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Diuretic Regimen Comparison in Ambulatory Congested HF Patients
Quick Takes
- For patients getting IV diuretics at an ambulatory care unit, a regimen of IV furosemide + oral metolazone resulted in higher urinary sodium excretion compared to IV furosemide alone and IV furosemide + IV acetazolamide.
- IV furosemide + oral metolazone also led to higher total urinary volume compared to IV furosemide + IV acetazolamide, but no significant difference compared to IV furosemide alone.
- The incidence of worsening renal function was higher with IV furosemide + oral metolazone (39%) compared to IV furosemide alone (16%) and IV furosemide + IV acetazolamide (2.6%).
Study Questions:
For patients with heart failure (HF) and refractory volume overload receiving treatment at an ambulatory care unit, how do three commonly used diuretic regimens compare in terms of potency and safety?
Methods:
This was a single-center, open-label, randomized, crossover study comparing three different diuretic regimens (intravenous [IV] furosemide 250 mg vs. IV furosemide 250 mg + oral metolazone 5 mg vs. IV furosemide 250 mg + IV acetazolamide 500 mg) in patients with HF being treated at an ambulatory care unit. Patients needed to be age ≥18 years, have New York Heart Association (NYHA) functional class II-IV symptoms, have at least one sign of congestion, and be on HF medical therapy with oral diuretics for 30 days prior to being included in the study. Patients with recent acute coronary syndrome, planned cardiac transplantation or ventricular assist device, recent hypotension or need for IV inotropes/vasopressors/vasodilators, or an estimated glomerular filtration rate <20 mL/min/1.73 m2 or recent need for renal replacement therapy or ultrafiltration were excluded from the study.
Patients received treatments at an ambulatory care unit once a week for 3 weeks and were randomized to receive one of six sequences of diuretic regimens (one diuretic regimen per week with planned exposure to all three regimens over the course of the study). Study visits were also completed during treatment sessions to assess clinical status. The primary endpoint for the study was total urinary sodium excretion at 6 hours post-treatment. The secondary endpoint was total urinary volume excretion at 6 hours post-treatment. The safety outcomes assessed were symptomatic hypotension, worsening renal function (WRF), hyponatremia, hypokalemia or hyperkalemia, and metabolic acidosis requiring treatment.
Results:
A total of 42 patients were enrolled in the study. Overall, patients had a mean age of 72 ± 9 years with 40% women and 50% with a left ventricular ejection fraction >50%. The majority of patients had NYHA class III symptoms (74%). Patients were generally similar between the six randomized treatment sequences. Of the initial 42 patients, 37 completed the entire treatment sequence.
For the primary endpoint, IV furosemide + oral metolazone led to higher urinary sodium excretion compared to IV furosemide alone (4691 vs. 3835 mg, p = 0.015) and compared to IV furosemide + IV acetazolamide (4691 vs. 3584 mg, p = 0.001). There was no significant difference in urinary sodium excretion between IV furosemide alone and IV furosemide + IV acetazolamide. For the secondary endpoint, IV furosemide + oral metolazone led to higher total urinary volume compared to IV furosemide + IV acetazolamide (1.84 vs. 1.58 L, p = 0.039). IV furosemide alone led to 1.71 L of total urinary volume but was not significantly different compared to the other two regimens. For the safety outcomes, incidence of WRF was higher with IV furosemide + oral metolazone (39%) compared to IV furosemide alone (16%) and IV furosemide + IV acetazolamide (2.6%). No significant differences for the other safety outcomes were noted.
Conclusions:
For patients with HF and refractory volume overload receiving treatment at an ambulatory care unit, a diuretic regimen of IV furosemide + oral metolazone resulted in greater urinary sodium excretion compared to IV furosemide alone or IV furosemide + IV acetazolamide.
Perspective:
For ambulatory patients with chronic HF, oral loop diuretics are integral to managing congestive symptoms but patients may eventually become refractory and develop progressive volume overload. Ambulatory care units that can provide IV diuretics have been used by some institutions to try and prevent the need for hospitalization for decompensated HF. Less is known about optimal diuretic regimens in this setting and this current study provides additional insights into this.
A few of the key findings of this study may impact practice. First, a regimen of IV furosemide and oral metolazone appears to be quite effective at increasing urinary sodium excretion compared to the other regimens but can come at the cost of WRF. A balance of risk and benefits of diuretic regimen choice should be considered based on individual patient factors. Notably, the safety profiles of the regimens were otherwise similar when considering electrolyte changes and blood pressure. Second, the addition of IV acetazolamide to IV furosemide did not have a significant impact on natriuresis or diuresis in this study. This is different than the findings of the ADVOR trial, though the patient population was different and high use of sodium-glucose cotransporter 2 (SGLT2) inhibitors in this current study could explain the difference. These factors should be considered when considering adjunctive use of IV acetazolamide.
This study is limited though by the crossover design. It is unclear if the treatment with a different regimen the prior week or changes in degree of congestion as a result could have impacted the subsequent response to the diuretic regimens. Future studies will need to focus on how to best tailor different diuretic regimens in this setting, the impact that baseline therapies like SGLT2 inhibitors have on response, and how other clinical outcomes are impacted.
Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure
Keywords: Diuresis, Heart Failure
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