SNOWMASS, COLO. – The primary treatment goal in patients hospitalized for acute decompensated heart failure is aggressive decongestion to get them feeling better and out of the hospital quicker – and the best way to achieve that is with high-dose loop diuretics administered intravenously at a dose equivalent to 2.5 times the previous oral dose, Dr. Akshay S. Desai said at the Annual Cardiovascular Conference at Snowmass.

This was the key lesson of the Diuretic Optimization Strategies Evaluation (DOSE) trial, a prospective double-blind randomized trial that provides physicians with the best available data on how to decongest patients with acute decompensated heart failure (ADHF), according to Dr. Desai, a coinvestigator. The study was conducted by the National Heart, Lung, and Blood Institute Heart Failure Clinical Research Network.

The DOSE trial showed that it really doesn’t matter whether the diuretic is administered intravenously by continuous infusion or a bolus every 12 hours. The important thing is the high-dose strategy. It proved to be safe and was associated with accelerated decongestion as manifest in greater relief of dyspnea, greater weight loss and fluid loss, and a larger reduction in serum brain natriuretic peptide at 72 hours than low-dose therapy equivalent to the patient’s previous oral dose (N Engl J Med. 2011 Mar 3;364[9]:797-805).

“The message for you in practice is that the route of diuretic administration is probably not important as long as you give an adequate dose. I would consider giving the higher dose of diuretic because it’s associated with more effective decongestion and perhaps shorter length of stay,” said Dr. Desai, director of heart failure disease management at Brigham and Women’s Hospital in Boston.

There is a trade-off in ADHF between effective decongestion and worsening renal function as reflected in increased serum creatinine levels. Transient worsening of renal function occurred more frequently with the high-dose strategy in the DOSE trial, but it had no impact on clinical outcomes at 60 days follow-up. This finding is consistent with the results of an important Italian study showing that worsening renal function alone isn’t independently associated with increased risk of death or ADHF readmission; the problems arise in patients with worsening renal function and persistent congestion (Circ Heart Fail. 2012 Jan;5[1]:54-62).

Worsening congestion drives most hospitalizations for heart failure. And patients who are still congested at discharge are at dramatically increased risk for death or readmission in the ensuing 6 months. Yet the limitations of current therapy mean that even in expert hands, a substantial proportion of patients are discharged with clinically significant congestion. For example, in a retrospective analysis of nearly 500 patients enrolled in ADHF studies conducted by physicians in the NHLBI Heart Failure Clinical Research Network, only 52% were discharged free of congestion (Circ Heart Fail. 2015 Jul;8[4]:741-8).

Beyond aggressive treatment with loop diuretics, what else is useful in achieving the goal of hospital discharge with normalized filling pressures? Not much, according to a considerable body of research on the topic.

“The data tell us more about what not to do than what to do,” according to Dr. Desai.

For example, even though aggressive salt and fluid restriction is often forced upon patients hospitalized for ADHF on the rationale that this strategy may make it easier for diuretics to work, it’s not an evidence-based practice. Indeed, in a randomized clinical trial with blinded outcome assessments, an in-hospital diet restricted to a maximum intake of 800 mg of sodium and 800 mL of fluid daily had no effect on weight loss or a clinical congestion score (JAMA Intern Med. 2013 June 24;173[12]:1058-64).

“What it did very effectively was make patients thirsty. There are probably some patients where restriction of sodium and fluid intake is important, but routine use of tight restrictions is probably more harmful than helpful,” he observed.

The list of failed once-promising alternatives to diuretics in the setting of ADHF is impressive. It includes milrinone, tolvaptan, nesiritide, levosimendan, tezosentan, low-dose dopamine, and ultrafiltration. All had a sound mechanistic basis for the belief that they might improve outcomes, but in clinical trials none of them did.

Although routine use of pulmonary artery catheters to guide decongestion therapy in ADHF isn’t warranted because it has not been shown to be better than clinical assessment, there are certain situations where it is extremely helpful. For example, in the patient who isn’t responding to adequate doses of loop diuretics, it becomes important to understand the hemodynamics, which may involve systemic vascular resistance or a cardiac output problem.

Other situations where it’s worthwhile to consider placement of a pulmonary artery catheter include the patient of uncertain fluid status where it’s not possible to confidently estimate cardiac output at the bedside or markedly worsening renal function with empiric therapy.

Dr. Desai reported receiving research funding from Novartis and St. Jude Medical and serving as a paid consultant to Merck, Relypsa, and St. Jude Medical.

bjancin@frontlinemedcom.com

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