhibitors (n = 4603), bivalirudin plus GP I

173 n 15.4% of patients assigned to heparin plus GP IIb/IIIa inhibitors and 16.0% assigned to bivalirudin

174 ed 3.9% of patients assigned to heparin plus GP IIb/IIIa inhibitors, 3.9% assigned to bivalirudin plu

175 /IIIa inhibitors (compared with heparin plus GP IIb/IIIa inhibitors, HR, 1.05; 95% CI, 0.95-1.16; P =

176 Sustained efficacy and safety of protracted GP IIb/IIIa blockade with an orally administered agent h

177 Bivalirudin (provisional GP IIb/IIIa blockade 7.2%) was noninferior to the hepari

178 b/IIIa inhibition, bivalirudin + provisional GP IIb/IIIa inhibition resulted in similar acute ischemi

179 rin group) with bivalirudin plus provisional GP IIb/IIIa blockade (bivalirudin group) during PCI.

180 bivalirudin group, 7.7% required provisional GP IIb/IIIa.

181 ized to receive bivalirudin with provisional GP IIb/IIIa (n = 2,319) versus heparin + routine GP IIb/

182 f a strategy of bivalirudin with provisional GP IIb/IIIa inhibition compared with routine GP IIb/IIIa

183 Recently, bivalirudin with provisional GP IIb/IIIa inhibition has been validated as an alternat

184 ion, the use of bivalirudin with provisional GP IIb/IIIa inhibitors in diabetic patients is associate

185 This benefit was lost in patients receiving GP IIb/IIIa inhibitors and those with normal or lean BMI

186 of platelet glycoprotein IIb/IIIa receptor (GP IIb/IIIa) blockade with abciximab in women undergoing

187 bidimetric platelet aggregation and reflects GP IIb/IIIa receptor blockade.

188 Ib/IIIa (n = 2,319) versus heparin + routine GP IIb/IIIa (n = 2,332).

189 dated as an alternative to heparin + routine GP IIb/IIIa inhibition for patients undergoing PCI.

190 Compared with heparin + routine GP IIb/IIIa inhibition, bivalirudin + provisional GP IIb

191 Ia inhibition with that of heparin + routine GP IIb/IIIa inhibition.

192 trolled trial comparing heparin plus routine GP IIb/IIIa blockade (heparin group) with bivalirudin pl

193 Compared with routine GP IIb/IIIa inhibition, the use of bivalirudin with prov

194 GP IIb/IIIa inhibition compared with routine GP IIb/IIIa inhibition.

195 Compared with routine GP IIb/IIIa, in-hospital and 30-day costs were reduced b

196 cantly greater surface-expressed P-selectin, GP IIb/IIIa-bound fibrinogen, and activated GP IIb/IIIa

197 stration and 4602 were deferred to selective GP IIb/IIIa inhibitor administration.

198 Across a variety of hospital settings, GP IIb/IIIa inhibition, after patients were admitted to

199 plored the relationship between patient sex, GP IIb/IIIa inhibitor use, dose, and bleeding in 32 601

200 ity (MFI) versus 42 +/- 4 MFI for stimulated GP IIb/IIIa expression (p < 0.001).

201 These data suggest that GP IIb/IIIa inhibitors or other antiplatelet strategies

202 the first day of coronary thrombolysis that GP IIb/IIIa is markedly expressed and platelets are most

203 The GP IIb/IIIa antagonists inhibit release of sCD40L from a

204 The GP IIb/IIIa receptor is the final common pathway of plat

205 fail to stably bind fibrinogen; and (4) the GP IIb/IIIa antagonist-induced fibrinogen binding in som

206 diating platelet thrombus formation, and the GP IIb/IIIa antagonist abciximab (c7E3 Fab; ReoPro) is e

207 PAC1, a monoclonal antibody that mimics the GP IIb-IIIa binding activity of fibrinogen.

208 tagonist SQ29548 inhibited activation of the GP IIb-IIIa complex about 30% but had minimal inhibitory

209 e-out signaling leading to activation of the GP IIb-IIIa complex after platelet adhesion to collagen

210 fibrillar collagen induced activation of the GP IIb-IIIa complex and complete spreading.

211 hesion, spreading, and the activation of the GP IIb-IIIa complex at 60 min.

212 g2+, there was significant activation of the GP IIb-IIIa complex but minimal spreading was observed.

213 I antibodies inhibited the activation of the GP IIb-IIIa complex by about 40 and 50%, respectively, a

214 of these glycoproteins on activation of the GP IIb-IIIa complex induced by platelet adhesion to type

215 both platelet adhesion and activation of the GP IIb-IIIa complex.

216 ited both adhesion and the activation of the GP IIb-IIIa complex.

217 s dependent on the chemical structure of the GP IIb/IIIa antagonist and that only 2% to 5% of human b

218 uantitative measure of the competence of the GP IIb/IIIa receptor as reflected in the ability of plat

219 nd peptide and nonpeptide antagonists of the GP IIb/IIIa receptor have been tested in randomized, pla

220 inogen-binding-competent conformation of the GP IIb/IIIa receptor, but stable fibrinogen binding does

221 telet aggregation: fibrinogen binding to the GP IIb/IIIa complex.

222 In large trials, the GP IIb/IIIa inhibitors tirofiban and eptifibatide were e

223 PURSUIT patients were treated with the GP IIb/IIIa antagonist eptifibatide or placebo; PCIs wer

224 thrombocytopenia in humans treated with the GP IIb/IIIa antagonist roxifiban is immune mediated.

225 Three GP IIb/IIIa antagonists, eptifibatide, MK-0852, and GR14

226 ed with citrate affect Integrilin binding to GP IIb-IIIa and the ex vivo pharmacodynamic measurements

227 aggregation or stable fibrinogen binding to GP IIb/IIIa.

228 nce for drug-dependent antibodies (DDABs) to GP IIb/IIIa in 5 of 6 subjects, suggestive of an immune

229 A simple and rapid assay sensitive to GP IIb/IIIa receptor blockade has been developed that ma

230 exposes only a small proportion of unblocked GP IIb/IIIa receptors at any time, and these also fail t

231 essel revascularization (TVR), and unplanned GP IIb/IIIa use, occurred in 10.5% of women and 7.9% of

232 ents, 4605 were assigned to routine upstream GP IIb/IIIa administration and 4602 were deferred to sel

233 itionally, vascular complication rates using GP IIb/IIIa inhibitor therapy regardless of the method o

234 latelet function inhibition is achieved with GP IIb/IIIa antagonist therapy among patients undergoing

235 atient and hospital features associated with GP IIb/IIIa inhibition within 24 h after presentation.

236 A strategy of clopidogrel with GP IIb/IIIa blockade resulted in superior inhibition of

237 were comparable and closely correlated with GP IIb/IIIa receptor blockade.

238 efficacy of bivalirudin versus heparin with GP IIb/IIIa blockade, irrespective of pretreatment durat

239 protection from major adverse outcomes with GP IIb/IIIa inhibition with abciximab.

240 ted that treatment of NSTE ACS patients with GP IIb/IIIa agents results in an approximate 12% relativ

241 othrombotic and proinflammatory protein with GP IIb/IIIa binding activity and an established role in

242 ivity in samples that have been treated with GP IIb/IIIa antagonists with high dissociation rates.

243 death or MI in patients already treated with GP IIb/IIIa antagonists.

244 in high-risk UA/NSTEMI patients treated with GP IIb/IIIa inhibition.

245 n patients who were or were not treated with GP IIb/IIIa inhibitor (p(interaction) = 0.19).

246 r bleeding than men among those treated with GP IIb/IIIa inhibitors (15.7% versus 7.3%, P<0.0001) and

247 han men whether or not they are treated with GP IIb/IIIa inhibitors; however, because of frequent exc

248 increasing DDAB titer during treatment with GP IIb/IIIa antagonists may reduce the incidence of drug