| 1. |
- O'Connor, C. M., et al.
(author)
-
Effect of nesiritide in patients with acute decompensated heart failure
- 2011
-
In: The New England journal of medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 365:1, s. 32-43
-
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
|
|
| 2. |
- Eapen, Z. J., et al.
(author)
-
Do Countries or Hospitals With Longer Hospital Stays for Acute Heart Failure Have Lower Readmission Rates?: Findings From ASCEND-HF
- 2013
-
In: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 6:4, s. 727-32
-
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.
|
|
| 3. |
- Metra, M., et al.
(author)
-
Geographic Differences in Patients in a Global Acute Heart Failure Clinical Trial (from the ASCEND-HF Trial)
- 2016
-
In: American Journal of Cardiology. - : Elsevier BV. - 0002-9149. ; 117:11, s. 1771-1778
-
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.
|
|
| 4. |
|
|
| 5. |
- Douketis, J D, et al.
(author)
-
Perioperative bridging anticoagulation during dabigatran or warfarin interruption among patients who had an elective surgery or procedure : Substudy of the RE-LY trial
- 2015
-
In: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 113:3, s. 625-632
-
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.
|
|
| 6. |
|
|
| 7. |
- Connolly, Stuart J., et al.
(author)
-
The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study
- 2013
-
In: Circulation. - 0009-7322 .- 1524-4539. ; 128:3, s. 237-243
-
Journal article (peer-reviewed)abstract
- Background During follow-up of between 1 and 3 years in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, 2 doses of dabigatran etexilate were shown to be effective and safe for the prevention of stroke or systemic embolism in patients with atrial fibrillation. There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses. Methods and Results Patients randomly assigned to dabigatran in RE-LY were eligible for the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial if they had not permanently discontinued study medication at the time of their final RE-LY study visit. Enrolled patients continued to receive the double-blind dabigatran dose received in RE-LY, for up to 28 months of follow up after RE-LY (median follow-up, 2.3 years). There were 5851 patients enrolled, representing 48% of patients originally randomly assigned to receive dabigatran in RE-LY and 86% of RELY-ABLE-eligible patients. Rates of stroke or systemic embolism were 1.46% and 1.60%/y on dabigatran 150 and 110 mg twice daily, respectively (hazard ratio, 0.91; 95% confidence interval, 0.69-1.20). Rates of major hemorrhage were 3.74% and 2.99%/y on dabigatran 150 and 110 mg (hazard ratio, 1.26; 95% confidence interval, 1.04-1.53). Rates of death were 3.02% and 3.10%/y (hazard ratio, 0.97; 95% confidence interval, 0.80-1.19). Rates of hemorrhagic stroke were 0.13% and 0.14%/y. Conclusions During 2.3 years of continued treatment with dabigatran after RE-LY, there was a higher rate of major bleeding with dabigatran 150 mg twice daily in comparison with 110 mg, and similar rates of stroke and death.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
- Granger, Christopher B., et al.
(author)
-
Apixaban versus Warfarin in Patients with Atrial Fibrillation
- 2011
-
In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 365:11, s. 981-992
-
Journal article (peer-reviewed)abstract
- Background Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin. Methods In this randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic embolism. The trial was designed to test for noninferiority, with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause. Results The median duration of follow-up was 1.8 years. The rate of the primary outcome was 1.27% per year in the apixaban group, as compared with 1.60% per year in the warfarin group (hazard ratio with apixaban, 0.79; 95% confidence interval [CI], 0.66 to 0.95; P<0.001 for noninferiority; P=0.01 for superiority). The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P<0.001), and the rates of death from any cause were 3.52% and 3.94%, respectively (hazard ratio, 0.89; 95% CI, 0.80 to 0.99; P=0.047). The rate of hemorrhagic stroke was 0.24% per year in the apixaban group, as compared with 0.47% per year in the warfarin group (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P<0.001), and the rate of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group and 1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to 1.13; P=0.42). Conclusions In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality.
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Lopes, Renato D., et al.
(author)
-
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
-
In: The Lancet. - 0140-6736 .- 1474-547X. ; 380:9855, s. 1749-1758
-
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.
|
|
| 15. |
- Westenbrink, B. D., et al.
(author)
-
Anemia predicts thromboembolic events, bleeding complications and mortality in patients with atrial fibrillation : insights from the RE-LY trial
- 2015
-
In: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 13:5, s. 699-707
-
Journal article (peer-reviewed)abstract
- BackgroundAnemia may predispose to thromboembolic events or bleeding in anticoagulated patients with atrial fibrillation (AF). ObjectivesTo investigate whether anemia is associated with thromboembolic events and bleeding in patients with AF. Patients and methodsWe retrospectively analyzed the RE-LY trial database, which randomized 18113 patients with AF and a risk of stroke to receive dabigatran or warfarin for a median follow-up of 2years. Cox regression analysis was used to determine whether anemia predicted cardiovascular events and bleeding complications in these patients. ResultsAnemia was present in 12% of the population at baseline, and the presence of anemia was associated with a higher risk of thromboembolic cardiovascular events, including the composite endpoint of all-cause mortality or myocardial infarction (adjusted hazard ratio [HR]1.50, 95% confidence interval [CI]1.32-1.71) and the primary RE-LY outcome of stroke or systemic embolism (adjusted HR1.41, 95%CI1.12-1.78). Anemia was also associated with a higher risk of major bleeding complications (adjusted HR2.14, 95%CI1.87-2.46) and discontinuation of anticoagulants (adjusted HR1.40, 95%CI1.28-1.79). The association between anemia and outcome was similar irrespective of cardiovascular comorbidities, randomized treatment allocation, or prior use of warfarin. The incidence of events was lower in patients with transient anemia than in patients in whom anemia was sustained (adjusted HR0.66, 95%CI0.49-0.91). ConclusionsAnemia is associated with an increased risk of thromboembolic events, bleeding complications and mortality in anticoagulated patients with AF. These findings suggest that patients with anemia should be monitored closely during all types of anticoagulant treatment.
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
- Armstrong, Paul W, et al.
(author)
-
Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction.
- 2020
-
In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 382:20, s. 1883-1893
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The effect of vericiguat, a novel oral soluble guanylate cyclase stimulator, in patients with heart failure and reduced ejection fraction who had recently been hospitalized or had received intravenous diuretic therapy is unclear.METHODS: In this phase 3, randomized, double-blind, placebo-controlled trial, we assigned 5050 patients with chronic heart failure (New York Heart Association class II, III, or IV) and an ejection fraction of less than 45% to receive vericiguat (target dose, 10 mg once daily) or placebo, in addition to guideline-based medical therapy. The primary outcome was a composite of death from cardiovascular causes or first hospitalization for heart failure.RESULTS: Over a median of 10.8 months, a primary-outcome event occurred in 897 of 2526 patients (35.5%) in the vericiguat group and in 972 of 2524 patients (38.5%) in the placebo group (hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P = 0.02). A total of 691 patients (27.4%) in the vericiguat group and 747 patients (29.6%) in the placebo group were hospitalized for heart failure (hazard ratio, 0.90; 95% CI, 0.81 to 1.00). Death from cardiovascular causes occurred in 414 patients (16.4%) in the vericiguat group and in 441 patients (17.5%) in the placebo group (hazard ratio, 0.93; 95% CI, 0.81 to 1.06). The composite of death from any cause or hospitalization for heart failure occurred in 957 patients (37.9%) in the vericiguat group and in 1032 patients (40.9%) in the placebo group (hazard ratio, 0.90; 95% CI, 0.83 to 0.98; P = 0.02). Symptomatic hypotension occurred in 9.1% of the patients in the vericiguat group and in 7.9% of the patients in the placebo group (P = 0.12), and syncope occurred in 4.0% of the patients in the vericiguat group and in 3.5% of the patients in the placebo group (P = 0.30).CONCLUSIONS: Among patients with high-risk heart failure, the incidence of death from cardiovascular causes or hospitalization for heart failure was lower among those who received vericiguat than among those who received placebo. (Funded by Merck Sharp & Dohme [a subsidiary of Merck] and Bayer; VICTORIA ClinicalTrials.gov number, NCT02861534.).
|
|
| 19. |
- Aulin, Julia, et al.
(author)
-
Serial measurement of interleukin-6 and risk of mortality in anticoagulated patients with atrial fibrillation : Insights from ARISTOTLE and RE-LY trials.
- 2020
-
In: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 18:9, s. 2287-2295
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The inflammatory biomarker interleukin-6 (IL-6) is associated with mortality in atrial fibrillation (AF).OBJECTIVE: To investigate if repeated IL-6 measurements improve the prognostication for stroke or systemic embolism, major bleeding, and mortality in anticoagulated patients with AF.METHODS: IL-6 levels by ELISA were measured at study entry and at 2 months in 4830 patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial with 1.8 years median follow-up. In the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial, IL-6 was measured at study entry, 3, 6, and 12 months in 2559 patients with 2.0 years median follow-up. Associations between a second IL-6 measurement and outcomes, adjusted for baseline IL-6, clinical variables, and other cardiovascular biomarkers, were analyzed by Cox regression.RESULTS: Median IL-6 levels were 2.0 ng/L (interquartile range [IQR] 1.30-3.20) and 2.10 ng/L (IQR 1.40-3.40) at the two time-points in ARISTOTLE, and, in RE-LY, 2.5 ng/L (IQR 1.6-4.3), 2.5 ng/L (IQR 1.6-4.2), 2.4 ng/L (IQR 1.6, 3.9), and 2.4 ng/L (IQR 1.5, 3.9), respectively. IL-6 was associated with mortality; hazard ratios per 50% higher IL-6 at 2 or 3 months, respectively, were 1.32 (95% confidence interval, 1.23-1.41; P < .0001) in ARISTOTLE, and 1.11 (1.01-1.22, P = .0290) in RE-LY; with improved C index from 0.74 to 0.76 in ARISTOTLE, but not in the smaller RE-LY cohort. There were no consistent associations with second IL-6 and stroke or systemic embolism, or major bleeding.CONCLUSIONS: Persistent systemic inflammatory activity, assessed by repeated IL-6 measurements, is associated with mortality independent of established clinical risk factors and other strong cardiovascular biomarkers in anticoagulated patients with AF.
|
|
| 20. |
- Das, D., et al.
(author)
-
Ivabradine in Heart Failure: The Representativeness of SHIFT (Systolic Heart Failure Treatment With the IF Inhibitor Ivabradine Trial) in a Broad Population of Patients With Chronic Heart Failure
- 2017
-
In: Circulation Heart Failure. - : LIPPINCOTT WILLIAMS & WILKINS. - 1941-3289 .- 1941-3297. ; 10:9
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The sinus node inhibitor ivabradine was approved for patients with heart failure (HF) after the ivabradine and outcomes in chronic HF (SHIFT [Systolic Heart Failure Treatment With the IF Inhibitor Ivabradine Trial]) trial. Our objective was to characterize the proportion of patients with HF eligible for ivabradine and the representativeness of the SHIFT trial enrollees compared with those in the Swedish Heart Failure Registry. METHODS AND RESULTS: We examined 26 404 patients with clinical HF from the Swedish Heart Failure Registry and divided them into SHIFT type (left ventricular ejection fraction <40%, New York Heart Association class II-IV, sinus rhythm, and heart rate >/=70 beats per minute) and non-SHIFT type. Baseline characteristics and medication use were compared and change in eligibility over time was reported at 6 months and 1 year in a subset of patients. Overall, 14.2% (n=3741) of patients were SHIFT type. These patients were more likely to be younger, men, have diabetes mellitus, ischemic heart disease, lower left ventricular ejection fraction, and more recent onset HF (<6 months; all, P<0.001). Although 88.9% of SHIFT type and 88.5% of non-SHIFT type (P=0.421) were receiving selected beta-blockers, only 58.8% and 67.3% (P<0.001) were on >50% of target dose. From those patients who had repeated visits within 6 months (n=5420) and 1 year (n=6840), respectively, 10.2% (n=555) and 10.6% (n=724) of SHIFT-type patients became ineligible, 77.3% (n=4188) and 77.3% (n=5287) remained ineligible, and 4.6% (n=252) and 4.9% (n=335) of non-SHIFT-type patients became eligible for initiation of ivabradine. CONCLUSIONS: From the Swedish Heart Failure Registry, 14.2% of patients with HF were eligible for ivabradine. These patients more commonly were not receiving target beta-blocker dose. Over time, a minority of patients became ineligible and an even smaller minority became eligible.
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
