| 1. |
- O'Connor, C. M., et al.
(författare)
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Effect of nesiritide in patients with acute decompensated heart failure
- 2011
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Ingår i: The New England journal of medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 365:1, s. 32-43
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Tidskriftsartikel (refereegranskat)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. |
- Packer, M., et al.
(författare)
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Angiotensin Receptor Neprilysin Inhibition Compared With Enalapril on the Risk of Clinical Progression in Surviving Patients With Heart Failure
- 2015
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Ingår i: Circulation. - 0009-7322. ; 131, s. 54-61
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: -Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients. METHODS AND RESULTS: -We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angiotensinconverting enzyme inhibitor enalapril (20 mg daily) in 8399 patients with heart failure and reduced ejection fraction in a double-blind trial. The analyses focused on prespecified measures of nonfatal clinical deterioration. In comparison with the enalapril group, fewer LCZ696-treated patients required intensification of medical treatment for heart failure (520 versus 604; hazard ratio, 0.84; 95% confidence interval, 0.74-0.94; P=0.003) or an emergency department visit for worsening heart failure (hazard ratio, 0.66; 95% confidence interval, 0.52-0.85; P=0.001). The patients in the LCZ696 group had 23% fewer hospitalizations for worsening heart failure (851 versus 1079; P<0.001) and were less likely to require intensive care (768 versus 879; 18% rate reduction, P=0.005), to receive intravenous positive inotropic agents (31% risk reduction, P<0.001), and to have implantation of a heart failure device or cardiac transplantation (22% risk reduction, P=0.07). The reduction in heart failure hospitalization with LCZ696 was evident within the first 30 days after randomization. Worsening of symptom scores in surviving patients was consistently more common in the enalapril group. LCZ696 led to an early and sustained reduction in biomarkers of myocardial wall stress and injury (N-terminal pro-Btype natriuretic peptide and troponin) versus enalapril. CONCLUSIONS: -Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotensin-converting enzyme inhibition. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255.
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| 3. |
- Metra, M., et al.
(författare)
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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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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149. ; 117:11, s. 1771-1778
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Voors, A. A., et al.
(författare)
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The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial
- 2022
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 28, s. 568-574
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Tidskriftsartikel (refereegranskat)abstract
- The sodium–glucose cotransporter 2 inhibitor empagliflozin reduces the risk of cardiovascular death or heart failure hospitalization in patients with chronic heart failure, but whether empagliflozin also improves clinical outcomes when initiated in patients who are hospitalized for acute heart failure is unknown. In this double-blind trial (EMPULSE; NCT04157751), 530 patients with a primary diagnosis of acute de novo or decompensated chronic heart failure regardless of left ventricular ejection fraction were randomly assigned to receive empagliflozin 10 mg once daily or placebo. Patients were randomized in-hospital when clinically stable (median time from hospital admission to randomization, 3 days) and were treated for up to 90 days. The primary outcome of the trial was clinical benefit, defined as a hierarchical composite of death from any cause, number of heart failure events and time to first heart failure event, or a 5 point or greater difference in change from baseline in the Kansas City Cardiomyopathy Questionnaire Total Symptom Score at 90 days, as assessed using a win ratio. More patients treated with empagliflozin had clinical benefit compared with placebo (stratified win ratio, 1.36; 95% confidence interval, 1.09–1.68; P = 0.0054), meeting the primary endpoint. Clinical benefit was observed for both acute de novo and decompensated chronic heart failure and was observed regardless of ejection fraction or the presence or absence of diabetes. Empagliflozin was well tolerated; serious adverse events were reported in 32.3% and 43.6% of the empagliflozin- and placebo-treated patients, respectively. These findings indicate that initiation of empagliflozin in patients hospitalized for acute heart failure is well tolerated and results in significant clinical benefit in the 90 days after starting treatment. © 2022, The Author(s).
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| 5. |
- Eapen, Z. J., et al.
(författare)
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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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Ingår i: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 6:4, s. 727-32
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Tidskriftsartikel (refereegranskat)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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| 6. |
- McMurray, J., et al.
(författare)
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A putative placebo analysis of the effects of LCZ696 on clinical outcomes in heart failure
- 2015
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 36:7, s. 434-439
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Although active-controlled trials with renin-angiotensin inhibitors are ethically mandated in heart failure with reduced ejection fraction, clinicians and regulators often want to know how the experimental therapy would perform compared with placebo. The angiotensin receptor-neprilysin inhibitor LCZ696 was compared with enalapril in PARADIGM-HF. We made indirect comparisons of the effects of LCZ696 with putative placebos. METHODS AND RESULTS: We used the treatment-arm of the Studies Of Left Ventricular Dysfunction (SOLVD-T) as the reference trial for comparison of an ACE inhibitor to placebo and the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity-Alternative trial (CHARM-Alternative) as the reference trial for comparison of an ARB to placebo. The hazard ratio of LCZ696 vs. a putative placebo was estimated through the product of the hazard ratio of LCZ696 vs. enalapril (active-control) and that of the historical active-control (enalapril or candesartan) vs. placebo. For the primary composite outcome of cardiovascular death or heart failure hospitalization in PARADIGM-HF, the relative risk reduction with LCZ696 vs. a putative placebo from SOLVD-T was 43% (95%CI 34-50%; P < 0.0001) with similarly large effects on cardiovascular death (34%, 21-44%; P < 0.0001) and heart failure hospitalization (49%, 39-58%; P < 0.0001). For all-cause mortality, the reduction compared with a putative placebo was 28% (95%CI 15-39%; P < 0.0001). Putative placebo analyses based on CHARM-Alternative gave relative risk reductions of 39% (95%CI 27-48%; P < 0.0001) for the composite outcome of cardiovascular death or heart failure hospitalization, 32% (95%CI 16-45%; P < 0.0001) for cardiovascular death, 46% (33-56%; P < 0.0001) for heart failure hospitalization, and 26% (95%CI 11-39%; P < 0.0001) for all-cause mortality. CONCLUSION: These indirect comparisons of LCZ696 with a putative placebo show that the strategy of combined angiotensin receptor blockade and neprilysin inhibition led to striking reductions in cardiovascular and all-cause mortality, as well as heart failure hospitalization. These benefits were obtained even though LCZ696 was added to comprehensive background beta-blocker and mineralocorticoid receptor antagonist therapy.
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| 7. |
- Pang, P. S., et al.
(författare)
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Effects of tolvaptan on dyspnoea relief from the EVEREST trials
- 2009
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 30:18, s. 2233-2240
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Tidskriftsartikel (refereegranskat)abstract
- Aims To describe the effects of tolvaptan therapy on dyspnoea relief based on timing of delivery, influence of concomitant therapies, and baseline patient and clinical characteristics. Also, the influence of clinical trial design on dyspnoea measurement, from the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trials. Methods and results Post hoc analysis was performed based on the endpoint of patient-assessed dyspnoea. Changes from baseline at inpatient Day 1 were compared between treatment groups by the van Elteren test. Pre-determined subgroup analyses were also performed. Tolvaptan's effects are greatest within 12 h after first dose with an additional, but modest dyspnoea improvement benefit irrespective of time after admission. Overall, patients continue to report dyspnoea improvement up to 60 h after admission. The window of enrolment, up to 48 h after admission, combined with measurement on 'Day 1' led to a wide range over when dyspnoea was assessed. Conclusion Post hoc analysis suggests that tolvaptan modestly improves dyspnoea compared with standard therapy alone, regardless if given early or relatively late after hospitalization, and also across major pre-specified subgroups, despite ongoing background therapy aimed at relieving signs and symptoms. Significant variability around when dyspnoea was assessed, in addition to the persistence of dyspnoea despite ongoing background therapy, may influence how future clinical trials assess dyspnoea in acute heart failure syndromes.
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| 8. |
- Massie, Barry M, et al.
(författare)
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Rolofylline, an adenosine A1-receptor antagonist, in acute heart failure.
- 2010
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Ingår i: The New England journal of medicine. - 1533-4406. ; 363:15, s. 1419-28
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Tidskriftsartikel (refereegranskat)abstract
- Worsening renal function, which is associated with adverse outcomes, often develops in patients with acute heart failure. Experimental and clinical studies suggest that counterregulatory responses mediated by adenosine may be involved. We tested the hypothesis that the use of rolofylline, an adenosine A1-receptor antagonist, would improve dyspnea, reduce the risk of worsening renal function, and lead to a more favorable clinical course in patients with acute heart failure.
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