Abstract:
AIMS:To assess the tolerability of initiating/uptitrating sacubitril/valsartan (LCZ696) from 50 to 200 mg twice daily (target dose) over 3 and 6 weeks in heart failure (HF) patients (ejection fraction ≤35%). METHODS AND RESULTS:A 5-day open-label run-in (sacubitril/valsartan 50 mg twice daily) preceded an 11-week, double-blind, randomization period [100 mg twice daily for 2 weeks followed by 200 mg twice daily ('condensed' regimen) vs. 50 mg twice daily for 2 weeks, 100 mg twice daily for 3 weeks, followed by 200 mg twice daily ('conservative' regimen)]. Patients were stratified by pre-study dose of angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker (ACEI/ARB; low-dose stratum included ACEI/ARB-naïve patients). Of 540 patients entering run-in, 498 (92%) were randomized and 429 (86.1% of randomized) completed the study. Pre-defined tolerability criteria were hypotension, renal dysfunction and hyperkalaemia; and adjudicated angioedema, which occurred in ('condensed' vs. 'conservative') 9.7% vs. 8.4% (P = 0.570), 7.3% vs. 7.6% (P = 0.990), 7.7% vs. 4.4% (P = 0.114), and 0.0% vs. 0.8% of patients, respectively. Corresponding proportions for pre-defined systolic blood pressure <95 mmHg, serum potassium >5.5 mmol/L, and serum creatinine >3.0 mg/dL were 8.9% vs. 5.2% (P = 0.102), 7.3% vs. 4.0% (P = 0.097), and 0.4% vs. 0%, respectively. In total, 378 (76%) patients achieved and maintained sacubitril/valsartan 200 mg twice daily without dose interruption/down-titration over 12 weeks (77.8% vs. 84.3% for 'condensed' vs. 'conservative'; P = 0.078). Rates by ACEI/ARB pre-study dose stratification were 82.6% vs. 83.8% (P = 0.783) for high-dose/'condensed' vs. high-dose/'conservative' and 84.9% vs. 73.6% (P = 0.030) for low-dose/'conservative' vs. low-dose/'condensed'. CONCLUSIONS:Initiation/uptitration of sacubitril/valsartan from 50 to 200 mg twice daily over 3 or 6 weeks had a tolerability profile in line with other HF treatments. More gradual initiation/uptitration maximized attainment of target dose in the low-dose ACEI/ARB group.
journal_name
Eur J Heart Failjournal_title
European journal of heart failureauthors
Senni M,McMurray JJ,Wachter R,McIntyre HF,Reyes A,Majercak I,Andreka P,Shehova-Yankova N,Anand I,Yilmaz MB,Gogia H,Martinez-Selles M,Fischer S,Zilahi Z,Cosmi F,Gelev V,Galve E,Gómez-Doblas JJ,Nociar J,Radomska M,Sdoi
10.1002/ejhf.548subject
Has Abstractpub_date
2016-09-01 00:00:00pages
1193-202issue
9eissn
1388-9842issn
1879-0844journal_volume
18pub_type
杂志文章,随机对照试验abstract::Renal dysfunction in heart failure with preserved ejection fraction (HFpEF) is common and is associated with increased mortality. Impaired renal function is also a risk factor for developing HFpEF. A new paradigm for HFpEF, proposing a sequence of events leading to myocardial remodelling and dysfunction in HFpEF, was ...
journal_title:European journal of heart failure
pub_type: 杂志文章,评审
doi:10.1002/ejhf.497
更新日期:2016-06-01 00:00:00
abstract:AIMS:Drug-induced changes in QT dispersion may be a way of detecting harmful repolarisation abnormalities for patients receiving antiarrhythmic drugs affecting ventricular repolarisation. METHODS AND RESULTS:In 463 congestive heart failure (CHF) patients enrolled in the Danish Investigations Of Arrhythmia and Mortalit...
journal_title:European journal of heart failure
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s1388-9842(01)00235-5
更新日期:2002-03-01 00:00:00
abstract:BACKGROUND:The angiotensin II type 2 (AT2) receptor is thought to play a role in cardiovascular disorders such as neointima formation after vascular injury, cardiac hypertrophy and myocardial infarction (MI). Recently, the biallelic polymorphism G + 1675A in intron 1 of the AT2 receptor gene has been associated with le...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1016/s1388-9842(02)00168-x
更新日期:2002-12-01 00:00:00
abstract:AIMS:Beta-blockers (BBs) improve outcomes in heart failure. Results from the Cardiac Insufficiency Bisoprolol Study in Elderly (CIBIS-ELD) trial previously demonstrated the feasibility of heart rate, not maximum dose, as a treatment goal. In this pre-specified analysis, we investigated the prognostic value of achieved ...
journal_title:European journal of heart failure
pub_type: 杂志文章,随机对照试验
doi:10.1002/ejhf.121
更新日期:2014-08-01 00:00:00
abstract:AIMS:Quantification of linear lung ultrasound (LUS) artefacts (B-lines) represents a novel, non-invasive approach to assess pulmonary congestion. We investigated the relationship between the number of B-lines (vertical artefacts arising from the pleural line) and intracardiac pressures. METHODS AND RESULTS:Prior to sc...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1093/eurjhf/hfs144
更新日期:2012-11-01 00:00:00
abstract:AIMS:Current guidelines for the diagnosis of heart failure with normal or preserved ejection fraction (HFpEF) are based on measurements at rest. However, in HFpEF ventricular dysfunction is more apparent on exercise. We hypothesized that Mitral annular plane systolic excursion (MAPSE) which is easy to acquire on exerci...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1093/eurjhf/hfr081
更新日期:2011-09-01 00:00:00
abstract:BACKGROUND:Most patients suspected of having heart failure (HF) will get a 12-lead electrocardiogram (ECG) but its utility for excluding HF or assisting in its management has rarely been investigated. METHODS:The EuroHeart Failure survey identified 11,327 patients hospitalised with a suspected diagnosis of HF from 115...
journal_title:European journal of heart failure
pub_type: 杂志文章,多中心研究
doi:10.1016/j.ejheart.2006.11.003
更新日期:2007-05-01 00:00:00
abstract:OBJECTIVE:To achieve angiogenic interaction between VEGF(165) and angiopoietin-1 (Ang-1) using a novel adenoviral bicistronic vector (Ad-Bic) encoding the two factors and delivered ex vivo using sex-mismatched human skeletal myoblasts. METHODS AND RESULTS:A myocardial infarction model was developed in 29 female pigs; ...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1016/j.ejheart.2006.04.008
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:Suppression of the renin-angiotensin-aldosterone system (RAAS) is therapeutically valuable in chronic heart failure (CHF). RAAS inhibition can be achieved in a number of ways though an orally active renin inhibitor (RI) has never been studied before. We describe the neurohumoral effects of an RI. METHODS AN...
journal_title:European journal of heart failure
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.ejheart.2007.09.002
更新日期:2007-11-01 00:00:00
abstract:AIMS:Right ventricular (RV) dysfunction and pulmonary hypertension (PH) are increasingly recognized in heart failure with preserved ejection fraction (HFpEF). The prevalence and prognostic value of RV dysfunction in HFpEF have been widely but variably reported. We therefore conducted a systematic review and meta-analys...
journal_title:European journal of heart failure
pub_type: 杂志文章,meta分析,评审
doi:10.1002/ejhf.630
更新日期:2016-12-01 00:00:00
abstract:AIMS:Right ventricular (RV) dysfunction has been associated with a worse outcome in heart failure patients undergoing CRT. However, evidence on the RV response to CRT is controversial and there are no data regarding the early effects of CRT on RV function (RVF). We sought to investigate whether a CRT device favourably ...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1002/ejhf.450
更新日期:2016-02-01 00:00:00
abstract:AIMS:The MITRA-FR trial showed that among symptomatic patients with severe secondary mitral regurgitation, percutaneous repair did not reduce the risk of death or hospitalization for heart failure at 12 months compared with guideline-directed medical treatment alone. We report the 24-month outcome from this trial. MET...
journal_title:European journal of heart failure
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1002/ejhf.1616
更新日期:2019-12-01 00:00:00
abstract::Aortic stenosis (AS) is the most frequent degenerative valvular heart disease in Western countries and its prevalence increases in parallel with the ageing process of the population. Heart failure (HF), defined by the presence of reduced left ventricular ejection fraction, may be present in up to a quarter of patients...
journal_title:European journal of heart failure
pub_type: 杂志文章,评审
doi:10.1002/ejhf.466
更新日期:2016-05-01 00:00:00
abstract::Nitric oxide (NO) appears to play a role in modulating cardiac function in both health and disease. Early studies in isolated rodent cardiac myocytes demonstrated a depressant effect of NO supplied by NO donors (exogenous) as well as NO generated within myocytes (endogenous). There is increasing evidence for a functio...
journal_title:European journal of heart failure
pub_type: 杂志文章,评审
doi:10.1016/s1388-9842(01)00163-5
更新日期:2001-10-01 00:00:00
abstract::This article provides information and a commentary on key trials relevant to the pathophysiology, prevention, and treatment of heart failure (HF) presented at the annual meeting of the European Society of Cardiology held in Stockholm in 2010. Unpublished reports should be considered as preliminary, since analyses may ...
journal_title:European journal of heart failure
pub_type:
doi:10.1093/eurjhf/hfq186
更新日期:2010-11-01 00:00:00
abstract:UNLABELLED:Aim Frequent ventricular premature contractions (VPCs) may cause haemodynamic deterioration and reversible left ventricular (LV) dysfunction. We aimed to clarify this mechanism. METHODS AND RESULTS:The haemodynamics, echocardiographic parameters, and plasma brain natriuretic peptide (BNP) level were assesse...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1093/eurjhf/hfs095
更新日期:2012-10-01 00:00:00
abstract:AIMS:This study aimed to determine the prognostic value of serum uric acid (SUA) on outcomes in heart failure (HF) with preserved ejection fraction (HFpEF), and whether sacubitril-valsartan reduces SUA and use of SUA-related therapies. METHODS AND RESULTS:We analysed 4795 participants from the Prospective Comparison o...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1002/ejhf.1984
更新日期:2020-11-01 00:00:00
abstract:BACKGROUND:We describe the baseline characteristics of subjects randomised in the largest placebo-controlled, morbidity-mortality trial to date in patients with heart failure and preserved ejection fraction - the irbesartan in heart failure with preserved systolic function trial (I-PRESERVE). METHODS AND RESULTS:4133 ...
journal_title:European journal of heart failure
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.ejheart.2007.12.010
更新日期:2008-02-01 00:00:00
abstract:UNLABELLED:The aim of this study was to evaluate the efficacy of adding the beta-blocker bucindolol to standard therapy shortly after a myocardial infarction in a high-risk population with reduced left ventricular function. METHODS:The study was planned to include 2000 patients with an enzyme confirmed myocardial infa...
journal_title:European journal of heart failure
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/s1388-9842(02)00032-6
更新日期:2002-08-01 00:00:00
abstract:BACKGROUND:Although discontinuation of chronic ACE inhibitor (ACEi) therapy after myocardial infarction (MI) is common in clinical practice, some clinical studies reported an increased incidence of ischemia-related events after withdrawal. To further address this issue, we assessed hemodynamic, neurohormonal and vascul...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1016/j.ejheart.2005.04.014
更新日期:2006-03-01 00:00:00
abstract:UNLABELLED:Experimental data have shown that rIL2 has negative inotropic properties. This has not been investigated in humans with normal left ventricular function. Seventeen consecutive renal cell carcinoma patients who received rIL2 therapy because of dissemination were analyzed before and after treatment with a low ...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1016/s1388-9842(00)00073-8
更新日期:2000-06-01 00:00:00
abstract:AIMS:To characterise the prevalence, in-hospital complications, management, and long-term outcome of patients with congestive heart failure but preserved left ventricular systolic function after acute myocardial infarction. METHODS:3166 consecutive patients screened for entry in the Bucindolol Evaluation in Acute Myoc...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1016/s1388-9842(03)00159-4
更新日期:2003-12-01 00:00:00
abstract:AIMS:The proteasome prevents the intracellular accumulation of proteins and its impairment can lead to structural and functional alterations, as noted for the coronary vasculature in a previous study. Utilizing the same model, this study was designed to test the hypothesis that chronic proteasome inhibition (PSI) also ...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1093/eurjhf/hft034
更新日期:2013-06-01 00:00:00
abstract:BACKGROUND:Beneficial effects of left ventricular (LV)-based pacing on acute hemodynamic parameters were reported in several series, but only a few studies examined the long-term effects of this new pacing procedure. AIMS:To assess long-term effects of permanent LV-based pacing on LV function and mitral regurgitation ...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1016/s1388-9842(01)00145-3
更新日期:2001-08-01 00:00:00
abstract:AIMS:Angiotensin receptor-neprilysin inhibitors (ARNis) acts an ARB and neprilysin inhibitor. Diabetes mellitus significantly increases the risk of cardiovascular disease and heart failure (HF). Therefore, we evaluated the effects and mechanisms of ARNi in HF with reduced ejection fraction (HFrEF) in streptozotocin-ind...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1002/ejhf.474
更新日期:2016-04-01 00:00:00
abstract:AIMS:Patients with intestinal malabsorption may develop cardiac dysfunction the origin of which is often unclear. We sought to investigate the pathogenesis of dilated cardiomyopathy in human malabsorption. METHODS AND RESULTS:Eighteen patients with intestinal bypass as treatment for severe obesity and cardiomyopathy u...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1093/eurjhf/hfr167
更新日期:2012-02-01 00:00:00
abstract:OBJECTIVE:To study changes in connexin, metalloproteinase and tissue inhibitor of metalloproteinase levels during tachycardia-induced cardiomyopathy (TIC). METHODS:Canine models of TIC were established by rapid right atrial pacing at 350-400 beats per min for 8 weeks in 11 dogs, six dogs acted as a sham operation grou...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1016/j.ejheart.2006.04.014
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:Cardiac resynchronization therapy (CRT) improves symptoms, left ventricular ejection fraction (LVEF) and survival in patients with heart failure and wide QRS, however, long term clinical outcome is unknown. AIMS:To identify predictors of mortality and evaluate the effects of CRT after long term follow-up. ...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1016/j.ejheart.2008.06.013
更新日期:2008-08-01 00:00:00
abstract:BACKGROUND:Plasma levels of N-terminal pro-brain natriuretic peptide (NT-pro BNP) are increased in patients with chronic heart failure (CHF). Beta-blockers (BB) may influence these levels but it is unclear whether changes in NT-pro BNP reflect concomitant changes in prognosis. OBJECTIVES:To assess the prognostic impor...
journal_title:European journal of heart failure
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.ejheart.2007.07.010
更新日期:2007-08-01 00:00:00
abstract:AIMS:To determine the impact of internationally recognized criteria for the diagnosis of heart failure with preserved ejection fraction (HF-PEF) on the feasibility of recruitment into a HF-PEF trial. METHODS AND RESULTS:We reviewed the medical records of 5883 consecutive patients admitted with heart failure across eig...
journal_title:European journal of heart failure
pub_type: 杂志文章
doi:10.1002/ejhf.106
更新日期:2014-07-01 00:00:00