Reduction in complications of angioplasty with abciximab occurs largely independently of baseline lesion morphology. EPIC and EPILOG Investigators. Evaluation of 7E3 for the Prevention of Ischemic Complications. Evaluation of PTCA To Improve Long-term Outcome with abciximab GPIIb/IIIa Receptor Blockade

OBJECTIVES: We investigated the hypothesis that abciximab might lead to a differential effect among patients with different lesion morphologies; hence, its cost/benefit ratio would be optimized if it were used selectively on the basis of baseline angiographic findings. BACKGROUND: Major complications of coronary angioplasty occur in 4% to 9% of patients. In the Evaluation of 7E3 for the Prevention of Ischemic Complications (EPIC) and Evaluation of PTCA To Improve Long-term Outcome with abciximab GPIIb/IIIa Receptor Blockade (EPILOG) trials, abciximab decreased the ischemic complications after intervention by 35% to 56%. However, the cost of this agent is appreciable, and there remain concerns about the safety of its readministration. METHODS: There were 1,362 patients in EPIC and 2,792 patients in EPILOG randomized to either bolus plus an infusion of abciximab or placebo, administered with aspirin and heparin at the time of the coronary intervention. Data from these studies were combined, and a differential effect of abciximab in relation to baseline lesion morphology on 30-day risk of death, myocardial infarction or urgent intervention was investigated using the Breslow Day test for statistical interaction. RESULTS: Abciximab consistently reduced the relative risk of complications across all lesion morphologies studied, with the possible exception of patients treated with degenerated saphenous vein grafts (risk with placebo 16.3% vs. risk with abciximab 18.6%, Breslow Day test for interaction, p=0.08). However, the absolute reduction of risk was somewhat greater in patients with more complex B2 or C lesions (7.6% and 5.8%, respectively) than in patients with morphologically simpler A or B1 lesions (3.7% and 3.2%, respectively). CONCLUSIONS: The reduction of early adverse ischemic events associated with angioplasty by abciximab occurs largely independent of pretreatment morphology.     

Reduction of recurrent ischemia with abciximab during continuous ECG-ischemia monitoring in patients with unstable angina refractory to standard treatment (CAPTURE)

BACKGROUND: In the CAPTURE (c7E3 Fab Anti Platelet Therapy in Unstable REfractory angina) trial, 1265 patients with refractory unstable angina were treated with abciximab or placebo, in addition to standard treatment from 16 to 24 hours preceding coronary intervention through 1 hour after intervention. To investigate the incidence of recurrent ischemia and the ischemic burden, a subset of 332 patients (26%) underwent continuous vector-derived 12-lead ECG-ischemia monitoring. METHODS and RESULTS: Patients were monitored from start of treatment through 6 hours after coronary intervention. Ischemic episodes were detected in 31 (18%) of the 169 abciximab and in 37 (23%) of the 163 placebo patients (NS). Only 9 (5%) of abciximab versus 22 (14%) of placebo patients had >/=2 ST episodes (P<0.01). In patients with ischemia, abciximab significantly reduced total ischemic burden (P<0.02), which was calculated alternatively as the total duration of ST episodes per patient, the area under the curve of the ST vector magnitude during episodes, or the sum of the areas under the curves of 12 leads during episodes. Twenty-one patients (6%) suffered a myocardial infarction (MI) (18) or died (3) within 5 days of treatment. The presence of asymptomatic and symptomatic ST episodes during the monitoring period preceding coronary intervention was associated with an increased relative risk of these events of 3.2 (95% CI 1.4, 7.4) and 4.1 (95% CI 1.4, 12.2), respectively. CONCLUSIONS: Recurrent ischemia predicts MI or death within 5 days of follow-up. Treatment with abciximab is associated with a reduction of frequent ischemia and a reduction of total ischemic burden in patients with refractory unstable angina. As such, patients with ischemia derive particularly high benefit from abciximab.     

Clinical determinants of mortality in patients with angiographically diagnosed ischemic or nonischemic cardiomyopathy

OBJECTIVES: We sought to characterize the clinical determinants of mortality in patients with angiographically diagnosed ischemic or nonischemic cardiomyopathy. BACKGROUND: Patients with ischemic cardiomyopathy may have a worse prognosis than patients with nonischemic cardiomyopathy. Few studies have assessed the effect of ischemic versus nonischemic etiology on outcomes. METHODS: We analyzed prospectively collected data on 3,787 patients with a left ventricular ejection fraction < or = 40% who underwent coronary angiography. Patients were considered to have ischemic cardiomyopathy (n = 3,112) if they had a history of myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass graft surgery or at least one major epicardial coronary artery with > or = 75% stenosis; all others were considered to have nonischemic cardiomyopathy (n = 675). RESULTS: The median age, ejection fraction and proportion of patients with New York Heart Association functional class III or IV symptoms for the nonischemic and ischemic groups were 55 years versus 63 years, 27% versus 32% and 57% versus 25%, respectively. After adjustment for baseline clinical risk factors and presenting characteristics, ischemic etiology remained an important independent predictor of 5-year mortality (p < 0.0001). The extent of coronary artery disease was a better predictor of survival than ischemic or nonischemic etiology (log likelihood chi-square 700 vs. 675, respectively). CONCLUSIONS: Ischemic etiology is a significant independent predictor of mortality in patients with cardiomyopathy. However, the extent of coronary artery disease contributes more prognostic information than the clinical diagnosis of ischemic or nonischemic cardiomyopathy. Further research is needed to refine the clinical definition of ischemic cardiomyopathy so that physicians can appropriately prescribe treatment and accurately predict outcome.     

Abciximab. An updated review of its use in ischaemic heart disease

Abciximab is a glycoprotein IIb/IIIa receptor antagonist that has proven to be of significant clinical value in improving patient outcome after percutaneous coronary revascularisation. Primarily, the drug inhibits platelet aggregation, but it may also have anticoagulant activity and other beneficial effects, such as inhibiting migration and promoting apoptosis of smooth muscle cells. Large well designed studies have found administration of abciximab (as an adjunct to heparin and aspirin) during percutaneous coronary revascularisation to significantly reduce the incidence of ischaemic complications occurring in the 30 days after the procedure. Significant benefit, particularly on the incidence of myocardial infarction, was still evident after 6 months in 2 of 4 major trials. Abciximab provides particular benefit in patients with unstable angina or myocardial infarction who are undergoing percutaneous coronary revascularisation. The benefits of the drug are additive to those achieved with coronary stenting. Very preliminary data suggest that abciximab may improve coronary blood flow after myocardial infarction and allow reperfusion to be achieved with reduced thrombolytic doses. Caution is required to minimise the risk of bleeding complications with the use of abciximab in combination with heparin and aspirin. Careful patient selection, use of an appropriate heparin regimen, early vascular sheath removal and meticulous femoral artery access site care are recommended. Thrombocytopenia can occur with abciximab treatment, but severe cases are uncommon (< 2% of patients) and can be treated with platelet transfusions. The high acquisition cost of abciximab may be partly or fully offset by the costs averted by the reduced incidence of ischaemic complications and need for urgent and/or repeat revascularisation in high risk patients who receive the drug. However, if bleeding complications occur, this adds to treatment costs. Cost effectiveness analyses generally support the use of abciximab in high risk patients. CONCLUSIONS: Abciximab can be recommended for the prevention of acute ischaemic events in most patients undergoing percutaneous coronary revascularisation, but careful patient selection and strict adherence to the recommended treatment protocol are required to reduce the risk of bleeding complications and thrombocytopenia. Its use in high risk patients is largely supported by pharmacoeconomic data. Further pharmacoeconomic information is needed to establish the drug as a standard of care for all patient groups. The indications for abciximab are likely to expand as more data on its use in acute coronary syndromes become available.     

Initial experience with the use of abciximab in the salvage treatment of acute coronary thrombosis in the Hemodynamics Laboratory

The optimal treatment of acute thrombotic complications in the Catheterization Laboratory has not been defined yet, due to the limited efficacy shown by various pharmacological regimens, even when associated to coronary angioplasty (PTCA). The aim of our study was therefore to evaluate the effects of abciximab (ReoPro), a new potent inhibitor of the platelet glycoprotein IIb/IIIa, when administered as a "rescue" treatment for acute thrombotic coronary occlusion during diagnostic or interventional procedures. Sixteen patients (12 males, 4 females, mean age 59.3 +/- 9.2 years, range 43-77 years), with unstable angina and consecutively treated with abciximab due to clinical instability attributable to coronary thrombosis angiographically proven during PTCA (9 cases) or diagnostic angiography (7 cases), were identified. The individual angiographic films and medical records were then reviewed in order to evaluate the effects of treatment on coronary flow, thrombus size and occurrence of in-hospital adverse events: death, non-fatal acute myocardial infarction (AMI), need for urgent myocardial revascularization and hemorrhage. The administration of abciximab, in association with PTCA (associated in turn with stent implantation in 8 cases), induced a significant increase of coronary TIMI flow grade (0.3 +/- 0.6 vs 2.4 +/- 0.9; p < 0.05) and a significant decrease of thrombus "score" (size) 2.4 +/- 0.9 vs 1.3 +/- 0.6; p < 0.01). No deaths nor need for urgent myocardial revascularization were observed; in 31% of cases (5 patients) evolution towards AMI occurred, while however 94% of cases (15 patients) had a coronary occlusion before treatment. No major hemorrhagic complications were observed, while in 12% of cases (2 patients) a groin hematoma associated with moderate hemoglobin drop, developed. In conclusion, the administration of abciximab, associated with the common "rescue" interventional procedures, in patients with acute thrombotic coronary occlusion in the Catheterization Laboratory, appears to be effective in restoring adequate coronary flow and reducing the thrombus size (limiting therefore the evolution towards AMI), and safe, not having been associated with significant hemorrhagic complications.     

Administration of abciximab during percutaneous coronary intervention reduces both ex vivo platelet thrombus formation and fibrin deposition: implications for a potential anticoagulant effect of abciximab

Abciximab (c7E3 Fab, ReoPro), a platelet glycoprotein (GP) IIb/IIIa inhibitor, decreases acute ischemic complications after percutaneous coronary interventions. Recently, abciximab was shown to decrease thrombin generation in vitro in a static system. To assess whether abciximab can decrease fibrin formation in blood from patients, we quantified both platelet thrombi and fibrin deposition by using an ex vivo flow chamber model. We prospectively studied 18 consecutive patients who underwent percutaneous interventions for unstable coronary syndromes. Blood was perfused directly from the patient through an ex vivo perfusion chamber at a high shear rate, thus mimicking mildly stenosed coronary arteries. Perfusion chamber studies were performed when patients were being treated with heparin plus aspirin before the procedure (baseline) and then repeated after the procedure, when patients were on either aspirin plus heparin alone (group 1, no abciximab, control) or aspirin plus heparin plus abciximab (group 2, abciximab treated). Each patient served as his or her own control. Specimens were stained with combined Masson's trichrome-elastin and antibodies specific for fibrinogen, fibrin, and platelet GP IIIa. Total thrombus area and areas occupied by platelet aggregates and fibrin layers were quantified by planimetry. Group 1 demonstrated no significant change in thrombus area before versus after the procedure; in contrast, treatment with abciximab reduced total thrombus area by 48% in group 2 (after the procedure versus baseline, P=0.01). This decline was due to significant reductions in both platelet aggregates (55%, P=0.005) and fibrin layers (45%, P=0.03). The addition of abciximab to heparin and aspirin in patients undergoing coronary interventions significantly decreases ex vivo thrombus formation on an injured vascular surface. Treatment with abciximab appears to reduce both the platelet and the fibrin thrombus components. This finding supports a potential role for GP IIb/IIIa receptor blockade in decreasing fibrin formation in addition to inhibition of platelet aggregation. Thus, potent inhibitors of GP IIb/IIIa may also act as anticoagulants.     

George Lyman Duff Memorial Lecture. Arterial imaging and atherosclerosis reversal

This review explores evidence for the reversibility of atherosclerosis and augmentation of angiography with non-invasive arterial wall imaging. Meta-analysis from coronary angiographic trials demonstrates that regression and stabilization are 1.5 to 2 times more common in treated than placebo subjects, and progression is reduced by half in treated subjects. Odds ratios for clinical coronary events are significantly reduced with treatment. Lesion improvement occurs more readily in women than men and more so in women receiving concomitant estrogen replacement therapy. Lesions with > or = 50% diameter stenosis (%S) at baseline respond more readily to lipid lowering than those < 50% S, whereas reduction in coronary events is related to stabilization of lesions < 50% S. Lipoproteins have a differential effect on lesion progression according to lesion size, and triglyceride-rich lipoproteins play an important role in the progression of coronary artery lesions < 50% S. Improved therapeutic regimens to alter progression of atherosclerosis may require adjunctive therapy, such as with antioxidants or hormone replacement therapy, in concert with low-density lipoprotein cholesterol reduction to prevent new lesion formation or early lesion progression. Sequential coronary angiographic determination of progression evaluated by both quantitative coronary angiography and global change score, a visual assessment of overall lesion change, predicts clinical coronary events. Only inferences about the state of the arterial wall can be made from angiography, because it delineates only the lumen. Therapy testing and study of atherosclerosis progression can be improved with noninvasive B-mode ultrasonographic imaging of the distal common carotid artery far-wall intima-media thickness (IMT), a reliable measure of early preintrusive atherosclerosis. Measurement of common carotid IMT is useful for the study of coronary artery risk factors and can augment studies of coronary artery intrusive lesions, because it is associated with coronary artery disease. B-mode measurement of common carotid IMT has the potential of serving as a noninvasive surrogate end point for clinical coronary events. Screening for peripheral vessel changes indicative of high risk for coronary artery disease is possible and cost-effective with the noninvasive procedures now available.     

Microemboli during carotid angiography. Association with stroke risk factors or subsequent magnetic resonance imaging changes?

BACKGROUND AND PURPOSE: Carotid angiography is associated with a 1% risk of major stroke. Recently, transcranial Doppler ultrasonography (TCD) has shown cerebral microemboli during carotid angiography. To determine their significance, we correlated the number of microemboli during angiography with clinical characteristics, angiography findings, and preangiography and postangiography cerebral magnetic resonance imaging (MRI). METHODS: One middle cerebral artery was monitored with TCD in 24 patients during angiography for carotid territory ischemia. The number of microemboli was correlated with angiographic and clinical characteristics. T2-weighted cerebral MRI was performed before and < or = 48 hours after angiography, and the number of new ischemic lesions was determined in a blinded review. RESULTS: Microemboli were seen in all patients, with an average of 51 per procedure (range, 12 to 154). The majority of microemboli had signal characteristics typical of air. Sixteen of the 24 patients had both preangiography and postangiography MRI. One of 24 patients had an angiographic stroke, with a single new thalamic lesion on MRI. No other patient had a new lesion. The microembolus count correlated with the angiographic contrast volume (P < .001) but not with any other radiological or clinical characteristic. CONCLUSIONS: This study confirmed the presence of numerous cerebral microemboli during carotid angiography. The microembolic signal characteristics and the correlation with contrast volume indicate that introduced air is the cause. These microemboli are usually clinically silent and do not lead to new changes on cerebral MRI.     

Glycoprotein IIb/IIIa receptor antagonists in the management of cardiovascular diseases

Recent studies of the effects of glycoprotein (GP) IIb/IIIa receptor antagonists on the clinical outcomes of patients with cardiovascular diseases are reviewed. The GP IIb/IIIa receptor antagonists studied include abciximab (a murine monoclonal antibody); eptifibatide (a synthetic peptide); and tirofiban, lamifiban, xemilofiban, sibrafiban, and lefradafiban (synthetic nonpeptides). A majority of clinical trials of GP IIb/IIIa receptor antagonists have been performed in patients with unstable angina or acute myocardial infarction and in patients undergoing percutaneous coronary interventions in whom an intracoronary thrombus may lead to ischemic complications. There is abundant evidence that GP IIb/IIIa receptor antagonists reduce the risk of death, acute myocardial infarction, and urgent revascularization procedures in high- and low-risk patients undergoing percutaneous coronary interventions. Abciximab remains the most studied of these agents in interventional settings. Data are accumulating on synthetic peptide and nonpeptide GP IIb/IIIa receptor antagonists that also demonstrate lower rates of death and ischemic complications in the treatment of acute coronary syndromes. In patients who have had a successful response to intravenous GP IIb/IIIa receptor antagonists, oral agents may represent an option for secondary prevention. Additional studies are required in order to determine further uses for these agents. A growing body of evidence supports the role of GP IIb/IIIa receptor antagonists in invasive and pharmacologic treatment approaches to acute coronary syndromes.     

Unstable angina: are we able to recognize high-risk patients?

It is difficult to identify characteristics of patients with unstable angina that are predictive of a high likelihood of developing clinical events. However, several features have been recognized. Patients with a clinical history of previous stable exertional angina symptoms who began to experience rest pain appear to be at risk and tend to have more extensively underlying coronary disease. When the ischemic episodes are accompanied by rates, a new or worsening mitral regurgitation murmur, or hypotension, there is a high likelihood of significant coronary artery disease and one should triage these patients to early cardiac catheterization and prompt revascularization. An angiographic feature that carries a high risk is a lesion in the proximal left anterior descending or in the left main coronary artery. Certain typical ECG patterns are very suggestive for a critical narrowing in these coronary arteries. If chest pain and ST-segment changes recur on vigorous medical management, early invasive evaluation should be strongly considered. Even so, the left ventricular function is very important prognostically. According to serologic tests, the level of C-reactive protein and serum amyloid A protein suggesting that there may be active inflammation predicts an early poor outcome. However, these serologic abnormalities do not have much clinical value. An increased platelet activation and a reduced fibrinolytic capacity play a role in the pathogenesis of unstable angina, but thrombolytic therapy does not improve the prognosis in patients with unstable angina.     

Correlation between clinical course and quantitative analysis of the ischemia related artery in patients with unstable angina pectoris, refractory to medical treatment. Results of two randomized trials. The European Cooperative Study Group

Patients with unstable angina, refractory to intensive medical therapy, are at high risk for developing thrombotic complications, such as recurrent ischemia, myocardial infarction and coronary occlusion during coronary angioplasty. As both platelet aggregation and/or thrombus formation play an important role in this ongoing ischemic process, a monoclonal platelet GPIIb/IIIa receptor antibody (c7E3) or thrombolytic therapy (alteplase) might be able to modify the clinical course and underlying coronary lesion morphology. To evaluate whether alteplase or c7E3 could influence the incidence of complications, we randomized 36 and 60 patients, respectively to alteplase or placebo, or c7E3 or placebo. All patients exhibited dynamic ECG changes and recurrent pain attacks, despite maximal tolerated medical therapy. Patients were randomized in both studies after initial angiography had demonstrated a culprit lesion amenable for angioplasty. After study drug infusion quantitative angiography was repeated and angioplasty performed. Recurrent ischemia during study drug infusion occurred in 5, 6, 9 and 16 patients from the alteplase, placebo, c7E3 and placebo group, respectively. Major events defined as death, myocardial infarction or urgent intervention occurred in 7, 3, 1 and 7 patients, respectively. Two patients died: one in the alteplase group and one in the placebo group from the c7E3 study. The first patient due to retroperitoneal hemorrhage, the second as a result of recurrent infarction. Qualitative angiography showed resolution of clots in the c7E3 group only, while the same group of patients showed in 20% an improvement in TIMI flow grade, without deterioration in any patient from this group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of nadroparin, a low-molecular-weight heparin, on clinical and angiographic restenosis after coronary balloon angioplasty: the FACT study. Fraxiparine Angioplastie Coronaire Transluminale

BACKGROUND: Experimental studies suggest that the antiproliferative effect of heparin after arterial injury is maximized by pretreatment. No previous studies of restenosis have used a pretreatment strategy. We designed this study to determine whether treatment with nadroparin, a low-molecular-weight heparin, started 3 days before the procedure and continued for 3 months, affected angiographic restenosis or clinical outcome after coronary angioplasty. METHODS AND RESULTS: In a prospective multicenter, double-blind, randomized trial, elective coronary angioplasty was performed on 354 patients who were treated with daily subcutaneous nadroparin (0.6 mL of 10,250 anti-Xa IU/mL) or placebo injections started 3 days before angioplasty and continued for 3 months. Angiography was performed just before and immediately after angioplasty and at follow-up. The primary study end point was angiographic restenosis, assessed by quantitative coronary angiography 3 months after balloon angioplasty. Clinical follow-up was continued up to 6 months. Clinical and procedural variables and the occurrence of periprocedural complications did not differ between groups. At angiographic follow-up, the mean minimal lumen diameter and the mean residual stenosis in the nadroparin group (1.37+/-0.66 mm, 51.9+/-21.0%) did not differ from the corresponding values in the control group (1.48+/-0.59 mm, 48.8+/-18.9%). Combined major cardiac-related clinical events (death, myocardial infarction, target lesion revascularization) did not differ between groups (30.3% versus 29.6%). CONCLUSIONS: Pretreatment with the low-molecular-weight heparin nadroparin continued for 3 months after balloon angioplasty had no beneficial effect on angiographic restenosis or on adverse clinical outcomes.     

Major benefit from antiplatelet therapy for patients at high risk for adverse cardiac events after coronary Palmaz-Schatz stent placement: analysis of a prospective risk stratification protocol in the Intracoronary Stenting and Antithrombotic Regimen (ISAR) trial

BACKGROUND: The Intracoronary Stenting and Antithrombotic Regimen (ISAR) Trial is a randomized study in which antiplatelet therapy is compared with anticoagulant therapy after coronary stent placement, showing a significantly lower rate of noncardiac and cardiac events with antiplatelet therapy. The present study is a report of the analysis of a prospective risk stratification protocol in the ISAR Trial and the association with the incidence of adverse cardiac events and stent vessel occlusion. METHODS AND RESULTS: In all 517 patients randomized in the ISAR Trial, risk stratification was done with a list of 18 clinical, procedural, and angiographic variables: 165 patients with two or fewer criteria were classified as low risk, 148 patients with three criteria were classified as intermediate risk, and 204 patients with four or more criteria were classified as high risk. Within a 30-day follow-up, cardiac event rate (death, myocardial infarction, repeat intervention) was 6.4% for high-risk, 3.4% for intermediate-risk, and 0% for low-risk patients (P<.01). Stent vessel occlusion occurred in 5.9%, 2.7%, and 0%, respectively (P<.01). There was no significant difference between anticoagulant and antiplatelet therapy in the low- and intermediate-risk groups. In high-risk patients, however, the cardiac event rate was 12.6% with anticoagulant therapy and 2.0% with antiplatelet therapy (P=.007), and the rate of stent vessel occlusion was 11.5% and 0%, respectively (P<.001). CONCLUSIONS: This risk stratification protocol can help to identify patients at risk for adverse cardiac events and stent vessel occlusion. Patients in the high-risk group had the most benefit from antiplatelet therapy. These data suggest that antiplatelet therapy is the therapy of choice after coronary stenting specifically for patients with acute ischemic syndromes, difficult procedures, or suboptimal final results.     

Enteral nutrition modifies gut-associated lymphoid tissue in rat regardless of the molecular form of nitrogen supply

OBJECTIVES: It is not known whether the results of randomized trials comparing coronary artery bypass grafting to percutaneous transluminal coronary angioplasty for initial revascularization apply to repeat revascularization in patients with prior bypass grafts. We studied the differences between the patients with prior bypass grafts referred for surgery or angioplasty to identify the clinical and angiographic characteristics that correlated best with either choice and to find clues that might aid in selecting one treatment over the other. METHODS: Between 1992 and 1994, 870 patients underwent first isolated reoperation and 793 patients underwent first balloon angioplasty after a previous operation. A jeopardy score (0 to 8 points) was derived for each patient on the basis of the relative size of the ischemic territory. Clinical and angiographic data were analyzed for association with the revascularization strategy. RESULTS: The following characteristics were more prevalent in the reoperation group: male sex, diabetes, hypertension, valvular disease, normocholesterolemia, and severe left ventricular systolic dysfunction; fewer functioning venous and arterial grafts; and a higher jeopardy score (p < 0.01 for all) than in the angioplasty group. A higher jeopardy score, diabetes, and a lower number of functioning arterial or venous grafts were strong, independent predictors of referral for reoperation (p < 0.01 for all). In hospital death and Q-wave infarction (p < 0.01 for both) were more frequent in the reoperation group. CONCLUSIONS: Reoperation was the revascularization procedure of choice when larger regions of myocardium were in jeopardy. Angioplasty was more frequently chosen in the presence of a patent arterial graft to the left anterior descending coronary artery or multiple functioning bypass grafts. Reoperation was associated with a higher risk of in-hospital complications than angioplasty.     

"Rescue" utilization of abciximab for the dissolution of coronary thrombus developing as a complication of coronary angioplasty

OBJECTIVES: This study sought to test the effect on thrombus score of the "rescue" utilization of the glycoprotein IIb/IIIa antagonist abciximab given to patients in whom intracoronary thrombus has developed as a complication after percutaneous transluminal coronary angioplasty (PTCA) and to determine its clinical utility. BACKGROUND: Abciximab is effective in the prevention of acute ischemic complications when given prophylactically to patients during high risk PTCA. However, its ability to therapeutically dissolve newly formed intracoronary thrombus occurring as a complication after PTCA is not known. METHODS: We performed an observational study in 29 consecutive patients who received abciximab (0.25 mg/kg body weight intravenous bolus, followed by a 12-h infusion at 10 microg/min) after attempted PTCA caused either the new development or further progression of thrombus. Angiograms were analyzed to determine thrombus score and Thrombolysis in Myocardial Infarction (TIMI) flow grade before and after abciximab. Procedural and clinical success and long-term outcome were also determined. RESULTS: Thrombus score decreased from 3.0 +/- 0.9 (mean +/- SD) to 0.86 +/- 0.92 (p < 0.001), and TIMI flow grade increased from 2.5 +/- 0.7 to 2.9 +/- 0.3 (p = 0.008). No instances of distal embolization or no-reflow were noted. The procedural success (< or = 50% residual stenosis) rate was 97%. The clinical success (procedural success with no in-hospital myocardial infarction, bypass surgery or death) rate was 93%. CONCLUSIONS: Dissolution of thrombus and restoration of TIMI grade 3 flow were readily achieved after administration of abciximab when delivered in a "rescue" manner after the development of thrombosis after PTCA. This novel use of abciximab will need to be validated in randomized trials.     

Forward. An update on jaundice in the newborn

We report a case of acute left main coronary artery subocclusion treated by stenting. The patient had a severe ostial left main coronary artery stenosis and after diagnostic coronary angiography developed subocclusion of the left main coronary artery, with TIMI 1 flow and life-threatening hemodynamic consequences. After two balloon dilatations had failed, a half Palmaz-Schatz stent (7 mm) was successfully deployed at the site of the lesion with immediate improvement of the angiographic and clinical picture. We claim that the placement of a half Palmaz-Schatz stent, hand-crimped on a high-pressure and non-compliance balloon, could provide a means for restoring adequate blood flow in patients who develop an important ischemia after diagnostic coronary angiography of a short, calcified left main coronary artery with severe ostial stenosis. Despite the satisfactory angiographic and clinical findings in these patients, the risk of restenosis and the presence of other multivessel diseases press us towards a more definitive surgical treatment.     

Differential expression patterns of GABA transporters (GAT1-3) in the rat olfactory bulb

OBJECTIVES: This report used intravascular ultrasound and quantitative coronary angiography to explore the relation between lesion-associated calcium and risk factors, clinical presentation and angiographic severity of coronary artery stenoses. BACKGROUND: Coronary artery calcium is a marker for significant coronary atherosclerosis. Noninvasive procedures are being proposed as screening tests for coronary artery disease. Intravascular ultrasound identification of tissue calcium has been validated in vitro. METHODS: Independent chart review, preintervention intravascular ultrasound imaging and coronary angiography were used to study primary native vessel lesions in 1,442 patients. Target lesions and reference segments were evaluated according to previously published quantitative and qualitative methods. Results are presented as mean value +/- SD. RESULTS: Overall, 1,043 lesions contained target lesion calcium (72%); the arc of target lesion calcium was 110 +/- 109 degrees. Lesions with an ultrasound plaque burden > 0.75 or an angiographic diameter stenosis > 0.25 had a prevalence of calcium of at least 65%, with a mean arc > 100 degrees. Intermediate lesions had as much target lesion calcium as did angiographically severe lesions. Using multivariate linear regression analysis, patient age, stable (vs. unstable) angina and the intravascular ultrasound lesion site and reference segment plaque burden (but not the angiographic diameter stenosis) were the independent predictors of the arc of target lesion calcium (all p < 0.0001). CONCLUSIONS: Intravascular ultrasound analysis shows that coronary calcification correlates with plaque burden but not with degree of lumen compromise. Thus, the noninvasive detection of coronary calcium is predictive of future cardiac events, presumably because coronary calcification is a marker for overall atherosclerotic plaque burden. Coronary calcium increases with increasing patient age and is less common in unstable lesion subsets.     

Pharmacodynamic profile of short-term abciximab treatment demonstrates prolonged platelet inhibition with gradual recovery from GP IIb/IIIa receptor blockade

BACKGROUND: The glycoprotein (GP) IIb/IIIa receptor antagonist abciximab is approved for use in high-risk percutaneous coronary interventions. The purpose of the present study was to establish the pharmacodynamic profile and platelet-bound life span of abciximab. METHODS AND RESULTS: The pharmacodynamics of abciximab (inhibition of ex vivo platelet aggregation and GP IIb/IIIa receptor blockade) were measured in 41 individuals who were randomized to receive a 0.25-mg/kg bolus and a 12-hour infusion of either 10 microg/min (EPIC regimen) or 0.125 microg x kg(-1) x min(-1) (EPILOG regimen) of the antiplatelet agent. At extended times, the amount and distribution of platelet-bound abciximab were monitored by flow cytometry. The EPIC and EPILOG infusion regimens exhibited equivalent blockade of both GP IIb/IIIa receptors and platelet aggregation throughout the duration of abciximab treatment. Flow cytometry revealed a single, highly fluorescent platelet population during treatment, consistent with complete saturation and homogeneous distribution of abciximab on circulating platelets. For 15 days after treatment, the fluorescence histograms remained unimodal with gradually diminishing fluorescence intensity, indicating decreasing levels of platelet-bound abciximab. At 8 and 15 days, which exceeds the normal circulating life span of platelets, median relative fluorescence intensity corresponded to 29100 (29% GP IIb/IIIa receptor blockade) and 13300 (13% GP IIb/IIIa receptor blockade) abciximab molecules bound per platelet, respectively. CONCLUSIONS: These results are consistent with continuous reequilibration of abciximab among circulating platelets and may explain the gradual recovery of platelet function and long-term prevention of ischemic complications by abciximab after coronary intervention.     

A risk-benefit assessment of abciximab in angioplasty

Advances in percutaneous coronary intervention (PCI) have allowed procedures to be performed on a variety of patients with a spectrum of challenging coronary anatomy. Abciximab has permitted further expansion and has made the procedure safer. Abciximab is a chimerised murine monoclonal antibody directed against the platelet glycoprotein (GP) IIb-IIIa receptor. Binding to this receptor inhibits platelet aggregation to a wide variety of biological agonists. It also binds to alphavbeta3 and leucocyte MAC-1 receptors; the biological significance of its affinity to these receptors is unclear. Abciximab has an extremely short plasma half-life. Since abciximab binds to the platelet GP IIb-IIIa receptor with great avidity it has an extremely long biological half-life. The use of abciximab is currently confined primarily to PCIs. The first large trial, EPIC, established that abciximab, given with aspirin (acetylsalicylic acid) and heparin, reduced the frequency of peri-procedural ischaemic events by 35% in high-risk patients. For this reduction a bolus of 0.25 mg/kg was followed by a 12-hour infusion of abciximab. However, the transfusion rate was doubled. A subsequent trial, EPILOG, indicated that reduction of the dose of heparin along with expeditious removal of arterial access sheaths, reduced the rate of haemorrhagic complications to a level comparable with placebo-treated patients. while also amplifying the reduction in ischaemic events. In a third trial, EPISTENT, this benefit was shown to include patients undergoing elective coronary stent implantation. Additional trials have demonstrated that the same effect is present in patients undergoing primary PCI for acute myocardial infarction and in patients undergoing PCI for refractory unstable angina pectoris. In the latter situation, treatment with abciximab for 18 to 24 hours preceding the intervention reduced the rate of myocardial infarction even before the procedure was begun. The rationale for the use abciximab is thus clearly established. Bleeding complications can be reduced by limiting the heparin dose, avoiding unneeded venous access site punctures, and expeditious removal of arterial sheaths. In emergency coronary artery bypass surgery, platelet transfusion reduces the number of receptors occupied per platelet and is likely to reduce the degree of postoperative bleeding. The cost of abciximab remains an issue; however, this is partially offset by the reduction in ischaemic complications and accompanying resource use. In patients undergoing elective coronary stenting, abciximab use reduced the long term rate of target vessel revascularisation. The degree to which this reduction results in further cost savings will require further analysis.     

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. Only subjects receiving the Gianturco-Roubin stent as a new device in an unplanned fashion are included. RESULTS: The mean age of the patient group was 61.8 years, and the majority of the patients were men. A history of percutaneous transluminal coronary angioplasty (PTCA) was present in 35.4% of the group, and 16.9% had previous coronary artery bypass graft surgery. Unstable angina was present in 67.7%. Double- or triple-vessel coronary artery disease was present in 55.4%, and the average ejection fraction was 58%. The presence of thrombus was noted in 7.3%, and 7.2% had moderate to severe tortuosity of the lesion. The angiographic success rate was 92%. Individual clinical sites reported that 66.3% of the stents were placed after suboptimal PTCA, 20.3% for abrupt closure and 13.4% for some other technical PTCA failure. Major in-hospital events occurred in 9.7% of patients, including death in 1.7%, Q wave myocardial infarction in 3.1% and emergency bypass surgery in 6%. Abrupt closure of a stented segment occurred in 3.1% of patients at a mean of 3.9 days. Cerebrovascular accident occurred in 0.3%, and transfusion was required in 10.6%. Vascular events with surgical repair occurred in 8.6% of patients. CONCLUSIONS: Despite these complications, the use of this device for the treatment of a failed or suboptimal PTCA result remains promising given the adverse outcome of abrupt closure with conventional (nonstent) treatment.