High-risk Percutaneous Transluminal Coronary Angioplasty Research Articles

Results of a pilot clinical trial of the safety and efficacy of an original glycoprotein IIb/IIIa receptor inhibitor in acute coronary syndrome

Aim. To study the safety and efficacy of Angipure in acute ST-segment elevation coronary syndrome (STE-ACS) and high-risk percutaneous transluminal coronary angioplasty (PTCA) compared with eptifibatide.Material and methods. The study included 157 patients with STE-ACS. High-risk PTCA included massive or total coronary artery thrombosis, noreflow/slow-reflow phenomenon, and acute stent thrombosis. Fifty-five people received Angipure at a dose of 0,72 mg/kg, 52 — at a dose of 0,40 mg/kg, while 50 patients received eptifibatide (Integrilin). We conducted clinical and laboratory studies, electrocardiography (ECG), coronary angiography.Results. According to the criteria "Frequency and severity of hemorrhagic events, including hemorrhagic stroke", "Frequency, severity of other adverse events", there were no differences in safety between Angipure at doses of 0,40 and 0,72 mg/kg and eptifibatide. Complaints, clinical symptoms, vital signs, complete blood count, biochemical and coagulation tests, ECG in patients of different groups were similar and had unidirectional dynamics. The use of Angipure or eptifibatide was considered effective if no adverse outcomes (death, recurrent acute ischemic event, need for urgent revascularization) were observed within 30 days. There were no lethal outcomes. One repeated acute ischemic event was registered in each group. In groups of patients receiving Angipure 0,40 mg/kg and eptifibatide, urgent revascularization was required once each.Conclusion. Angipure and eptifibatide have similar safety and efficacy.

Elective versus provisional intra-aortic balloon pumping in high-risk percutaneous transluminal coronary angioplasty

Background Elective intra-aortic balloon pump (IABP) support may reduce acute complications occurring during percutaneous coronary interventions (PCI) in patients with severe depression of the left ventricular ejection fraction (EF ≤ 30%). Methods Since February 1998, 133 consecutive patients with EF ≤30% underwent elective PCI in our institution; 61 had elective preprocedural IABP support (group A) and 72 patients had conventional PCI (group B). Jeopardy score was calculated in each patient from the coronary angiograms to quantify the myocardium at risk. Results EF was similar in the 2 groups. Jeopardy score was higher in group A (8.0 ± 2.8 vs 6.7 ± 2.4, P = .008). The other principal clinical and angiographic characteristics were similar in the 2 groups. Severe hypotension and/or shock occurred in 11 patients, all in group B ( P = .001). All required urgent IABP support, and 3 eventually died. Intraprocedural major adverse cardiac and cerebral events (eg, myocardial infarction, severe hypotension and/or shock, urgent bypass surgery, stroke, and death) were higher in group B (17% vs 0%, P = .001). By stepwise logistic regression analysis, elective IABP support (odds ration [OR] 0.11 [95% CI 0.21-0.60], P = .011), jeopardy score (OR 5.37 [95% CI 1.10-8.70], P = .040), and female sex (OR 2.72 [95% CI 1.85-3.10], P = .015), were the correlates of intraprocedural events. Conclusions This study supports the potential usefulness of elective versus provisional IABP to prevent intraprocedural major adverse cardiac and cerebral events in high-risk PCI. (Am Heart J 2003;145:700-7.)

Platelet Glycoprotein IIb/IIIa Inhibitors

Glycoprotein IIb/IIIa (GPIIb-IIIa) complexes (integrin αIIbβ3) mediate platelet aggregation by binding fibrinogen or von Willebrand factor (vWF), protein cofactors that form bridges between adjacent platelets. The cross-linked adhesive proteins assemble platelets into the aggregate. Agents that block the function of the GPIIb-IIIa complex of platelets constitute a powerful new generation of antithrombotic drugs.1 Among the short- and long-term aims of such drugs are (1) to provide immediate relief in the case of ongoing arterial thrombosis and (2) to eliminate excessive platelet reactivity in diseased vessels so that occlusive thrombi and restenosis do not occur, while allowing sufficient hemostasis to prevent spontaneous bleeding. It should be emphasized that stenosis and partial occlusion are both prothrombotic, with increased shear stress promoting platelet activation. Under these conditions, vWF plays a major role in the mediation of thrombus formation, interacting with GPIIb-IIIa and the adhesion receptor GPIb.2 Otherwise, fibrinogen is the major cofactor of platelet aggregation, essentially binding through a dodecapeptide sequence (aa400 to aa411) present at the carboxy terminus of each γ chain. Binding of vWF and other adhesive proteins, such as fibronectin, to GPIIb-IIIa is mediated by the Arg-Gly-Asp (RGD) sequence, a universal mediator of cellular interactions with the extracellular matrix.1 2 3 Anti–GPIIb-IIIa drugs block this final step of the platelet aggregation process. They also block the “outside-in” signaling that follows the binding of adhesive proteins to activated GPIIb-IIIa and the onset of platelet aggregation.3 This signaling may promote events such as secretion, clot retraction, and the expression of procoagulant activity; therefore, its inhibition extends the influence of anti–GPIIb-IIIa drugs beyond the blocking of platelet-to-platelet cohesion. The present review will mostly be illustrated by results obtained with abciximab (c7E3 Fab, ReoPro), a chimeric antibody fragment that is the most widely used of the new …

Cost-effectiveness analysis of abciximab: a Canadian hospital perspective.

To assess the cost-effectiveness of abciximab therapy versus traditional practice in high-risk patients receiving percutaneous transluminal coronary angioplasty (PTCA) from a Canadian hospital perspective. A predictive decision analytic model using published clinical and economic evaluations, as well as costs of medical care in Canada. High-risk PTCA patients as defined by the Evaluation of c7E3 for Prevention of Ischemic Complications trial and the c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina trial. Two treatment strategies were compared: (1) abciximab 0.25 mg/kg intravenous bolus 10 minutes prior to PTCA followed by abciximab 10 micrograms/min intravenous infusion for 12 hours after the procedure, and (2) no abciximab adjunctive therapy at the time of PTCA. Both treatment strategies were combined with intravenous heparin up to 100 units/kg bolus pre-PTCA followed by bolus doses for 1 hour after PTCA per the protocol. Cumulative outcomes were considered up to 6 months after initial PTCA. At 6 months, 29% of the patients in the abciximab treatment arm compared with 33% in the no abciximab arm achieved one of the primary events. The most common adverse event experienced was major bleeding at 4% in the abciximab treatment arm versus 1.6% in the no abciximab arm. The average cost per patient for each strategy was $3261 Can ($1 Can = $0.686 US) (abciximab arm) versus $2073 Can (no abciximab arm), resulting in an incremental cost-effectiveness ratio of $29,700 Can per event-free patient. In univariate sensitivity analyses, the only controllable factor that changed the results of the cost-effectiveness outcome was the cost of abciximab. Although the use of abciximab as an adjunct to PTCA results in a reduction in event rates in high-risk patients compared with traditional treatment, there is an increased cost associated with this strategy.

Abciximab: platelet IIb/IIIa receptor blockade in the management of patients with acute coronary syndromes

Summary Complications of percutaneous transluminal coronary angioplasty (PTCA) include abrupt vessel closure in 5% of patients, and restenosis, which can occur in up to 45% of patients. Abciximab is a chimeric monoclonal antibody to the platelet glycoprotein IIb/IIa receptor and inhibits platelet aggregation. It also binds to the vitronectin receptor in the vessel wall, which is involved in the process of smooth muscle cell migration and proliferation, components of the restenosis process. Abciximab is licensed for use in high-risk PTCA (due to the presenting clinical syndrome and/or lesion morphology) with the aim of reducing peri-procedural complications and improving long-term outcomes. Several multi-centre randomized trials have proven the efficacy of abciximab in various clinical situations and have also shown that using lower doses of heparin with abciximab not only minimizes bleeding complications but also optimizes clinical outcomes. Abciximab can be administered in high-risk clinical situations from primary PTCA to sub-acute stent thrombosis, and recent experience is discussed. Although this drug is an expensive addition to an already formidable cardiology budget, pharmaco-economic data have shown that, when used appropriately, it is cost effective.

Does Intracoronary Thrombus Influence the Outcome of High Risk Percutaneous Transluminal Coronary Angioplasty? Clinical and Angiographic Outcomes in a Large Multicenter Trial

Objectives. We sought to evaluate the impact of angiographically visible thrombus on short- and long-term clinical outcomes after percutaneous transluminal coronary angioplasty (PTCA).Background. Intracoronary thrombus is frequently seen on angiography in patients with acute ischemic coronary syndromes or complex lesion morphology, or both, and is often considered to predict a higher rate of complications in patients undergoing PTCA.Methods. Prospectively collected data from 2,099 patients undergoing high risk PTCA in the Evaluation of IIb/IIIa Platelet Receptor Antagonist 7E3 in Preventing Ischemic Complications (EPIC) trial were analyzed. In addition to aspirin and heparin, patients were randomized to receive either abciximab bolus and infusion, abciximab bolus alone or placebo. Based on an angiographic core laboratory interpretation, patients were classified into three groups: thrombus absent, thrombus possible or thrombus present. The primary end point at 30 days was the composite of death, myocardial infarction or urgent revascularization. The 6-month end point was the composite of death, myocardial infarction or any revascularization.Results. Although abrupt closure was most common in patients with thrombus present compared with thrombus absent or possible (13%, 10.0% and 7.4%, respectively), neither the 30-day nor the 6-month clinical end points were different among the three groups (9%, 11% and 11.7%, respectively, and 30%, 34% and 31%, respectively). Most notably, the benefit of treatment with abciximab was present in all three thrombus groups, and the magnitude of benefit was not different among the thrombus groups.Conclusions. In high risk patients undergoing percutaneous coronary revascularization, features of thrombus on the preprocedure angiogram do not indicate an augmented risk of adverse clinical outcomes. Abciximab therapy reduces the rate of adverse outcomes regardless of the presence of thrombus and should therefore not necessarily be reserved for patients whose angiograms have features of intraluminal thrombus.

“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 μg/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 (≤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.

Tirofiban: an investigational plateletglycoprotein IIb/IIIa receptor antagonist

The deposition of a platelet rich thrombus on an atherosclerotic plaque is a critical step in the development of unstable coronary syndromes. Currently available therapeutic agents such as aspirin and ticlopidine are relatively weak inhibitors of platelet aggregation. Recently, antagonists to platelet glycoprotein IIb/IIIa (GPIIb/IIIa), a platelet surface integrin whose activation and subsequent binding to fibrinogen is the final common step in the formation of platelet aggregates, have been utilised to treat unstable angina and myocardial infarction. Tirofiban is a novel, specific, low molecular weight GPIIb/IIIa receptor antagonist, which competitively inhibits the platelet fibrinogen receptor. Tirofiban is administered as an intravenous infusion with a mean half-life of 1.6 h. In healthy volunteers, the plasma concentration and half-life of tirofiban are unaffected by pre-treatment with aspirin, although aspirin increases the bleeding time prolongation caused by tirofiban. Tirofiban is excreted by both renal (37%) and non renal mechanisms. Three clinical trials, PRISM, PRISM PLUS, and RESTORE, have evaluated the safety and efficacy of tirofiban in unstable angina and in high-risk percutaneous transluminal coronary angioplasty (PTCA). When compared to heparin in the management of unstable angina, tirofiban decreased the odds of recurrent ischaemia, myocardial infarction, or death by 36% at 48 h, and death by 39% at 30 days. Similarly, the addition of tirofiban to heparin reduced the odds of recurrent ischaemic events for death at 7 days by 34%. RESTORE, a clinical trial evaluating the efficacy and safety of tirofiban in patients undergoing PTCA within 72 h of presentation with unstable angina or myocardial infarction, demonstrated a 38% reduction in a composite end-point at 48 h; the need for urgent PTCA and coronary artery bypass graft (CABG) at 30 days was reduced by 36%. Adverse side-effects, including major bleeding, were not significantly higher with tirofiban treatment. Tirofiban and other GPIIb/IIIa inhibitors represent a major advance in the treatment of unstable coronary syndromes and high-risk PTCA.

Clinical trials of Hirulog in patients undergoing high-risk percutaneous transluminal coronary angioplasty

Clinical trials of Hirulog in patients undergoing high-risk percutaneous transluminal coronary angioplasty

Distal coronary hemoperfusion during percutaneous transluminal coronary angioplasty.

Distal coronary hemoperfusion during percutaneous transluminal coronary angioplasty (PTCA)-with an autoperfusion balloon or active system-facilitates prolonged balloon inflation. Prolonged inflations may tack up intimal dissections and improve the primary angioplasty result in complex lesions. Additionally, distal perfusion may reduce the likelihood of cardiogenic shock during high-risk PTCA. Autoperfusion balloons are most frequently used to treat acute or threatened closure. There currently is no prospective clinical study showing that stent implantation for this complication is more successful and more cost-effective. The blood flow rates through autoperfusion balloons may not abolish myocardial ischemia, and higher flow rates can often be achieved with pumps. Therefore, during high-risk PTCA, pumps may be preferred to prevent hemodynamic collapse. Clinical application of perfusion pumps is hampered by the risk for mechanical hemolysis during prolonged perfusion and the high velocity of the bloodstream that exits the PTCA catheter, causing distal vessel wall trauma.

Bleeding complications with new antithrombotics used in ischaemic heart disease.

Despite adjunctive therapy with heparin and aspirin, patients undergoing percutaneous transluminal coronary angioplasty (PTCA) continue to be at risk of abrupt vessel closure and acute ischaemic events. In an attempt to overcome the limitations of traditional antithrombotics, more potent agents have been developed, including direct thrombin inhibitors (e.g., hirudin and hirulog) and new antiplatelet agents [e.g., the glycoprotein IIb/IIIa receptor inhibitor c7E3 Fab (ReoProTM)]. Initial phase-III trials of hirudin in patients with acute coronary syndromes identified an excess incidence of major bleeding complications. Some of these trials have been recommenced using lower doses. Reports on phase-III trials of hirulog should be forthcoming soon. Of the new agents, the chimeric monoclonal antibody fragment c7E3 Fab has the most extensive available data. In the phase-III evaluation of 7E3 for the Prevention of Ischemic Complications trial, the administration of a c7E3 Fab bolus plus c7E3 Fab infusion reduced the rate of major ischaemic events by 35% at 30 days (p = 0.008) in patients undergoing high-risk PTCA. Major bleeding episodes occurred more frequently with this regimen than with placebo, although rates of intracranial haemorrhage or surgery for bleeding did not differ between groups. The findings suggest that the risk of bleeding complications might be reduced, without compromising efficacy, by administering heparin on a weight-adjusted basis in patients treated with c7E3 Fab.

Circulatory support devices in clinical cardiology. Current concepts.

Percutaneous transluminal coronary angioplasty (PTCA) has extended its indications to multivessel disease and impaired left-ventricular function. In these patients, failed PTCA may induce cardiogenic shock or arrest. Coronary and circulatory support devices such as antegrade perfusion catheters, coronary sinus retrograde perfusion, intraaortic balloon pumping, left-ventricular pumping (Hemopump) and percutaneously applicable cardiopulmonary support are the tools necessary for high-risk PTCAs. The devices are a prerequisite for developing a minimally invasive cardiac surgery.

Lack of usefulness of prolonged bleeding times in predicting hemorrhagic events in patients receiving the 7E3 glycoprotein IIb/IIIa platelet antibody

Hemorrhagic events remain the most worrisome complication in patients receiving drugs that after hemostasis for treatment of acute coronary syndromes. The 7E3 Fab monoclonal antibody provides a dose-dependent inhibition of platelet aggregation via the glycoprotein IIb/IIIa receptor. This study examines the correlation of hemostatic parameters with bleeding events in patients receiving intravenous 7E3 while enrolled in acute myocardial infarction and high-risk percutaneous transluminal coronary angioplasty pilot studies. Patients with acute myocardial infarction received 100 mg of tissue-type plasminogen activator over 3 hours followed by an escalating intravenous bolus dose of murine 7E3 (0.1 mg/kg [n = 5], 0.2 mg/kg [n = 22], 0.15 mg/kg [n = 13], 0.25 mg/kg [n = 20]). Patients in the high-risk angioplasty trial received a chimeric 7E3 bolus (up to 0.25 mg/kg) with (n = 32) or without (n = 15) intravenous continuous infusion of 7E3 (10 μg/min for 6 to 24 hours) after elective angioplasty. Patients in both studies received aspirin therapy (325 mg/day) and partial thromboplastin time-guided (1.5 to 2 times normal) heparin infusion. Bleeding events occurred in 34 of 124 patients (27%). The median template bleeding times (minutes) for patients in the groups with bleeding versus no bleeding events in the trials was 13.5 versus 14 and 30 versus 30, respectively (p = NS). In patients with myocardial infarction, a substantial decline in platelet count at 24 hours was associated with bleeding (p = 0.02). These findings suggest, in contrast to a previous report, that the template bleeding time is an imprecise index for predicting hemorrhagic events in patients receiving platelet fibrinogen receptor inhibitor, with or without thrombolytic therapy, and raises questions about the use of this hemostatic parameter in future clinical trials.

Causes and correlates of death after unsupported coronary angioplasty: Implications for use of angioplasty and advanced support techniques in high-risk settings

To better understand the factors predisposing a patient to death after elective percutaneous transluminal coronary angioplasty (PTCA) and to gain insight into indications for high-risk PTCA both with and without adjunctive use of support devices, the outcomes of 8,052 consecutive procedures were reviewed. Death occurred after 32 procedures (0.4%) and was directly related to coronary artery closure in 26 (81%) of these cases. Left ventricular failure due to vessel closure at the dilated site, the most common cause of death, was independently correlated with female sex (p < 0.001), “jeopardy score” (p < 0.001) and PTCA of a proximal right coronary artery site (p = 0.002), but not with left ventricular ejection fraction or presence of multivessel disease. Right ventricular failure after closure of the proximal right coronary artery, and left main coronary dissection accounted for the majority of the remaining deaths. Systolic blood pressure immediately after coronary artery closure was also closely correlated with jeopardy score, and cardiogenic shock was frequent in women with scores ≥3.5 and in men with scores ≥5.0. These data highlight the superiority of the jeopardy score versus ejection fraction in the determination of risk, stress the importance of gender in determining outcome and point to the need for better means of right ventricular protection from severe ischemia. Therefore, an initial framework for rational use of PTCA and support devices in the high-risk setting is established.

Effects of hemoperfusion during percutaneous transluminal coronary angioplasty on left ventricular function

The effect of autologous blood perfusion, delivered through an angiographic power injector, on alleviating left ventricular (LV) hemodynamic deterioration during percutaneous transluminal coronary angioplasty (PTCA) was examined. LV systolic and diastolic pressures, LV peak positive and peak negative first derivative of LV pressure ( dP dt ), and ST-segment shift were recorded in 9 patients with and without hemoperfusion. Hemoperfusion resulted in an improved LV hemodynamic profile during balloon occlusion, as reflected in LV systolic pressure (127 ± 14 vs 120 ± 15 mm Hg, p = 0.01), LV end-diastolic pressure (17 ± 14 vs 25 ± 6 mm Hg, p < 0.001), peak positive (1,237 ± 240 vs 1,149 ± 225 mm Hg/s, p < 0.05) and peak negative (1,666 ± 357 vs 1,485 ± 385 mm Hg/s, p = 0.003) dP dt . Hemoperfusion provides substantial protection for significant LV dysfunction induced by conventional PTCA in 1-vessel angioplasty and is a feasible option to protect against potential cardiovascular collapse in high-risk PTCA.

Cardiopulmonary bypass.

There has been a recent renewed interest in certain aspects of cardiopulmonary bypass employing extracorporeal circulation. Several areas have received special attention. Among these is the institution of extracorporeal circulation using a percutaneous technique for circulatory assistance during high-risk percutaneous transluminal coronary angioplasty. A national registry has been established to review and monitor results using this percutaneous technique. Several recent developments in the delivery of cardioplegia during ischemic arrest have stimulated investigative efforts. In particular, the delivery of cardioplegia in a retrograde manner through the coronary sinus has proved an effective and useful adjunct to myocardial protection during cardiopulmonary bypass with extracorporeal circulation. A newer investigative technique employing only warm cardioplegia delivered primarily through the retrograde coronary sinus route seems to offer some promise in providing optimal myocardial protection while minimizing hemorrhagic complications and other cold-induced myocardial injury. Because of concerns regarding blood transfusion-related communicable disease (eg, acquired immune deficiency syndrome and non-A, non-B hepatitis), there has been increasing research effort into postoperative hemorrhage related to cardiopulmonary bypass with extracorporeal circulation. Specifically, various drugs that may serve as hemostatic adjuncts have been investigated extensively. These drugs include aprotinin and desmopressin acetate. Likewise, several studies have evaluated other drugs (mainly aspirin) that have a negative influence on postoperative hemostasis. Additionally, there has been continued research interest in the activation of the inflammatory system during cardiopulmonary bypass.(ABSTRACT TRUNCATED AT 250 WORDS)