Higher Furosemide Dosing Shows Advantages

The study's main efficacy end point was each patient's cumulative self-assessment of symptoms at five points during the first 3 days of treatment. The bolus and continuous infusion routes showed no difference for this outcome. The low- and high-dose groups also showed no significant difference, but the high-dose regimen produced an improvement in symptoms that just missed statistical significance, at P = .06.

The primary safety outcome was the average change in serum creatinine 72 hours after onset of treatment, and both pairs of treatment produced small, virtually identical creatinine changes.

During 60 days of follow-up, there were no significant differences in a combined outcome of death, rehospitalization, or emergency department visits.

In three secondary efficacy measures at 72 hours, the high dose produced significantly better results compared with the low dose: dyspnea severity, total weight loss, and total net fluid volume loss. The high dose also produced a larger reduction in serum levels of NT-proBNP that missed statistical significance, at P = .06.

The high-dose regimen also linked with worsening renal function at 72 hours, but the effect disappeared by a week after treatment onset. At 72 hours, 23% of patients in the high-dose group and 14% in the low-dose group had a 0.3-mg/dL or greater rise in serum creatinine, a significant difference.

Dr. Solomon and Dr. Mann had no disclosures relevant to this study.

'There are a lot of suggestions that you get quicker, more favorable results with the high dose' of furosemide.

Source DR. FELKER

My Take

Ultrafiltration Bests Diuretics at Any Dose for Acute HF

The DOSE findings will reassure physicians that even smaller diuretic doses, given as boluses, have some efficacy. If a physician is going to use a diuretic for heart failure, it should be at the lowest effective dose.

However, both low-dose and high-dose furosemide regimens in patients hospitalized with acute decompensated heart failure are associated with relatively high rates of hospital readmissions because diuretics do not effectively reduce total sodium burden, which is an important cause of congestion in these patients. Other drug treatments, including vasopressin antagonists and adenosine receptor blockers, have the same limitation.

The only treatment that effectively reduces sodium burden is ultrafiltration, also known as aquapheresis. It is therefore the best treatment for heart failure patients with recurrent, acute congestion episodes.

My associates and I showed the superiority of ultrafiltration over intravenous treatment with a loop diuretic in results from the Ultrafiltration Versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated Congestive Heart Failure (UNLOAD) trial (J. Am. Coll. Cardiol. 2007;49:675-83). This multicenter study randomized 200 patients, and showed that ultrafiltration resulted in significantly better weight and net fluid loss within 2 days of treatment. During 90-day follow-up, the ultrafiltration patients had significantly fewer rehospitalizations and significantly fewer days spent rehospitalized compared with diuretic-treated patients.

Unfortunately, ultrafiltration has not caught on as the preferred method for managing acute heart failure in U.S. patients. It may be because only a single study has been done, and some physicians may want results from a confirmatory study before they adopt ultrafiltration.

Other factors have helped keep diuretics on top: First is habit; diuretics have traditionally been the primary therapy for acute decompensation. Also, the ultrafiltration equipment manufacturer, CHF Solutions, has had a limited marketing effort, although this may change now that the larger Gambro has acquired it. Another important issue is availability. Although most centers with a heart failure program have access to ultrafiltration, many U.S. patients with acute heart failure decompensation receive treatment at hospitals without heart failure centers.

Despite these limitations, I believe that ultrafiltration is the preferred treatment. Diuretics are less effective because they remove hypotonic fluid, without relieving sodium burden. Diuretics also enhance neurohormonal activation, another detrimental effect on patients. Ultrafiltration is unique in its ability to remove isotonic fluid, which gets sodium out of patients. No treatment of acute decompensation can be effective unless it reduces a patient's sodium burden.

A study now in progress, run by the National Heart, Lung, and Blood Institute's Heart Failure Network, involves a second comparison of ultrafiltration and diuretic treatment, specifically in patients who have worsening renal function during their decompensation episode.

MARIA ROSA COSTANZO, M.D., is medical director of the heart failure and pulmonary arterial hypertension programs at Midwest Heart Specialists in Naperville, Ill. She has served as speaker and consultant to, and received research support from, CHF Solutions.