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Liraglutide and weight loss among patients with advanced heart failure and a reduced ejection fraction: insights from the FIGHT trial.

ABSTRACT: AIMS:Obesity is present in up to 45% of patients with heart failure (HF). Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor antagonist, facilitates weight loss in obese patients. The efficacy of liraglutide as a weight loss agent among patients with HF and reduced ejection fraction (HFrEF) and a recent acute HF hospitalization remains unknown. METHODS AND RESULTS:The Functional Impact of GLP-1 for Heart Failure Treatment study randomized 300 patients with HFrEF (ejection fraction ? 40%), both with and without diabetes and a recent HF hospitalization to liraglutide or placebo. The primary outcome for this post hoc analysis was the change in weight from baseline to last study visit. We conducted an 'on-treatment' analysis of patients with at least one follow-up visit on study drug (123 on liraglutide and 124 on placebo). The median age was 61 years, 21% were female, and 69% of patients had New York Heart Association functional Class III or IV symptoms. The median ejection fraction was 25% (25th, 75th percentile 19-32%). Liraglutide use was associated with a significant weight reduction [liraglutide -1.00 lbs vs. placebo 2.00 lbs; treatment difference -4.10 lbs; 95% confidence interval (CI) -7.94, -0.25; P = 0.0367; percentage treatment difference -2.07%, 95% CI -3.86, -0.28; P = 0.0237]. Similar results were seen after multivariable adjustments. Liraglutide also significantly reduced triglyceride levels (liraglutide 7.5 mg/dL vs. placebo 12.0 mg/dL; treatment difference -33.1 mg/dL; 95% CI -60.7, -5.6; P = 0.019). CONCLUSIONS:Liraglutide is an efficacious weight loss agent in patients with HFrEF. These findings will require further exploration in a well-powered cardiovascular outcomes trial.

SUBMITTER: Sharma A

PROVIDER: S-EPMC6300815 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Liraglutide and weight loss among patients with advanced heart failure and a reduced ejection fraction: insights from the FIGHT trial.

Sharma Abhinav A Ambrosy Andrew P AP DeVore Adam D AD Margulies Kenneth B KB McNulty Steven E SE Mentz Robert J RJ Hernandez Adrian F AF Michael Felker Gary G Cooper Lauren B LB Lala Anuradha A Vader Justin J Groake John D JD Borlaug Barry A BA Velazquez Eric J EJ

ESC heart failure 20180817 6

<h4>Aims</h4>Obesity is present in up to 45% of patients with heart failure (HF). Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor antagonist, facilitates weight loss in obese patients. The efficacy of liraglutide as a weight loss agent among patients with HF and reduced ejection fraction (HFrEF) and a recent acute HF hospitalization remains unknown.<h4>Methods and results</h4>The Functional Impact of GLP-1 for Heart Failure Treatment study randomized 300 patients with HFrEF (ejection fra ...[more]

PMID: 30120812

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Project description:AimTo perform a post hoc analysis of the FIGHT trial, evaluating the effect of liraglutide (vs. placebo) on the totality of events in patients with heart failure with reduced ejection fraction (HFrEF).Materials and methodsFIGHT was a double-blind randomized controlled trial (RCT) that studied liraglutide versus placebo in 300 recently hospitalized patients with HFrEF followed for 180 days. The main outcome of the present analysis was total events of hospitalizations for heart failure (HF) or all-cause death. Secondary outcomes included total arrhythmic events and prespecified total events of interest (arrhythmias, sudden cardiac death, acute coronary syndrome, worsening HF, cerebrovascular event, venous thromboembolism, lightheadedness, presyncope/syncope or worsening renal function). Treatment effect was evaluated with negative binomial regression.ResultsCompared to placebo, there was a trend towards increased risk with liraglutide of total HF hospitalizations or all-cause deaths (96 vs. 143 events, incidence rate ratio [IRR] 1.41, 95% confidence interval [CI] 0.98-2.04; P = 0.064) and total arrhythmias (21 vs. 39, IRR 1.76, 95% CI 0.92-3.37; P = 0.088). Total prespecified events of interest were increased with liraglutide compared to placebo (196 vs. 295, IRR 1.43, 95% CI 1.06-1.92; P = 0.018). The risk of HF hospitalizations or all-cause deaths with liraglutide was higher among patients in New York Heart Association (NYHA) Class III to IV (IRR 1.86, 95% CI 1.21-2.85) than in those in NYHA Class I to II (IRR 0.62, 95% CI 0.31-1.23; interaction P = 0.008), and among patients with diabetes (interaction P = 0.051). The risk of arrhythmic events was higher among those without an implanted cardiac device (interaction P = 0.047).ConclusionsIn patients with HFrEF, liraglutide might increase the risk of cardiovascular adverse effects, an effect possibly driven by excess risk of arrhythmias and worsening HF events. As this was a post hoc analysis, these results should be interpreted as exploratory and hypothesis-generating. Further RCTs must be conducted before drawing definitive conclusions.

Project description:ImportanceAbnormal cardiac metabolism contributes to the pathophysiology of advanced heart failure with reduced left ventricular ejection fraction (LVEF). Glucagon-like peptide 1 (GLP-1) agonists have shown cardioprotective effects in early clinical studies of patients with advanced heart failure, irrespective of type 2 diabetes status.ObjectiveTo test whether therapy with a GLP-1 agonist improves clinical stability following hospitalization for acute heart failure.Design, setting, and participantsPhase 2, double-blind, placebo-controlled randomized clinical trial of patients with established heart failure and reduced LVEF who were recently hospitalized. Patients were enrolled between August 2013 and March 2015 at 24 US sites.InterventionsThe GLP-1 agonist liraglutide (n = 154) or placebo (n = 146) via a daily subcutaneous injection; study drug was advanced to a dosage of 1.8 mg/d during the first 30 days as tolerated and continued for 180 days.Main outcomes and measuresThe primary end point was a global rank score in which all patients, regardless of treatment assignment, were ranked across 3 hierarchical tiers: time to death, time to rehospitalization for heart failure, and time-averaged proportional change in N-terminal pro-B-type natriuretic peptide level from baseline to 180 days. Higher values indicate better health (stability). Exploratory secondary outcomes included primary end point components, cardiac structure and function, 6-minute walk distance, quality of life, and combined events.ResultsAmong the 300 patients who were randomized (median age, 61 years [interquartile range {IQR}, 52-68 years]; 64 [21%] women; 178 [59%] with type 2 diabetes; median LVEF of 25% [IQR, 19%-33%]; median N-terminal pro-B-type natriuretic peptide level of 2049 pg/mL [IQR, 1054-4235 pg/mL]), 271 completed the study. Compared with placebo, liraglutide had no significant effect on the primary end point (mean rank of 146 for the liraglutide group vs 156 for the placebo group, P = .31). There were no significant between-group differences in the number of deaths (19 [12%] in the liraglutide group vs 16 [11%] in the placebo group; hazard ratio, 1.10 [95% CI, 0.57-2.14]; P = .78) or rehospitalizations for heart failure (63 [41%] vs 50 [34%], respectively; hazard ratio, 1.30 [95% CI, 0.89-1.88]; P = .17) or for the exploratory secondary end points. Prespecified subgroup analyses in patients with diabetes did not reveal any significant between-group differences. The number of investigator-reported hyperglycemic events was 16 (10%) in the liraglutide group vs 27 (18%) in the placebo group and hypoglycemic events were infrequent (2 [1%] vs 4 [3%], respectively).Conclusions and relevanceAmong patients recently hospitalized with heart failure and reduced LVEF, the use of liraglutide did not lead to greater posthospitalization clinical stability. These findings do not support the use of liraglutide in this clinical situation.Trial registrationclinicaltrials.gov Identifier: NCT01800968.

Project description:AimsThis study aimed to investigate the prognostic value of dynamic changes in left ventricular ejection fraction (EF) for cardiovascular (CV) outcomes in an all-comer heart failure (HF) population with reduced EF (HFrEF, EF < 40%). We sought to identify independent factors related to improvement in EF and to identify risk factors for increased risk of CV events in the subgroups of improved EF (iEF) and non-improved EF (niEF), respecively.Methods and resultsThis is a retrospective sub-analysis from the REDEAL HF trial, which included consecutive patients with chronic HF who were hospitalized from July 2009 to December 2017. Baseline and follow-up echocardiography data (interval ≥12 months) of 573 consecutive patients with HFrEF were analysed. iEF was defined as absolute improvement in EF ≥ 10% and follow-up EF over 40%. The primary endpoint was defined as a composite endpoint of cardiovascular (CV) death, CV hospitalization, or appropriate implantable cardioverter-defibrillator (ICD) therapy for ventricular arrhythmia. EF improved in 37.2% of patients with HFrEF during follow-up (median period of 17 months). iEF was independently associated with shorter HF duration (>4 vs. ≤4 years, odd ratio [OR] = 0.477, 95% CI 0.305-0.745), no coronary artery disease (CAD vs. no CAD, OR = 0.583, 95% CI 0.396-0.858), and no ICD implantation (ICD vs. no ICD, OR = 0.341, 95% CI 0.228-0.511). Compared with niEF, iEF was significantly and independently associated with lower all-cause mortality (22.1% vs. 31.1%, P = 0.019; hazard ratio [HR] = 0.674, 95% CI 0.469-0.968), lower CV mortality (8.9% vs. 16.1%, P = 0.015; HR = 0.539, 95% CI 0.317-0.916), and lower CV events risk (27.2% vs. 49.2%, P < 0.001; HR 0.519, 95% CI 0.381-0.708), after adjustment for age, sex, duration of HF, and other clinical risk factors. Hypertension (HR = 2.452, P = 0.032) and elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP >1153 pg/mL, HR = 4.372, P < 0.001) were identified as independent risk factors for CV events in the iEF subgroup. ICD implantation (HR = 1.533, P = 0.011), elevated NT-proBNP (HR = 1.626, P = 0.018), increased left atrial volume index (HR = 1.461, P = 0.021), reduced lateral mitral annular plane systolic excursion (HR = 1.478, P = 0.025), and reduced tricuspid plane systolic excursion (HR = 1.491, P = 0.039) were identified as risk factors for CV events in the niEF subgroup.ConclusionsImprovement in EF is independently related to the longer survival and lower CV related mortality and hospitalization rate of HFrEF. Elevated baseline NT-proBNP is identified as the strongest prognostic factor associated with increased CV events risk in HFrEF patients both with and without improved EF, regardless of age, sex, duration of HF, and other clinical risk factors.

Project description:AimsHeart failure with mildly reduced ejection fraction (HFmrEF) is associated with a favourable prognosis compared with heart failure (HF) with reduced ejection fraction (EF). We assessed whether left ventricular ejection fraction (LVEF) trajectory can be used to identify groups of patients with HFmrEF who have different clinical outcomes in a large retrospective study of patients with serial imaging.Methods and resultsPatients with HF and ≥2 echocardiograms performed ≥6 months apart were included if the LVEF measured 40-49% on the second study. Patients were classified as HFmrEF-Increasing if LVEF had increased ≥10% (n = 450), HFmrEF-Decreasing if LVEF had decreased ≥10% (n = 512), or HFmrEF-Stable if they did not meet other criteria (n = 389). The primary outcome was all-cause mortality or cardiovascular hospitalization after the second echocardiogram. Associations with time to first event were assessed with multivariable Cox analyses adjusted for age, co-morbidities, and medications. In total, 1351 patients with HFmrEF (median age 74, 64.2% male) were included with 28.8% exhibiting stable LVEF. During median follow-up of 15.3 months, the composite outcome occurred in 811 patients. During follow-up, patients with HFmrEF-Increasing were less likely to experience the primary outcome [adjusted hazard ratio (HR) 0.72, 95% confidence interval (CI) 0.60-0.88, P < 0.001] compared with HFmrEF-Stable. Patients with HFmrEF-Decreasing were more likely to experience the composite outcome in unadjusted analyses (unadjusted HR 1.19, 95% CI 1.01-1.40, P = 0.040) but not adjusted analyses (adjusted HR 1.16, 95% CI 0.98-1.37, P = 0.092). Associations with death or HF hospitalizations were similar (HFmrEF-Increasing: adjusted HR 0.72, 95% CI 0.59-0.88, P = 0.005; HFmrEF-Decreasing: adjusted HR 1.20, 95% CI 1.01-1.44, P = 0.044). Patients with HFmrEF-Decreasing had a similar risk of the composite outcome as patients with HF with reduced EF (adjusted HR 1.03, 95% CI 0.89-1.20, P = 0.670). Patients with HFmrEF-Increasing were less likely to experience the composite outcome compared with patients with HF with preserved EF (adjusted HR 0.73, 95% CI 0.62-0.87, P < 0.001).ConclusionsAmongst patients with HFmrEF, those exhibiting positive LVEF trajectory were less likely to experience adverse outcomes after correcting for important confounders including medical therapy. Categorizing HFmrEF patients based on LVEF trajectory provides meaningful clinical information and may assist clinicians with management decisions.

Dataset Information

Liraglutide and weight loss among patients with advanced heart failure and a reduced ejection fraction: insights from the FIGHT trial.

Publications

Liraglutide and weight loss among patients with advanced heart failure and a reduced ejection fraction: insights from the FIGHT trial.

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