RESUMO
Background Homozygous familial hypercholesterolemia (HoFH) is a rare, treatment-resistant disorder characterized by early-onset atherosclerotic and aortic valvular cardiovascular disease if left untreated. Contemporary information on HoFH in the United States is lacking, and the extent of underdiagnosis and undertreatment is uncertain. Methods and Results Data were analyzed from 67 children and adults with clinically diagnosed HoFH from the CASCADE (Cascade Screening for Awareness and Detection) FH Registry. Genetic diagnosis was confirmed in 43 patients. We used the clinical characteristics of genetically confirmed patients with HoFH to query the Family Heart Database, a US anonymized payer health database, to estimate the number of patients with similar lipid profiles in a "real-world" setting. Untreated low-density lipoprotein cholesterol levels were lower in adults than children (533 versus 776 mg/dL; P=0.001). At enrollment, atherosclerotic cardiovascular disease and supravalvular and aortic valve stenosis were present in 78.4% and 43.8% and 25.5% and 18.8% of adults and children, respectively. At most recent follow-up, despite multiple lipid-lowering treatment, low-density lipoprotein cholesterol goals were achieved in only a minority of adults and children. Query of the Family Heart Database identified 277 individuals with profiles similar to patients with genetically confirmed HoFH. Advanced lipid-lowering treatments were prescribed for 18%; 40% were on no lipid-lowering treatment; atherosclerotic cardiovascular disease was reported in 20%; familial hypercholesterolemia diagnosis was uncommon. Conclusions Only patients with the most severe HoFH phenotypes are diagnosed early. HoFH remains challenging to treat. Results from the Family Heart Database indicate HoFH is systemically underdiagnosed and undertreated. Earlier screening, aggressive lipid-lowering treatments, and guideline implementation are required to reduce disease burden in HoFH.
Assuntos
Anticolesterolemiantes , Aterosclerose , Doenças Cardiovasculares , Hipercolesterolemia Familiar Homozigota , Hiperlipoproteinemia Tipo II , Estados Unidos/epidemiologia , Humanos , Doenças Cardiovasculares/tratamento farmacológico , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/genética , LDL-Colesterol , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Aterosclerose/genética , Sistema de Registros , Anticolesterolemiantes/uso terapêutico , HomozigotoRESUMO
BACKGROUND: We sought to determine whether circulating modifiers of endothelial function are associated with cardiac structure and clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). METHODS: We measured 25 proteins related to endothelial function in 99 patients from the GUIDE-IT study. Protein levels were evaluated for association with echocardiographic parameters and the incidence of all-cause death and hospitalization for heart failure (HHF). RESULTS: Higher concentrations of angiopoietin 2 (ANGPT2), vascular endothelial growth factor receptor 1 (VEGFR1) and hepatocyte growth factor (HGF) were significantly associated with worse function and larger ventricular volumes. Over time, decreases in ANGPT2 and, to a lesser extent, VEGFR1 and HGF, were associated with improvements in cardiac size and function. Individuals with higher concentrations of ANGPT2, VEGFR1 or HGF had increased risks for a composite of death and HHF in the following year (HR 2.76 (95% CI 1.73-4.40) per 2-fold change in ANGPT2; HR 1.76 (95% CI 1.11-2.79) for VEGFR1; and HR 4.04 (95% CI 2.19-7.44) for HGF). CONCLUSIONS: Proteins related to endothelial function associate with cardiac size, cardiac function and clinical outcomes in patients with HFrEF. These results support the concept that endothelial function may be an important contributor to the progression to and the recovery from HFrEF.
Assuntos
Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Humanos , Volume Sistólico/fisiologia , Fatores de Risco , Insuficiência Cardíaca/epidemiologia , Fator A de Crescimento do Endotélio Vascular , Causas de Morte , Doença Crônica , Função Ventricular Esquerda/fisiologiaRESUMO
BACKGROUND: Volitional physical activity level is predictive of a variety of health outcomes, but has not been examined in patients recently hospitalized for acute decompensated HF (ADHF). METHODS: Ten to 14 days after index hospitalization for ADHF, 93 participants wore a wrist-mounted triaxial accelerometer (ActiGraph GT3X+) to objectively quantify sedentary behavior, light physical activity, and moderate-to-vigorous physical activity. Levels were compared to 2 groups of age-matched NHANES participants: healthy and chronic, stable HF. The relationship between physical activity levels and physical function [Short Physical Performance Battery (SPPB)], HF-specific quality-of-life (QOL) [Kansas City Cardiomyopathy Questionnaire (KCCQ)], and cognition [Montreal Cognitive Assessment (MOCA)] were examined. RESULTS: ADHF participants accumulated a median 1,008 (IQR 896, 1,109) minutes of sedentary time, 88 (57, 139) minutes of light physical activity, and 10 (6, 25) minutes of moderate-to-vigorous physical activity per day. Sedentary time, light physical activity, or moderate-to-vigorous activity did not differ by sex or EF subtype. ADHF participants spent only 9% of awake time nonsedentary, compared to 34% and 27% for healthy adults and adults with chronic, stable HF, respectively. Among ADHF participants, SPPB, KCCQ, and MOCA scores did not differ among quartiles of total physical activity. CONCLUSIONS: Older patients recently hospitalized for ADHF have very low levels of physical activity and high levels of sedentary time, both of which may be potential targets for interventions in this high-risk population. Physical activity level was not significantly associated with objectively measured physical function, QOL, or cognition, suggesting that this measure provides independent information regarding the patient experience of living with HF. TRIAL REGISTRATION: NCT02196038, https://clinicaltrials.gov/ct2/show/NCT02196038.
Assuntos
Insuficiência Cardíaca , Qualidade de Vida , Adulto , Idoso , Humanos , Cognição , Exercício Físico , Inquéritos Nutricionais , Masculino , FemininoRESUMO
AIMS: N-terminal pro-b-type natriuretic peptide (NT-proBNP) values may be influenced by patient factors beyond the severity of illness, including atrial fibrillation (AF), renal dysfunction, or increased body mass index (BMI). We hypothesized that these factors may influence the achievement of NT-proBNP targets and clinical outcomes. METHODS: A total of 894 patients with heart failure with reduced ejection fraction were enrolled in The Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment trial. NT-proBNP was analysed every 3 months. RESULTS: Forty per cent of patients had AF, the median estimated glomerular filtration rate (eGFR) was 59 mL/min/1.73 m2 [interquartile range (IQR) 43-76], and median BMI was 29 kg/m2 (IQR 25-34). Patients with AF, eGFR < 60 mL/min/1.73 m2 , or a BMI < 29 kg/m2 had a higher level of NT-proBNP at randomization and over all study visits (all P values < 0.001). Over 18 months, the rate of change of NT-proBNP was less for patients with AF (compared with those without AF, P = 0.037) and patients with an eGFR < 60 mL/min/1.73 m2 (compared with eGFR > 60 mL/min/1.73 m2 , P < 0.001). The rate of change of NT-proBNP was similar for patients with a BMI above or below the median value. Using the 90 day NT-proBNP, patients with AF, lower eGFR, or lower BMI were less likely to achieve the target NT-proBNP < 1000 pg/mL than patients without AF, higher eGFR, or higher BMI, respectively. None of these differed between the Usual Care or Guided Care arm for AF, eGFR, or BMI (Pinteractions all NS). CONCLUSIONS: Patients with AF, a lower BMI, or worse renal function are less likely to achieve a lower or target NT-proBNP. Clinicians should be aware of these factors both when interpreting NT-proBNP levels and making therapeutic decisions about heart failure therapies.
Assuntos
Fibrilação Atrial , Insuficiência Cardíaca , Humanos , Peptídeo Natriurético Encefálico , Fragmentos de PeptídeosRESUMO
Obesity is a growing worldwide epidemic with significant economic burden that carries with it impacts on every physiologic system including the cardiovascular system. Specifically, the risk of heart failure has been shown to increase dramatically in obese individuals. The purpose of this review is to provide background on the individual burdens of heart failure and obesity, followed by exploring proposed physiologic mechanisms that interconnect these conditions, and furthermore introduce treatment strategies for weight loss focusing on bariatric surgery. Review of the existing literature on patients with obesity and heart failure who have undergone bariatric surgery is presented, compared, and contrasted.
Assuntos
Cirurgia Bariátrica , Insuficiência Cardíaca , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/cirurgia , Humanos , Obesidade/complicações , Obesidade/cirurgia , Redução de PesoRESUMO
PURPOSE: A body mass index (BMI) > 35 kg/m2 is a relative contraindication to heart transplantation in patients with end-stage heart failure. Bariatric surgery can be considered either concomitantly with continuous-flow left ventricular assist device (CF-LVAD) placement, or staged after CF-LVAD has been placed. We sought to evaluate the outcomes of these approaches. MATERIALS AND METHODS: An electronic search was performed to identify all relevant studies. After assessment for inclusion and exclusion criteria, eight studies were pooled for systematic review and metaanalysis. RESULTS: Overall, of 59 patients, 22 (37%) underwent simultaneous sleeve gastrectomy with CF-LVAD implantation while 37 (63%) underwent staged sleeve gastrectomy after CF-LVAD. The mean age of patients was 46 years (95% CI: 39-53) with 40% females. Mean BMI at most recent follow-up (33.4 kg/m2, 95% CI: 30.2-36.6) was significantly lower compared with mean preoperative BMI (46.7 kg/m2, 95% CI: 42.9-50.6) (p < 0.01). There was no significant difference in total incidence of postoperative complications (simultaneous, 16% (95% CI: 1-87%) versus staged, 23% (95% CI: 7-53%)) or in overall survival (simultaneous, 93% (95% CI: 72-99%) versus staged, 79% (95% CI: 60-90%), p = 0.17) for average follow-up time of 12.7 months. Bariatric surgery resulted in 66% of patients (95% CI: 51-79) to be listed for heart transplantation, including 33% (95% CI: 22-47) who were transplanted. CONCLUSIONS: Both simultaneous and staged bariatric surgeries with CF-LVAD placement have comparable outcomes and significantly reduce BMI. This can allow previously ineligible patients to undergo heart transplantation.
Assuntos
Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Obesidade Mórbida , Feminino , Gastrectomia , Insuficiência Cardíaca/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Resultado do TratamentoAssuntos
Disfunção Cognitiva/diagnóstico , Ponte de Artéria Coronária/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/psicologia , Ponte de Artéria Coronária/tendências , Humanos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/psicologia , Resultado do TratamentoRESUMO
Angina pectoris (AP) is associated with worse outcomes in heart failure (HF). We investigated the association of AP with health-related quality of life (HRQoL), exercise capacity, and clinical outcomes and its interaction with exercise training in an HF population. We grouped 2,331 patients with HF with reduced ejection fraction in the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) trial of usual care ± exercise training according to whether they had self-reported AP by Canadian classification score. HRQoL and clinical outcomes were assessed by AP status. In HF-ACTION, 406 patients (17%) had AP at baseline (44% with Canadian classification score ≥II) with HF severity similar to those without AP. Patients with AP had similar baseline exercise capacity but worse depressive symptoms and HRQoL. AP was associated with 22% greater adjusted risk for all-cause mortality/hospitalizations, driven by hospitalizations. There was significant interaction between baseline AP and exercise training peak VO2 change (p = 0.019) but not other end points. Exercise training was associated with greater peak VO2 improvement after 3 months in patients with AP (treatment effect = 1.25 ml/kg/min, 95% CI 0.6 to 1.9). In conclusion, AP was associated with worse HRQoL and depressive symptoms. Despite greater peak VO2 improvement with exercise training, patients with AP experienced more adverse outcomes.
Assuntos
Angina Pectoris/complicações , Terapia por Exercício , Tolerância ao Exercício , Insuficiência Cardíaca/reabilitação , Consumo de Oxigênio , Qualidade de Vida , Idoso , Causas de Morte , Doença Crônica , Feminino , Insuficiência Cardíaca/complicações , Hospitalização/estatística & dados numéricos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Resultado do TratamentoRESUMO
Aspirin for secondary cardiovascular disease prevention is well established, but treatment discontinuation, often because of gastrointestinal mucosal injury or symptoms, can lead to increased risk for cardiovascular events. Proton pump inhibitor therapy is recommended for aspirin-treated patients at gastrointestinal risk. PA32540 [enteric-coated aspirin (EC-ASA) 325 mg + immediate-release omeprazole 40 mg] was compared with EC-ASA 325 mg alone once daily for 6 months in 2 duplicate, randomized double-blind trials in gastrointestinal-risk patients taking aspirin for ≥3 months for secondary prevention. In this post hoc analysis, we determined the prevalence of endoscopic upper gastrointestinal ulcers at screening and whether baseline endoscopic gastric erosions impacted subsequent ulcer development. At the screening endoscopy, 6% of subjects had upper gastrointestinal ulcers (not eligible for randomization) and 40% had gastric erosions. Conditional logistic regression modeling showed that baseline gastric erosions are significantly associated with endoscopic gastric ulcer development (OR = 2.12, 95% confidence interval, 1.26-3.57). In subjects with baseline gastric erosion, 4.2% of PA32540-treated versus 13.0% of EC-ASA-treated subjects (P = 0.001) subsequently developed endoscopic gastric ulcers. These data suggest that gastric injury predisposes to gastric ulcer development when taking EC-ASA, and exposure to immediate-release omeprazole in the presence of aspirin therapy significantly reduces the likelihood of progressing to gastric ulcers.
Assuntos
Aspirina/administração & dosagem , Fármacos Cardiovasculares/administração & dosagem , Doenças Cardiovasculares/prevenção & controle , Úlcera Duodenal/prevenção & controle , Mucosa Gástrica/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Omeprazol/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Prevenção Secundária/métodos , Úlcera Gástrica/prevenção & controle , Adolescente , Adulto , Aspirina/efeitos adversos , Aspirina/química , Fármacos Cardiovasculares/efeitos adversos , Fármacos Cardiovasculares/química , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Progressão da Doença , Método Duplo-Cego , Combinação de Medicamentos , Composição de Medicamentos , Úlcera Duodenal/induzido quimicamente , Úlcera Duodenal/diagnóstico , Endoscopia Gastrointestinal , Feminino , Mucosa Gástrica/patologia , Humanos , Mucosa Intestinal/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Omeprazol/efeitos adversos , Omeprazol/química , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/química , Medição de Risco , Fatores de Risco , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/diagnóstico , Comprimidos com Revestimento Entérico , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Robotic technology is one of the most recent technological changes in coronary artery bypass graft (CABG) operations. The current analysis was conducted to identify trends in the use and outcomes of robotic-assisted CABG (RA-CABG). METHODS: A retrospective analysis was performed using data from The Society of Thoracic Surgeons Adult Cardiac Surgery Database between 2006 and 2012. Patient and site-level characteristics were compared between traditional CABG and RA-CABG. Operative death, postoperative length of stay, and postoperative complications were compared between the two groups. RESULTS: The number of sites using RA-CABG remained relatively constant during the study period (from 148 in 2006 to 151 in 2012). The volume of RA-CABG as a percentage of the total CABG procedures increased slightly from 0.59% (872 RA-CABG of 127,717 total CABG) in 2006 to 0.97% (1,260 RA-CABG of 97,249 total CABG) in 2012. The RA-CABG patients were significantly younger (64 vs 65 years, p < 0.0001), had fewer comorbidities, and had lower rates of cardiopulmonary bypass use (22.4% vs 80.4%, p < 0.0001). RA-CABG patients had significantly lower unadjusted major complication rates (10.2% vs 13.5%, p < 0.0001), including postoperative renal failure (2.2% vs 2.9%, p < 0.0001), and shorter length of stay (4 vs 5 days, p < 0.0001). The difference in operative death was not significant (odds ratio, 1.10; 95% confidence interval, 0.92 to 1.30, p = 0.29). CONCLUSIONS: RA-CABG use remained relatively stagnant during the analysis period despite lower rates of major perioperative complications and no difference in operative deaths. Additional analysis is needed to fully understand the role that robotic technology will play in CABG operations in the future.
Assuntos
Ponte de Artéria Coronária/métodos , Doença da Artéria Coronariana/cirurgia , Complicações Pós-Operatórias/epidemiologia , Robótica/métodos , Sociedades Médicas , Cirurgia Torácica , Idoso , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
Prescribed in patients with a history of myocardial infarction, stroke, transient ischemic attack, coronary intervention or bypass surgery, aspirin is one of the medications most commonly used in the secondary prevention of cardiovascular diseases. It has become a mainstay of therapy after years of solid evidence supporting its efficacy in clinical trials. However, a number of risks and side effects accompany its benefits, including the notable risk of bleeding and gastrointestinal side effects. Numerous mechanisms have been proposed to attenuate these effects to promote adherence and to expand the population for which aspirin is a reasonable treatment option. A polypill or combination formulation that includes a proton pump inhibitor, a drug commonly prescribed alongside aspirin, is one potential avenue of therapy. One such combination pill, PA32540, has undergone Phase I and Phase III trials and shows promising safety and efficacy results in these preliminary trials.
Assuntos
Aspirina/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Inibidores da Agregação Plaquetária/uso terapêutico , Prevenção Secundária , Úlcera Gástrica , Doenças Cardiovasculares/tratamento farmacológico , Quimioterapia Combinada , Humanos , Úlcera Gástrica/complicações , Úlcera Gástrica/tratamento farmacológicoRESUMO
PURPOSE: To investigate the efficacy and safety of aerobic training (AT) in patients with cancer with medically stable heart failure (HF). PATIENTS AND METHODS: A retrospective analysis of 90 patients with cancer who have HF and who were randomly assigned to AT (n = 47) or guideline-based usual care (UC; n = 43) was performed. AT consisted of three supervised sessions per week at 20 to 45 minutes per session at 60% to 70% of heart rate reserve for 12 weeks followed by home-based sessions for 4 to 12 months. The primary end point was all-cause mortality and hospitalization. Secondary end points were other clinical events, safety, and change in exercise capacity (VO(2peak)) and health-related quality of life (HRQOL). RESULTS: Median follow-up was 35 months. In intention-to-treat (ITT) analyses, all-cause mortality or hospitalization at 2 years was 74% in the AT group compared with 67% in the UC group (adjusted hazard ratio [HR], 1.11; 95% CI, 0.69 to 1.77; P = .676). The incidence of cardiovascular mortality or cardiovascular hospitalization was significantly higher in the AT group compared with the UC group (41% v 67%; adjusted HR, 1.94; 95% CI, 1.12 to 3.16; P = .017). There were no differences in any VO(2peak) or HRQOL end points. In post hoc analyses based on adherence to AT, all-cause mortality and hospitalization was 66% in adherent patients (≥ 90 minutes per week) compared with 84% in nonadherent patients (< 90 minutes per week). CONCLUSION: In ITT analyses, AT did not improve clinical outcomes in patients with cancer who had HF. Post hoc analyses suggested that patients not capable of adhering to the planned AT prescription may be at increased risk of clinical events.
Assuntos
Terapia por Exercício/métodos , Exercício Físico/fisiologia , Insuficiência Cardíaca/reabilitação , Neoplasias/reabilitação , Idoso , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Neoplasias/fisiopatologia , Qualidade de Vida , Estudos RetrospectivosRESUMO
Stage D heart failure (HF) is associated with poor prognosis, yet little consensus exists on the care of patients with HF approaching the end of life. Treatment options for end-stage HF range from continuation of guideline-directed medical therapy to device interventions and cardiac transplantation. However, patients approaching the end of life may elect to forego therapies or procedures perceived as burdensome, or to deactivate devices that were implanted earlier in the disease course. Although discussing end-of-life issues such as advance directives, palliative care, or hospice can be difficult, such conversations are critical to understanding patient and family expectations and to developing mutually agreed-on goals of care. Because patients with HF are at risk for rapid clinical deterioration or sudden cardiac death, end-of-life issues should be discussed early in the course of management. As patients progress to advanced HF, the need for such discussions increases, especially among patients who have declined, failed, or been deemed to be ineligible for advanced HF therapies. Communication to define goals of care for the individual patient and then to design therapy concordant with these goals is fundamental to patient-centered care. The objectives of this white paper are to highlight key end-of-life considerations in patients with HF, to provide direction for clinicians on strategies for addressing end-of-life issues and providing optimal patient care, and to draw attention to the need for more research focusing on end-of-life care for the HF population.
Assuntos
Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Assistência Terminal/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Insuficiência Cardíaca/diagnóstico , Cuidados Paliativos na Terminalidade da Vida/métodos , Humanos , Masculino , Cuidados Paliativos/métodos , Sistema de Registros , Taxa de Sobrevida/tendênciasRESUMO
OBJECTIVES: This study evaluated effects of protease-activated receptor-1 antagonist vorapaxar (Merck, Whitehouse Station, New Jersey) versus placebo among the TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) study patients with non-ST-segment elevation acute coronary syndromes undergoing coronary artery bypass grafting (CABG). BACKGROUND: Platelet activation may play a key role in graft occlusion, and antiplatelet therapies may reduce ischemic events, but perioperative bleeding risk remains a major concern. Although the TRACER study did not meet the primary quintuple composite outcome in the overall population with increased bleeding, an efficacy signal with vorapaxar was noted on major ischemic outcomes, and preliminary data suggest an acceptable surgical bleeding profile. We aimed to assess efficacy and safety of vorapaxar among CABG patients. METHODS: Associations between treatment and ischemic and bleeding outcomes were assessed using time-to-event analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the Cox hazards model. Event rates were estimated using the Kaplan-Meier method. RESULTS: Among 12,944 patients, 1,312 (10.1%) underwent CABG during index hospitalization, with 78% on the study drug at the time of surgery. Compared with placebo CABG patients, vorapaxar-treated patients had a 45% lower rate of the primary endpoint (i.e., a composite of death, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization during index hospitalization) (HR: 0.55; 95% CI: 0.36 to 0.83; p = 0.005), with a significant interaction (p = 0.012). The CABG-related Thrombolysis In Myocardial Infarction major bleeding was numerically higher with vorapaxar, but not significantly different between vorapaxar and placebo (9.7% vs. 7.3%; HR: 1.36; 95% CI: 0.92 to 2.02; p = 0.12), with no excess in fatal bleeding (0% vs. 0.3%) or need for reoperation (4.7% vs. 4.6%). CONCLUSIONS: In non-ST-segment elevation acute coronary syndrome patients undergoing CABG, vorapaxar was associated with a significant reduction in ischemic events and no significant increase in major CABG-related bleeding. These data show promise for protease-activated receptor 1 antagonism in patients undergoing CABG and warrant confirmatory evidence in randomized trials. (Trial to Assess the Effects of SCH 530348 in Preventing Heart Attack and Stroke in Patients With Acute Coronary Syndrome [TRA·CER] [Study P04736AM3]; NCT00527943).
Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/mortalidade , Ponte de Artéria Coronária/métodos , Mortalidade Hospitalar , Lactonas/administração & dosagem , Piridinas/administração & dosagem , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/cirurgia , Idoso , Intervalos de Confiança , Ponte de Artéria Coronária/efeitos adversos , Eletrocardiografia/métodos , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Hemorragia Pós-Operatória/prevenção & controle , Modelos de Riscos Proporcionais , Estudos Prospectivos , Receptores de Trombina/antagonistas & inibidores , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença , Acidente Vascular Cerebral/prevenção & controle , Análise de Sobrevida , Resultado do TratamentoRESUMO
Cangrelor is an intravenous P2Y12 inhibitor under investigation as an antiplatelet drug in the setting of acute coronary syndromes. To determine the electrophysiologic safety of parenteral cangrelor, cardiac repolarization effects were measured in 67 healthy volunteers (aged 18-45 years) in a randomized crossover design, including 4 treatment sequences of therapeutic cangrelor, supratherapeutic cangrelor, placebo, and moxifloxacin (positive control). Triplicate electrocardiogram measurements and pharmacokinetic samples were collected at baseline and 9 time points postdose on day 1. For both cangrelor and moxifloxacin, time-matched, placebo-adjusted change in QT from baseline was evaluated using an individual (QTcI) heart rate correction. After cangrelor dosing, change in QTcI was <5 ms at all times points and all corresponding upper 2-sided 90% confidence intervals (CIs) were <10 ms. Although moxifloxacin failed to show a lower CI >5 ms, expected time trends and lower CI >4.0 ms demonstrate assay sensitivity. QTcI was not affected by plasma concentrations of cangrelor metabolites, and cangrelor had no other adverse effects on electrocardiographic parameters. Clinically, cangrelor exposure was well tolerated. Thus, this thorough QT study demonstrated that therapeutic and supratherapeutic cangrelor doses do not adversely affect cardiac repolarization in normal volunteers (clinicaltrials.gov; identifier NCT00699504).
Assuntos
Monofosfato de Adenosina/análogos & derivados , Compostos Aza/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Quinolinas/efeitos adversos , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/farmacocinética , Adolescente , Adulto , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Eletrocardiografia , Feminino , Fluoroquinolonas , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Moxifloxacina , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/farmacocinética , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/farmacocinética , Fatores de Tempo , Adulto JovemRESUMO
Saphenous vein graft (SVG) disease after coronary artery bypass grafting (CABG) occurs in three phases: thrombosis, intimal hyperplasia, and atherosclerosis. Within the first month, thrombosis plays a major role. From month 1 to month 12, intimal hyperplasia occurs. Beyond 12 months, atherosclerosis becomes the primary cause for late graft failure. Endothelial damage has been shown to be the major underlying pathophysiology of SVG disease. Many factors contribute to endothelial damage from the moment the vein is harvested to when the vein is grafted into an arterial environment. To address this disease process, various therapeutic modalities, from surgical methods to medical treatment, have been evaluated. Surgically, the technical method of harvesting the vein has been shown to affect SVG patency. From a pharmacologic perspective, only two guideline class I recommended medications, aspirin and statins, have been shown to improve short- and long-term SVG patency after CABG. Despite these surgical and medical advances, SVG disease remains a significant problem with 1-year patency rates of 89% dropping to 61% after 10 years. This review discusses the pathogenesis of SVG disease, predictors of SVG failure, and current surgical and pharmacologic therapies to address SVG disease, including possible future treatment.
Assuntos
Ponte de Artéria Coronária/efeitos adversos , Oclusão de Enxerto Vascular/etiologia , Veia Safena/transplante , Aterosclerose/etiologia , Humanos , Hiperplasia , Trombose/etiologia , Túnica Íntima/patologiaRESUMO
BACKGROUND: Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation. METHODS: In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization. RESULTS: Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (Kaplan-Meier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P=0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P=0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events were similar in the two groups. CONCLUSIONS: In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.).
Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Hemorragia/induzido quimicamente , Lactonas/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Piridinas/uso terapêutico , Receptor PAR-1/antagonistas & inibidores , Síndrome Coronariana Aguda/terapia , Idoso , Angioplastia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Terapia Combinada , Ponte de Artéria Coronária , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Hemorragias Intracranianas/induzido quimicamente , Estimativa de Kaplan-Meier , Lactonas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/efeitos adversos , Piridinas/efeitos adversosRESUMO
BACKGROUND: Heart failure is a common cause of death among Medicare beneficiaries, but little is known about health care resource use at the end of life. METHODS: In a retrospective cohort study of 229,543 Medicare beneficiaries with heart failure who died between January 1, 2000, and December 31, 2007, we examined resource use in the last 180 days of life, including all-cause hospitalizations, intensive care unit days, skilled nursing facility stays, home health, hospice, durable medical equipment, outpatient physician visits, and cardiac procedures. We calculated overall costs to Medicare and predictors of costs. RESULTS: Approximately 80% of patients were hospitalized in the last 6 months of life; days in intensive care increased from 3.5 to 4.6 (P<.001). Use of hospice increased from 19% to nearly 40% of patients (P<.001). Unadjusted mean costs to Medicare per patient rose 26% from $28,766 to $36,216 (P<.001). After adjustment for age, sex, race, comorbid conditions, and geographic region, costs increased by 11% (cost ratio, 1.11; 95% confidence interval, 1.10-1.13). Increasing age was strongly and independently associated with lower costs. Renal disease, chronic obstructive pulmonary disease, and black race were independent predictors of higher costs. CONCLUSIONS: Among Medicare beneficiaries with heart failure, health care resource use at the end of life increased over time with higher rates of intensive care and higher costs. However, the use of hospice services also increased markedly, representing a shift in patterns of care at the end of life.
Assuntos
Recursos em Saúde/estatística & dados numéricos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Cuidados Paliativos/estatística & dados numéricos , Assistência Terminal/estatística & dados numéricos , Idoso , Assistência Ambulatorial/economia , Assistência Ambulatorial/estatística & dados numéricos , Causas de Morte , Estudos de Coortes , Comorbidade , Cuidados Críticos/economia , Cuidados Críticos/estatística & dados numéricos , Custos de Cuidados de Saúde/estatística & dados numéricos , Recursos em Saúde/economia , Insuficiência Cardíaca/economia , Serviços de Assistência Domiciliar/estatística & dados numéricos , Hospitais para Doentes Terminais/economia , Hospitais para Doentes Terminais/estatística & dados numéricos , Humanos , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos , Masculino , Medicare/economia , Medicare/estatística & dados numéricos , Cuidados Paliativos/economia , Admissão do Paciente/economia , Admissão do Paciente/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Assistência Terminal/economia , Estados Unidos , Revisão da Utilização de Recursos de SaúdeRESUMO
BACKGROUND: Renal failure (RF) represents a major postoperative complication for elderly patients undergoing cardiac surgery. This observational cohort study examines effects of preoperative use of renin-angiotensin system (RAS) inhibitors on postoperative renal failure in aging patients undergoing cardiac surgery. METHODS AND RESULTS: We retrospectively analyzed a cohort of 1287 patients who underwent cardiac surgery at this institution (2003-2007). The patients included were ≥65 years old, scheduled for elective cardiac surgery, and without preexisting RF (defined by the criteria of the Society of Thoracic Surgeons as described in Method). Of all patients evaluated, 346 patients met the inclusion criteria and were divided into two groups: using (n = 122) or not using (n = 224) preoperative RAS inhibitors. A comparison of the two groups showed no significant differences in baseline parameters, including creatinine clearance, body mass index, history of diabetes and smoking, preoperative medicines (except that more patients with RAS inhibitors had a history of hypertension or congestive heart failure, fewer RAS inhibitor patients had chronic lung disease), in intraoperative perfusion and aortic cross-clamp time, and in postoperative complications and 30-d mortality. Multivariate logistic regression analysis demonstrated, however, that preoperative RAS inhibitors significantly and independently reduced the incidence of postoperative RF in the patients undergoing cardiac surgery compared with those not taking RAS inhibitors: 1.6% versus 7.6%, yielding an odds ratio of 0.19 (95 % CI 0.04-0.84, P = 0.029). CONCLUSIONS: Preoperative RAS inhibitors may have significant renoprotective effects for aging patients undergoing elective cardiac surgery.
Assuntos
Antagonistas Adrenérgicos/farmacologia , Envelhecimento/fisiologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Procedimentos Cirúrgicos Cardiovasculares , Rim/efeitos dos fármacos , Sistema Renina-Angiotensina/efeitos dos fármacos , Antagonistas Adrenérgicos/uso terapêutico , Idoso , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Feminino , Humanos , Incidência , Rim/fisiologia , Modelos Logísticos , Masculino , Complicações Pós-Operatórias , Cuidados Pré-Operatórios , Insuficiência Renal/epidemiologia , Insuficiência Renal/etiologia , Insuficiência Renal/prevenção & controle , Estudos Retrospectivos , Fatores de RiscoRESUMO
G protein-coupled receptor kinase 2 (GRK2), which is upregulated in the failing human myocardium, appears to have a role in heart failure (HF) pathogenesis. In peripheral lymphocytes, GRK2 expression has been shown to reflect myocardial levels. This study represents an attempt to define the role for GRK2 as a potential biomarker of left ventricular function in HF patients. We obtained blood from 24 HF patients before and after heart transplantation and followed them for up to 1 year, also recording hemodynamic data and histological results from endomyocardial biopsies. We determined blood GRK2 protein by Western blotting and enzyme-linked immunosorbent assay. GRK2 levels were obtained before transplant and at first posttransplant biopsy. GRK2 levels significantly declined after transplant and remained low over the course of the study period. After transplantation, we found that blood GRK2 significantly dropped and remained low consistent with improved cardiac function in the transplanted heart. Blood GRK2 has potential as a biomarker for myocardial function in end-stage HF.