Author + information
- Zubin J. Eapen, MD, MHS∗ ( and )
- Jacob P. Kelly, MD
- ↵∗Reprint requests and correspondence:
Dr. Zubin J. Eapen, Duke Clinical Research Institute, PO Box 17969, Durham, North Carolina 27715.
The discovery and use of diuretics are ancient history. Paleolithic humans may have discovered the original diuretic when they found caffeine-containing plants whose seeds and bark were used to prepare beverages (1). In the 16th century, the renowned physician Paracelsus identified mercurous chloride as a diuretic to be used in the management of edema, known then as dropsy. In the 20th century, the medical student Alfred Vogel observed that the injection of organomercurial compounds for syphilis also caused a substantial diuresis (2). A new chapter of discovery and development of diuretics ensued.
Today, diuretics are among the most commonly prescribed drugs, particularly to decongest the patient with heart failure (HF). This approach to decompensated HF has not changed much over several decades, but the emphasis on the treatment venue has. Public reporting and financial accountability have motivated hospitals to seek safe and effective alternatives to rehospitalization. The evolution of Medicare from a traditional fee-for-service system to a value-based payment system focused on quality of care and patient outcomes will motivate hospitals further. Ambulatory interventions are needed to safely prevent the seemingly inexorable patient journey from hospital to home and back.
One approach is to decentralize treatment strategies that have traditionally been found in acute settings. In this issue of JACC: Heart Failure, Buckley et al. (3) report their findings on ambulatory administration of intravenous diuretics to decongest hemodynamically stable patients with worsening HF. Adapting the approach used in the DOSE (Diuretic Optimization Strategies Evaluation) trial, the authors used a standard protocol to determine the intravenous furosemide regimen, which primarily consisted of a bolus followed by a 3-h infusion (4). Dosing and adjunctive therapies were determined by a standardized conversion algorithm based on the furosemide equivalent of patients’ home oral diuretic total daily dose: low (≤40 mg), standard (41 to 160 mg), high (161 to 300 mg), and mega (301 to 800 mg). There was considerable diuresis and weight loss across all groups within 3 h. The median urine output and clinic weight loss were lowest in the mega-dose group compared with the high- and standard-dose groups (950 ml, 1,150 ml, and 1,402 ml, respectively, for urine output, and 0.9, 1.1, and 1.3 kg, respectively for weight loss), with HF with reduced ejection fraction versus HF with preserved ejection fraction patients having similar urine output and weight loss. Among the 60 enrolled outpatients, the observed rate of all-cause hospitalization was 31.7% at 30 days without any deaths. In comparison, the clinicians who referred these patients anticipated imminent hospitalization in 52.8% (n = 28). The authors concluded that intravenous furosemide was safe and potentially efficacious in the outpatient treatment of patients with chronic ambulatory advanced HF and signs and symptoms of worsening congestion.
Although the observed all-cause hospitalization rates are higher than the 20% to 25% reported rehospitalization rates for HF (5), this was a relatively advanced HF population. At the time of enrollment, 58.3% were considered New York Heart Association (NYHA) functional class III, and 20% were considered NYHA functional class IV. Virtually one-half were receiving >300 mg of total daily furosemide, suggesting that diuretic resistance was prevalent in this cohort. This may explain the observation that the high-dose and mega-dose maintenance dose groups had less diuresis and weight loss than the lower maintenance dose group despite higher doses of intravenous furosemide and the supplementary use of thiazide diuretics.
As the authors note, this study builds on a body of literature supporting a role for intravenous diuretics in the ambulatory setting. Previous studies reported their experience with the use of intravenous diuretics in the ambulatory setting, demonstrating safe use with reduced hospitalizations and costs (6,7). This study adds supportive evidence for a standardized algorithm that can be used to administer even higher doses of intravenous diuretics than previously studied. Importantly, the title of the authors’ paper suggests that this intensive treatment strategy represents only 1 tool in the armamentarium of an effective outpatient HF unit. Disease management efforts can further increase their effectiveness through other evidence-based strategies such as involving a multidisciplinary care team and offering high-intensity home visits (8).
The Duke Heart Failure Same Day Access Clinic is another example of incorporating ambulatory intravenous diuretic capabilities into an established, multidisciplinary disease management program (9). Designed to provide on-demand access to intensive, patient-centered care for HF, the Duke Heart Failure Same-Day Access Clinic features nurse practitioners equipped with disease management expertise and treatment protocols to manage patients who have signs or symptoms of worsening HF or need early post-discharge follow-up. Open every weekday, the clinic initiates and manages established and emerging evidence-based therapies, coordinates care with other subspecialists to treat comorbidities, and collaborates with skilled nursing facilities and home health and hospice agencies in an effort to improve quality of life for shared patients. The clinic also features intensive therapeutic services including intravenous diuretic infusions and electrolyte repletion. In the first 3 years, the Duke Heart Failure Same-Day Access Clinic has seen >3,000 patient visits with Duke University Hospital observing a 10.2% reduction in the 30-day readmission rate for HF patients and avoiding financial penalties for excess readmissions (10).
These dedicated outpatient HF clinics are the ideal living laboratories in which to test ambulatory management strategies that may prove to be safe and effective alternatives to hospitalization. For example, the use of intravenous diuretics could be studied further in such clinics using a clustered randomized design to better understand the true impact on rehospitalizations and total inpatient days. Comparative effectiveness studies of the effect of different loop diuretics on quality of life could be conducted (11). New formulations and delivery mechanisms of diuretics, such as subcutaneous administration or even depot injection, could be tested (12).
Dedicated outpatient HF clinics are also the ideal hub to monitor a HF patient population. Remote monitoring of data collected by the patient in the home (e.g., weight, blood pressure, patient-reported outcomes, hemodynamic data from implantable sensors) may become even more actionable in the hands of dedicated clinics equipped with proven interventions. By intervening in worrisome trends in these data, these clinics can tailor HF care for the tenuous patient with precision. Coupling ambulatory monitoring with interventions is now facilitating the safe and effective decentralization of services from the hospital to the clinic. Such integrated services may ultimately help move care into the home to provide patient-centered care that is proactive, predictive, and preemptive.
↵∗ Editorials published in JACC: Heart Failure reflect the views of the authors and do not necessarily represent the views of JACC: Heart Failure or the American College of Cardiology.
Dr. Eapen is on the advisory board of Novartis, Amgen, and Cytokinetics; is a consultant for Novartis, Amgen, and SHL Telemedicine; and has received honoraria from Janssen. Dr. Kelly has received National Institutes of Health (NIH) training grant 5 T32 HL 7101-39.
- American College of Cardiology Foundation
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- ↵Pizzi RA. Developing diuretics. Modern Drug Discovery, February 2003. Available at: http://pubs.acs.org/subscribe/archive/mdd/v06/i02/pdf/203timeline.pdf. Accessed July 29, 2015.
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