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1.
Circulation ; 140(23): 1921-1932, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31557056

RESUMO

BACKGROUND: The safety and efficacy of antithrombotic regimens may differ between patients with atrial fibrillation who have acute coronary syndromes (ACS), treated medically or with percutaneous coronary intervention (PCI), and those undergoing elective PCI. METHODS: Using a 2×2 factorial design, we compared apixaban with vitamin K antagonists and aspirin with placebo in patients with atrial fibrillation who had ACS or were undergoing PCI and were receiving a P2Y12 inhibitor. We explored bleeding, death and hospitalization, as well as death and ischemic events, by antithrombotic strategy in 3 prespecified subgroups: patients with ACS treated medically, patients with ACS treated with PCI, and those undergoing elective PCI. RESULTS: Of 4614 patients enrolled, 1097 (23.9%) had ACS treated medically, 1714 (37.3%) had ACS treated with PCI, and 1784 (38.8%) had elective PCI. Apixaban compared with vitamin K antagonist reduced International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding in patients with ACS treated medically (hazard ratio [HR], 0.44 [95% CI, 0.28-0.68]), patients with ACS treated with PCI (HR, 0.68 [95% CI, 0.52-0.89]), and patients undergoing elective PCI (HR, 0.82 [95% CI, 0.64-1.04]; Pinteraction=0.052) and reduced death or hospitalization in the ACS treated medically (HR, 0.71 [95% CI, 0.54-0.92]), ACS treated with PCI (HR, 0.88 [95% CI, 0.74-1.06]), and elective PCI (HR, 0.87 [95% CI, 0.72-1.04]; Pinteraction=0.345) groups. Compared with vitamin K antagonists, apixaban resulted in a similar effect on death and ischemic events in the ACS treated medically, ACS treated with PCI, and elective PCI groups (Pinteraction=0.356). Aspirin had a higher rate of bleeding than did placebo in patients with ACS treated medically (HR, 1.49 [95% CI, 0.98-2.26]), those with ACS treated with PCI (HR, 2.02 [95% CI, 1.53-2.67]), and those undergoing elective PCI (HR, 1.91 [95% CI, 1.48-2.47]; Pinteraction=0.479). For the same comparison, there was no difference in outcomes among the 3 groups for the composite of death or hospitalization (Pinteraction=0.787) and death and ischemic events (Pinteraction=0.710). CONCLUSIONS: An antithrombotic regimen consisting of apixaban and a P2Y12 inhibitor without aspirin provides superior safety and similar efficacy in patients with atrial fibrillation who have ACS, whether managed medically or with PCI, and those undergoing elective PCI compared with regimens that include vitamin K antagonists, aspirin, or both. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02415400.

2.
N Engl J Med ; 380(16): 1509-1524, 2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-30883055

RESUMO

BACKGROUND: Appropriate antithrombotic regimens for patients with atrial fibrillation who have an acute coronary syndrome or have undergone percutaneous coronary intervention (PCI) are unclear. METHODS: In an international trial with a two-by-two factorial design, we randomly assigned patients with atrial fibrillation who had an acute coronary syndrome or had undergone PCI and were planning to take a P2Y12 inhibitor to receive apixaban or a vitamin K antagonist and to receive aspirin or matching placebo for 6 months. The primary outcome was major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and a composite of ischemic events. RESULTS: Enrollment included 4614 patients from 33 countries. There were no significant interactions between the two randomization factors on the primary or secondary outcomes. Major or clinically relevant nonmajor bleeding was noted in 10.5% of the patients receiving apixaban, as compared with 14.7% of those receiving a vitamin K antagonist (hazard ratio, 0.69; 95% confidence interval [CI], 0.58 to 0.81; P<0.001 for both noninferiority and superiority), and in 16.1% of the patients receiving aspirin, as compared with 9.0% of those receiving placebo (hazard ratio, 1.89; 95% CI, 1.59 to 2.24; P<0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the vitamin K antagonist group (23.5% vs. 27.4%; hazard ratio, 0.83; 95% CI, 0.74 to 0.93; P = 0.002) and a similar incidence of ischemic events. Patients in the aspirin group had an incidence of death or hospitalization and of ischemic events that was similar to that in the placebo group. CONCLUSIONS: In patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, an antithrombotic regimen that included apixaban, without aspirin, resulted in less bleeding and fewer hospitalizations without significant differences in the incidence of ischemic events than regimens that included a vitamin K antagonist, aspirin, or both. (Funded by Bristol-Myers Squibb and Pfizer; AUGUSTUS ClinicalTrials.gov number, NCT02415400.).


Assuntos
Síndrome Coronariana Aguda/complicações , Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Intervenção Coronária Percutânea , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Vitamina K/antagonistas & inibidores , Síndrome Coronariana Aguda/terapia , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Aspirina/efeitos adversos , Fibrilação Atrial/complicações , Método Duplo-Cego , Quimioterapia Combinada , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Pirazóis/efeitos adversos , Piridonas/efeitos adversos
3.
J Am Coll Cardiol ; 72(25): 3274-3284, 2018 12 25.
Artigo em Inglês | MEDLINE | ID: mdl-30573030

RESUMO

BACKGROUND: Diabetes confers an increased risk for atherosclerotic cardiovascular disease, but less is known about the independent risk diabetes confers on major cardiovascular and limb events in patients with symptomatic peripheral artery disease (PAD) on contemporary management. OBJECTIVES: The authors sought to assess the risk of cardiovascular and limb events in patients with PAD and diabetes as compared with those with PAD alone. METHODS: In the EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) trial, 13,885 patients with symptomatic PAD were evaluated with a primary endpoint of an adjudicated composite of major adverse cardiovascular events (MACE) (cardiovascular death, myocardial infarction, ischemic stroke) followed over a median of ∼30 months. The diabetes subgroup was analyzed compared with the subgroup without diabetes, and further examined for diabetes-specific factors such as glycosylated hemoglobin (HbA1c) that might affect risk for major cardiovascular and limb outcomes. RESULTS: A total of 5,345 patients (38.5%) had diabetes; the majority (n = 5,134 [96.1%]) had type 2 diabetes. The primary endpoint occurred in 15.9% of patients with PAD and diabetes as compared with 10.4% of those without diabetes (absolute risk difference 5.5%; adjusted hazard ratio: 1.56; 95% confidence interval [CI]: 1.41 to 1.72; p < 0.001). Every 1% increase in HbA1c was associated with a 14.2% increased relative risk for MACE (95% CI: 1.09 to 1.20; p < 0.0001). CONCLUSIONS: Patients with PAD and diabetes are at high risk for cardiovascular and limb ischemic events, even on contemporary therapies. Every 1% increase in HbA1c was associated with a 14.2% increased relative risk for MACE (95% CI: 1.09 to 1.20; p < 0.0001). (A Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease [EUCLID]; NCT01732822).


Assuntos
Diabetes Mellitus Tipo 2/mortalidade , Isquemia/mortalidade , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/mortalidade , Inibidores da Agregação de Plaquetas/uso terapêutico , Ticagrelor/uso terapêutico , Idoso , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Isquemia/diagnóstico , Isquemia/tratamento farmacológico , Extremidade Inferior/patologia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/tratamento farmacológico , Resultado do Tratamento
4.
Vasc Med ; 23(6): 523-530, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29992857

RESUMO

Patients with peripheral artery disease (PAD) are at heightened risk of cardiovascular morbidity and mortality. We sought to evaluate the risk of concomitant coronary artery disease (CAD) in patients with symptomatic PAD versus PAD without diagnosed CAD, and whether ticagrelor was superior to clopidogrel in reducing that risk. The EUCLID trial randomized 13,885 patients with PAD to antithrombotic monotherapy with ticagrelor or clopidogrel. CAD was defined as prior myocardial infarction (MI), percutaneous coronary intervention (PCI), or coronary artery bypass graft (CABG) surgery. Median follow-up was 30 months. Among 4032 (29%) patients with PAD and CAD, 63% had prior MI, 54% prior PCI, and 38% prior CABG. After adjustment for baseline characteristics, patients with PAD and CAD had significantly higher rates of the primary endpoint (cardiovascular death/MI/stroke, 15.3% vs 8.9%, hazard ratio (HR) 1.50, 95% CI: 1.13-1.99; p=0.005), but no statistically significant increase in acute limb ischemia (HR 1.28, 95% CI: 0.57-2.85; p=0.55) or major bleeding (HR 1.10, 95% CI: 0.49-2.48; p=0.81) versus PAD without CAD. Among patients with PAD and CAD, there was no differential treatment effect between ticagrelor versus clopidogrel for the primary efficacy endpoint (HR 1.02, 95% CI: 0.87-1.19; p=0.84), acute limb ischemia (HR 1.03, 95% CI: 0.63-1.69; p=0.89), or major bleeding (HR 1.06, 95% CI: 0.66-1.69; p=0.81). There was a statistically significant interaction between prior coronary stent placement and study treatment ( p=0.03) with a numerical reduction in the primary efficacy endpoint with ticagrelor versus clopidogrel (13.8% vs 16.8%, HR 0.82, 95% CI: 0.65-1.03; p=0.09). Patients with PAD and prior CAD had higher composite rates of cardiovascular death, MI, and ischemic stroke versus PAD without diagnosed CAD. There were no significant differences between ticagrelor and clopidogrel in cardiovascular events or major bleeding. ClinicalTrials.gov Identifier: NCT01732822.


Assuntos
Clopidogrel/uso terapêutico , Ponte de Artéria Coronária , Doença da Artéria Coronariana/terapia , Fibrinolíticos/uso terapêutico , Intervenção Coronária Percutânea , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Ticagrelor/uso terapêutico , Idoso , Clopidogrel/efeitos adversos , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/mortalidade , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Método Duplo-Cego , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/mortalidade , Doença Arterial Periférica/complicações , Doença Arterial Periférica/diagnóstico , Inibidores da Agregação de Plaquetas/efeitos adversos , Estudos Prospectivos , Fatores de Risco , Stents , Acidente Vascular Cerebral/etiologia , Ticagrelor/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
5.
N Engl J Med ; 376(1): 32-40, 2017 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-27959717

RESUMO

BACKGROUND: Peripheral artery disease is considered to be a manifestation of systemic atherosclerosis with associated adverse cardiovascular and limb events. Data from previous trials have suggested that patients receiving clopidogrel monotherapy had a lower risk of cardiovascular events than those receiving aspirin. We wanted to compare clopidogrel with ticagrelor, a potent antiplatelet agent, in patients with peripheral artery disease. METHODS: In this double-blind, event-driven trial, we randomly assigned 13,885 patients with symptomatic peripheral artery disease to receive monotherapy with ticagrelor (90 mg twice daily) or clopidogrel (75 mg once daily). Patients were eligible if they had an ankle-brachial index (ABI) of 0.80 or less or had undergone previous revascularization of the lower limbs. The primary efficacy end point was a composite of adjudicated cardiovascular death, myocardial infarction, or ischemic stroke. The primary safety end point was major bleeding. The median follow-up was 30 months. RESULTS: The median age of the patients was 66 years, and 72% were men; 43% were enrolled on the basis of the ABI and 57% on the basis of previous revascularization. The mean baseline ABI in all patients was 0.71, 76.6% of the patients had claudication, and 4.6% had critical limb ischemia. The primary efficacy end point occurred in 751 of 6930 patients (10.8%) receiving ticagrelor and in 740 of 6955 (10.6%) receiving clopidogrel (hazard ratio, 1.02; 95% confidence interval [CI], 0.92 to 1.13; P=0.65). In each group, acute limb ischemia occurred in 1.7% of the patients (hazard ratio, 1.03; 95% CI, 0.79 to 1.33; P=0.85) and major bleeding in 1.6% (hazard ratio, 1.10; 95% CI, 0.84 to 1.43; P=0.49). CONCLUSIONS: In patients with symptomatic peripheral artery disease, ticagrelor was not shown to be superior to clopidogrel for the reduction of cardiovascular events. Major bleeding occurred at similar rates among the patients in the two trial groups. (Funded by AstraZeneca; EUCLID ClinicalTrials.gov number, NCT01732822 .).


Assuntos
Adenosina/análogos & derivados , Doenças Cardiovasculares/prevenção & controle , Perna (Membro)/irrigação sanguínea , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Ticlopidina/análogos & derivados , Adenosina/efeitos adversos , Adenosina/uso terapêutico , Idoso , Doenças Cardiovasculares/mortalidade , Clopidogrel , Método Duplo-Cego , Feminino , Hemorragia/induzido quimicamente , Humanos , Claudicação Intermitente/tratamento farmacológico , Isquemia/tratamento farmacológico , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ticagrelor , Ticlopidina/efeitos adversos , Ticlopidina/uso terapêutico
6.
Circulation ; 135(3): 241-250, 2017 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-27840336

RESUMO

BACKGROUND: In patients with symptomatic peripheral artery disease with a history of limb revascularization, the optimal antithrombotic regimen for long-term management is unknown. METHODS: The EUCLID trial (Examining Use of Ticagrelor In PAD) randomized 13 885 patients with peripheral artery disease to treatment with ticagrelor 90 mg twice daily or clopidogrel 75 mg daily. Patients were enrolled based on an abnormal ankle-brachial index ≤0.80 or a previous lower extremity revascularization. This analysis focuses on the 7875 (57%) patients enrolled based on the previous lower extremity revascularization criterion. Patients could not be enrolled within 30 days of most recent revascularization, and patients with an indication for dual antiplatelet therapy were excluded. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. The primary safety end point was major bleeding. RESULTS: Patients with a previous revascularization had a mean age of 66 years, 73% were male, and the median baseline ankle-brachial index was 0.78. After adjustment for baseline characteristics, patients enrolled based on previous revascularization had similar rates of the primary composite end point (hazard ratio [HR] 1.10, 95% confidence interval [CI] 0.98-1.23, P=0.12) and statistically significantly higher rates of myocardial infarction (HR 1.29, 95% CI 1.08-1.55, P=0.005) and acute limb ischemia (HR 4.23, 95% CI 2.86-6.25, P<0.001) when compared with patients enrolled based on ankle-brachial index criteria. No differences in ticagrelor- versus clopidogrel-treated patients were found for the primary efficacy end point (11.4% vs 11.3%; HR 1.01, 95% CI 0.88-1.15; P=0.90), all-cause mortality (9.2% vs 9.2%; HR 0.99, 95% CI 0.86-1.15; P=0.93), acute limb ischemia (2.5% vs 2.5%; HR 1.03, 95% CI 0.78-1.36; P=0.84), or major bleeding (1.9% vs 1.8%; HR 1.15, 95% CI 0.83-1.59; P=0.41). The median duration of follow-up was ≈30 months. CONCLUSIONS: After adjustment for baseline characteristics, patients enrolled based on previous revascularization for peripheral artery disease had higher rates of myocardial infarction and acute limb ischemia, with similar composite rates of cardiovascular death, myocardial infarction, and stroke when compared with patients enrolled based on the ankle-brachial index criterion. No significant differences were found between ticagrelor and clopidogrel for reduction of cardiovascular or acute limb events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01732822.


Assuntos
Adenosina/análogos & derivados , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/tratamento farmacológico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ticlopidina/análogos & derivados , Adenosina/administração & dosagem , Adenosina/farmacologia , Adenosina/uso terapêutico , Idoso , Clopidogrel , Feminino , Humanos , Masculino , Doença Arterial Periférica/patologia , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/farmacologia , Ticagrelor , Ticlopidina/administração & dosagem , Ticlopidina/farmacologia , Ticlopidina/uso terapêutico , Resultado do Tratamento
7.
Am Heart J ; 175: 86-93, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27179727

RESUMO

BACKGROUND: Despite overwhelming data demonstrating the efficacy of antiplatelet therapy in heart disease and stroke, data in peripheral artery disease (PAD) are less compelling. Aspirin has modest evidence supporting a reduction in cardiovascular events in patients with PAD, whereas clopidogrel monotherapy may be more effective in PAD. Ticagrelor, a potent, reversibly binding P2Y12 receptor antagonist, is beneficial in patients with acute coronary syndrome and prior myocardial infarction. The EUCLID trial is designed to address the need for effective antiplatelet therapy in PAD to decrease the risk of cardiovascular events. STUDY DESIGN: EUCLID is a randomized, double-blind, parallel-group, multinational clinical trial designed to evaluate the efficacy and safety of ticagrelor compared with clopidogrel for the prevention of major adverse cardiovascular events in subjects with symptomatic PAD. Subjects with established PAD will be randomized in a 1:1 fashion to ticagrelor 90 mg twice daily or clopidogrel 75 mg daily. The primary end point is a composite of cardiovascular death, myocardial infarction, or ischemic stroke. Other end points address limb events including acute leg ischemia, need for revascularization, disease progression by ankle-brachial index, and quality of life. The primary safety objective is Thrombolysis in Myocardial Infarction-defined major bleeding. Recruitment began in December 2012 and was completed in March 2014; 13,887 patients were randomized. The trial will continue until at least 1,364 adjudicated primary end points occur. CONCLUSIONS: The EUCLID study is investigating whether treatment with ticagrelor versus clopidogrel, given as antiplatelet monotherapy, will reduce the incidence of cardiovascular and limb-specific events in patients with symptomatic PAD.


Assuntos
Adenosina/análogos & derivados , Doença Arterial Periférica , Acidente Vascular Cerebral , Ticlopidina/análogos & derivados , Adenosina/administração & dosagem , Adenosina/efeitos adversos , Idoso , Índice Tornozelo-Braço , Clopidogrel , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/prevenção & controle , Doença Arterial Periférica/complicações , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/efeitos adversos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Ticagrelor , Ticlopidina/administração & dosagem , Ticlopidina/efeitos adversos , Resultado do Tratamento
8.
Am J Cardiol ; 117(11): 1771-8, 2016 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-27108685

RESUMO

A growing number of countries and geographical regions are involved in major clinical trials. Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure is the largest trial in acutely decompensated heart failure (HF) with patients from 5 geographical regions: North America (NA), Latin America (LA), Western Europe (WE), Central Europe (CE), and Asia-Pacific (AP). Data from the 5 geographical areas were compared including baseline characteristics, medications, 30-day outcomes (mortality and mortality or HF hospitalization), and 180-day mortality. Of the 7,141 study patients, 3,243 (45.4%) were from NA (average of 15.2 patients/site), 1,762 (24.7%) from AP (28.4 patients/site), 967 (13.5%) from CE (20.2 patients/site), 665 (9.3%) from LA (17.1 patients/site), and 504 (7.1%) from WE (14.4 patients/site). There were marked differences in co-morbidities, clinical profile, medication use, length of stay, 30-day event rates, and 180-day mortality by region. Compared with NA, the adjusted risk for death or HF hospitalization at 30 days was significantly lower in CE (odds ratio [OR] 0.46, 95% CI 0.33 to 0.64), WE (OR 0.52 95% CI 0.35 to 0.75), and AP (OR 0.62 95% CI 0.48 to 0.79) and numerically lower in LA (OR 0.77, 95% CI 0.57 to 1.04) with similar results for 180-day mortality. In conclusion, in patients with acutely decompensated HF, major differences in baseline characteristics, treatments, length of the hospital stay, and 30-day HF rehospitalization rates, and 180-day mortality were found in patients enrolled from different geographical areas.


Assuntos
Insuficiência Cardíaca/epidemiologia , Hospitalização/tendências , Medição de Risco/métodos , Doença Aguda , Idoso , Causas de Morte/tendências , Feminino , Saúde Global , Insuficiência Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida/tendências
9.
Eur J Heart Fail ; 18(6): 684-92, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26817735

RESUMO

AIMS: It remains unclear if early administration of i.v. nesiritide in patients hospitalized with acute heart failure (AHF) is associated with improved clinical outcomes. METHODS AND RESULTS: We analysed data from 7007 patients enrolled in ASCEND-HF to examine the associations between time to treatment with study medication (nesiritide or placebo) and clinical endpoints: (i) moderate to marked dyspnoea relief on a 7-point Likert scale at 6 h; (ii) 30-day all-cause mortality or re-hospitalization; and (iii) 30-day all-cause mortality. The median time to study drug administration was 16.7 h (25th, 75th percentiles = 6.5, 23.1), with significant regional variation (e.g. median of 13.0 h in Asia-Pacific vs. 18.4 h in North America). After risk adjustment, each hour delay in study medication after the first 10 h from initial hospital presentation was associated with modestly reduced odds of dyspnoea relief [(adjusted odds ratio (OR) 0.98, 95% confidence interval (CI) 0.98-0.99; P < 0.0001]. Every hour delay in study medication was associated with modestly higher all-cause mortality or re-hospitalization (unadjusted OR 1.01, 95% CI 1.01-1.02; P < 0.001) due to pre-randomization therapies and known predictors of 30-day outcomes (adjusted P = 0.12). There was no significant association between time to study drug and all-cause mortality (P > 0.08). CONCLUSION: In a large international AHF trial, time to treatment with study medication varied markedly across regions. Earlier administration of study medication was associated with modestly better dyspnoea relief, but not 30-day clinical outcomes. The association between timing of treatment with study medication and study endpoints may have implications for the interpretation of AHF studies and future trial design.


Assuntos
Dispneia/fisiopatologia , Insuficiência Cardíaca/tratamento farmacológico , Natriuréticos/administração & dosagem , Peptídeo Natriurético Encefálico/administração & dosagem , Tempo para o Tratamento/estatística & dados numéricos , Doença Aguda , Idoso , Ásia , Causas de Morte , Dispneia/etiologia , Europa (Continente) , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/fisiopatologia , Hospitalização , Humanos , América Latina , Masculino , Pessoa de Meia-Idade , Mortalidade , Natriuréticos/uso terapêutico , Peptídeo Natriurético Encefálico/uso terapêutico , América do Norte , Razão de Chances , Readmissão do Paciente , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
10.
Am Heart J ; 170(2): 290-7, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26299226

RESUMO

BACKGROUND: Patients hospitalized for acute decompensated heart failure (ADHF) are at high risk for early mortality and rehospitalization. Risk stratification of ADHF using clinically available data on admission is increasingly important to integrate with clinical pathways. Our goal was to create a simple method of screening patients upon admission to identify those with increased risk of future adverse events. METHODS: Using ASCEND-HF, a pragmatic clinical trial conducted in 398 sites globally, we developed and validated logistic regression risk models for (a) 30-day mortality/HF rehospitalization, (b) 30-day mortality/all-cause rehospitalization, (c) 30-day all-cause mortality, and (d) 180-day all-cause mortality. Fifty-one candidate variables were evaluated based on prior publications and clinical review. Final models were selected based on stepwise selection with entry and a staying criterion of P < .01. The 30-day mortality model was externally validated, and coefficients were converted to an additive risk score. RESULTS: Among 7,141 patients, the median age was 67 years, 34% were female, and 80% had a left ventricular ejection fraction <40%. The models had between 5 and 12 risk factors with c-indices ranging from 0.68 to 0.75. A simplified score, including age, systolic blood pressure, sodium, blood urea nitrogen, and dyspnea at rest, discriminated 30-day mortality risk from 0.5% (score 0) to 53% (score 10). CONCLUSIONS: Commonly available clinical variables provide simple risk stratification for clinical outcomes among patients with ADHF, and these models may be considered for integration into routine clinical care.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Peptídeo Natriurético Encefálico/administração & dosagem , Medição de Risco/métodos , Função Ventricular Esquerda/fisiologia , Doença Aguda , Idoso , Causas de Morte/tendências , Método Duplo-Cego , Europa (Continente)/epidemiologia , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Injeções Intravenosas , América Latina/epidemiologia , Masculino , Pessoa de Meia-Idade , Natriuréticos/administração & dosagem , Readmissão do Paciente/tendências , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia , Função Ventricular Esquerda/efeitos dos fármacos
11.
Circ Heart Fail ; 7(6): 918-25, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25281655

RESUMO

BACKGROUND: Outcomes associated with episodes of hypotension while hospitalized with acute decompensated heart failure are not well understood. METHODS AND RESULTS: Using data from Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF), we assessed factors associated with in-hospital hypotension and subsequent 30-day outcomes. Patients were classified as having symptomatic or asymptomatic hypotension. Multivariable logistic regression was used to determine factors associated with in-hospital hypotension, and Cox proportional hazards models were used to assess the association between hypotension and 30-day outcomes. We also tested for treatment interaction with nesiritide on 30-day outcomes and the association between in-hospital hypotension and renal function at hospital discharge. Overall, 1555 of 7141 (21.8%) patients had an episode of hypotension, of which 73.1% were asymptomatic and 26.9% were symptomatic. Factors strongly associated with in-hospital hypotension included randomization to nesiritide (odds ratio, 1.98; 95% confidence interval [CI], 1.76-2.23; P<0.001), chronic metolazone therapy (odds ratio, 1.74; 95% CI, 1.17-2.60; P<0.001), and baseline orthopnea (odds ratio, 1.31; 95% CI, 1.13-1.52; P=0.001) or S3 gallop (odds ratio, 1.21; 95% CI, 1.06-1.40; P=0.006). In-hospital hypotension was associated with increased hazard of 30-day mortality (hazard ratio, 2.03; 95% CI, 1.57-2.61; P<0.001), 30-day heart failure hospitalization or mortality (hazard ratio, 1.58; 95% CI, 1.34-1.86; P<0.001), and 30-day all-cause hospitalization or mortality (hazard ratio, 1.40; 95% CI, 1.22-1.61; P<0.001). Nesiritide had no interaction on the relationship between hypotension and 30-day outcomes (interaction P=0.874 for death, P=0.908 for death/heart failure hospitalization, P=0.238 death/all-cause hospitalization). CONCLUSIONS: Hypotension while hospitalized for acute decompensated heart failure is an independent risk factor for adverse 30-day outcomes, and its occurrence highlights the need for modified treatment strategies. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00475852.


Assuntos
Insuficiência Cardíaca/mortalidade , Mortalidade Hospitalar , Hipotensão/complicações , Idoso , Feminino , Insuficiência Cardíaca/tratamento farmacológico , Hospitalização , Humanos , Hipotensão/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Natriuréticos/uso terapêutico , Peptídeo Natriurético Encefálico/uso terapêutico , Prognóstico , Modelos de Riscos Proporcionais
12.
Eur J Heart Fail ; 15(4): 456-64, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23159547

RESUMO

AIMS: To examine the characteristics associated with early dyspnoea relief during acute heart failure (HF) hospitalization, and its association with 30-day outcomes. METHODS AND RESULTS: ASCEND-HF was a randomized trial of nesiritide vs. placebo in 7141 patients hospitalized with acute HF in which dyspnoea relief at 6 h was measured on a 7-point Likert scale. Patients were classified as having early dyspnoea relief if they experienced moderate or marked dyspnoea improvement at 6 h. We analysed the clinical characteristics, geographical variation, and outcomes (mortality, mortality/HF hospitalization, and mortality/hospitalization at 30 days) associated with early dyspnoea relief. Early dyspnoea relief occurred in 2984 patients (43%). In multivariable analyses, predictors of dyspnoea relief included older age and oedema on chest radiograph; higher systolic blood pressure, respiratory rate, and natriuretic peptide level; and lower serum blood urea nitrogen (BUN), sodium, and haemoglobin (model mean C index = 0.590). Dyspnoea relief varied markedly across countries, with patients enrolled from Central Europe having the lowest risk-adjusted likelihood of improvement. Early dyspnoea relief was associated with lower risk-adjusted 30-day mortality/HF hospitalization [hazard ratio (HR) 0.81; 95% confidence interval (CI) 0.68-0.96] and mortality/hospitalization (HR 0.85; 95% CI 0.74-0.99), but similar mortality. CONCLUSION: Clinical characteristics such as respiratory rate, pulmonary oedema, renal function, and natriuretic peptide levels are associated with early dyspnoea relief, and moderate or marked improvement in dyspnoea was associated with a lower risk for 30-day outcomes.


Assuntos
Dispneia/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Natriuréticos/uso terapêutico , Peptídeo Natriurético Encefálico/uso terapêutico , Doença Aguda , Fatores Etários , Idoso , Pressão Sanguínea , Nitrogênio da Ureia Sanguínea , Dispneia/mortalidade , Dispneia/fisiopatologia , Edema , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos Natriuréticos/sangue , Taxa Respiratória , Medição de Risco , Resultado do Tratamento
13.
Eur J Heart Fail ; 14(11): 1257-64, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22764184

RESUMO

AIMS: We examined the prognostic importance of cardiac troponin I (cTnI) in a cohort of patients enrolled in the ASCEND-HF study of nesiritide in acute decompensated heart failure (ADHF). Circulating troponins are a prognostic marker in patients with ADHF. Contemporary assays with greater sensitivity require reassessment of the significance of troponin elevation in HF. METHODS AND RESULTS: Cardiac troponin I was measured in a core laboratory in 808 ADHF patients enrolled in the ASCEND-HF biomarkers substudy using a sensitive assay (VITROS Trop I ES, Ortho Clinical Diagnostics) with a lower limit of detection of 0.012 ng/mL and a 99th percentile upper reference limit (URL) of 0.034 ng/mL. Patients with clinical evidence of acute coronary syndrome or troponin >5× the URL were excluded. Multivariable modelling was used to assess the relationship between log(cTnI) and in-hospital and post-discharge outcomes. Baseline cTnI was undetectable in 22% and elevated above the 99th percentile URL in 50% of subjects. cTnI levels did not differ based on HF aetiology. After multivariable adjustment, higher cTnI was associated with worsened in-hospital outcomes such as length of stay (P = 0.01) and worsening HF during the index hospitalization (P = 0.01), but was not associated with worsened post-discharge outcomes at 30 or 180 days. The relationship between cTnI and outcomes was generally linear and there was no evidence of a threshold effect at any particular level of cTnI. CONCLUSION: cTnI is elevated above the 99th percentile URL in 50% of ADHF patients and predicts in-hospital outcome, but is not an independent predictor of long-term outcomes.


Assuntos
Cardiopatias/sangue , Natriuréticos/sangue , Peptídeo Natriurético Encefálico/sangue , Troponina I/sangue , Idoso , Intervalos de Confiança , Feminino , Cardiopatias/mortalidade , Cardiopatias/patologia , Humanos , Masculino , Modelos Estatísticos , Análise Multivariada , Razão de Chances , Prognóstico , Estatística como Assunto
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