RESUMO
BACKGROUND: The relative anti-aggregatory effects of currently prescribed platelet glycoprotein IIb/IIIa receptor antagonists during and after percutaneous coronary intervention for acute coronary syndromes have not been established. METHODS AND RESULTS: We randomized 70 acute coronary syndrome patients undergoing percutaneous coronary intervention to receive abciximab, eptifibatide, or tirofiban at doses used in the Evaluation of Platelet IIb/IIIa Inhibitor for STENTing (EPISTENT), Platelet glycoprotein IIb/IIIa in Unstable angina Receptor Suppression Using Integrilin Therapy (PURSUIT), and Platelet Receptor Inhibition in ischemic Syndrome Management in Patients Limited by Unstable Signs and symptoms (PRISM-PLUS)/Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis (RESTORE) trials, respectively. Platelet aggregation (PA) in response to 20 micro mol/L of adenosine diphosphate was measured with turbidimetric aggregometry in both D-phenylalanyl-L-prolyl-L-arginine chloromethylketone and citrate-anticoagulated blood early (15 and 30 minutes) and late (4, 12, and 18 to 24 hours) after drug initiation. At 15 and 30 minutes, PA was significantly less inhibited by the tirofiban-RESTORE regimen compared with abciximab (P=0.028) and eptifibatide regimens (P=0.0001). The abciximab regimen, however, showed increasingly varied anti-aggregatory effects during continued infusion for > or =4 hours. Citrate exaggerated ex vivo platelet inhibition after eptifibatide and tirofiban, but had the opposite effect on abciximab. Of all regimens evaluated, the eptifibatide regimen inhibited PA most consistently throughout both the early and late periods. CONCLUSIONS: Currently recommended drug regimens to inhibit the platelet glycoprotein IIb/IIIa receptor have distinct pharmacodynamic profiles that might affect their relative efficacy in acute coronary syndromes and percutaneous coronary intervention.
Assuntos
Anticorpos Monoclonais/farmacologia , Doença das Coronárias/tratamento farmacológico , Fragmentos Fab das Imunoglobulinas/farmacologia , Peptídeos/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Tirosina/análogos & derivados , Tirosina/farmacologia , Abciximab , Doença Aguda , Idoso , Clorometilcetonas de Aminoácidos/farmacologia , Angina Instável/sangue , Angina Instável/tratamento farmacológico , Angina Instável/terapia , Angioplastia Coronária com Balão , Anticorpos Monoclonais/uso terapêutico , Anticoagulantes/farmacologia , Ácido Cítrico/farmacologia , Doença das Coronárias/sangue , Doença das Coronárias/terapia , Eptifibatida , Feminino , Humanos , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Cinética , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/terapia , Peptídeos/uso terapêutico , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/uso terapêutico , Síndrome , Tirofibana , Tirosina/uso terapêuticoRESUMO
OBJECTIVES: We evaluated the relationship between the degree of heparin anticoagulation and clinical efficacy and bleeding in patients undergoing contemporary percutaneous coronary intervention (PCI) with stent implantation. BACKGROUND: Despite universal acceptance of heparin anticoagulation as a standard of care in PCI, considerable controversy still exists regarding the appropriate dosing of heparin. METHODS: The study population (n = 2,064) comprised all patients enrolled in the Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial. The index activated clotting time (ACT) was defined as the ACT measured after the last heparin dose and before first device activation and was correlated with outcome and bleeding events. RESULTS: No association was observed between decreasing ACT levels and the rate of ischemic events in the treatment or placebo arms. The incidence of the primary composite end point (death, myocardial infarction, urgent target vessel revascularization, and thrombotic bailout glycoprotein IIb/IIIa inhibitor therapy at 48 h) was actually lowest in the lowest ACT tertile for both the placebo (10.0%) and treatment groups (6.1%). When analyzed by tertile, major bleeding rates did not increase in the lowest ACT tertile in patients given placebo (0.6%) versus those receiving eptifibatide (0.7%). Major bleeding rates increased as the ACT increased in the eptifibatide-treated patients. CONCLUSIONS: Ischemic end points in patients undergoing contemporary PCI with stent placement do not increase by decreasing ACT levels, at least to a level of 200 s. Bleeding events do increase with increasing ACT levels and are enhanced with eptifibatide treatment. An ACT of 200 to 250 s is reasonable in terms of efficacy and safety with the use of contemporary technology and pharmacotherapy.
Assuntos
Angioplastia Coronária com Balão/efeitos adversos , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Implante de Prótese Vascular/efeitos adversos , Doença da Artéria Coronariana/terapia , Hemorragia/etiologia , Heparina/administração & dosagem , Heparina/uso terapêutico , Avaliação de Resultados em Cuidados de Saúde , Stents/efeitos adversos , Anticoagulantes/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Heparina/efeitos adversos , Humanos , Masculino , Tempo de Coagulação do Sangue TotalRESUMO
We studied stent thrombosis in 4,607 patients with acute coronary syndromes who received a coronary stent as part of routine care during 2 trials of aspirin versus sibrafiban for secondary prevention. In these patients, stent thrombosis occurred more often than in previous patients who underwent elective percutaneous coronary intervention. These patients and their outcomes may be more representative of patients with typical acute coronary syndromes undergoing stenting in clinical practice.
Assuntos
Doença das Coronárias/terapia , Trombose Coronária/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Stents/efeitos adversos , Doença Aguda , Aspirina/uso terapêutico , Causalidade , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/prevenção & controle , Oximas/uso terapêutico , Piperidinas/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , SíndromeRESUMO
OBJECTIVES: The RESOLUTE US (R-US) trial is a prospective, observational study designed to evaluate the clinical effectiveness of the Resolute zotarolimus-eluting stent (R-ZES) in a U.S. population. BACKGROUND: The R-ZES releases zotarolimus over a 6-month period in order to achieve optimal clinical effectiveness and safety. METHODS: The R-US trial recruited patients with de novo native coronary lesions suitable for 1- or 2-vessel treatment with stents from 2.25 to 4.0 mm in diameter. In the main analysis cohort (2.5- to 3.5-mm stents and single-lesion treatment), the primary endpoint was 12-month target lesion failure (TLF) defined as the composite of cardiac death, myocardial infarction (MI), and clinically-driven target lesion revascularization (TLR), compared with data from Endeavor zotarolimus-eluting stent (E-ZES) trials, adjusting for baseline covariates through propensity scores. RESULTS: Overall, 1,402 patients were enrolled with a mean reference vessel diameter of 2.59 ± 0.47 mm and diabetes prevalence of 34.4%. In the main analysis cohort, TLF was 3.7% at 12 months compared with historical E-ZES results (TLF = 6.5%). The R-ZES met the 3.3% margin of noninferiority (rate difference = -2.8%, upper 1-sided 95% confidence interval: -1.3%, p < 0.001). The overall TLF rate was 4.7%, and rates of cardiac death, MI, and TLR were 0.7%, 1.4%, and 2.8%, respectively. The 12-month rate of stent thrombosis was 0.1%. CONCLUSIONS: The R-ZES achieved a very low rate of clinical restenosis while maintaining low rates of important clinical safety events such as death, MI, and stent thrombosis at 1-year follow-up. (The Medtronic RESOLUTE US Clinical Trial [R-US]; NCT00726453).
Assuntos
Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/epidemiologia , Vasos Coronários/efeitos dos fármacos , Stents Farmacológicos , Sirolimo/análogos & derivados , Idoso , Estudos de Coortes , Doença da Artéria Coronariana/patologia , Reestenose Coronária/epidemiologia , Reestenose Coronária/patologia , Reestenose Coronária/prevenção & controle , Vasos Coronários/patologia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Sirolimo/administração & dosagem , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
OBJECTIVES: The ENDEAVOR IV (Randomized Comparison of Zotarolimus-Eluting and Paclitaxel-Eluting Stents in Patients with Coronary Artery Disease) trial evaluated the safety and efficacy of the zotarolimus-eluting stent (ZES) compared with the paclitaxel-eluting stent (PES). BACKGROUND: First-generation drug-eluting stents have reduced angiographic and clinical restenosis, but long-term safety remains controversial. A second-generation drug-eluting stent, which delivers zotarolimus, a potent antiproliferative agent, via a biocompatible phosphorylcholine polymer on a cobalt alloy thin-strut stent has shown promising experimental and early clinical results. METHODS: This is a prospective, randomized (1:1), single-blind, controlled trial comparing outcomes of patients with single de novo coronary lesions treated with ZES or PES. The primary end point was noninferiority of 9-month target vessel failure defined as cardiac death, myocardial infarction, or target vessel revascularization. RESULTS: Among a total of 1,548 patients assigned to ZES (n = 773) or PES (n = 775), at 9 months, ZES was noninferior to PES with rates of target vessel failure 6.6% versus 7.1%, respectively (p(noninferiority) < or = 0.001). There were fewer periprocedural myocardial infarctions with ZES (0.5% vs. 2.2%; p = 0.007), whereas at 12 months, there were no significant differences between groups in rates of cardiac death, myocardial infarction, target vessel revascularization, or stent thrombosis. Although incidence of 8-month binary angiographic in-segment restenosis was higher in patients treated with ZES versus PES (15.3% vs. 10.4%; p = 0.284), rates of 12-month target lesion revascularization were similar (4.5% vs. 3.2%; p = 0.228), especially in patients without planned angiographic follow-up (3.6% vs. 3.2%; p = 0.756). CONCLUSIONS: These findings demonstrate that ZES has similar clinical safety and efficacy compared with PES in simple and medium complexity single de novo coronary lesions. (ENDEAVOR IV Clinical Trial; NCT00217269).
Assuntos
Doença da Artéria Coronariana/tratamento farmacológico , Stents Farmacológicos , Imunossupressores/administração & dosagem , Paclitaxel/administração & dosagem , Sirolimo/análogos & derivados , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Sirolimo/administração & dosagem , Resultado do TratamentoRESUMO
OBJECTIVES: This analysis sought to investigate the complementary effect of thienopyridine pretreatment and platelet glycoprotein (GP) IIb/IIIa integrin blockade in coronary stent intervention. BACKGROUND: Definitive evidence supporting combined antiplatelet therapy consisting of thienopyridine pretreatment and GP IIb/IIIa receptor blockade in patients undergoing percutaneous coronary intervention (PCI) with stent implantation is limited. METHODS: We retrospectively analyzed clinical outcomes by thienopyridine use in the 2,040 patients randomized to eptifibatide or placebo who underwent PCI in the ESPRIT trial. RESULTS: A total of 901 patients received a loading dose of thienopyridine before PCI (group 1), 123 received thienopyridine pretreatment without a loading dose (group 2), and 1,016 were not treated with thienopyridine before PCI (group 3). The composite incidence of death or myocardial infarction at 30 days was significantly lower in group 1 than in groups 2 and 3 combined (OR, 0.71 [95%CI, 0.52-0.99]; P = 0.0417). A similar trend was seen for the composite of death, myocardial infarction, or urgent target vessel revascularization (unadjusted OR, 0.77 [0.57-1.05]; P = 0.1025). After adjusting for baseline characteristics, these differences were no longer significant. No interactions were identified with eptifibatide assignment for any of the group comparisons. CONCLUSIONS: Pretreatment with a loading dose of thienopyridine lowers the rate of ischemic complications regardless of treatment with a GP IIb/IIIa inhibitor. Conversely, the efficacy of eptifibatide is maintained whether or not a loading dose of a thienopyridine is administered. Optimal outcomes are achieved in patients receiving thienopyridine pretreatment along with platelet GP IIb/IIIa inhibitor therapy.
Assuntos
Angioplastia Coronária com Balão/efeitos adversos , Infarto do Miocárdio/prevenção & controle , Peptídeos/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Piridinas/uso terapêutico , Stents , Idoso , Angioplastia Coronária com Balão/instrumentação , Angioplastia Coronária com Balão/mortalidade , Clopidogrel , Esquema de Medicação , Quimioterapia Combinada , Eptifibatida , Feminino , Hemorragia/induzido quimicamente , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Razão de Chances , Peptídeos/administração & dosagem , Peptídeos/efeitos adversos , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico , Fatores de Tempo , Resultado do TratamentoRESUMO
Percutaneous coronary intervention (PCI) in an anomalous right coronary artery arising from the left sinus of valsalva can be technically challenging because of difficulty in selectively cannulating the vessel. We present two cases of successful stent implantation in an anomalous right coronary artery arising from the left sinus of valsalva. In both cases, we used an oversized 6 Fr Judkins left guiding catheter, which provided excellent angiographic visualization and guide support for stent delivery.