Evidence for Prevention of Death and Myocardial Infarction With Platelet Membrane Glycoprotein IIb/IIIa Receptor Blockade by Abciximab (c7E3 Fab) Among Patients With Unstable Angina Undergoing Percutaneous Coronary Revascularization fn1fn1This study was supported by Centocor, Inc., Malvern, Pennsylvania.

AbstractObjectives. We sought to evaluate whether patients with unstable angina undergoing coronary intervention derive particular clinical benefit from potent platelet inhibition.Background. Plaque rupture and platelet aggregation are pathogenetic processes common to unstable angina and ischemic complications of percutaneous coronary intervention.Methods. Of the 2,099 patients undergoing a coronary intervention in the Evaluation of 7E3 in Preventing Ischemic Complications (EPIC) trial, 489 were enrolled with the diagnosis of unstable angina and randomized to receive placebo, an abciximab (c7E3) bolus immediately before the intervention or an abciximab bolus followed by a 12-h infusion. The primary end point was a composite of death, myocardial infarction (MI) or urgent repeat revascularization within 30 days of randomization. The occurrence of death, MI or any revascularization within 6 months was also assessed.Results. Compared with placebo, the bolus and infusion of abciximab resulted in a 62% reduction in the rate of the primary end point (12.8% vs. 4.8%, p = 0.012) among patients with unstable angina, due primarily to a reduction in the incidences of death (3.2% vs. 1.2%, p = 0.164) and MI (9% vs. 1.8%, p = 0.004). By 6 months, cumulative death and MI were further reduced by abciximab (6.6% vs. 1.8%, p = 0.018 and 11.1% vs. 2.4%, p = 0.002, respectively). The magnitude of the risk reduction with abciximab was greater among the patients with unstable angina than among other patients in the EPIC trial without unstable angina for the end points of death (interaction: p = 0.008 at 30 days, p = 0.002 at 6 months) and MI (interaction: p = 0.004 at 30 days, p = 0.003 at 6 months).Conclusions. The syndrome of unstable angina identifies patients who will experience particularly marked reductions in the risk of death and MI with abciximab during coronary intervention.(J Am Coll Cardiol 1997;30:149–56

Clinical outcomes after detection of elevated cardiac enzymes in patients undergoing percutaneous intervention

AbstractObjectives. We examined the relations of elevated creatine kinase (CK) and its myocardial band isoenzyme (CK-MB) to clinical outcomes after percutaneous coronary intervention (PCI) in patients enrolled in Integrilin (eptifibatide) to Minimize Platelet Aggregation and Coronary Thrombosis-II (trial) (IMPACT-II), a trial of the platelet glycoprotein IIb/IIIa inhibitor eptifibatide.Background. Elevation of cardiac enzymes often occurs after PCI, but its clinical implications are uncertain.Methods. Patients undergoing elective, scheduled PCI for any indication were analyzed. Parallel analyses investigated CK (n = 3,535) and CK-MB (n = 2,341) levels after PCI (within 4 to 20 h). Clinical outcomes at 30 days and 6 months were stratified by postprocedure CK and CK-MB (multiple of the site’s upper normal limit).Results. Overall, 1,779 patients (76%) had no CK-MB elevation; CK-MB levels were elevated to 1 to 3 times the upper normal limit in 323 patients (13.8%), to 3 to 5 times normal in 84 (3.6%), to 5 to 10 times normal in 86 (3.7%), and to >10 times normal in 69 patients (2.9%). Elevated CK-MB was associated with an increased risk of death, reinfarction, or emergency revascularization at 30 days, and of death, reinfarction, or surgical revascularization at 6 months. Elevated total CK to above three times normal was less frequent, but its prognostic significance paralleled that seen for CK-MB. The degree of risk correlated with the rise in CK or CK-MB, even for patients with successful procedures not complicated by abrupt closure.Conclusions. Elevations in cardiac enzymes, including small increases (between one and three times normal) often not considered an infarction, are associated with an increased risk for short-term adverse clinical outcomes after successful or unsuccessful PCI

Effects of abciximab on key pattern of human coronary restenosis in vitro: impact of the SI/MPL-ratio

BACKGROUND: The significant reduction of angiographic restenosis rates in the ISAR-SWEET study (intracoronary stenting and antithrombotic regimen: is abciximab a superior way to eliminate elevated thrombotic risk in diabetes) raises the question of whether abciximab acts on clopidogrel-independent mechanisms in suppressing neointimal hyperplasia. The current study investigates the direct effect of abciximab on ICAM-1 expression, migration and proliferation. METHODS: ICAM-1: Part I of the study investigates in cytoflow studies the effect of abciximab (0.0002, 0.002, 0.02, 0.2, 2.0, and 20.0 μg/ml) on TNF-α induced expression of intercellular adhesion molecule 1 (ICAM-1). Migration: Part II of the study explored the effect of abciximab (0.0002, 0.002, 0.02, 0.2, 2.0, and 20.0 μg/ml) on migration of HCMSMC over a period of 24 h. Proliferation: Part III of the study investigated the effect of abciximab (0.0002, 0.002, 0.02, 0.2, 2.0, and 20.0 μg/ml) on proliferation of HUVEC, HCAEC, and HCMSMC after an incubation period of 5 days. RESULTS: ICAM-1: In human venous endothelial cells (HUVEC), human coronary endothelial cells (HCAEC) and human coronary medial smooth muscle cells (HCMSMC) no inhibitory or stimulatory effect on expression of ICAM-1 was detected. Migration: After incubation of HCMSMC with abciximab in concentrations of 0.0002 – 2 μg/ml a stimulatory effect on cell migration was detected, statistical significance was achieved after incubation with 0.002 μg/ml (p < 0.05), 0.002 μg/ml (p < 0.001), and 0.2 μg/ml (p < 0.05). Proliferation: Small but statistically significant antiproliferative effects of abciximab were detected after incubation of HUVEC (0.02 and 2.0 μg/ml; p = 0.01 and p < 0.01), HCAEC (2.0 and 20.0 μg/ml; p < 0.05 and p < 0,01), and HCMSMC (2.0 and 20.0 μg/ml; p < 0.05 and p < 0.05). The significant inhibition (SI) of cell proliferation found in HCAEC and HCMSMC was achieved with drug concentrations more than 10 times beyond the maximal plasma level (MPL), resulting in a SI/MPL-ratio > 1. CONCLUSION: Thus, the anti-restenotic effects of systemically administered abciximab reported in the ISAR-SWEET-study were not caused by a direct inhibitory effect on ICAM-1 expression, migration or proliferation