Major Finding: In patients hospitalized for acute decompensated heart failure, treatment with intravenous furosemide produced similar outcomes whether patients received the drug as a twice-daily bolus or by continuous infusion, or whether patients received a low dose (80–240 mg/day) or high dose (200–600 mg/day).
Data Source: DOSE, a prospective, multicenter, randomized trial with 308 patients hospitalized for acute decompensated heart failure.
Disclosures: Dr. Felker has financial relationships with Corthera, Geron, Roche Diagnostics, Cytokinetics, BGMedicine, and Amgen. Dr. O'Connor has received grants from Roche Diagnostics and GE Healthcare. DOSE was funded by the National Heart, Lung, and Blood Institute.
ATLANTA — The first prospective, randomized trial to compare two different diuretic doses in patients with acute decompensated heart failure showed no clear-cut advantage to either a low or high dose, but the results may have shown a hint that higher doses have a few advantages, study investigators said.
Among experts not involved with the trial, opinion split on whether any valid difference by dose could be inferred from a study that failed to show significant differences in its primary end points.
“The top-line, take-home results were no differences,” between furosemide doses, or between twice-daily bolus injections or continuous infusion, Dr. G. Michael Felker said at the annual meeting of the American College of Cardiology.
“But when you look at the totality of the data, there are a lot of suggestions that you get quicker, more favorable results with the high dose,” including greater decongestion, a bigger reduction in blood levels of natriuretic peptide, and greater symptom relief,” said Dr. Felker, co-principal investigator of the study and a cardiologist and heart failure specialist at Duke University in Durham, N.C.
“If you're a practicing physician, there were important trends that suggest the higher-dose strategy had some favorable effects,” said Dr. Christopher M. O'Connor, co-principal investigator on the study and director of the Duke Heart Center. “We have no standard treatment for acute heart failure with diuretics. These results suggest a way to standardize care. Sometimes you need to make decisions based on imperfect data, on trends and secondary end points. These are the best available data in the world today on how to choose a furosemide dose.”
Others were less sure that results from the Diuretic Optimization Strategies Evaluation in Acute Heart Failure (DOSE) trial favored the higher furosemide dosage for patients hospitalized with acute decompensated heart failure.
“Based on this trial, I don't think there is a difference” between the doses used, said Dr. Scott D. Solomon of Brigham and Women's Hospital in Boston. “You still have to look at the overall trial results,” and in this case they showed no significant difference between the doses tested.”
“Many of us have been concerned that high-dose furosemide may hurt patients, and lead to cardiorenal hypoperfusion that may account for a lot of the negative outcomes that happen when we discharge patients,” but this study didn't show this, said Dr. Douglas Mann, professor and chief of the cardiovascular division at Washington University in St. Louis. Overall, patients “did a little better with symptoms” with the higher dose, “and you pay a small price with a slightly higher rise in serum creatinine levels.” The new findings “will have a major impact by giving us a baseline on how to approach treatment. One can take a conservative strategy at first, and then maybe escalate to a higher dose, which will probably be safe. The results tell you that you can decongest patients a bit more without excessive renal risk.”
DOSE enrolled 308 patients at U.S. hospitals within 24 hours of admission for acute decompensated heart failure. The amount of intravenous furosemide they received depended on the oral dose on which they had been maintained prior to hospitalization. Patients randomized to the low-dose group received the identical daily dose of furosemide they had been on before entering the hospital, from 80 to 240 mg/day. Patients randomized to the high-dose group received a daily dose of 200–600 mg/day, 2.5-fold higher than their usual oral dose. Patients who had routinely received a different loop diuretic before hospitalization had their prehospitalization dose converted to its furosemide equivalent. Patients also underwent a second, independent randomization based on whether they received the drug in hospital as a twice-daily bolus injection or as continuous infusion. In-hospital treatment continued for an average of about 60 hours.
Enrolled patients had an average age of 66, 73% were men, and 74% had been hospitalized for heart failure within the prior year. Their average left ventricular ejection fraction was 35%, their average creatinine level was 1.6 mg/dL, and their average level of N-terminal–pro brain natriuretic peptide (NT-proBNP) was more than 7,000 pg/mL.