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| 9. |
- 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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| 10. |
- 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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| 11. |
- Kitai, T., et al.
(författare)
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Insufficient reduction in heart rate during hospitalization despite beta-blocker treatment in acute decompensated heart failure: insights from the ASCEND-HF trial
- 2017
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 19:2, s. 241-249
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Heart failure (HF) can be associated with a higher resting heart rate (HR), and an elevated HR is associated with adverse long-term events. However, the mechanistic and causal role of HR in HF is unclear. This study aimed to investigate changes in HR during hospitalization, and the association between discharge HR and clinical outcomes as well as an interaction with beta-blocker therapy in patients with acute decompensated HF (ADHF). METHODS AND RESULTS: We studied 2906 patients with an LVEF /=70 b.p.m. at baseline and 1580 (54.4%) patients were on beta-blocker treatment. Although HR was gradually reduced from baseline to discharge (85.5 +/- 15.9 b.p.m. at baseline, 81.7 +/- 14.1 b.p.m. at 24 h from treatment initiation, and 79.1 +/- 12.2 b.p.m. at discharge), 80.2% of the patients still had a HR >/=70 b.p.m. at discharge. Patients with a HR >/=70 b.p.m. at discharge had significantly lower survival rates than those with a HR <70 b.p.m. (adjusted hazard ratio 1.02, 95% confidence interval 1.01-1.04, P = 0.002). Moreover, HR at discharge had a curvilinear association with mortality, and had no significant interaction effect with beta-blocker therapy at discharge (P = 0.82). CONCLUSIONS: Despite current beta-blocker therapy, many patients with hospitalized ADHF with reduced LVEF have relatively high discharge HR, and discharge HR is associated with higher mortality. Further studies are warranted to determine the optimal strategy for HR control to improve outcomes.
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| 12. |
- Mentz, R. J., et al.
(författare)
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Influence of documented history of coronary artery disease on outcomes in patients admitted for worsening heart failure with reduced ejection fraction in the EVEREST trial
- 2013
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Ingår i: European journal of heart failure. - : Wiley. - 1879-0844 .- 1388-9842. ; 15:1, s. 61-68
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Data on the prognosis of heart failure (HF) patients with coronary artery disease (CAD) have been conflicting. We describe the clinical characteristics and mode-specific outcomes of HF patients with reduced ejection fraction (EF) and documented CAD in a large randomized trial. METHODS AND RESULTS: EVEREST was a prospective, randomized trial of vasopressin-2 receptor blockade, in addition to standard therapy, in 4133 patients hospitalized with worsening HF and reduced EF. Patients were classified as having CAD based on patient-reported myocardial infarction (MI) or coronary revascularization. We analysed the characteristics and outcomes [all-cause mortality and cardiovascular (CV) mortality/HF hospitalization] of patients with and without documented CAD. All events were centrally adjudicated. Documented CAD was present in 2353 patients (57%). Patients with CAD were older and had more co-morbidities compared with those without CAD. Patients with CAD were more likely to receive a beta-blocker, but less likely to receive an angiotensin-converting enzyme (ACE) inhibitor or aldosterone antagonist (P < 0.01). After risk adjustment, patients with documented CAD had similar mortality [hazard ratio (HR) 1.12, 95% confidence interval (CI) 0.97-1.30], but were at an increased risk for CV mortality/HF hospitalization (HR 1.25, 95% CI 1.12-1.41) due to an increased risk for HF hospitalization (HR 1.26, 95% CI 1.10-1.44). Patients with CAD had increased HF- and MI-related events, but similar rates of sudden cardiac death. CONCLUSION: Documented CAD in patients hospitalized for worsening HF with reduced EF was associated with a higher burden of co-morbidities, lower use of HF therapies (except beta-blockers), and increased HF hospitalization, while all-cause mortality was similar.
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| 13. |
- Ambrosy, A. P., et al.
(författare)
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Changes in Dyspnea Status During Hospitalization and Postdischarge Health-Related Quality of Life in Patients Hospitalized for Heart Failure: Findings From the EVEREST Trial
- 2016
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Ingår i: Circulation-Heart Failure. - : Ovid Technologies (Wolters Kluwer Health). - 1941-3289 .- 1941-3297. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- Background-Dyspnea is the most common symptom among hospitalized patients with heart failure and represents a therapeutic target. However, the association between short-term dyspnea relief and postdischarge clinical outcomes and health-related quality of life (HRQOL) remains uncertain. Methods and Results-A post hoc analysis was performed of the Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan (EVEREST) trial, which enrolled 4133 patients within 48 hours of admission for heart failure with an ejection fraction <= 40%. Physician-assessed dyspnea was recorded on a daily basis from baseline until discharge or day 7 as none, seldom, frequent, or continuous. Patient-reported dyspnea was measured using a 7-point Likert scale, and patients experiencing moderate or marked dyspnea improvement on day 1 were classified as early responders. The Kansas City Cardiomyopathy Questionnaire summary score, which ranges from 0 to 100, was collected postdischarge at week 1. The primary outcome was unfavorable HRQOL, defined a priori as a Kansas City Cardiomyopathy Questionnaire score <45. Secondary outcomes included 30-day all-cause mortality, and all-cause and cause-specific hospitalizations. The final analytic cohort included 1567 patients discharged alive with complete HRQOL data. Patients were 66.0 +/- 12.7 years old and had a mean ejection fraction of 25 +/- 8%. Physician-assessed dyspnea was rated as frequent or continuous in 1399 patients (90%) at baseline, which decreased to 250 patients (16%) by discharge, whereas patient-reported early dyspnea relief was reported by 610 patients (40%). The median Kansas City Cardiomyopathy Questionnaire score at week 1 was 50 (35, 65). All-cause mortality was 3.0%, and all-cause hospitalization was 20.5% within 30 days of discharge. Physician-assessed and patient-reported dyspnea was not independently associated with HRQOL, all-cause mortality, or all-cause or cause-specific hospitalization. Conclusions-In-hospital physician-assessed, and patient-reported dyspnea was not independently associated with postdischarge HRQOL, survival, or readmissions. Although dyspnea relief remains a goal of therapy for hospitalized patients with heart failure with reduced ejection fraction, this measure may not be a reliable surrogate for long-term patient-centered or hard clinical outcomes.
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| 14. |
- Sarma, S., et al.
(författare)
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Association between diabetes mellitus and post-discharge outcomes in patients hospitalized with heart failure: findings from the EVEREST trial
- 2013
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Ingår i: European journal of heart failure. - : Wiley. - 1879-0844 .- 1388-9842. ; 15:2, s. 194-202
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: We evaluated the impact of diabetes mellitus (DM) and diabetic therapy on outcomes in patients with reduced ejection fraction (EF) after hospitalization for heart failure (HF). DM is prevalent in patients hospitalized with HF, yet inconclusive data exist on the post-discharge outcomes of this patient population. METHODS AND RESULTS: Post-hoc analysis was performed on the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan) study, a randomized trial of patients hospitalized with HF (n = 4133) with median follow-up of 9.9 months. DM status was determined from intake questionnaires and cross-verified by medication history. Univariate relationships were examined using chi(2) test, t-test, and Wilcoxon tests. The two primary outcomes of (i) all-cause mortality (ACM) and (ii) cardiovascular mortality or HF hospitalization (CVM + HFH) were assessed for those with and without DM and by diabetic treatment strategy using log rank tests and multivariable Cox regression models. DM was present in 40% of participants. Patients with DM were more likely to have hypertension, coronary artery disease, and chronic kidney disease. Diabetes was associated with ACM and CVM + HFH (both P < 0.001). Following multivariate risk adjustment, DM was associated with ACM, but this estimate was imprecise [hazard ratio (HR) 1.16; 95% confidence interval (CI) 1.00-1.34] and remained associated with CVM or HFH (HR 1.17; 95% CI 1.04-1.31). Diabetic control strategy did not independently affect outcomes. CONCLUSION: Diabetes is common in patients hospitalized for heart failure with a reduced EF. These patients have a higher post-discharge CVM and higher HF hospitalizations compared with patients with no diabetes. Different diabetic treatment regimens did not appear to influence post-discharge outcomes.
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| 15. |
- Zannad, F., et al.
(författare)
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Mineralocorticoid receptor antagonists for heart failure with reduced ejection fraction: integrating evidence into clinical practice
- 2012
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Ingår i: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 33:22, s. 2782-2795
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Tidskriftsartikel (refereegranskat)abstract
- Mineralocorticoid receptor antagonists (MRAs) improve survival and reduce morbidity in patients with heart failure, reduced ejection fraction (HF-REF), and mild-to-severe symptoms, and in patients with left ventricular systolic dysfunction and heart failure after acute myocardial infarction. These clinical benefits are observed in addition to those of angiotensin converting enzyme inhibitors or angiotensin receptor blockers and beta-blockers. The morbidity and mortality benefits of MRAs may be mediated by several proposed actions, including antifibrotic mechanisms that slow heart failure progression, prevent or reverse cardiac remodelling, or reduce arrhythmogenesis. Both eplerenone and spironolactone have demonstrated survival benefits in individual clinical trials. Pharmacologic differences exist between the drugs, which may be relevant for therapeutic decision making in individual patients. Although serious hyperkalaemia events were reported in the major MRA clinical trials, these risks can be mitigated through appropriate patient selection, dose selection, patient education, monitoring, and follow-up. When used appropriately, MRAs significantly improve outcomes across the spectrum of patients with HF-REF.
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| 16. |
- Mentz, R. J., et al.
(författare)
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Atrial fibrillation or flutter on initial electrocardiogram is associated with worse outcomes in patients admitted for worsening heart failure with reduced ejection fraction: Findings from the EVEREST Trial
- 2012
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703. ; 164:6
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Tidskriftsartikel (refereegranskat)abstract
- Background Heart failure (HF) complicated by atrial fibrillation/flutter (AF/AFL) is associated with worse outcomes. However, the clinical profile and outcomes of patients following hospitalization for HF with AF/AFL on initial electrocardiogram (ECG) has not been well studied. Methods EVEREST was a randomized trial of vasopressin-2 receptor blockade, in addition to standard therapy, in 4133 patients hospitalized with HF with ejection fraction <= 40%. A post hoc analysis was performed comparing the clinical characteristics and outcomes [all-cause mortality and cardiovascular mortality/HF hospitalization] of patients with AF/AFL versus sinus rhythm (SR) on baseline ECG, which were centrally analyzed. Times to events were compared using log-rank tests and Cox regression models. Results Of the 4133 patients, 1195 (29%) were classified with AF/AFL and 2071(50%) with SR. The remaining patients (21%) were excluded because ECGs were unavailable (n = 106), rhythm was paced (n = 727), or junctional/other supraventricular (n = 34). AF/AFL patients were older, with increased weight, faster heart rate, higher blood urea nitrogen, and natriuretic peptide levels compared to SR patients. Anticoagulation was prescribed in 67% of AF/AFL patients on discharge. AF/AFL patients were less likely to receive beta-blockers or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (all P < .05). After risk adjustment, AF/AFL was associated with increased mortality (hazard ratio 1.23; 95% CI, 1.04-1.46) and cardiovascular mortality/HF hospitalization (hazard ratio 1.26; 95% CI, 1.07-1.47). Conclusion AF/AFL on initial ECG in patients hospitalized with HF with reduced ejection fraction is associated with lower use of evidence-based therapies and increased mortality and rehospitalization compared to patients in SR. (Am Heart J 2012;164:884-892.e2.)
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| 17. |
- Mentz, R. J., et al.
(författare)
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Clinical Profile and Prognostic Value of Anemia at the Time of Admission and Discharge Among Patients Hospitalized for Heart Failure With Reduced Ejection Fraction: Findings From the EVEREST Trial
- 2014
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Ingår i: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 7:3, s. 401-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Anemia has been associated with worse outcomes in patients with chronic heart failure (HF). We aimed to characterize the clinical profile and postdischarge outcomes of hospitalized HF patients with anemia at admission or discharge. METHODS AND RESULTS: An analysis was performed on 3731 (90%) of 4133 hospitalized HF patients with ejection fraction 100 days) on adjusted analysis (both P>0.1). CONCLUSIONS: Among hospitalized HF patients with reduced ejection fraction, modest anemia at discharge but not baseline was associated with increased all-cause mortality and short-term cardiovascular mortality plus HF hospitalization. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00071331.
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| 18. |
- Mentz, R. J., et al.
(författare)
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The past, present and future of renin-angiotensin aldosterone system inhibition
- 2013
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Ingår i: International journal of cardiology. - : Elsevier BV. - 1874-1754 .- 0167-5273. ; 167:5, s. 1677-1687
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Forskningsöversikt (refereegranskat)abstract
- The renin-angiotensin aldosterone system (RAAS) is central to the pathogenesis of cardiovascular disease. RAAS inhibition can reduce blood pressure, prevent target organ damage in hypertension and diabetes, and improve outcomes in patients with heart failure and/or myocardial infarction. This review presents the history of RAAS inhibition including a summary of key heart failure, myocardial infarction, hypertension and atrial fibrillation trials. Recent developments in RAAS inhibition are discussed including implementation and optimization of current drug therapies. Finally, ongoing clinical trials, opportunities for future trials and issues related to the barriers and approvability of novel RAAS inhibitors are highlighted.
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| 19. |
- Shah, A. N., et al.
(författare)
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Gender Does Not Affect Postdischarge Outcomes in Patients Hospitalized for Worsening Heart Failure With Reduced Ejection Fraction (from the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan [EVEREST] Trial)
- 2012
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Ingår i: The American journal of cardiology. - : Elsevier BV. - 1879-1913 .- 0002-9149. ; 110:12, s. 1803-1808
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Tidskriftsartikel (refereegranskat)abstract
- Women have traditionally been underrepresented in heart failure (HF) trials, and their baseline characteristics and outcomes after hospitalization for HF are unclear. We retrospectively analyzed the clinical characteristics and outcomes of patients according to gender in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial. EVEREST randomized 4,133 patients hospitalized for HF and ejection fraction of 0.30). Despite a high event rate, no difference was seen in all-cause mortality (men 27% vs women 24%, multivariate hazard ratio 1.04, p = 0.61) or cardiovascular mortality plus HF hospitalization (men 42% vs women 39%, multivariate hazard ratio 1.11, p = 0.10) on univariate analysis or after adjusting for baseline covariates. In conclusion, women hospitalized for worsening HF with an ejection fraction of
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| 20. |
- Vaduganathan, M., et al.
(författare)
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Predictive Value of Low Relative Lymphocyte Count in Patients Hospitalized for Heart Failure With Reduced Ejection Fraction: Insights from the EVEREST Trial
- 2012
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Ingår i: Circulation. Heart failure. - 1941-3297. ; 5:6, s. 750-758
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Tidskriftsartikel (refereegranskat)abstract
- Background- Low lymphocyte count has been shown to be an independent prognostic marker in heart failure (HF) in the outpatient setting. Limited data exist regarding whether relative lymphocyte count correlates with postdischarge outcomes in patients hospitalized for HF. Methods and Results- We performed a post hoc analysis of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial, which randomized 4133 patients hospitalized for worsening HF with an ejection fraction
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| 21. |
- Vaduganathan, M., et al.
(författare)
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Predictive Value of Low Relative Lymphocyte Count in Patients Hospitalized for Heart Failure With Reduced Ejection Fraction Insights from the EVEREST Trial
- 2012
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Ingår i: Circulation-Heart Failure. - : Ovid Technologies (Wolters Kluwer Health). - 1941-3289 .- 1941-3297. ; 5:6, s. 750-758
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Tidskriftsartikel (refereegranskat)abstract
- Background—Low lymphocyte count has been shown to be an independent prognostic marker in heart failure (HF) in the outpatient setting. Limited data exist regarding whether relative lymphocyte count correlates with postdischarge outcomes in patients hospitalized for HF. Methods and Results—We performed a post hoc analysis of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial, which randomized 4133 patients hospitalized for worsening HF with an ejection fraction ≤40% within 48 hours of admission to tolvaptan or placebo for a median follow-up of 9.9 months. The primary end points of all-cause mortality and cardiovascular mortality or HF hospitalization were analyzed in patients with available baseline complete blood counts (n=3717). Lymphocyte percentage was analyzed as a continuous variable. Times to events were compared using log-rank tests and multivariable Cox regression models. Patients with low lymphocyte percentage tended to be older and had higher rates of comorbid disease (diabetes mellitus, atrial fibrillation, and renal insufficiency). Low lymphocyte counts were associated with wide QRS duration, high natriuretic peptides, and low ejection fraction, blood pressure, and serum sodium. These patients were less likely to receive evidence-based HF medications. After adjusting for 22 known clinical risk factors, a 10% decrease in lymphocytes was associated with an increased hazard of all-cause mortality (adjusted hazard ratio 1.31 [95% CI: 1.14–1.150], P<0.001) and cardiovascular mortality or HF hospitalization (adjusted hazard ratio 1.14 [95% CI: 1.04–1.25], P=0.007) in the first 100 days postdischarge. Lymphopenia during hospitalization normalizes in majority of patients in the early postdischarge period. Conclusions—Low relative lymphocyte count during hospitalization for HF is an independent predictor of poor outcomes in the early postdischarge period, beyond traditional prognostic indicators.
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| 22. |
- Vaduganathan, M., et al.
(författare)
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Relation of Serum Uric Acid Levels and Outcomes Among Patients Hospitalized for Worsening Heart Failure With Reduced Ejection Fraction (from the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan Trial)
- 2014
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149. ; 114:11, s. 1713-21
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the clinical profiles associated with serum uric acid (sUA) levels in a large cohort of patients hospitalized for worsening chronic heart failure with ejection fraction (EF) /=30 ml/min/1.73 m(2), sUA was strongly associated with increased all-cause mortality (hazard ratio 1.44, 95% confidence interval 1.22 to 1.69, p <0.001) and the composite end point (hazard ratio 1.44, 95% confidence interval 1.26 to 1.64, p <0.001). However, in patients with estimated glomerular filtration rate <30 ml/min/1.73 m(2), sUA was not related with either end point (both p >0.4). Adjusted interaction analyses for gender, race, and admission allopurinol use were not significant. In conclusion, sUA is commonly elevated in patients hospitalized for worsening chronic heart failure and reduced EF, especially in men and blacks. The prognostic use of sUA differs by baseline renal function, suggesting different biologic and pathophysiologic significance of sUA among those with and without significant renal dysfunction.
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| 23. |
- Ambrosy, A. P., et al.
(författare)
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Clinical profile and prognostic value of low systolic blood pressure in patients hospitalized for heart failure with reduced ejection fraction: insights from the Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan (EVEREST) trial
- 2013
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 165:2, s. 216-25
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Systolic blood pressure (SBP) is related to the pathophysiologic development and progression of heart failure (HF) and is inversely associated with adverse outcomes during hospitalization for HF (HHF). The prognostic value of SBP after initiating inhospital therapy and the mode of death and etiology of cardiovascular readmissions based on SBP have not been well characterized in HHF. METHODS: A post hoc analysis was performed of the placebo group (n = 2061) of the EVEREST trial, which enrolled patients within 48 hours of admission for worsening HF with an ejection fraction (EF) /=90 mm Hg, for a median follow-up of 9.9 months. Systolic blood pressure was measured at baseline, daily during hospitalization, and at discharge/day 7. Patients were divided into the following quartiles by SBP at baseline: /=131 mm Hg. Outcomes were all-cause mortality (ACM) and the composite of cardiovascular mortality or HHF (CVM + HHF). The associations between baseline, discharge, and inhospital change in SBP and ACM and CVM + HHF were assessed using multivariable Cox proportional hazards regression models adjusted for known covariates. RESULTS: Median (25th, 75th) SBP at baseline was 120 (105, 130) mm Hg and ranged from 82 to 202 mm Hg. Patients with a lower SBP were younger and more likely to be male; had a higher prevalence of prior revascularization and ventricular arrhythmias; had a lower EF, worse renal function, higher natriuretic peptide concentrations, and wider QRS durations; and were more likely to require intravenous inotropes during hospitalization. Lower SBP was associated with increased mortality, driven by HF and sudden cardiac death, and cardiovascular hospitalization, primarily caused by HHF. After adjusting for potential confounders, SBP was inversely associated with risk of the coprimary end points both at baseline (ACM: hazard ratio [HR]/10-mm Hg decrease 1.15, 95% CI1.08-1.22; CVM + HHF: HR 1.09/10-mm Hg decrease, 95% CI 1.04-1.14) and at the time of discharge/day 7 (ACM: HR 1.15/10-mm Hg decrease, 95% CI 1.08-1.22; CVM + HHF: HR 1.07/10-mm Hg decrease, 95% CI 1.02-1.13), but the association with inhospital SBP change was not significant. CONCLUSION: Systolic blood pressure is an independent clinical predictor of morbidity and mortality after initial therapy during HHF with reduced EF.
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| 24. |
- Butler, J., et al.
(författare)
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Relationship Between Clinical Trial Site Enrollment With Participant Characteristics, Protocol Completion, and Outcomes Insights From the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan) Trial
- 2013
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 61:5, s. 571-579
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The study investigated whether the number of participants enrolled per site in an acute heart failure trial is associated with participant characteristics and outcomes. Background Whether and how site enrollment volume affects clinical trials is not known. Methods A total of 4,133 participants enrolled among 359 sites were grouped on the basis of total enrollment into 1 to 10, 11 to 30, and >30 participants per site and were compared for outcomes (cardiovascular mortality or heart failure hospitalization). Results Per-site enrollment ranged from 0 to 75 (median 6; 77 sites had no enrollment). Regional differences in enrollment were noted between North and South America, and Western and Eastern Europe (p < 0.001). Participants from sites with fewer enrollments were more likely to be older and male, have lower ejection fraction and blood pressure as well as worse comorbidity and laboratory profile, and were less likely to be on angiotensin-converting enzyme inhibitors or aldosterone antagonists. During a median follow-up of 9.9 months, 1,700 (41%) participants had an outcome event. Compared to event rate at sites with >30 participants (32%), those with 1 to 10 (51%, hazard ratio [HR]: 1.77, 95% confidence interval [CI]: 1.56 to 2.02) and 11 to 30 (42%, HR: 1.44, 95% CI: 1.28 to 1.62) participants per site groups had worse outcomes. This relationship was comparable across regions (p = 0.43). After adjustment for risk factors, participants enrolled at sites with fewer enrollees were at higher risk for adverse outcomes (HR: 1.26, 95% CI: 1.08 to 1.46 for 1 to 10; HR: 1.22, 95% CI: 1.07 to 1.38 for 11 to 30 vs. >30 participant sites). Higher proportion of participants from site with >30 participants completed the protocol (45.5% for <10, 61.7% for 11 to 30, and 68.4% for sites enrolling >30 participants; p < 0.001). Conclusions Baseline characteristics, protocol completion, and outcomes differed significantly among higher versus lower enrolling sites. These data imply that the number of participant enrolled per site may influence trials beyond logistics. (J Am Coll Cardiol 2013; 61: 571-9) (C) 2013 by the American College of Cardiology Foundation
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| 25. |
- Holman, Rury R, et al.
(författare)
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Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.
- 2017
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 377:13, s. 1228-1239
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown.METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy.RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups.CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .).
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| 26. |
- Mentz, R. J., et al.
(författare)
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The Impact of Chronic Obstructive Pulmonary Disease in Patients Hospitalized for Worsening Heart Failure With Reduced Ejection Fraction: An Analysis of the EVEREST Trial
- 2012
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Ingår i: Journal of Cardiac Failure. - : Elsevier BV. - 1071-9164. ; 18:7, s. 515-523
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic obstructive pulmonary disease (COPD) is prevalent in heart failure (HF) patients, yet these patients are poorly characterized. We aimed to describe the characteristics and outcomes of patients with systolic dysfunction and COPD in a contemporary HF randomized trial. Methods and Results: EVEREST investigated 4,133 patients hospitalized with worsening HF and an ejection fraction (EF) <= 40%. We analyzed the characteristics and outcomes (all-cause mortality and cardiovascular mortality/HF hospitalization) of patients according to baseline COPD status. COPD was present in 10% (n = 416) of patients. Patients with COPD had a higher prevalence of comorbidities and were less likely to receive a beta-blocker, angiotensin-converting enzyme inhibitor, or aldosterone antagonist. On univariate analysis, COPD was associated with increased all-cause mortality (HR 1.41, 95% CI 1.18-1.67) and cardiovascular mortality/HF hospitalization (HR 1.29, 95% CI 1.11-1.49). After adjusting for potential confounders, the risk associated with COPD remained increased, but was not statistically significant. Conclusion: The presence of COPD in HF patients is associated with an increased burden of comorbidities, lower use of HF therapies, and a trend toward worse outcomes. These findings provide a starting point for prospective investigations of the treatment of HF comorbidities to reduce the high postdischarge event rates. CI Cardiac Fail 2012;18:515-523)
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| 27. |
- Vaduganathan, M, et al.
(författare)
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Sudden Death After Hospitalization for Heart Failure With Reduced Ejection Fraction (from the EVEREST Trial)
- 2018
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Ingår i: Am J Cardiol. - : Elsevier BV. - 1879-1913. ; 122:2, s. 255-260
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Tidskriftsartikel (refereegranskat)abstract
- Patients with chronic heart failure with reduced ejection fraction (HFrEF) benefit from medical and device therapies targeting sudden cardiac death (SCD). Contemporary estimates of SCD risk after hospitalization for heart failure are limited. We describe the incidence, timing, and clinical predictors of SCD after hospitalization for HFrEF (30 baseline covariates (including treatment randomization, demographics, comorbid conditions, natriuretic peptides, ejection fraction, and medical and device therapies) to identify predictors of 1-year SCD. Of the 4,024 trial patients discharged alive (97%), there were 268 who experienced SCD (7%) and 703 who experienced non-SCD (17%) during median follow-up of 9.9 months. Implantable cardioverter defibrillator use at baseline was 14.5%. Estimates of SCD at 1, 3, 6, and 12 months were 0.8%, 2.3%, 4.1%, and 7.4%, respectively. Most patients were readmitted before SCD (n = 147, 55%). Male gender, black race, diabetes mellitus, and angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use were potential predictors of 1-year SCD after hospitalization for HFrEF (all p <0.10); however, this final model demonstrated poor discrimination (C-statistic 0.57). In conclusion, in the EVEREST trial, patients hospitalized for HFrEF faced risks of 1-year postdischarge SCD of 7%, which accrued gradually over time, and were balanced with high competing risks of nonsudden death (17%). Traditional clinical characteristics fail to adequately predict SCD risk. Further data are needed to identify patients at greatest relative risk for SCD (compared with non-SCD) after hospitalization for HFrEF.
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| 28. |
- Bhatt, A. S., et al.
(författare)
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Achieving a Maximally Tolerated beta-Blocker Dose in Heart Failure Patients Is There Room for Improvement?
- 2017
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 69:20, s. 2542-2550
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Tidskriftsartikel (refereegranskat)abstract
- Heart failure (HF) is associated with significant morbidity and mortality. Although initially thought to be harmful in HF, beta-adrenergic blockers (beta-blockers) have consistently been shown to reduce mortality and HF hospitalization in chronic HF with reduced ejection fraction. Proposed mechanisms include neurohormonal blockade and heart rate reduction. A new therapeutic agent now exists to target further heart rate lowering in patients who have been stable on a "maximally tolerated b-blocker dose," but this definition and how to achieve it are incompletely understood. In this review, the authors summarize published reports on the mechanisms by which beta-blockers improve clinical outcomes. The authors describe differences in doses achieved in landmark clinical trials and those observed in routine clinical practice. They further discuss reasons for intolerance and the evidence behind using b-blocker dose and heart rate as therapeutic targets. Finally, the authors offer recommendations for clinicians actively initiating and up-titrating b-blockers that may aid in achieving maximally tolerated doses. (C) 2017 by the American College of Cardiology Foundation.
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| 29. |
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| 30. |
- Green, Jennifer B., et al.
(författare)
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Sex differences in the complications, care and clinical outcomes of patients with type 2 diabetes in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL)
- 2023
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Ingår i: Diabetes, obesity and metabolism. - : WILEY. - 1462-8902 .- 1463-1326. ; 25:6, s. 1473-1484
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To examine sex differences in the characteristics and outcomes in participants with type 2 diabetes (T2D), with or without cardiovascular disease (CVD), randomized to once-weekly exenatide (EQW) or placebo in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL).Materials and Methods: Baseline characteristics were summarized and compared by sex. Cox proportional hazards regression models were used for clinical outcomes, including the primary composite outcome of cardiovascular (CV) death, non-fatal myocardial infarction or non-fatal stroke (MACE3). Models including sex-by-treatment interaction were used to evaluate differences in effects of EQW.Results: Overall, 5603 women and 9149 men were followed for a median of 3.2 years. Women were younger (mean 61.4 vs. 62.2 years, P < .001) and had a shorter duration of diabetes (mean 12.9 vs. 13.2 years, P = .039) and less coronary artery disease (35.2% vs. 61.0%, P < .001) than men, but also a less favourable metabolic risk profile and lower use of cardioprotective medications. MACE3 occurred in 9.1% of women and 13.5% of men, corresponding to 2.82 versus 4.40 events/100 participant-years (adjusted hazard ratio 0.80, 95% CI: 0.70-0.93, P = .003). There was no difference in MACE3 with EQW compared with placebo, or evidence of heterogeneity of treatment effect by sex.Conclusions: This analysis of a large population of individuals with T2D, with or without established CVD, identified between-sex differences in clinical characteristics and care. Despite having worse management of CV risk factors, women had significantly lower rates of important CV events not attributable to the effects of study treatment.
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