Safe use of platelet GP IIb/IIIa inhibitors.

The platelet membrane glycoprotein IIb/IIIa receptor inhibitor abciximab is used for the treatment of patients undergoing high-risk percutaneous coronary interventions and is used in approximately one third of coronary interventions in the United States and a growing number of procedures in Europe. Recent clinical trials have shown that this potent antiplatelet agent significantly reduces the incidence of death and nonfatal myocardial infarction and the need for revascularization. With expanding experience since the commercial release of abciximab in February 1995, several strategies to enhance the safety of abciximab have emerged.

Abciximab therapy and unplanned coronary stent deployment: favorable effects on stent use, clinical outcomes, and bleeding complications. EPILOG Trial Investigators.

Background: The clinical and angiographic demographics of patients requiring unplanned coronary stent deployment and the optimal adjunct pharmacotherapy in this population are not well described. This report details the EPILOG trial experience with unplanned coronary stent deployment and the effect of abciximab platelet glycoprotein IIb/IIIa blockade to improve clinical outcomes during 6 months of follow-up.

Methods And Results: After randomization in the EPILOG double-blind, placebo-controlled trial of abciximab therapy during percutaneous coronary intervention, 326 (12%) of 2792 patients required unplanned coronary stent deployment.

The use of the Gianturco-Roubin intracoronary stent: the New Approaches to Coronary Intervention (NACI) registry experience.

The objective of this study is to compare the in-hospital and follow-up outcome in patients receiving the Gianturco-Roubin stent (GRS) who were enrolled in the New Approaches to Coronary Intervention (NACI) registry. The GRS was approved by the US Food and Drug Administration (FDA) in August 1992 for the treatment of acute or threatened closure after a percutaneous intervention. The application of intracoronary stenting has broadened substantially in the last few years, but less is known about the use of this device for other indications.

Directional coronary atherectomy (DCA): a report from the New Approaches to Coronary Intervention (NACI) registry.

Directional coronary atherectomy (DCA) with the Simpson coronary atherocath seeks to debulk rather than simply displace obstructive tissue and is a means of enlarging the stenotic coronary lumen. This report from the New Approaches to Coronary Intervention (NACI) registry describes the experience of 1,196 patients who underwent DCA as the sole treatment for either native vessel or vein graft lesions. Device success (post-DCA residual stenosis <50% and > or =20% improvement) was achieved in 87.

Postinfarction left ventricular pseudoaneurysm.

Left ventricular wall rupture after myocardial infarction is a mechanical complication that may result in a pseudoaneurysm. Between January 1994 and October 1996, false or pseudoaneurysms were detected in 6 (0.0026%) of 2,600 consecutive patients (4 women, 2 men; mean age 59.

Assessment of coronary reperfusion after thrombolysis with a model combining myoglobin, creatine kinase-MB, and clinical variables. TAMI-7 Study Group. Thrombolysis and Angioplasty in Myocardial Infarction-7.

Background: Several biochemical markers have been investigated for the noninvasive assessment of reperfusion after myocardial infarction. Because myoglobin is released very soon after myocardial injury and clears rapidly after reperfusion, it may prove to be an excellent marker of occlusion and reperfusion.

Methods And Results: We examined the relation between various myoglobin measures and Thrombolysis In Myocardial Infarction (TIMI) flow grade in 96 patients enrolled in a study of front-loaded thrombolysis who underwent 90-minute angiography.

Partial reversal of heparin anticoagulation by intravenous protamine in abciximab-treated patients undergoing percutaneous intervention.

Serious hemorrhage and vascular complications after abciximab therapy are associated with elevated activated clotting time values. Our preliminary experience suggests that low-dose intravenous protamine administration is both safe and effective in reducing elevated in-laboratory activated clotting time values and the potential for serious hemorrhage in abciximab-treated patients.

Sustained platelet glycoprotein IIb/IIIa blockade with oral xemilofiban in 170 patients after coronary stent deployment.

Background: Inhibition of platelet aggregation with parenteral glycoprotein (GP) IIb/IIIa receptor blockers can reduce the ischemic complications of angioplasty. Sustained efficacy and safety of protracted GP IIb/IIIa blockade with an orally administered agent have not previously been determined. This study is the first randomized, dose-ranging, single-blind, placebo-controlled trial of xemilofiban, an oral platelet GP IIb/IIIa receptor antagonist, administered to patients after intracoronary stent deployment.

Clinical characteristics and long-term outcome of patients in whom congestive heart failure develops after thrombolytic therapy for acute myocardial infarction: development of a predictive model.

Ischemic heart disease is the most common cause of congestive heart failure, which often begins after acute myocardial infarction. To better delineate the clinical characteristics and outcomes of patients in whom congestive heart failure develops after acute myocardial infarction in the thrombolytic era, we prospectively evaluated patients enrolled in six of the TAMI trials. The study cohort comprised 1619 consecutive patients who had at least 1 mm of ST-segment elevation in two contiguous electrocardiographic leads within 6 hours of the onset of acute myocardial infarction and who received intravenous thrombolytic therapy.

Bailout and corrective use of Gianturco-Roubin flex stents after percutaneous transluminal coronary angioplasty: operator reports and angiographic core laboratory verification from the National Heart, Lung, and Blood Institute/New Approaches to Coronary Intervention Registry.

Objectives: We sought to determine the in-hospital clinical outcome and angiographic results of patients prospectively entered into the National Heart, Lung, and Blood Institute/New Approaches to Coronary Intervention (NHLBI/NACI) Registry who received Gianturco-Roubin stents as an unplanned new device.

Background: Between August 1990 and March 1994, nine centers implanted Gianturco-Roubin flex stents as an unplanned new device in the initial treatment of 350 patients (389 lesions) who were prospectively enrolled in the NHLBI/NACI Registry.

Methods: Patients undergoing implantation of the Gianturco-Roubin flex stent were prospectively entered into the Gianturco-Roubin stent portion of the NHLBI/NACI Registry.

Combined accelerated tissue-plasminogen activator and platelet glycoprotein IIb/IIIa integrin receptor blockade with Integrilin in acute myocardial infarction. Results of a randomized, placebo-controlled, dose-ranging trial. IMPACT-AMI Investigators.

Background: Platelet activation and aggregation may be key components of thrombolytic failure to restore and maintain perfusion in acute myocardial infarction. We performed a placebo-controlled, dose-ranging trial of Integrilin, a potent inhibitor of platelet aggregation, with heparin, aspirin, and accelerated alteplase.

Methods And Results: We assigned 132 patients in a 2:1 ratio to receive a bolus and continuous infusion of one of six Integrilin doses or placebo.

Abciximab-associated profound thrombocytopenia: therapy with immunoglobulin and platelet transfusion.

First-time abciximab administration was associated with acute profound thrombocytopenia in 4 of 575 consecutive patients. Therapy with platelet transfusion, but not intravenous immunoglobulin, was associated with a rapid and sustained increment in circulating platelet count and clinical hemostasis.

Differential dose-response to oral xemilofiban after antecedent intravenous abciximab. Administration for complex coronary intervention.

Background: Placebo-controlled randomized trials of parenteral platelet glycoprotein (GP) IIb/IIIa receptor antagonists have demonstrated reduced ischemic complications of coronary angioplasty. Orally active GP IIb/IIIa blockers are being developed to allow more sustained receptor antagonism with potential for long-term secondary prevention. Sequential therapy with abciximab followed by an oral IIb/IIIa antagonist has not previously been reported.

Percutaneous transcatheter therapy of aorto-ostial stenoses.

The treatment of native coronary and saphenous vein graft aorto-ostial stenoses with balloon angioplasty (PTCA) has been associated with lower procedural success rates, more frequent in-hospital complications and a greater likelihood of late restenosis when compared with PTCA of non-ostial stenoses. The advent of ablative technologies and intracoronary stents have significantly altered both early and late outcomes of percutaneous intervention for aorto-ostial disease. The optimal approach to this complex lesion subset often involves decalcification or tissue ablation followed by stent deployment.

Planning, implementation, and process monitoring for prehospital 12-lead ECG diagnostic programs.

Prehospital 12-lead electrocardiographic (ECG) diagnostic strategies have been proven feasible and effective, provided they are designed and implemented properly. The authors of this communication have expended considerable time and effort in determining appropriate planning, implementation, and process monitoring necessary for successful implementation of a variety of prehospital diagnostic strategies. Many of these issues may not be obvious to an emergency medical services (EMS) director initiating a 12-lead ECG program.

Randomized, double-blind, placebo-controlled dose-ranging study of tirofiban (MK-383) platelet IIb/IIIa blockade in high risk patients undergoing coronary angioplasty.

Objectives: The objectives of this double-blind, placebo-controlled, randomized dose-ranging study were 1) to examine the safety and tolerability of tirofiban (MK-383), a new nonpeptide platelet IIb/IIIa receptor antagonist, on a background of intravenous heparin and aspirin therapy; 2) to study the pharmacodynamics and pharmacokinetics of tirofiban; and 3) to evaluate the incidence of adverse cardiac outcomes (urgent repeat revascularization, myocardial infarction and death) with tirofiban versus placebo in a high risk subset of patients undergoing coronary angioplasty.

Background: Abrupt vessel closure complicates 4% to 8% of angioplasty procedures. Recent data have suggested that agents that antagonize the platelet glycoprotein IIb/IIIa receptor may reduce the incidence of adverse ischemic outcomes after coronary angioplasty.

Frequency, significance, and cost of recurrent ischemia after thrombolytic therapy for acute myocardial infarction. TAMI Study Group.

Early postinfarction angina implies an unfavorable prognosis. Most published information on this outcome represents data collected in the prethrombolytic era, in which definitions and populations differed considerably. Our purpose was to evaluate the incidence and importance of recurrent ischemia after administration of thrombolytic therapy.

Creatine kinase MM and MB isoforms in patients receiving thrombolytic therapy and acute angiography. TAMI Study Group.

Creatine kinase isoforms markers, including MB2 concentration, MB2/MB1 and MM3/MM1 ratios, and MT index (based on the "tissue" M subunits), were measured in serial specimens from 207 patients receiving thrombolytic therapy followed by acute angiography. The slope of release showed a significant relation (P < 0.05) between MB2 concentrations and patency, graded as TIMI 0 through TIMI 3; with regard to the precatheterization/baseline ratio, the MB2 concentrations, the MM3/MM1 ratio, and the MT index were all significantly related to graded patency (P < 0.

Multicenter, randomized, double-blind, placebo-controlled trial of the platelet integrin glycoprotein IIb/IIIa blocker Integrelin in elective coronary intervention. IMPACT Investigators.

Background: Platelet aggregation and thrombosis have been implicated in the pathogenesis of coronary angioplasty complications. Integrelin, a synthetic cyclic heptapeptide with high affinity and marked specificity for platelet integrin glycoprotein IIb/IIIa, effectively blocks ADP-induced platelet aggregation.

Methods And Results: In 150 patients undergoing elective percutaneous coronary intervention, random assignment was made to one of three treatment regimens: placebo; a 90-micrograms/kg bolus of Integrelin before angioplasty followed by a 1.

Effect of cigarette smoking on outcome after thrombolytic therapy for myocardial infarction.

Background: Smoking is known to be a strong risk factor for premature atherosclerosis, myocardial infarction, and sudden cardiac death. Unexpectedly, in the reperfusion era, investigators have reported that patients who smoke have a more favorable prognosis after thrombolysis compared with non-smokers. Since smoking is associated with a relatively hyper-coagulable state, we hypothesized that the coronary occlusion responsible for infarction may be primarily thrombotic, with improved outcome relating to enhanced patency or the absence of a residual stenosis after thrombolytic therapy.

Pharmacodynamics of chimeric glycoprotein IIb/IIIa integrin antiplatelet antibody Fab 7E3 in high-risk coronary angioplasty.

Background: Thrombosis has been implicated as central to the clinical complications of coronary angioplasty (PTCA). Chimeric monoclonal 7E3 Fab (c7E3 Fab) is the first of a new class of antiplatelet drugs directed at the platelet glycoprotein IIb/IIIa integrin. This study was performed to determine the pharmacodynamics of c7E3 Fab administration during PTCA and to gain an initial clinical experience with this novel agent.