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- O'Connor, C. M., et al.
(author)
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Effect of nesiritide in patients with acute decompensated heart failure
- 2011
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In: The New England journal of medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 365:1, s. 32-43
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Journal article (peer-reviewed)abstract
- BACKGROUND: Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. METHODS: We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. RESULTS: Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but the prespecified level for significance (P
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| 2. |
- Metra, M., et al.
(author)
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Geographic Differences in Patients in a Global Acute Heart Failure Clinical Trial (from the ASCEND-HF Trial)
- 2016
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In: American Journal of Cardiology. - : Elsevier BV. - 0002-9149. ; 117:11, s. 1771-1778
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Journal article (peer-reviewed)abstract
- 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. (C) 2016 Elsevier Inc. All rights reserved.
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| 3. |
- Eapen, Z. J., et al.
(author)
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Do Countries or Hospitals With Longer Hospital Stays for Acute Heart Failure Have Lower Readmission Rates?: Findings From ASCEND-HF
- 2013
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In: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 6:4, s. 727-32
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Journal article (peer-reviewed)abstract
- Background- Hospital readmission is an important clinical outcome of patients with heart failure. Its relation to length of stay for the initial hospitalization is not clear. Methods and Results- We used hierarchical modeling of data from a clinical trial to examine variations in length of stay across countries and across hospitals in the United States and its association with readmission within 30 days of randomization. Main outcomes included associations between country-level length of stay and readmission rates, after adjustment for patient-level case mix; and associations between length of stay and readmission rates across sites in the United States. Across 27 countries with 389 sites and 6848 patients, mean length of stay ranged from 4.9 to 14.6 days (6.1 days in the United States). Rates of all-cause readmission ranged from 2.5% to 25.0% (17.8% in the United States). There was an inverse correlation between country-level mean length of stay and readmission (r=-0.52; P<0.01). After multivariable adjustment, each additional inpatient day across countries was associated with significantly lower risk of all-cause readmission (odds ratio, 0.86; 95% confidence interval, 0.75-0.98; P=0.02) and heart failure readmission (odds ratio, 0.79; 95% confidence interval, 0.69-0.99; P=0.03). Similar trends were observed across US study sites concerning readmission for any cause (odds ratio, 0.92; 95% confidence interval, 0.85-1.00; P=0.06) and readmission for heart failure (odds ratio, 0.90; 95% confidence interval, 0.80-1.01; P=0.07). Across countries and across US sites, longer median length of stay was independently associated with lower risk of readmission. Conclusions- Countries with longer length of stay for heart failure hospitalizations had significantly lower rates of readmission within 30 days of randomization. These findings may have implications for developing strategies to prevent readmission, defining quality measures, and designing clinical trials in acute heart failure. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00475852.
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| 4. |
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| 5. |
- Toma, M., et al.
(author)
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The relationship between left ventricular ejection fraction and mortality in patients with acute heart failure: insights from the ASCEND-HF Trial
- 2014
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In: European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 16:3, s. 334-41
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Journal article (peer-reviewed)abstract
- AIM: Acute decompensated heart failure (ADHF) is associated with significant morbidity and mortality but the relationship between LVEF and outcomes is unclear. We explored the association between LVEF and 30 and 180 day mortality in 7007 ADHF patients enrolled in the Acute Studies of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial. METHODS AND RESULTS: We explored the association between LVEF and 30 and 180 day mortality in 7007 ADHF patients enrolled in the Acute Studies of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial. LVEF was analysed both as a continuous variable and according to three categories: < 40% (LowEF), 40-50% [intermediate EF (IntEF)], and > 50% [preserved ejection fraction (PresEF)]. Of the patients in the trial, 4474 (78.7%) had LowEF, 674 (11.9%) had IntEF, and 539 (9.5%) had PresEF. The unadjusted 30 and 180 day mortality was similar for LowEF (3.7%, 12.3%), IntEF (3.4%, 13.1%), and PresEF (4.3%, 14.1%), respectively (P > 0.05). After multivariable adjustment, the hazard ratio (HR) for 180 day mortality remained similar for the LowEF [HR 0.96, 95% confidence interval (CI) 0.75-1.24; P = 0.77] and IntEF (0.91, 95% CI 0.66-1.3; P = 0.58) compared to PresEF patients. By contrast, when LVEF was evaluated as a continuous measure, it exhibited a U-shaped pattern with mortality. After matching for age and sex, the mortality risk attributed to LVEF was attenuated, as the LVEF increased as a continuous variable over 35%. However, in patients with EF < 35%, the mortality risk continue to increase as the LVEF declined. CONCLUSIONS: Among patients with ADHF, the unadjusted mortality rates are similar across LVEF strata. However, after accounting for key patient variables, the mortality risk increases as EF falls below 35%. These data will be useful in planning future studies of ADHF. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier: NCT00475852.
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| 6. |
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| 7. |
- Douketis, J D, et al.
(author)
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Perioperative bridging anticoagulation during dabigatran or warfarin interruption among patients who had an elective surgery or procedure : Substudy of the RE-LY trial
- 2015
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In: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 113:3, s. 625-632
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Journal article (peer-reviewed)abstract
- In patients with atrial fibrillation (AF) who require interruption of dabigatran or warfarin for an elective surgery/procedure, the risks and benefits of perioperative bridging anticoagulation is uncertain. We accessed the database from RE-LY, a randomised trial comparing dabigatran with warfarin for stroke prevention in AF, to assess the potential benefits and risks of bridging. In patients who had a first interruption of dabigatran or warfarin for an elective surgery/procedure, we compared the risk for major bleeding (MB), stroke or systemic embolism (SSE) and any thromboembolism (TE) in patients who were bridged or not bridged during the period of seven days before until 30 days after surgery/procedure. We used multivariable Cox regression to adjust for potential confounders. Bridging was used more during warfarin interruption than dabigatran interruption (27.5 % vs 15.4 %; p< 0.001). With dabigatran interruption, bridged patients had more MB (6.5 % vs. 1.8 %, P< 0.001) than those not bridged but bridged and not bridged groups did not differ for any TE (1.2 % vs 0.6 %, p=0.16) and SSE (0.5 % vs 0.3 %, p=0.46). With warfarin interruption, bridged patients had more MB (6.8 % vs 1.6 %, p< 0.001) and any TE (1.8 % vs 0.3 %, p=0.007) than those not bridged but bridged and not bridged groups did not differ for SSE (0.5 % vs 0.2 %, p=0.321). In conclusion, in patients who interrupted dabigatran or warfarin for a surgery/procedure in the RE-LY trial, use of bridging anticoagulation appeared to increase the risk for major bleeding irrespective of dabigatran or warfarin interruption.
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| 8. |
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| 9. |
- Hohnloser, Stefan H., et al.
(author)
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Efficacy and Safety of Apixaban Versus Warfarin in Patients With Atrial Fibrillation and Extremes in Body Weight : Insights From the ARISTOTLE Trial
- 2019
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In: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 139:20, s. 2292-2300
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Journal article (peer-reviewed)abstract
- BACKGROUND: Guidelines caution against the use of non-vitamin K antagonist oral anticoagulants in patients with extremely high (> 120 kg) or low (= 60 kg) body weight because of a lack of data in these populations.METHODS: In a post hoc analysis of ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation; n= 18 201), a randomized trial comparing apixaban with warfarin for the prevention of stroke in patients with atrial fibrillation, we estimated the randomized treatment effect (apixaban versus warfarin) stratified by body weight (= 60, > 60-120, > 120 kg) using a Cox regression model and tested the interaction between body weight and randomized treatment. The primary efficacy and safety outcomes were stroke or systemic embolism and major bleeding.RESULTS: Of the 18 139 patients with available weight and outcomes data, 1985 (10.9%) were in the low-weight group (= 60 kg), 15 172 (83.6%) were in the midrange weight group (> 60-120 kg), and 982 (5.4%) were in the high-weight group (> 120 kg). The treatment effect of apixaban versus warfarin for the efficacy outcomes of stroke/systemic embolism, all-cause death, or myocardial infarction was consistent across the weight spectrum (interaction P value> 0.05). For major bleeding, apixaban had a better safety profile than warfarin in all weight categories and even showed a greater relative risk reduction in patients in the low (= 60 kg; HR, 0.55; 95% CI, 0.36-0.82) and midrange (> 60-120 kg) weight groups (HR, 0.71; 95% CI, 0.61-0.83; interaction P value= 0.016).CONCLUSIONS: Our findings provide evidence that apixaban is efficacious and safe across the spectrum of weight, including in low-(= 60 kg) and highweight patients (> 120 kg). The superiority on efficacy and safety outcomes of apixaban compared with warfarin persists across weight groups, with even greater reductions in major bleeding in patients with atrial fibrillation with low to normal weight as compared with high weight. The superiority of apixaban over warfarin in regard to efficacy and safety for stroke prevention seems to be similar in patients with atrial fibrillation across the spectrum of weight, including in low-and very high-weight patients. Thus, apixaban appears to be appropriate for patients with atrial fibrillation irrespective of body weight.
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| 10. |
- Lopes, Renato D., et al.
(author)
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Efficacy and safety of apixaban compared with warfarin according to patient risk of stroke and of bleeding in atrial fibrillation : a secondary analysis of a randomised controlled trial
- 2012
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In: The Lancet. - 0140-6736 .- 1474-547X. ; 380:9855, s. 1749-1758
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Journal article (peer-reviewed)abstract
- Background The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial showed that apixaban is better than warfarin at prevention of stroke or systemic embolism, causes less bleeding, and results in lower mortality. We assessed in this trial's participants how results differed according to patients' CHADS(2), CHA(2)DS(2)VASc, and HAS-BLED scores, used to predict the risk of stroke and bleeding. Methods ARISTOTLE was a double-blind, randomised trial that enrolled 18 201 patients with atrial fibrillation in 39 countries. Patients were randomly assigned apixaban 5 mg twice daily (n=9120) or warfarin (target international normalised ratio 2.0-3.0; n=9081). The primary endpoint was stroke or systemic embolism. The primary safety outcome was major bleeding. We calculated CHADS(2), CHA(2)DS(2)VASc, and HAS-BLED scores of patients at randomisation. Efficacy analyses were by intention to treat, and safety analyses were of the population who received the study drug. ARISTOTLE is registered with ClinicalTrials.gov, number NCT00412984. Findings Apixaban significantly reduced stroke or systemic embolism with no evidence of a differential effect by risk of stroke (CHADS(2) 1, 2, or >= 3, p for interaction=0.4457; or CHA(2)DS(2)VASc 1, 2, or >= 3, p for interaction=0.1210) or bleeding (HAS-BLED 0-1, 2, or >= 3, p for interaction=0.9422). Patients who received apixaban had lower rates of major bleeding than did those who received warfarin, with no difference across all score categories (CHADS(2), p for interaction=0.4018; CHA(2)DS(2)VASc, p for interaction=0.2059; HAS-BLED, p for interaction=0.7127). The relative risk reduction in intracranial bleeding tended to be greater in patients with HAS-BLED scores of 3 or higher (hazard ratio [HR] 0.22, 95% CI 0.10-0.48) than in those with HAS-BLED scores of 0-1 (HR 0.66, 0.39-1.12; p for interaction=0.0604). Interpretation Because apixaban has benefits over warfarin that are consistent across patient risk of stroke and bleeding as assessed by the CHADS(2), CHA(2)DS(2)VASc, and HAS-BLED scores, these scores might be less relevant when used to tailor apixaban treatment to individual patients than they are for warfarin. Further improvement in risk stratification for both stroke and bleeding is needed, particularly for patients with atrial fibrillation at low risk for these events.
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