For more information about the Heart Failure Network trials, please use the links provided. These links will open a new window to the National Institutes of Health website: www.clinicaltrials.gov/
ATHENA-HF (Study of High-dose Spironolactone vs. Placebo Therapy in Acute Heart Failure)
The ATHENA-HF study (JACC Heart Fail. 2016;4(9):726-35 (PMC5010507)) showed that high dose spironolactone (commercial name Aldactone, 100 mg/day) given early during an episode of acute heart failure, when compared to placebo, did not improve the symptoms and outcomes in persons with acute heart failure. High dose spironolactone was well-tolerated but these data do not support the routine use of high dose spironolactone in acute heart failure. The role of high dose MRA targeted to patients resistant to loop diuretics needs to be further studied.
CARRESS (CARdiorenal REScue Study in Acute Decompensated Heart Failure)
The CARRESS study (N Engl J Med. 2012 Dec 13; 367(24): 2296-304 (PMC3690472)) showed that for worsened renal function, and persistent congestion, the use of a stepped pharmacologic-therapy algorithm was superior to a strategy of ultrafiltration for the preservation of renal function at 96 hours, with a similar amount of weight loss with the two approaches. Ultrafiltration was associated with a higher rate of adverse events.
CHART (Characterizing HIV-relaTed Diastolic Dysfunction: A Cross-Sectional Study Leveraging the NHLBI Heart Failure Clinical Research Network)
The objective of this observational study of 198 patients with human immunodeficiency virus (HIV) type 1 infection, half with diastolic dysfunction and half with normal ventricular function, is to characterize the determinants, mechanisms, and consequences of diastolic dysfunction in this population. All data have been collected and the analysis/publication are pending.
DOSE (Diuretic Optimization Strategies Evaluation in Acute Heart Failure)
The DOSE study (N Eng J Med. 2011 Mar 3;364(9):797-805(PMC3412356)) showed that among patients with acute decompensated heart failure, there were no significant differences in patients’ global assessment of symptoms or in the change in renal function when diuretic therapy was administered by bolus as compared with continuous infusion or at a high dose as compared with a low dose.
EXACT-HF (Using Allopurinol to Relieve Symptoms in Patients With Heart Failure and High Uric Acid Levels)
The EXACT study (Circ Heart Failure 2013; 6; 862-868, PMC4438785)) showed accumulating evidence to suggest that the potential efficacy and safety of Xanthine Oxidase inhibition in cardiovascular disease states, in general, and heart failure, in particular.
FIGHT (Functional Impact of GLP-1 for Heart Failure Treatment)
The FIGHT study (JAMA 2016;316(5):500-8 (PMC5021525)) showed that the GLP-1 agonist liraglutide does not improve post-hospitalization clinical stability in patients with relatively advanced HF and reduced LVEF. Larger studies are needed to establish the safety of liraglutide or other GLP-1 agonists for diabetes management or weight loss in patients with advanced HF.
INDIE-HFpEF (Inorganic Nitrite Delivery to Improve Exercise Capacity in HFpEF)
This is a study of 110 patients with HFpEF, objective evidence of HF and a reduced exercise capacity (peak VO2<75%), who were treated with 4 weeks of inhaled, nebulized inorganic nitrite vs. placebo. As compared to placebo, inhaled nitrite did not improve peak exercise capacity, daily activity levels, QOL scores, NT-proBNP levels or other indicators of clinical status in patients with HFpEF. Further study is urgently needed to identify effective, alternative interventions to restore NO-related signaling deficiencies and improve clinical status in HFpEF. The publication is pending.
IRONOUT (Oral Iron Repletion Effects On Oxygen Uptake in Heart Failure)
The IRONOUT study (JAMA. 2017;317(19):1958-66 (PMC5703044)), a randomized clinical trial of 225 adults with heart failure and reduced ejection fraction, showed that high dose oral iron polysaccharide had no significant effect on exercise capacity at 16 weeks compared with placebo (+23ml/min vs. -2 ml/min, respectively). These findings do not support the use of oral iron supplementation in patients with heart failure and reduced left ventricular ejection fraction.
NEAT (Nitrate’s Effect on Activity Tolerance in Heart Failure With Preserved Ejection Fraction)
The NEAT study (N Engl J Med 2015;373(24):2314-24(PMC4712067)) showed that, as compared to placebo, isosorbide mononitrate decreased daily activity levels and did not improve submaximal exercise capacity, quality-of-life scores or NT-proBNP levels in HFpEF patients. In addition, patient worn “accelerometry” devices provide unique information about the impact of therapies on patients daily functional status.
PRESERVE (Study of Renal Denervation in Patients With Heart Failure)
The PRESERVE study was terminated.
RELAX (PhosphodiesteRasE-5 Inhibition to Improve CLinical Status And EXercise Capacity in Diastolic Heart)
The RELAX study (JAMA. 2013 Mar 27;309(12):1268-77(PMC3835156)) showed that among patients with HFPEF, phosphodiesterase-5 inhibition with administration of sildenafil for 24 weeks, compared with placebo, did not result in significant improvement in exercise capacity or clinical status.
ROSE-AHF (Renal Optimization Strategies Evaluation in Acute Heart Failure) and RED ROSE (Reliable Evaluation of Dyspnea in the Heart Failure Network ROSE Study)
The ROSE studies (JAMA. 2013 Dec 18;310(23):2533-43 (PMC3934929)) showed that in participants with acute heart failure and renal dysfunction, neither low-dose dopamine nor low-dose nesiritide enhanced decongestion or improved renal function when added to diuretic therapy.
SMMART (Effectiveness of Surgical Mitral Valve Repair Versus Medical Treatment for People With Significant Mitral Regurgitation and Non-ischemic Congestive Heart Failure)
The SMMART study was terminated.