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Effects of liraglutide on hemodynamic parameters in patients with heart failure.

ABSTRACT: Glucagon-like peptide-1 analogues improve left ventricular function in patients with acute myocardial infarction. This study aimed to evaluate the effects of liraglutide on hemodynamic parameters in patients with heart failure. A total of 78 patients with heart failure were enrolled in this study between August 2014 and November 2015. Of these, 52 patients were randomized 1:1 to receive either liraglutide or placebo for 7 days. Hemodynamic measurements were made using transpulmonary thermodilution and arterial pulse contour analysis. At 7 days, the difference in change of the primary endpoint of cardiac output between the liraglutide group and control group was +1.1 1/min (95% CI +0.1 to +2.2; P < 0.001). Stroke volume was significantly higher in the liraglutide group compared with the control group (difference: +14.6 ml; P < 0.001). The difference in an increase in the left ventricular contractile index after 7 days of treatment was +210.7 mmHg/s (liraglutide versus control, 95% CI-92.1 to +501.5; P < 0.001). Liraglutide causes favorable changes in markers of inflammation and oxidative stress. Glucagon-like peptide-1 may be associated with improvement in left ventricular function in patients with heart failure. These findings need to be confirmed by larger invasive trials.

SUBMITTER: Zhang JY

PROVIDER: S-EPMC5617541 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Effects of liraglutide on hemodynamic parameters in patients with heart failure.

Zhang Jin Ying JY Wang Xin Yun XY Wang Xiang X

Oncotarget 20170619 37

Glucagon-like peptide-1 analogues improve left ventricular function in patients with acute myocardial infarction. This study aimed to evaluate the effects of liraglutide on hemodynamic parameters in patients with heart failure. A total of 78 patients with heart failure were enrolled in this study between August 2014 and November 2015. Of these, 52 patients were randomized 1:1 to receive either liraglutide or placebo for 7 days. Hemodynamic measurements were made using transpulmonary thermodiluti ...[more]

PMID: 28977981

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Project description:Abnormal 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.To test whether therapy with a GLP-1 agonist improves clinical stability following hospitalization for acute heart failure.Phase 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.The 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.The 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.Among 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).Among 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.clinicaltrials.gov Identifier: NCT01800968.

Project description:ObjectivesThe aim of this study was to compare the relative impairment in different exercise hemodynamic reserve parameters in patients with heart failure with preserved ejection fraction (HFpEF) and control patients using a study-level meta-analysis.BackgroundA cardinal manifestation of chronic HFpEF is severely decreased exercise capacity. Developing effective therapies for exercise intolerance in HFpEF requires optimal understanding of the factors underlying exercise intolerance.MethodsData were included from 17 unique cohorts that measured peak oxygen uptake and hemodynamic or echocardiographic parameters during exercise in patients with HFpEF and control subjects in this meta-analysis. Standardized mean differences (SMDs) in the exercise reserve (exercise - resting) measures of hemodynamic or echocardiographic parameters between the HFpEF and control groups were pooled in a random-effects meta-analysis.ResultsThe pooled analysis included 910 patients with HFpEF and 476 control subjects. In pooled analysis, patients with HFpEF had significantly lower peak oxygen uptake (SMD: -2.13; 95% confidence interval [CI]: -2.68 to -1.57). Among hemodynamic exercise reserve parameters, the largest impairment was observed in chronotropic response reserve (change in heart rate from rest to peak exercise; SMD: -1.87; 95% CI: -2.44 to -1.29), followed by exaggerated increase in pulmonary capillary wedge pressure with exercise (SMD: 1.78; 95% CI: 1.46 to 2.09). Significant abnormalities were also observed in the arteriovenous oxygen difference reserve and stroke volume reserve between the HFpEF and control groups.ConclusionsThe most consistent and severe hemodynamic reserve abnormalities observed in patients with HFpEF were impairment in chronotropic reserve and exaggerated increase in pulmonary capillary wedge pressure with exercise. These may be important targets for therapeutic strategies to improve exercise tolerance in patients with HFpEF.

Project description:Background Patients with recurring heart failure (HF) following cardiac resynchronization therapy fare poorly. Their management is undecided. We tested remote hemodynamic-guided pharmacotherapy. Methods and Results We evaluated cardiac resynchronization therapy subjects included in the CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in New York Heart Association Class III Heart Failure Patients) trial, which randomized patients with persistent New York Heart Association Class III symptoms and ≥1 HF hospitalization in the previous 12 months to remotely managed pulmonary artery (PA) pressure-guided management (treatment) or usual HF care (control). Diuretics and/or vasodilators were adjusted conventionally in control and included remote PA pressure information in treatment. Annualized HF hospitalization rates, changes in PA pressures over time (analyzed by area under the curve), changes in medications, and quality of life (Minnesota Living with Heart Failure Questionnaire scores) were assessed. Patients who had cardiac resynchronization therapy (n=190, median implant duration 755 days) at enrollment had poor hemodynamic function (cardiac index 2.00±0.59 L/min per m2), high comorbidity burden (67% had secondary pulmonary hypertension, 61% had estimated glomerular filtration rate <60 mL/min per 1.73 m2), and poor Minnesota Living with Heart Failure Questionnaire scores (57±24). During 18 months randomized follow-up, HF hospitalizations were 30% lower in treatment (n=91, 62 events, 0.46 events/patient-year) versus control patients (n=99, 93 events, 0.68 events/patient-year) (hazard ratio, 0.70; 95% CI, 0.51-0.96; P=0.028). Treatment patients had more medication up-/down-titrations (847 versus 346 in control, P<0.001), mean PA pressure reduction (area under the curve -413.2±123.5 versus 60.1±88.0 in control, P=0.002), and quality of life improvement (Minnesota Living with Heart Failure Questionnaire decreased -13.5±23 versus -4.9±24.8 in control, P=0.006). Conclusions Remote hemodynamic-guided adjustment of medical therapies decreased PA pressures and the burden of HF symptoms and hospitalizations in patients with recurring Class III HF and hospitalizations, beyond the effect of cardiac resynchronization therapy. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00531661.

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Effects of liraglutide on hemodynamic parameters in patients with heart failure.

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Effects of liraglutide on hemodynamic parameters in patients with heart failure.

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