RESUMO
Deoxyribonucleic acid polymerase-beta (EC 2.7.7.7) has been purified over 100 000-fold from a whole cell extract of guinea pig liver. The enzyme yields a single stainable band when subjected to non-denaturing polyacrylamide gel electrophoresis, and this band corresponds to the DNA polymerase activity when a sister gel is sliced and assayed. The final fraction has a specific activity of 21 000 units/mg; this value can be increased significantly by addition of various components, including glycols, polyamines or any of several protein factors which can be purified from the crude extract. The DNA polymerase-beta lacks detectable exonuclease or endonuclease activity, has an alkaline pH optimum and has a requirement for all four deoxyribonucleoside triphosphates, a divalent cation and a primer-template for maximal activity. While activated DNA is the preferred primer-template, the enzyme is capable of utilizing native and denatured DNA as well as several synthetic polynucleotides as primer-templates. The latter are especially effective when manganese is the divalent cation. Magnesium, at 10 mM, is the preferred divalent cation when activated DNA is used. Manganese, and to a lesser extent cobalt, can substitute for magnesium while zinc and calcium cannot. The beta-polymerase has a half-life of 10 min at 40 degrees C and this is increased in the presence of either DNA or NaCl. The enzyme is stimulated by glycols, polyamines and NaCal or KCl, and is inhibited by several known inhibitors of DNA polymerase activity including o-phenanthroline, heparin, organic solvents and sulfhydryl blocking agents. Guinea pig liver DNA polymerase-beta is remarkably similar to the rat Novikoff hepatoma beta-polymerase with respect to its isoelectric point of 8.4 and its molecular weight of 32 000 as determined by sucrose gradient centrifugation under high or low salt conditions or sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This similarity is further extended to the removal, at the final step in purification, of a protein capable of stimulating the homogeneous enzyme. Removal of this protein could explain the lower molecular weight of the guinea pig and other rodent-derived beta-polymerases, when compared to the beta-polymerases from other systems.
Assuntos
DNA Polimerase I/isolamento & purificação , DNA Polimerase Dirigida por DNA/isolamento & purificação , Fígado/enzimologia , Animais , DNA Polimerase I/metabolismo , Estabilidade de Medicamentos , Cobaias , Cinética , Peso MolecularRESUMO
BACKGROUND: Pharmacodynamics of eptifibatide, a cyclic heptapeptide antagonist of platelet glycoprotein IIb/IIIa, are substantially altered by anticoagulants that chelate calcium, resulting in overestimation ex vivo of the in vivo effects of this agent. We conducted a dose-ranging study to characterize the pharmacodynamics and pharmacokinetics of eptifibatide under physiological conditions. METHODS AND RESULTS: Patients (n=39) undergoing elective percutaneous coronary intervention were randomly assigned to an eptifibatide bolus followed by an infusion (180-microgram/kg bolus followed by 2 microgram/kg per minute or 250-microgram/kg bolus followed by 3 microgram/kg per minute) for 18 to 24 hours. In a 2:1 ratio, these patients received either a second bolus of eptifibatide (90 microgram/kg or 125 microgram/kg for the initial 180-microgram/kg or 250-microgram/kg groups, respectively) or placebo 30 minutes after the initial bolus. Bleeding times, ex vivo platelet aggregation, receptor occupancy, and plasma eptifibatide levels at baseline and at 1, 2, 3, 4, 6, and 8 hours were evaluated. Platelet inhibition was dose dependent and >80% in all groups by steady state. The single-bolus regimens had a transient loss of inhibition at 1 hour, consistent with rapid distribution and drug elimination. Pharmacokinetic modeling suggested that optimal dosing of eptifibatide would be obtained with a 180-microgram/kg bolus and a 2-microgram/kg per minute infusion followed by a second 180-microgram/kg bolus 10 minutes later. CONCLUSIONS: A novel higher-dose, double-bolus regimen of eptifibatide in coronary intervention attains and maintains >90% inhibition of platelet aggregation in >90% of patients, providing the pharmacodynamic construct for the design of the Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial of adjunctive eptifibatide in coronary stent implantation.
Assuntos
Angioplastia Coronária com Balão , Peptídeos/farmacocinética , Inibidores da Agregação Plaquetária/farmacocinética , Área Sob a Curva , Relação Dose-Resposta a Droga , Eptifibatida , Feminino , Humanos , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Agregação Plaquetária/efeitos dos fármacos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Fatores de TempoRESUMO
BACKGROUND: In the EPILOG trial (Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade), abciximab administered with weight-adjusted heparin diminished the risk of ischemic complications within 30 days by 56% among patients undergoing percutaneous coronary revascularization, without increased bleeding complications. METHODS AND RESULTS: A prospective economic assessment was performed in the 2792 patients enrolled in EPILOG. Patients were randomized to receive placebo with standard-dose weight-adjusted heparin, abciximab with low-dose weight-adjusted heparin, or abciximab with standard-dose weight-adjusted heparin during percutaneous coronary intervention. Hospital billing data for the baseline hospitalization were collected for 2581 patients (92.4% of total) and imputed for the remainder, with physician fees estimated from the Medicare Fee Schedule. For the baseline hospitalization, medical costs (hospitalization and physician fees) averaged $9632 for the placebo arm compared with $8758 (P:=0.005) and $9092 (P:=0.176) for the abciximab with low-dose and standard-dose heparin arms, respectively. Inclusive of average drug cost ($1454 to $1457), the net incremental baseline cost of these 2 abciximab strategies was $583 with low-dose weight-adjusted heparin and $914 with standard-dose weight-adjusted heparin. During 6-month follow-up, average hospital costs were not significantly different in the 3 treatment groups; cumulative net incremental costs were $1236 and $1268 in the abciximab with low-dose and standard-dose heparin groups, respectively. CONCLUSIONS: Treatment with abciximab and low-dose, weight-adjusted heparin during percutaneous coronary revascularization reduces ischemic events and associated costs, thereby offsetting some of the cost of the drug. The suppression of bleeding complications associated with this agent by heparin dose reduction optimizes the economic attractiveness of this treatment strategy.
Assuntos
Anticorpos Monoclonais/economia , Custos de Cuidados de Saúde , Heparina/economia , Fragmentos Fab das Imunoglobulinas/economia , Revascularização Miocárdica/economia , Complexo Glicoproteico GPIb-IX de Plaquetas/antagonistas & inibidores , Glicoproteínas da Membrana de Plaquetas , Abciximab , Idoso , Anticorpos Monoclonais/uso terapêutico , Quimioterapia Combinada , Hemorragia/prevenção & controle , Heparina/administração & dosagem , Heparina/uso terapêutico , Humanos , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Pessoa de Meia-Idade , Isquemia Miocárdica/prevenção & controle , Inibidores da Agregação Plaquetária/economia , Inibidores da Agregação Plaquetária/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Platelet glycoprotein IIb/IIIa blockade with abciximab (ReoPro) improves the clinical outcomes of percutaneous coronary intervention. This registry was conducted to characterize the effects of repeated administration of abciximab during intervention. METHODS AND RESULTS: We recruited 500 consecutive patients at 22 centers in the United States who were receiving abciximab for at least a second time during percutaneous coronary intervention. Safety was measured as the incidence of hypersensitivity reactions, major bleeding, and thrombocytopenia. Efficacy was assessed as event-free clinical success. Human antichimeric antibody (HACA) responses were also characterized. There were no cases of hypersensitivity (95% upper confidence bound, 0.3%), major bleeding, or death. Clinical success was 94.4%. Thrombocytopenia occurred in 23 patients (4.6%; 95% CI, 2.8% to 6.4%), including 12 (2.4%; 95% CI, 1.1% to 3.7%) who developed profound thrombocytopenia (<20x10(9) cells/L). In 2 patients (0.4%), profound thrombocytopenia did not develop until after hospital discharge; in 4 (0.8%), profound thrombocytopenia recurred despite platelet transfusion. Before a first readministration, a positive HACA titer was present in 22 of 454 patients (4.8%); after a first readministration, an additional 82 of 432 (19.0%) became HACA-positive. HACA did not neutralize the in vitro inhibition of platelet aggregation by abciximab or correlate with clinical events. CONCLUSIONS: The results, including overall rates of thrombocytopenia, were consistent with randomized clinical trials of first abciximab treatment. However, there was a shift from mild to profound thrombocytopenia, and cases of delayed presentation and of recurrent thrombocytopenia were seen. These findings suggest that indications and guidelines for first-time use apply to retreatment, particularly the systematic monitoring for thrombocytopenia.
Assuntos
Angioplastia Coronária com Balão , Anticorpos Monoclonais/administração & dosagem , Doença das Coronárias/terapia , Fragmentos Fab das Imunoglobulinas/administração & dosagem , Sistema de Registros/estatística & dados numéricos , Trombocitopenia/diagnóstico , Grau de Desobstrução Vascular/efeitos dos fármacos , Abciximab , Angioplastia Coronária com Balão/efeitos adversos , Anticorpos/sangue , Anticorpos/farmacologia , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/imunologia , Aspirina/administração & dosagem , Doença das Coronárias/sangue , Intervalo Livre de Doença , Esquema de Medicação , Hemorragia/etiologia , Heparina/administração & dosagem , Humanos , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Fragmentos Fab das Imunoglobulinas/imunologia , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/imunologia , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Complicações Pós-Operatórias/prevenção & controle , Trombocitopenia/etiologia , Resultado do Tratamento , Estados UnidosRESUMO
BACKGROUND: Blockade of the platelet glycoprotein IIb/IIIa receptor with the monoclonal antibody fragment abciximab was shown in a placebo-controlled randomized trial to reduce the incidence of acute ischemic complications within 30 days among a broad spectrum of patients undergoing percutaneous coronary revascularization. The durability of clinical benefit in this setting has not been established. METHODS AND RESULTS: A total of 2792 patients enrolled in the Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade (EPILOG) trial were followed with maintenance of double-blinding for 1 year. Patients had been assigned at the time of their index coronary interventional procedure to receive placebo with standard-dose, weight-adjusted heparin (100 U/kg initial bolus), abciximab with standard-dose, weight-adjusted heparin, or abciximab with low-dose, weight-adjusted heparin (70 U/kg initial bolus). The primary outcome was the composite of death, myocardial infarction, or urgent repeat revascularization by 30 days; this composite end point and its individual components were also assessed at 6 months and 1 year. Rates of any repeat revascularization (urgent or elective), target vessel revascularization, and a composite of death, myocardial infarction, or any repeat revascularization were also reported. Follow-up at 1 year was 99% complete for survival status and 97% complete for other end points. By 1 year, the incidence of the primary composite end point was 16.1% in the placebo group, 9.6% in the abciximab with low-dose heparin group (P<0.001), and 9.5% in the abciximab with standard-dose heparin group (P<0.001). Each of the components of this composite end point was reduced to a similar extent. Nonurgent or target vessel repeat revascularization rates were not significantly decreased by abciximab therapy. Mortality rates over 1 year increased with increasing levels of periprocedural creatine kinase MB fraction elevation. CONCLUSIONS: Acute reductions in ischemic events after percutaneous coronary intervention by abciximab are sustained over follow-up to at least 1 year. Early periprocedural myocardial infarctions suppressed by this therapy are associated with long-term mortality rates.
Assuntos
Angioplastia Coronária com Balão , Anticorpos Monoclonais/uso terapêutico , Doença das Coronárias/terapia , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Isquemia Miocárdica/prevenção & controle , Inibidores da Agregação Plaquetária/uso terapêutico , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Abciximab , Idoso , Angioplastia Coronária com Balão/estatística & dados numéricos , Biomarcadores , Causas de Morte , Terapia Combinada , Ponte de Artéria Coronária/estatística & dados numéricos , Doença das Coronárias/complicações , Doença das Coronárias/enzimologia , Creatina Quinase/sangue , Método Duplo-Cego , Quimioterapia Combinada , Emergências , Feminino , Seguimentos , Heparina/administração & dosagem , Heparina/uso terapêutico , Humanos , Incidência , Isoenzimas , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/prevenção & controle , Isquemia Miocárdica/mortalidade , Estudos Prospectivos , Recidiva , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: The optimal level of platelet inhibition with a glycoprotein (GP) IIb/IIIa antagonist necessary to minimize thrombotic complications in patients undergoing a percutaneous coronary intervention (PCI) is currently unknown. METHODS AND RESULTS: Five hundred patients undergoing a PCI with the planned use of a GP IIb/IIIa inhibitor had platelet inhibition measured at 10 minutes, 1 hour, 8 hours, and 24 hours after the initiation of therapy with the Ultegra Rapid Platelet Function Assay (Accumetrics). Major adverse cardiac events (MACES: composite of death, myocardial infarction, and urgent target vessel revascularization) were prospectively monitored, and the incidence correlated with the measured level of platelet function inhibition at all time points. One quarter of all patients did not achieve >/=95% inhibition 10 minutes after the bolus and experienced a significantly higher incidence of MACEs (14.4% versus 6.4%, P=0.006). Patients whose platelet function was <70% inhibited at 8 hours after the start of therapy had a MACE rate of 25% versus 8.1% for those >/=70% inhibited (P=0.009). By multivariate analysis, platelet function inhibition >/=95% at 10 minutes after the start of therapy was associated with a significant decrease in the incidence of a MACE (odds ratio 0.46, 95% CI 0.22 to 0.96, P=0.04). CONCLUSIONS: Substantial variability in the level of platelet function inhibition is achieved with GP IIb/IIIa antagonist therapy among patients undergoing PCI. The level of platelet function inhibition as measured by a point-of-care assay is an independent predictor for the risk of MACEs after PCI.
Assuntos
Angioplastia Coronária com Balão , Cardiopatias/prevenção & controle , Inibidores da Agregação Plaquetária/uso terapêutico , Tirosina/análogos & derivados , Abciximab , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Plaquetas/efeitos dos fármacos , Plaquetas/fisiologia , Estudos de Coortes , Eptifibatida , Feminino , Cardiopatias/induzido quimicamente , Humanos , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Modelos Logísticos , Masculino , Análise Multivariada , Peptídeos/efeitos adversos , Peptídeos/uso terapêutico , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/efeitos adversos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Tirofibana , Tirosina/efeitos adversos , Tirosina/uso terapêuticoRESUMO
OBJECTIVES: To predict which patients might not require stent implantation, we identified clinical and angiographic characteristics associated with repeat revascularization after standard balloon angioplasty. BACKGROUND: Stents reduce the risk of repeat revascularization but are costly and may lead to in-stent restenosis, which remains difficult to treat. Identification of patients at low risk for repeat revascularization may allow clinicians to reserve stents for patients most likely to benefit. METHODS: Data from five interventional trials (5,146 patients) were pooled for analysis. We identified patients with optimal angiographic results (final diameter stenosis < or =30% and no dissection) after balloon angioplasty and determined the multivariable predictors of repeat revascularization. RESULTS: Optimal angiographic results were achieved in 18% of patients after angioplasty. The repeat revascularization rate at six months was lower for patients with optimal results (20% vs. 26%, p < 0.001) but still higher than observed in stent trials. Independent predictors of repeat revascularization were female gender (odds ratio [OR] 1.67, p = 0.01), lesion length > or =10 mm (OR 1.62, p = 0.03) and proximal left anterior descending coronary artery lesions (OR 1.62, p = 0.03). For the 8% of patients with optimal angiographic results and none of these risk factors, the repeat revascularization and target vessel revascularization rates were 14% and 8% respectively, similar to rates after stent implantation. Cost analysis estimated that $78 million per year might be saved in the U.S. with a provisional stenting strategy using these criteria compared with elective stenting. CONCLUSIONS: A combination of baseline characteristics and angiographic results can be used to identify a small group of patients at very low risk for repeat revascularization after balloon angioplasty. Provisional stenting for these low risk patients could substantially reduce costs without compromising clinical outcomes.
Assuntos
Angioplastia com Balão , Doença das Coronárias/terapia , Angioplastia com Balão/economia , Doença das Coronárias/economia , Custos e Análise de Custo , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , StentsRESUMO
OBJECTIVES: We sought to determine the efficacy and safety of platelet glycoprotein IIb/IIIa receptor (GP IIb/IIIa) blockade with abciximab in women undergoing percutaneous coronary intervention. BACKGROUND: Although gender differences in response to platelet glycoprotein IIb/IIIa receptor blockade have been described, there have been no large clinical studies to assess these differences. METHODS: Outcomes were determined using meta-analysis technique. RESULTS: In the pooled analysis, the primary end point of death, myocardial infarction (MI) or urgent revascularization within 30 days was reduced from 11.3% to 5.8% (p<0.001) in men and from 12.7% to 6.5% (p<0.001) in women treated with abciximab. At six months, death, MI or urgent revascularization was reduced from 14.1% to 8.3% (p<0.001) in men and 16.0% to 9.9% (p<0.001) in women receiving abciximab. At one year, mortality was reduced from 2.7% to 1.9% (p = 0.06) in men and 4.0% to 2.5% (p = 0.03) in women treated with abciximab. Major bleeding events occurred in 2.9% versus 3.0% (p = 0.96) of women and 2.7% versus 1.3% (p = 0.003) of men treated with placebo versus abciximab, respectively. Minor bleeding events occurred in 4.7% versus 6.7% (p = 0.01) of women and 2.3% versus 2.2% (p = 0.94) of men treated with placebo versus abciximab, respectively. CONCLUSIONS: This pooled analysis demonstrated no gender difference in protection from major adverse outcomes with GP IIb/IIIa inhibition with abciximab. Although women had higher rates of both major and minor bleeding events with abciximab compared with men, major bleeding in women was similar with and without abciximab. There was a small increased risk of minor bleeding with abciximab in women.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Abciximab , Idoso , Angioplastia Coronária com Balão , Anticorpos Monoclonais/efeitos adversos , Feminino , Humanos , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/terapia , Inibidores da Agregação Plaquetária/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores Sexuais , Resultado do TratamentoRESUMO
Coronary stents reduce the rates of abrupt closure, emergency coronary artery bypass graft surgery and restenosis, but do not prevent myocardial infarction or death at six months. The financial burden of increased stent use and the difficulty in managing in-stent restenosis have provided the impetus to develop provisional stenting strategies. Patients at low risk for restenosis after balloon angioplasty may not derive additional benefit from stent implantation and may be successfully managed with percutaneous transluminal coronary angioplasty (PTCA) alone. Numerous patient, lesion and procedural predictors of restenosis have been identified. Postprocedural assessment using quantitative coronary angiography, intravascular ultrasound (IVUS), coronary flow velocity reserve (CVR) or fractional flow reserve (FFR) may further enhance the ability to predict adverse outcomes after PTCA. Several studies have been performed to investigate the feasibility of provisional stenting strategies using various modalities to identify low risk patients who could be managed with PTCA alone. An optimal or "stent-like" angiographic result after PTCA is associated with favorable clinical outcomes. Preliminary results of studies using IVUS or CVR to guide provisional stenting appear promising. Angiography alone may be inadequate to identify truly low risk patients and may need to be combined with clinical factors, assessment of recoil, IVUS or physiologic indexes. Strategies that avoid unnecessary stenting in even a small proportion of patients may have large impacts on health care costs. Provisional stenting may potentially reduce costs and rates of in-stent restenosis without compromising the quality of health care delivery.
Assuntos
Implante de Prótese Vascular , Doença das Coronárias/cirurgia , Tomada de Decisões , Stents , Angiografia Coronária , Doença das Coronárias/diagnóstico , Doença das Coronárias/economia , Oclusão de Enxerto Vascular/diagnóstico , Oclusão de Enxerto Vascular/economia , Oclusão de Enxerto Vascular/prevenção & controle , Custos de Cuidados de Saúde , Humanos , Seleção de Pacientes , Desenho de Prótese , Ultrassonografia de IntervençãoRESUMO
OBJECTIVES: The aim of this study was to analyze the risk of vessel perforation during excimer laser angioplasty. BACKGROUND: Vessel perforation is a serious complication of angioplasty. METHODS: A total of 764 patients had 858 stenoses treated with excimer laser angioplasty. Laser catheters had a diameter of 1.4, 1.7 or 2 mm. Laser energy was delivered in pulses of 135 ns, at a frequency of 25 s-1 and at a fluence of 30 to 60 mJ/mm2. Follow-up angiography was requested for all patients who did not require emergency bypass surgery. RESULTS: In the 764 consecutive patients treated with excimer laser coronary angioplasty, vessel perforation occurred in 23 patients (3%). Nine patients had a major complication resulting directly from vessel perforation (cardiac tamponade, myocardial infarction or need for bypass surgery) and 14 had no clinical complications after successful sealing of the puncture site. No patient with a perforation died. Multivariate analysis showed that bifurcation lesions (odds ratio [OR] = 3.5; p = 0.049), diabetes mellitus (OR = 3.15; p = 0.029) and female gender (OR = 2.86; p = 0.013) were associated with an increased risk of vessel perforation. Lesions > 10 mm in length (OR = 0.45; p = 0.206), calcified stenoses (OR = 0.26; p = 0.088) and saphenous vein graft lesions (OR = 0.50; p = 0.295) were not at increased risk. Vessel perforation was seen in 10 (8.3%) of 120 lesions in which the laser catheter was equivalent in diameter to the target vessel (< or = 0.5 mm smaller in size) but in only 8 (1.5%) of 525 lesions in which the laser catheter was > 1 mm smaller than the target vessel (p = 0.001). CONCLUSIONS: Most lesions thought to be suitable for excimer laser treatment are not at increased risk of perforation. The complication may be avoided by improved patient and laser catheter size selection.
Assuntos
Angioplastia a Laser/efeitos adversos , Vasos Coronários/lesões , Complicações Intraoperatórias/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia Coronária , Feminino , Humanos , Complicações Intraoperatórias/etiologia , Complicações Intraoperatórias/cirurgia , Complicações Intraoperatórias/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Sistema de Registros , Fatores de RiscoRESUMO
OBJECTIVES: This study sought to determine the frequency of thrombocytopenia and its relation with clinical outcomes in high risk patients undergoing percutaneous coronary revascularization who received either the platelet glycoprotein (GP) IIb/IIIa receptor antagonist abciximab (ReoPro, c7E3 Fab) or conventional therapy. BACKGROUND: The development of thrombocytopenia on exposure to GPIIb/IIIa antagonists threatens the utility and economic viability of this drug class for patients with vascular disease. METHODS: We analyzed data from the Evaluation of c7E3 for the Prevention of Ischemic Complications trial (EPIC), a 2,099-patient, randomized trial of placebo, abciximab bolus or abciximab bolus plus a 12-h infusion during high-risk coronary revascularization. RESULTS: Thrombocytopenia (nadir platelet count <100 x 10(9)/ liter) developed in 81 patients (3.9%) during their hospital stay, with 19 (0.9%) developing severe (<50 x 10(9)/liter) thrombocytopenia. Both thrombocytopenia and severe thrombocytopenia were more frequent in the bolus-plus-infusion arm (5.2% and 1.6%, respectively) than in the bolus-only and placebo arms combined (p = 0.020 and p = 0.025, respectively). Acute profound thrombocytopenia developed in two patients in the bolus-plus-infusion arm. Patients with thrombocytopenia experienced more unfavorable clinical outcomes than those who did not develop thrombocytopenia, regardless of treatment assignment, but those with thrombocytopenia who received abciximab had fewer worse outcomes at 30 days. Multivariable logistic modeling revealed a lower baseline platelet count, older age and lighter weight to be important predictors of thrombocytopenia. In a logistic regression model, bolus-plus-infusion treatment was a significant predictor of thrombocytopenia (p = 0.016) and remained so after adjustment for procedures and baseline risk factors (p = 0.0077). CONCLUSIONS: Thrombocytopenia was associated with adverse clinical outcomes and excessive bleeding, but patients receiving abciximab fared better than those receiving placebo.
Assuntos
Angioplastia Coronária com Balão/métodos , Anticorpos Monoclonais/efeitos adversos , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Isquemia Miocárdica/prevenção & controle , Inibidores da Agregação Plaquetária/efeitos adversos , Trombocitopenia/etiologia , Abciximab , Fatores Etários , Idoso , Anticorpos Monoclonais/administração & dosagem , Peso Corporal , Feminino , Previsões , Hemorragia/etiologia , Humanos , Fragmentos Fab das Imunoglobulinas/administração & dosagem , Infusões Intravenosas , Injeções Intravenosas , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Placebos , Inibidores da Agregação Plaquetária/administração & dosagem , Contagem de Plaquetas , Fatores de Risco , Resultado do TratamentoRESUMO
Patients with a chronic coronary occlusion often undergo coronary angiography after weeks to months of occlusion. The published reports underestimate the extent of this problem because such patients are often arbitrarily assigned to receive medical therapy or undergo bypass surgery as a result of poor success with percutaneous revascularization and substantial restenosis. Thus, there is controversy about the role of angioplasty in this patient cohort. The goal of this overview was to evaluate the available information about angioplasty in chronic coronary occlusions. The primary indication for attempted recanalization of a chronic coronary occlusion has been symptomatic angina pectoris. Anginal status often improves after successful procedures (70% vs. 31% with a failed procedure); left ventricular function may improve; and subsequent referral for coronary artery bypass graft surgery is uncommon (3% vs. 28% in unsuccessful cases). Successful recanalization is achieved in approximately 65% of attempted procedures. Inability to cross the stenosis with a guide wire is the most common cause of procedural failure. Statistically significant predictors of procedural success include older occlusions (75% < 3 months old vs. 37% > or = 3 months old), absence of any anterograde flow through the occlusion (76% with vs. 58% without), angiographically abrupt-appearing occlusions (50% vs. 77% with tapered occlusions), presence of bridging collateral vessels (23% with vs. 71% without) and lesions > 15 mm. Procedural complications occur at a slightly lower incidence than in angioplasty of high grade subtotal stenoses. Long-term success is limited, and restenosis can be expected in > 50% of the patients. The experience with chronic total occlusions of saphenous vein bypass grafts is small, but there appear to be limited procedural success and significant procedural complications, particularly associated with distal emboli. The role of new pharmacologic agents has yet to be defined and that of new devices has been disappointing so far, but further technologic advances are on the horizon.
Assuntos
Angioplastia Coronária com Balão , Doença das Coronárias/terapia , Angioplastia Coronária com Balão/efeitos adversos , Doença Crônica , Terapia Combinada , Ponte de Artéria Coronária , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/mortalidade , Fibrinolíticos/uso terapêutico , Humanos , Prognóstico , Falha de TratamentoRESUMO
OBJECTIVES: The aim of this study was to document and analyze the incidence and consequences of complications of excimer laser coronary angioplasty. BACKGROUND: Excimer laser coronary angioplasty has been reported to be a safe and feasible alternative or adjunct to conventional balloon angioplasty, but serious and unique complications have been observed. METHODS: Data on 1,595 interventions of excimer laser coronary angioplasty in 1,521 patients were analyzed, using a merged data base from the U.S. and European Percutaneous Excimer Laser Coronary Angioplasty (PELCA) registries. RESULTS: Procedural success was achieved in 89.3% of interventions. Stand-alone laser angioplasty was performed in 17.8% of interventions. Complications included dissection (22.0%), vasospasm (6.1%), filling defects (4.8%), abrupt reclosure (6.1%), embolization (2.3%), perforation (2.4%), arrhythmia (0.7%) and aneurysm formation (0.3%). Major complications were non-Q wave myocardial infarction (2.3%), Q wave myocardial infarction (1.0%), coronary artery bypass grafting (3.1%) and death (0.7%). Logistic regression analysis revealed correlation between dissections and the use of larger catheter size (p = 0.0005), high energy per pulse levels (p = 0.0001 for native vessels), lesion length > 10 mm (p = 0.001) and presence of a side branch (p = 0.01). The incidence of perforations was higher in women (p = 0.004), in treatment of total occlusions (p = 0.02) and in the presence of a side branch (p = 0.03). Fatal complications were correlated with patients with multivessel disease (p < 0.0001), patients with acute myocardial infarction (p = 0.0009) and older patients (> 70 years old, p = 0.004). The incidence of major complications decreased after performance of 50 laser angioplasty procedures at one institution (p = 0.02). CONCLUSIONS: This analysis defines both the learning curve and the profile of complications for excimer laser angioplasty and provides insight into the selection of appropriate patients and proper performance of the procedure.
Assuntos
Angioplastia Coronária com Balão/efeitos adversos , Angioplastia com Balão a Laser/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Angioplastia Coronária com Balão/estatística & dados numéricos , Angioplastia com Balão a Laser/estatística & dados numéricos , Distribuição de Qui-Quadrado , Doença das Coronárias/complicações , Doença das Coronárias/epidemiologia , Doença das Coronárias/cirurgia , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Sistema de Registros/estatística & dados numéricos , Estados Unidos/epidemiologiaRESUMO
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.
Assuntos
Angioplastia Coronária com Balão/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Isquemia Miocárdica/prevenção & controle , Inibidores da Agregação Plaquetária/uso terapêutico , Abciximab , Idoso , Angiografia Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Resultado do TratamentoRESUMO
OBJECTIVES: We proposed to examine the relation between angiographic morphologic characteristics and abrupt closure after coronary angioplasty and to develop an empirically based risk stratification system. BACKGROUND: Certain lesion morphologic characteristics are associated with higher rates of abrupt closure after coronary angioplasty. Previous approaches have been limited by relatively small sample sizes and an inability to combine multiple characteristics to predict risk in an individual patient. METHODS: Lesion morphology was determined for 779 lesions in 658 patients undergoing an elective first angioplasty. Abrupt closure occurred in 63 lesions (8.1%). Variables associated with abrupt closure were identified by univariate and stepwise multiple logistic regression analysis, and internal validity was assessed by use of bootstrapping. An empirically based scoring system was developed by assigning different weights to each predictive characteristic and was then validated. RESULTS: Almost all lesion characteristics previously labeled "adverse" were associated with an increased risk of abrupt closure, but only total occlusion, location at a branch point, increasing lesion length, evidence for thrombus and right coronary artery location were statistically significant independent predictors. Despite the large sample size, the study was underpowered to detect even a 50% increase in risk with many characteristics. Using a scoring system, we assigned each lesion a specific risk of abrupt closure. The distribution of risk was broad, with 20% of patients having < or = 2.5% risk and 25% having > 10% risk. Internal validation techniques revealed that when 10% of patients were randomly eliminated from the sample in multiple iterations, the risk estimates varied, again pointing to the need for a larger sample. CONCLUSIONS: Empirically based weighting of lesion characteristics could quantify the risk of abrupt closure for individual patients, but a very large sample will be required to understand the interplay of complex lesion characteristics in altering expected outcomes.
Assuntos
Angioplastia Coronária com Balão , Doença das Coronárias/terapia , Vasos Coronários/patologia , Idoso , Constrição Patológica/diagnóstico por imagem , Constrição Patológica/patologia , Constrição Patológica/terapia , Angiografia Coronária , Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/patologia , Estudos de Viabilidade , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , RiscoRESUMO
OBJECTIVES: We sought to determine whether eptifibatide decreases the incidence of in-laboratory angiographic complications and to determine the relationship of angiographically evident complications to elevations of creatine kinase-MB (CK-MB) enzyme levels during percutaneous coronary intervention. BACKGROUND: In the Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial, eptifibatide during coronary intervention was associated with decreased ischemic complications at 48 h and 30 days. METHODS: Patients (n = 2,064) were randomized to placebo versus eptifibatide (two 180 microg/kg boluses 10 min apart and as a continuous infusion of 2 microg/kg per min) during percutaneous coronary stenting. Angiographic complications including major dissection, distal embolization, residual thrombus, abrupt closure, residual stenosis >50% and side-branch occlusion were prospectively recorded by the operator. Creatine kinase-MB levels were measured after the procedure and every 6 h thereafter. The incidence of angiographic complications and CK-MB elevation was determined for eptifibatide versus placebo groups. RESULTS: Eptifibatide-treated patients demonstrated nonsignificant trends toward fewer angiographic complications (10 vs. 12% for placebo patients, p = 0.13) and, for patients with angiographic complications, fewer subsequent CK-MB elevations (43 vs. 50% for placebo patients, p = 0.31). In patients without any angiographic complications, the incidence of CK-MB elevation >3 times the normal was 7% with placebo and 4% with eptifibatide (p = 0.003). CONCLUSIONS: Eptifibatide during nonurgent coronary stent intervention only minimally (and insignificantly) reduces the incidence of angiographic complications and subsequent CK-MB elevations in patients developing an angiographic complication. The greater effect is to reduce myocardial infarction in patients undergoing otherwise uneventful coronary stent implantation as well as in the overall study population.
Assuntos
Angioplastia Coronária com Balão , Angiografia Coronária/efeitos adversos , Peptídeos/uso terapêutico , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Doença das Coronárias/terapia , Creatina Quinase/sangue , Creatina Quinase Forma MB , Eptifibatida , Humanos , Isoenzimas/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , StentsRESUMO
OBJECTIVES: The purpose of this study was to further explore the procedural safety of prolonged (15-min) dilation using an autoperfusion coronary angioplasty balloon by assessing the degree of myocardial damage or hemolysis, if any, occurring as a result of the procedure. BACKGROUND: Prolonged balloon inflation periods may be beneficial during percutaneous transluminal coronary angioplasty. The duration of standard balloon angioplasty is often limited by the occurrence of myocardial ischemia due to loss of anterograde blood flow. Autoperfusion angioplasty allows continued myocardial perfusion during balloon inflation and has previously been shown to reduce but not totally eliminate acute myocardial ischemia during prolonged (up to 15 min) balloon inflation. The risk of intravascular hemolysis as a result of autoperfusion angioplasty has not yet been fully delineated. METHODS: Sixty-two consecutive patients (76% men; mean age 58 years) undergoing elective percutaneous transluminal coronary angioplasty of a single lesion were studied. Serial electrocardiographic and creatine kinase MB isoenzyme data were examined to detect evidence of myocardial damage. Tests for hemolysis (plasma free hemoglobin, serum haptoglobin and serum lactate dehydrogenase) were obtained in the 1st 24 consecutive patients. RESULTS: Inflation time was 14 +/- 4 min (mean +/- SD) and the procedure was successful (less than or equal to 50% residual lesion stenosis) in 59 patients (95%). Electrocardiographic evidence of myocardial infarction (greater than 1 mm persistent ST segment depression, greater than 1 mm ST segment elevation or new Q waves) was not observed in any patient. Cardiac enzyme assays were within the normal range in all patients. No evidence of hemolysis was found in the 24 consecutive patients studied. CONCLUSIONS: We conclude that prolonged autoperfusion angioplasty can be performed in patients without clinical evidence of myocardial damage or hemolysis.
Assuntos
Angioplastia Coronária com Balão/instrumentação , Hemólise , Miocárdio/patologia , Idoso , Angioplastia Coronária com Balão/efeitos adversos , Angioplastia Coronária com Balão/métodos , Creatina Quinase/sangue , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
Despite substantial basic and clinical efforts to address the problem of restenosis after percutaneous coronary intervention, effective preventive therapies have not yet been developed. Nevertheless, the accumulated information has provided much insight into the process of restenosis in addition to allowing standards to be developed for adequate clinical trials. The pathophysiology of restenosis increasingly appears to be distinct from that of primary atherosclerosis. Restenosis involves elastic recoil, incorporation of thrombus into the lesion and fibrocellular proliferation in varying degrees in different patients. Lack of an animal model that satisfactorily mimics restenosis is a major impediment to further understanding of the process. Clinical studies are hampered by difficulties in finding a single unifying definition of restenosis and by variable methods of reporting follow-up. Reporting of clinical outcomes of all patients in angiographic substudies would allow a more satisfactory interpretation of the results of clinical trials. Current noninvasive test results are not accurate enough to substitute for angiographic and clinical outcome data in intervention trials. In the majority of observational studies, only diabetes and unstable angina have emerged as consistently associated with restenosis; whereas most of the standard risk factors for atherosclerosis have a less consistent relation. Disappointingly, the new atherectomy and laser technologies have not affected restenosis rates. The one possible exception is coronary stenting, as a result of the larger luminal diameter achieved by the placement of the stent. In conclusion, although substantial continued effort is necessary to explore the basic aspects of cellular proliferation and mechanical alteration of atherosclerotic vessels, attention to the principles of clinical trials and observation are required to detect the impact of risk factors and interventions on the multifactorial problem of restenosis. Adequate sample sizes, collection of clinical and angiographic outcomes and factorial study designs hold promise for unraveling this important limitation of percutaneous intervention.
Assuntos
Angioplastia Coronária com Balão , Doença das Coronárias/etiologia , Angioplastia Coronária com Balão/métodos , Angioplastia Coronária com Balão/estatística & dados numéricos , Angioplastia a Laser , Animais , Angiografia Coronária , Doença das Coronárias/diagnóstico , Doença das Coronárias/epidemiologia , Doença das Coronárias/prevenção & controle , Doença das Coronárias/terapia , Modelos Animais de Doenças , Seguimentos , Humanos , Recidiva , StentsRESUMO
OBJECTIVES: 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.
Assuntos
Doença das Coronárias/terapia , Creatina Quinase/sangue , Infarto do Miocárdio/terapia , Peptídeos/administração & dosagem , Inibidores da Agregação Plaquetária/administração & dosagem , Idoso , Angioplastia Coronária com Balão , Angioplastia a Laser , Aterectomia Coronária , Doença das Coronárias/diagnóstico , Doença das Coronárias/enzimologia , Eptifibatida , Feminino , Seguimentos , Humanos , Isoenzimas , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/enzimologia , Peptídeos/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Recidiva , Risco , Stents , Resultado do TratamentoRESUMO
OBJECTIVES: This study was designed to identify potential predictors of vascular access site (VAS) complications in the large-scale Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis (IMPACT) II trial, which studied angioplasty with versus without a new glycoprotein (GP) IIb/IIIa receptor inhibitor (eptifibatide). BACKGROUND: GP IIb/IIIa receptor inhibition during coronary interventions has been associated with excess VAS complications. If other predictors of VAS complications could be identified, they might be manipulated to reduce complications. METHODS: A total of 4,010 patients undergoing percutaneous transluminal coronary revascularization (PTCR) were randomized into one of three bolus/20- to 24-h infusion arms: placebo bolus/placebo infusion; 135-microg/kg body weight eptifibatide bolus/0.5-microg/kg per min eptifibatide infusion; or 135-microg/kg eptifibatide bolus/0.75-microg/kg per min eptifibatide infusion. Heparin during the procedure was weight adjusted and stopped 4 h before sheaths were removed. Logistic regression modeling was used to identify independent predictors of VAS complications. RESULTS: VAS complications were more common in patients treated with eptifibatide (9.9% vs. 5.9% placebo-treated patients, p < 0.001). Multivariate analysis identified eptifibatide therapy (p < 0.0001), advanced age (p = 0.0001), longer time to sheath removal (p = 0.0002), stent placement (with intense post-stent anticoagulation) (p = 0.0004), female gender (p = 0.0006), PTCR within 24 h of thrombolytic therapy (p = 0.002), larger heparin doses during PTCR (p = 0.009), major coronary dissection (p = 0.03) and placement of a venous sheath (p = 0.04) as independent predictors of VAS complications. CONCLUSIONS: VAS complications may be reduced by early sheath removal, by avoiding placement of venous sheaths and by limiting heparin dosing to avoid excessive activated clotting times. Early sheath removal during inhibition of platelet aggregation by eptifibatide is feasible.