RESUMO
BACKGROUND: Congress established the Appropriate Use Criteria (AUC) Program to reduce unnecessary advanced imaging studies. Organizations that wish to develop AUC can apply to the Centers for Medicare & Medicaid Services (CMS) to qualify as provider-led entities (PLEs) under this program. Variable methods, content, and formatting of PLE-generated AUC could lead to clinician uncertainty about whether an advanced imaging test is appropriate or not. PURPOSE: To review AUC published by CMS-qualified PLEs focused on advanced imaging tests for coronary artery disease (CAD), a "priority clinical area" identified by CMS. DATA SOURCES: Publicly available data from the worldwide web searched on 29 August 2022. STUDY SELECTION: Approved AUC with recommendations related to testing for CAD. DATA EXTRACTION: Manual review of published AUC by all authors. DATA SYNTHESIS: Among the 17 CMS-qualified PLEs, only 7 had published AUC related to CAD. Substantial variation in the methods and formatting of these AUCs was observed. The number of clinical scenarios covered ranged from 6 to 210, and the number of advanced imaging methods covered ranged from 1 to 25. When specifically applied to clinical scenarios, many AUC offered no guidance on appropriateness; those that did conflicted with respect to appropriateness. LIMITATION: Other CMS-identified priority clinical areas were not evaluated. CONCLUSION: CMS-qualified AUC for imaging of CAD are heterogeneous and sometimes discrepant, creating substantial potential for uncertainty among clinicians seeking to provide their patients with appropriate imaging tests. PRIMARY FUNDING SOURCE: No funding was received for this study.
Assuntos
Doença da Artéria Coronariana , Idoso , Estados Unidos , Humanos , Doença da Artéria Coronariana/diagnóstico , Medicare , Internet , IncertezaRESUMO
BACKGROUND: The aim of this research was to asses perfusion-defect detection-accuracy by human observers as a function of reduced-counts for 3D Gaussian post-reconstruction filtering vs deep learning (DL) denoising to determine if there was improved performance with DL. METHODS: SPECT projection data of 156 normally interpreted patients were used for these studies. Half were altered to include hybrid perfusion defects with defect presence and location known. Ordered-subset expectation-maximization (OSEM) reconstruction was employed with the optional correction of attenuation (AC) and scatter (SC) in addition to distance-dependent resolution (RC). Count levels varied from full-counts (100%) to 6.25% of full-counts. The denoising strategies were previously optimized for defect detection using total perfusion deficit (TPD). Four medical physicist (PhD) and six physician (MD) observers rated the slices using a graphical user interface. Observer ratings were analyzed using the LABMRMC multi-reader, multi-case receiver-operating-characteristic (ROC) software to calculate and compare statistically the area-under-the-ROC-curves (AUCs). RESULTS: For the same count-level no statistically significant increase in AUCs for DL over Gaussian denoising was determined when counts were reduced to either the 25% or 12.5% of full-counts. The average AUC for full-count OSEM with solely RC and Gaussian filtering was lower than for the strategies with AC and SC, except for a reduction to 6.25% of full-counts, thus verifying the utility of employing AC and SC with RC. CONCLUSION: We did not find any indication that at the dose levels investigated and with the DL network employed, that DL denoising was superior in AUC to optimized 3D post-reconstruction Gaussian filtering.
Assuntos
Aprendizado Profundo , Imagem de Perfusão do Miocárdio , Humanos , Imagem de Perfusão do Miocárdio/métodos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Coração , Curva ROC , Imagens de Fantasmas , Processamento de Imagem Assistida por Computador/métodosRESUMO
INTRODUCTION: Patient-centered cardiac testing is predicated on choosing the right test for the right patient. We studied the effects of changing from script-driven scheduling to nurse-driven protocoling of stress tests. METHODS AND RESULTS: A protocol nurse reviewed records before scheduling and communicated with patients and ordering providers if needed. We found that instituting nurse protocolling of all non-imaging (ETT) and nuclear (MPI) stress tests (N = 3071) resulted in protocol changes in 37% of our patients, and reduced the proportion of tests that could not be performed as scheduled by 56% and cancelations by 71% (P < 0.001 for each). These changes were sustained over two successive 6-month periods following a baseline observation period of 6 months. For MPI, the most frequent nurse interventions were re-protocoling as stress-first MPI (12% of tests), changing test location for clinical reasons (13%), changing stress modality (7%), and care coordination (5%). CONCLUSIONS: Changing from script-driven scheduling to protocol nursing contributed measurably to patient-centered testing.
Assuntos
Cardiologia/organização & administração , Cardiologia/normas , Teste de Esforço/enfermagem , Imagem de Perfusão do Miocárdio/enfermagem , Enfermeiras e Enfermeiros , Assistência Centrada no Paciente , Idoso , Índice de Massa Corporal , Sistemas de Apoio a Decisões Clínicas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Segurança do Paciente , Estudos Prospectivos , Melhoria de Qualidade , Projetos de Pesquisa , Tomografia Computadorizada de Emissão de Fóton Único , Estados UnidosRESUMO
BACKGROUND: Postopertive troponin elevation may occur without typical or atypical cardiac symptoms and is associated with an increased 30-day morbidity and mortality. The objective of the study was to implement a quality improvement initiative of postoperative troponin surveillance algorithm aimed at intensifying medical management after vascular surgery. METHODS: We conducted a single-center study of postoperative troponin surveillance after vascular surgery (n = 201) at a tertiary care, academic medical center from January to December 2016. Troponin surveillance was performed on postoperative days 1-3 after carotid endarterectomy, endovascular aortic repair, infrainguinal bypass, open abdominal aortic aneurysm repair, peripheral vascular intervention, and suprainguinal bypass, regardless of cardiac symptoms. Patients with troponin I elevation (>0.034 ng/mL) were managed with a treatment algorithm which included single or dual antiplatelet (AP) agent, high-intensity statin therapy, smoking cessation consultation, and outpatient cardiology consultation and stress testing. Patients with troponin elevation ≥1.0 ng/mL received inpatient cardiology consultation. We assessed adherence to the protocol for intensification of best medical therapy defined as high-dose statin therapy, increase in AP therapy, and smoking cessation consultation according to the established algorithm. RESULTS: Troponin elevation was recorded in 17% (34/201) of patients and was associated with cardiac symptoms in 8 patients (24%), while 26 (76%) patients had an asymptomatic abnormal troponin on postoperative surveillance. One patient was excluded due to death immediately after SUPRA, resulting in 200 patients. Troponin elevation ≥1.0 ng/mL occurred in 11 asymptomatic patients (5.5%). Any intensification of medical therapy was instituted in 76% of patients with elevated troponin and included high-intensity statin therapy (58%), increase in AP therapy (18%), and smoking cessation consultation (66%). Once an elevated troponin level was recognized, 52% of our patients received cardiology consultation with an increased likelihood (100%) in patients with troponin ≥1 ng/mL (P < 0.001). Adherence to outpatient stress testing was 66%. Intensification of medical therapy was not significantly different between patients with abnormal troponin values, >0.034-1.0 (n = 23) versus ≥1.0 ng/mL (n = 10); statin therapy (P = 1.0), AP (P = 0.34), and smoking cessation (P = 1.0). One-year mortality was higher in patients with postoperative troponin elevation than those with normal postoperative troponin levels (12% vs. 2.4%; P = 0.03). CONCLUSIONS: Routine postoperative troponin surveillance results in intensification of statin therapy in patients with asymptomatic troponin elevation. Further study is needed to determine if this approach reduces long-term cardiovascular morbidity and mortality.
Assuntos
Cardiopatias/diagnóstico , Melhoria de Qualidade , Indicadores de Qualidade em Assistência à Saúde , Troponina/sangue , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Cardiopatias/sangue , Cardiopatias/etiologia , Cardiopatias/terapia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Abandono do Hábito de Fumar , Fatores de Tempo , Resultado do Tratamento , Regulação para CimaRESUMO
The procoagulant activity (PA) of stored units of red blood cells (RBC) increases over time, which is related to the expression/exposure of tissue factor (TF). However, there is a discrepancy between the TF measured and changes in PA observed, suggesting that other blood components contribute to this activity. Our goal was to evaluate changes in PA of stored RBCs and to determine possible contributors to it. RBC units from 4 healthy donors were prepared and stored at 4 °C. On selected days, RBC aliquots were reconstituted with autologous plasma and tested in the thromboelastography assay. Corresponding supernatants were tested in a clotting assay. For all donors, the clotting time (CT) of reconstituted RBC units decreased from â¼3000-4000s on day 1 to â¼1000-1600s on day 30, with the most dramatic changes occurring between days 1 and 5. Anti-TF antibody slightly prolonged the CT. The concentration of TF did not change significantly over time and was within the range of 0.3-2.3 pM. Bovine lactadherin (LTD) prolonged the CT of the RBC (by 2.4-3.4-fold in days 3-5 and by 1.3-1.8-fold at day 30). Anti-TF antibody together with LTD had a cumulative effect on the CT prolongation. CT of supernatants responded to both anti-TF and anti-FXIa antibodies. Three contributors to the PA of stored RBC were identified, i.e. FXIa in solution and phosphatidylserine and TF exposed on blood cells and microparticles. Failure of LTD and antibodies to completely eliminate PA suggests that other components of blood could contribute to it.
Assuntos
Coagulação Sanguínea/fisiologia , Preservação de Sangue/métodos , Eritrócitos/fisiologia , Fator XIa/metabolismo , Manejo de Espécimes/métodos , Tromboplastina/metabolismo , Células Cultivadas , HumanosAssuntos
Circulação Coronária , Imagem de Perfusão do Miocárdio/economia , Tomografia por Emissão de Pósitrons/economia , Cardiologia , Codificação Clínica/normas , Current Procedural Terminology , Documentação/normas , Custos de Cuidados de Saúde , Humanos , Medicina Nuclear , Tomografia por Emissão de Pósitrons/normas , Estados UnidosRESUMO
Background: The COVID-19 pandemic catalyzed unprecedented changes to medical education, including CV fellowship programs. CV fellowship PDs offer a unique perspective regarding the impact of the pandemic on CV medical education. Objectives: The 4th annual Cardiovascular Diseases (CV) Fellowship Program Directors (PDs) Survey sought to understand the impact of the COVID-19 pandemic on CV fellows and fellowship programs. Methods: The survey contained 31 items examining the clinical, educational, and academic impact of the COVID-19 pandemic on CV fellowship programs. Results: Survey response rate was 54%. Most respondents (58%) represented university-based programs. Most PDs felt that changes to clinical practice during the COVID-19 negatively impacted fellow education in cardiac catheterization (66%), outpatient cardiology (52%), nuclear imaging (51%), and echocardiography (50%). Despite improving attendance, 75% of PDs felt that virtual educational conferences adversely impacted interaction between participants. Only 22% felt they improved fellow education. Most PDs (85%) reported a negative impact of the pandemic on fellow well-being and burnout, and 57% reported a decrease in research productivity among fellows. Even though virtual recruitment allowed programs to interview more competitive candidates, most PDs felt that virtual interviews adversely impacted interactions between their fellows and candidates (71%) and their ability to convey the culture of their program (60%). Conclusions: Most CV fellowship PDs felt the COVID-19 pandemic brought changes that negatively impacted the clinical training, didactic learning, academic productivity, and well-being among cardiology fellows. The implications of these changes on the competency of cardiologists that trained during the COVID-19 pandemic deserve future study.
RESUMO
BACKGROUND: Stress only SPECT myocardial perfusion imaging (MPI) is a validated strategy to streamline cardiac diagnostic imaging. The potential use of Rb82 PET stress only MPI has not been investigated. METHODS AND RESULTS: Stress images from 200 Rb82 PET-MPI were reviewed by two blinded readers and categorized as not requiring additional rest images (normal) or requiring additional images (abnormal or equivocal). No additional images were deemed necessary for 95 (48%) and 99 (50%) by the two blinded readers. The stress only interpretation was compared to the previous read of the complete rest-stress study. The rate of detecting a normal result with stress only reading was 76%-79% with a negative predictive value of 94%-95%. Clinical predictors of a normal stress only PET-MPI included lower age, the absence of CAD, and female gender, but not body mass index. Blinded reads of 50 additional consecutive PET-MPI from patients with selected clinical predictors (age <65 years, no known CAD) were then performed. Of these, 40 (80%) were normal by previous rest-stress reading, and 34 (68%) were categorized as not requiring additional images after stress only reading. PET stress only imaging would have resulted in a mean reduction of radiation exposure of 2.4 mSv per study according to a published radiation estimate. CONCLUSION: Stress only Rb82 PET-MPI is a feasible strategy to reduce resource utilization and radiation exposure associated with MPI. This strategy would be most applicable to patients with a lower pretest likelihood.
Assuntos
Teste de Esforço , Imagem de Perfusão do Miocárdio/métodos , Tomografia por Emissão de Pósitrons/métodos , Radioisótopos de Rubídio , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
BACKGROUND: Nonleukoreduced units of red blood cells (RBCs) contain activated platelets (PLTs) that interact with white blood cells (WBCs) and may promote inflammation and thrombosis in the recipient. The aim of this study was to characterize PLT-WBC interactions (PLT-WBC aggregates [PLAs]), WBC apoptosis, WBC death, and the development of procoagulant activity in RBCs during storage. STUDY DESIGN AND METHODS: RBCs were prepared from volunteer donor blood and stored. Samples were analyzed with flow cytometry between Days 1 and 15 to measure PLT-monocyte aggregate (PMA) and PLT-neutrophil aggregate (PNA) formation, WBC apoptosis (annexin V binding), and cell death (binding of 7-aminoactinomycin D). Procoagulant activity in the supernatant of four RBC preparations was assessed between Days 1 and 39 using a clotting assay with and without the addition of an inhibitory anti-tissue factor (TF) antibody, αTF-5. RESULTS: PLA formation was extensive and maximal on Day 3 of storage (PNA, 23 ± 13%; PMA, 93 ± 4%; n = 6). Apoptosis was progressive throughout storage, with 95 ± 4% of neutrophils and 73 ± 19% of monocytes binding annexin V on Day 15. Cell death became measurable after apoptosis. Procoagulant activity was observed in all RBCs but with varying temporal patterns. It was partially TF dependent and removed with high-speed centrifugation, suggestive of an association with microparticles. CONCLUSION: The activation of PLTs during the storage of RBCs induces PLA formation that precedes WBC apoptosis and death. Procoagulant activity, likely associated with microparticles derived from apoptotic WBCs, may contribute to adverse effects of stored, nonleukoreduced RBCs.
Assuntos
Fatores de Coagulação Sanguínea/metabolismo , Plaquetas/citologia , Preservação de Sangue/efeitos adversos , Eritrócitos/citologia , Monócitos/citologia , Apoptose/fisiologia , Plaquetas/fisiologia , Comunicação Celular/fisiologia , Micropartículas Derivadas de Células/fisiologia , Eritrócitos/metabolismo , Citometria de Fluxo , Humanos , Neutrófilos/citologia , Ativação Plaquetária/fisiologia , Tromboplastina/metabolismoRESUMO
OBJECTIVES: The third annual Cardiovascular Diseases (CV) Fellowship Program Directors (PDs) Survey sought to understand burnout and well-being among CV fellowship PDs. BACKGROUND: Physician burnout is a common phenomenon. Data on burnout among cardiologists, specifically CV PDs, remain limited. METHODS: The survey contained 8 questions examining satisfaction, stress, and burnout among CV fellowship PDs. Burnout was defined based on the self-reported presence of ≥1 symptom of burnout, constant feelings of burnout, or complete burnout. RESULTS: Survey response rate was 57%. Most respondents were men (78%) and 54% represented university-based programs. Eighty percent reported satisfaction with their current job as PD, and 96% identified interactions with fellows as a driver of their satisfaction. Forty-five percent reported feeling a great deal of stress from their job. Stress was higher among women PDs, early-career PDs, and PDs of larger and university-based programs. Twenty-one percent reported some symptoms of burnout, and only 36% reported enjoyment without stress or burnout. Rates of enjoyment without stress or burnout were higher among men and late-career PDs, PDs of smaller programs, and PDs of community-based programs. Seventeen percent of PDs reported a high likelihood of resigning in the next year, of which the most common reason was the tasks of PDs were becoming overwhelming. CONCLUSIONS: Most CV fellowship PDs are satisfied with their position, but stress and burnout remain common. Women PDs, early-career PDs, and PDs of larger, university-based programs demonstrate more adverse markers of well-being. Opportunities exist to support CV fellowship PDs in their critical role.
Assuntos
Esgotamento Profissional , Esgotamento Psicológico , Cardiologistas , Cardiologia/educação , Cardiologia/organização & administração , Diretores Médicos , Adulto , Idoso , Educação de Pós-Graduação em Medicina , Bolsas de Estudo , Feminino , Humanos , Satisfação no Emprego , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Women and minorities are under-represented in cardiovascular disease (CVD) specialties. It remains unknown how characteristics of the CVD learning environment affect diversity and how program directors (PDs) approach these critical issues. OBJECTIVES: The second annual Cardiovascular PD Survey aimed to investigate characteristics of the CVD learning environment that may affect diversity and strategies PDs use to approach these issues. METHODS: The survey contained 20 questions examining U.S.-based CVD PD perceptions of diversity in CVD and related characteristics of the CVD fellowship learning environment. RESULTS: In total, 58% of PDs completed the survey. Responding programs demonstrated geographic diversity. The majority were university-based or -affiliated. A total of 86% of PDs felt diversity in CVD as a field needs to increase, and 70% agreed that training programs could play a significant role in this. In total, 89% of PDs have attempted to increase diversity in fellowship recruitment. The specific strategies used were associated with PD sex and the presence of under-represented minority trainees in the program. PDs identified lack of qualified candidates and overall culture of cardiology as the 2 most significant barriers to augmenting diversity. A majority of programs have support systems in place for minority fellows or specific gender groups, including procedures to report issues of harassment or an unsafe learning environment. PDs identified shared best practices for recruitment and implicit bias training, among others, as important resources in their efforts to support diversity in CVD training. CONCLUSIONS: Diversity is important to CVD PDs. They are striving to increase it in their programs through recruitment and strategies directed toward the fellowship learning environment. The CVD community has opportunities to standardize strategies and provide national resources to support PDs in these critical efforts.
Assuntos
Cardiologia/educação , Doenças Cardiovasculares/terapia , Grupos Minoritários/educação , Diretores Médicos , Sexismo , Inquéritos e Questionários , Cardiologia/tendências , Feminino , Humanos , Masculino , Diretores Médicos/tendências , Sexismo/tendênciasRESUMO
We assessed the effect of the intercellular mediator of inflammation, platelet activating factor (PAF), on platelet function. The interaction between PAF and the platelet agonists ADP, thrombin and convulxin was analyzed in vitro in whole blood with the use of flow cytometry and was further characterized with the use of receptor antagonists to PAF (ABT-491), P2Y1 (MRS-2179), and P2Y12 (cangrelor) as well as a monoclonal anti-PSGL-1 antibody (anti-CD162). Low concentrations of PAF (0.1 nM) synergistically augmented platelet activation induced by other agonists (P < 0.01). Augmentation by PAF was receptor mediated and did not require platelet-leukocyte interaction. With >99% inhibition of P2Y receptor-mediated platelet activation, greater than additive activation was still observed with the combination of ADP plus PAF. Accordingly, PAF synergistically augments platelet activation in response to ADP and thrombin, and the extent of inhibition exerted by P2Y receptor antagonists is decreased in the presence of PAF.
Assuntos
Difosfato de Adenosina/farmacologia , Plaquetas/metabolismo , Fator de Ativação de Plaquetas/farmacologia , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Trombina/farmacologia , Difosfato de Adenosina/agonistas , Adulto , Idoso , Idoso de 80 Anos ou mais , Venenos de Crotalídeos/farmacologia , Sinergismo Farmacológico , Feminino , Humanos , Lectinas Tipo C , Masculino , Pessoa de Meia-Idade , Fator de Ativação de Plaquetas/agonistas , Inibidores da Agregação Plaquetária/agonistas , Testes de Função Plaquetária , Agonistas do Receptor Purinérgico P2 , Antagonistas do Receptor Purinérgico P2 , Trombina/agonistasRESUMO
For many patients with ST-segment elevation myocardial infarctions (STEMIs), the time from presentation to percutaneous coronary intervention exceeds established goals. This study was conducted to examine the effects of formalized data assessment and systematic feedback on treatment times. All patients with STEMIs treated with percutaneous coronary intervention in a semi-rural 3-hospital network from January 1, 2006, to December 31, 2006, were prospectively analyzed (n = 114). Patients presenting during the first 3-month period (January 1, 2006, to March 31, 2006) were included as the reference group (n = 33). Time points from initial contact with the medical system to revascularization were assessed, analyzed, and presented in an interactive session to hospital and emergency services staff members. Data from patients with STEMIs presenting during the next 3 quarters were presented in the same manner (n = 28, 25, and 28). The median contact-to-balloon time was 113 minutes in the reference quarter, decreasing to 83, 66, and 74 minutes in the intervention groups (p <0.0001), whereas the median door-to-balloon time decreased from 54 minutes in the reference group to 35, 31, and 26 minutes in the intervention groups (p <0.0001). The proportion of patients with contact-to-balloon times <90 minutes increased from 21% to 79% (p <0.0001). There were significant reductions in the durations of initial treatment on location and in the emergency room and in puncture-to-balloon-time in the catheterization laboratory, and more patients were transported directly to the catheterization laboratory, bypassing the emergency room (from 23% in the reference quarter to 76% in the last intervention quarter, p <0.0001). In conclusion, formalized data feedback leads to marked reduction in revascularization times in patients with STEMIs.
Assuntos
Angioplastia Coronária com Balão/normas , Serviços Médicos de Emergência/organização & administração , Retroalimentação , Infarto do Miocárdio/terapia , Programas Médicos Regionais/organização & administração , Idoso , Redes Comunitárias , Eletrocardiografia , Serviço Hospitalar de Emergência/organização & administração , Feminino , Alemanha , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Telemetria , Fatores de Tempo , Transporte de PacientesRESUMO
INTRODUCTION: Platelet-leukocyte aggregates have been implicated in atherogenesis. This study was designed to determine the influence in vivo of a direct thrombin inhibitor, bivalirudin, compared with unfractionated heparin (UFH) plus the GP IIb-IIIa inhibitor eptifibatide (E) on platelet reactivity, the formation of platelet-leukocyte aggregates, and leukocyte activation. MATERIALS AND METHODS: Blood was taken before and after percutaneous coronary intervention (PCI) from 60 patients randomized to UFH+E (n=26) or bivalirudin (n=34). Platelet function and the formation in vivo of platelet-monocyte aggregates (PMA) and platelet-neutrophil aggregates (PNA) were assessed with the use of flow cytometry. Myeloperoxidase (MPO) elaborated during leukocyte activation was measured by ELISA. RESULTS: Compared with those treated with bivalirudin, patients treated with UFH+E exhibited a 45% decrease in the capacity of platelets to bind fibrinogen (p=0.006) but a 2-fold increase in platelet surface expression of P-selectin (p=0.04) in samples taken from the coronary ostium before PCI. Platelet-leukocyte aggregation in vivo was greater (PMA=2-fold, p=0.04; PNA=3-fold, p=0.006) with UFH+E as was the concentration in blood of MPO (1.5-fold, p=0.007). CONCLUSIONS: Increased platelet surface expression of P-selectin, augmented platelet-leukocyte aggregation in vivo, and consequent activation of leukocytes was seen before PCI in blood from patients treated with UFH+E compared with bivalirudin. Benefits associated with decreased platelet aggregation when PCI is performed with UFH plus GP IIb-IIIa inhibition may be partially offset by increased platelet-leukocyte aggregation.
Assuntos
Heparina/administração & dosagem , Hirudinas/administração & dosagem , Selectina-P/imunologia , Fragmentos de Peptídeos/administração & dosagem , Peptídeos/administração & dosagem , Agregação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/imunologia , Trombose/imunologia , Anticoagulantes/administração & dosagem , Células Cultivadas , Combinação de Medicamentos , Eptifibatida , Feminino , Humanos , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/administração & dosagem , Proteínas Recombinantes/administração & dosagem , Trombose/sangue , Trombose/prevenção & controleRESUMO
OBJECTIVES: Both tirofiban and eptifibatide release rapidly from glycoprotein IIb-IIIa but have different dissociation constants (KD of tirofiban=15 nmol/l, of eptifibatide=120 nmol/l). Binding of fibrinogen to glycoprotein IIb-IIIa is biphasic, forming an initial reversible complex (KD=155-180 nmol/l) and a second more stable complex (KD=20-70 nmol/l). Diabetes is known to alter platelet function. To determine the influence of affinity on inhibitory effects in blood from patients with (n=20) and without (n=20) diabetes mellitus, we characterized the extent of inhibition as a function of time. METHODS: Blood was added to reaction tubes containing tirofiban 100 ng/ml or eptifibatide 1.7 microg/ml (concentrations previously defined to be optimal) plus a platelet agonist (1 micromol/l adenosine diphosphate or 25 micromol/l thrombin receptor agonist peptide), and fluorochrome-labeled fibrinogen before analysis by flow cytometry. RESULTS: The extent of inhibition early on (30 s to 3 min) was similar (>85%) with either agent in blood from those with and without diabetes mellitus, whereas the extent of inhibition 10-15 min later was maintained more effectively with tirofiban than with eptifibatide (difference in slope P<0.01). After 15 min, the extent of inhibition in response to adenosine diphosphate in those with diabetes mellitus was 95+/-6% for tirofiban and 70+/-15% for eptifibatide (P<0.001); in those without diabetes mellitus, it was 91+/-9% for tirofiban and 73+/-19% for eptifibatide (P<0.001). CONCLUSION: For glycoprotein IIb-IIIa antagonists with a rapid rate of release, the biphasic binding of fibrinogen influences to a similar extent their ability to maintain inhibitory effects in blood from patients with and without diabetes mellitus.
Assuntos
Diabetes Mellitus/sangue , Fibrinogênio/efeitos dos fármacos , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Tirosina/análogos & derivados , Idoso , Diabetes Mellitus/tratamento farmacológico , Feminino , Fibrinogênio/metabolismo , Citometria de Fluxo , Humanos , Técnicas In Vitro , Masculino , Tirofibana , Tirosina/farmacologiaRESUMO
OBJECTIVE: To characterize effects of bivalirudin compared with unfractionated heparin plus eptifibatide on inflammation, and thrombin generation and activity after percutaneous coronary intervention. METHODS: We measured the concentration in blood of fibrinopeptide A, prothrombin fragment 1+2, soluble CD40 ligand, interleukin 1 receptor antagonist, interleukin 6, and high sensitivity C-reactive protein in 63 patients treated with aspirin and clopidogrel and undergoing elective percutaneous coronary intervention, who were randomized to treatment with either bivalirudin (n=34) or unfractionated heparin plus eptifibatide (n=29). RESULTS: Neither generation nor activity of thrombin increased 10 min after percutaneous coronary intervention in patients randomized to bivalirudin or unfractionated heparin plus eptifibatide. However, prothrombin fragment 1+2 increased modestly and comparably in both groups after 1 day. Inflammation, reflected by concentrations of interleukin 6 and high sensitivity C-reactive protein in blood, increased similarly 1 day after percutaneous coronary intervention in patients treated with either regimen. In a subset of patients (n=12 in each group) from whom blood was obtained 30 days after percutaneous coronary intervention, the concentration of high sensitivity C-reactive protein was lower in those who had been treated with bivalirudin (by 3.5 mg/l, P=0.002). CONCLUSION: The early effects on inflammation and thrombin generation and activity are similar after treatment with bivalirudin alone compared with unfractionated heparin plus eptifibatide in patients treated with aspirin and clopidogrel who are undergoing percutaneous coronary intervention for symptoms of stable angina. The decreased concentration of high sensitivity C-reactive protein seen 30 days after percutaneous coronary intervention in those treated with bivalirudin is consistent with greater attenuation of inflammation that may have contributed to the trend toward reduced mortality 1 year later in those treated with bivalirudin in REPLACE-2.
Assuntos
Angioplastia Coronária com Balão , Doença da Artéria Coronariana/terapia , Heparina/uso terapêutico , Fragmentos de Peptídeos/uso terapêutico , Peptídeos/uso terapêutico , Trombina/metabolismo , Idoso , Anticoagulantes/uso terapêutico , Proteína C-Reativa/metabolismo , Ligante de CD40/sangue , Terapia Combinada , Doença da Artéria Coronariana/sangue , Eptifibatida , Feminino , Fibrinopeptídeo A/metabolismo , Hirudinas , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/metabolismo , Inibidores da Agregação Plaquetária/uso terapêutico , Precursores de Proteínas/metabolismo , Protrombina/metabolismo , Receptores de Interleucina-1/sangue , Proteínas Recombinantes/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of this study was to determine the impact of cangrelor and prasugrel on the pharmacodynamic effects of each agent. BACKGROUND: The development of an intravenous P2Y12 antagonist necessitates transition between intravenous and oral therapy. METHODS: Patients (n=15) with stable coronary artery disease who were taking 81 mg aspirin daily were recruited. On study day 1, they received a bolus plus 2-h infusion of cangrelor plus a 60 mg dose of prasugrel at 1 h (n=3), 1.5 h (n=6), 2 h (n=3), or 2.5 h (n=3). Pharmacodynamic effects (light transmission platelet aggregation in response to 20 µmol/l ADP, VerifyNow, and flow cytometry) were assessed during and after the cangrelor infusion. Patients took 10 mg of prasugrel daily for either 5 days (n=6) or 6 days (n=6). On study day 8, pharmacodynamic effects were assessed before and during a bolus plus 2-h infusion of cangrelor. RESULTS: During cangrelor infusion (days 1 and 8), extensive inhibition of platelet function, reflected by limited residual platelet reactivity, was apparent. On day 1, transient (limited to the first hour after cangrelor was stopped) but substantial (>50%) recovery of platelet reactivity was observed. This recovery was attenuated when prasugrel was given at 1.5 h (30 min before cangrelor was stopped). CONCLUSION: Prasugrel did not alter the antiplatelet effects of cangrelor, but transient recovery of platelet reactivity was apparent during the transition from cangrelor to prasugrel. Recovery of platelet reactivity was limited when prasugrel was administered 30 min before the end of the cangrelor infusion.