RESUMO
A best evidence topic was written addressing the question 'in patients with saphenous vein graft lesions requiring percutaneous coronary intervention, do long-term clinical outcomes differ between drug-eluting and bare-metal stents?' Altogether 1466 papers were found, of which seven represented the best evidence. Although one major recent randomised trial was neutral, the weight of earlier evidence supports drug-eluting stents as standard of care. Bare-metal stents may represent a reasonable, efficacious, and less expensive alternative to drug-eluting stents in well selected patient groups.
Assuntos
Angioplastia Coronária com Balão , Stents Farmacológicos , Oclusão de Enxerto Vascular/cirurgia , Veia Safena/cirurgia , Stents , Ponte de Artéria Coronária , Humanos , Metais , Paclitaxel , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Veia Safena/patologia , Veia Safena/transplanteRESUMO
Peripheral arterial disease (PAD) affects 15% of the Australian population and is a powerful and serious predictor of cardiovascular mortality yet continues to be under-recognised and undertreated. Diagnosis is simple and management is centred upon symptom relief and risk minimisation. While novel and specialised therapies play a role, the bulk of management is approachable and feasible. In this review, we cover the epidemiology, risk factors, associated conditions, classification, and natural history of PAD. We then discuss current diagnostic and therapeutic options as well as emerging therapies for this common condition.
Assuntos
Gerenciamento Clínico , Doença Arterial Periférica , Medição de Risco , Saúde Global , Humanos , Morbidade/tendências , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/epidemiologia , Doença Arterial Periférica/terapia , Fatores de Risco , Taxa de Sobrevida/tendênciasRESUMO
BACKGROUND: The short-term clinical impact of intramyocardial gene transfer (GT) of the angiogenic protein vascular endothelial growth factor-2 (VEGF-2) has been previously reported to significantly reduce Canadian Cardiovascular Society (CCS) angina class and to prolong exercise treadmill test (ETT) time. We describe the safety and long-term events (>1 year) in consecutive, nonrandomized, patients who received intramyocardial VEGF-2. METHODS: Thirty patients with intractable CCS class III or IV angina and no options for revascularization underwent direct intramyocardial GT of VEGF-2 naked DNA via limited thoracotomy at total doses of 0.2, 0.8, or 2.0 mg. Patients were followed for clinical events after 1 year by hospital records, follow-up visits or telephone contact. Due to one perioperative death, 29 patients were followed. RESULTS: At a mean follow-up of 751 +/- 102.5 days (range 459-959) there were four deaths (13.8%), five myocardial infarctions (MIs) (17.2%), and seven revascularization procedures (24.1%). There were 15 hospitalizations in 12 patients. At the end of the follow-up period no patient (0%) had CCS class IV angina, 3 patients (11.5%) had class III angina, and 23 (88.5%) had class I to II angina. There were two new diagnoses of cancer. CONCLUSION: Transthoracic intramyocardial injection of VEGF-2 is associated with an improvement of symptoms of angina in the majority of patients beyond the first year of treatment. Major clinical events such as death, MI, and repeat revascularization are uncommon during the first year but more frequent after 1 year at a rate consistent with the severity of underlying disease in this population with advanced atherosclerosis. The majority of events were the result of progression of disease in areas of the heart remote from the site of GT. A large randomized trial is planned to determine the efficacy of intramyocardial VEGF-2 injections in inoperable patients.
Assuntos
Angina Pectoris/terapia , Técnicas de Transferência de Genes , Fatores de Crescimento do Endotélio Vascular/genética , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do TratamentoRESUMO
Cardiovascular atherosclerotic diseases remain leading causes of morbidity and mortality in the world. Despite the significant progress that has been made in the management of these diseases using medical, surgical and percutaneous therapies over the last three decades, there remains a significant population of patients who are not optimal candidates for surgical or percutaneous revascularization. Substantial research has focused on the administration of angiogenic growth factors, either as recombinant protein or by gene transfer, to promote the development of supplemental collateral blood vessels that will constitute endogenous bypass conduits around occluded native arteries; a strategy termed "therapeutic angiogenesis". While many cytokines have angiogenic activity, the best studied both in animal models and clinical trials are vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). This review will discuss gene transfer strategies for therapeutic angiogenesis in critical limb and myocardial ischemia.
Assuntos
Inibidores da Angiogênese/genética , Inibidores da Angiogênese/uso terapêutico , Arteriopatias Oclusivas/fisiopatologia , Arteriopatias Oclusivas/terapia , Citocinas/genética , Citocinas/uso terapêutico , Extremidades/irrigação sanguínea , Técnicas de Transferência de Genes , Terapia Genética/efeitos adversos , Isquemia Miocárdica/prevenção & controle , Neovascularização Fisiológica/genética , Animais , Terapia Genética/estatística & dados numéricos , Humanos , Isquemia/fisiopatologia , Isquemia/prevenção & controle , Isquemia/terapia , Isquemia Miocárdica/fisiopatologia , Coelhos , RatosRESUMO
BACKGROUND: This phase 1/2 study investigated the safety of percutaneous catheter-based gene transfer of naked plasmid DNA encoding for vascular endothelial growth factor 2 (phVEGF2) to left ventricular (LV) myocardium in a prospective, randomized, double-blind, placebo-controlled, dose-escalating study of inoperable patients with class III or IV angina. METHODS AND RESULTS: A steerable deflectable 8F catheter with a 27-gauge needle at its distal tip was advanced percutaneously to the endocardial surface of the LV in 19 patients (age, 61+/-2 years) with chronic myocardial ischemia who were not candidates for conventional revascularization. Patients were randomized in a double-blind fashion to receive 6 injections (total volume, 6.0 mL) of placebo or phVEGF2 in doses of 200 microg (n=9), 800 microg (n=9), or 2000 microg (n=1) guided by LV electromechanical (NOGA) mapping with a gene-to-placebo ratio of 2:1. A total of 114 LV injections were delivered and caused no hemodynamic alterations, sustained ventricular arrhythmias, ECG evidence of infarction, or ventricular perforation. End-point analysis at 12 weeks disclosed a statistically significant improvement in Canadian Cardiovascular Society (CCS) angina class in phVEGF2-treated versus placebo-treated patients (-1.3 versus -0.1, P=0.04). Remaining efficacy end points--including change in exercise duration (91.8 versus 3.9 seconds), functional improvement by > or =2 CCS classes (9 of 12 versus 1 of 6), and Seattle Angina Questionnaire data--all showed strong trends favoring efficacy of phVEGF2 versus placebo treatment. CONCLUSIONS: This phase 1/2, double-blind, randomized trial provides preliminary data that support safety of phVEGF2 catheter-mediated myocardial gene transfer. The statistically significant reduction in anginal class and strong positive trends for remaining end points suggest that a larger phase 2/3 trial is warranted.
Assuntos
Fatores de Crescimento Endotelial/genética , Terapia Genética , Ventrículos do Coração , Linfocinas/genética , Isquemia Miocárdica/terapia , Angina Pectoris/diagnóstico , Angina Pectoris/diagnóstico por imagem , Angina Pectoris/terapia , Mapeamento Potencial de Superfície Corporal , Cateterismo , Doença Crônica , Método Duplo-Cego , Teste de Esforço , Feminino , Terapia Genética/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
Over the last three decades, significant progress has been made in the management of patients with atherosclerotic coronary and peripheral vascular diseases using medical, surgical, and percutaneous therapies. Despite these advances, there remains a significant population of patients who are not optimal candidates for surgical or percutaneous revascularization. These patients continue to suffer from the debilitating symptoms of their disease and remain at risk for myocardial infarction, limb loss, or death. It was this clinical need, coupled with the advances in the understanding of angiogenesis, that has led to efforts to develop angiogenic therapies for patients with peripheral and myocardial ischemia. In general, these conditions are characterized by local hypovascularity, and the approach to treatment is therefore focused on stimulating neovascularization.