Subcutaneous furosemide for the treatment of heart failure: a state-of-the art review Maxwell Eyram Afari 1 & Joe Aoun 2 & Sarthak Khare 2 & Lana Tsao 1 # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract The prevalence of heart failure (HF) is on the rise. By 2030, over eight million Americans (46% increase from current prevalence) will have heart failure. In the USA, approximately 30 billion dollars is spent annually on heart failure and this number will likely double in 2030. Thus, HF represents a significant economic burden. Acute decompensated heart failure (ADHF) is a clinical spectrum, which refers to increasing symptoms and signs of heart failure prompting an emergency room visit or hospitalization. In ADHF, inpatient administration of intravenous diuretic is the standard of care due to the variability in the absorption of oral diuretics. Within 30 days, 25–30% of these patients are readmitted with recurrent ADHF. Recent efforts have focused in reducing HF readmission, and thereby decreasing costs; hence, innovative outpatient treatment options have emerged. Subcutaneous furosemide use will potentially overcome the need to place intravenous lines, reduce associated expenses, and enable manage- ment of ADHF at home. This review presents data on the pharmacodynamics and pharmacokinetics of subcutaneous furosemide, scientific evidence on the use of this therapy in the palliative and hospice population, and its experimental use as an outpatient therapy and/or as a bridge from inpatient to home. Keywords Subcutaneous . Furosemide . Heart failure . At-home treatment . Palliative care Introduction The prevalence of heart failure (HF) is estimated around 6.5 million people and is expected to increase to eight million by the year 2030. HF is responsible for one million hospitaliza- tions annually. Each year, there are 650,000 new cases [1]. In the USA, approximately 30 billion dollars is spent annually on heart failure and this number will likely double in 2030. This represents a significant economic burden on the health care system. Acute decompensated heart failure (ADHF) is a clin- ical spectrum which refers to increasing symptoms and signs of heart failure prompting an emergency room visit or hospitali- zation. Readmission rates at 30 days and 6 months are estimat- ed to be 25% and 50% respectively. Since October 2012, the Hospital Readmissions Reduction Program (HRRP) has man- dated public reporting of readmission rates which resulted in financial penalties for hospitals with higher readmission rates. Among Medicare beneficiaries, heart failure is the leading cause of readmissions and a major contributor to penalties [2]. When patients present with signs of ADHF, the bioavail- ability of oral medications is unpredictable (20–90% for furo- semide) [3, 4]; hence, parenteral diuretic therapy is the main- stay of treatment. Intravenous therapy requires the placement of intravenous lines by a health care practitioner with associ- ated maintenance expense and inherent risk for infections and thrombosis. A novel approach to reduce heart failure readmissions is the use of subcutaneous (SC) furosemide for ADHF. The emergence of subcutaneous furosemide The mechanism of action of furosemide is through the inhibi- tion of sodium and chloride reabsorption in the proximal and distal tubules as well as the loop of Henle. Furosemide has been available since the 1960s and is commonly administered via oral, intravenous (IV), or intramuscular formulations. Subcutaneous furosemide offers the possibility of avoiding IV line placement and/or inpatient admission for parenteral diuresis. Conventional furosemide is alkaline (pH 8.5 to 9), * Maxwell Eyram Afari maxieafari@yahoo.co.uk 1 Division of Cardiovascular Medicine, St. Elizabeth’ s Medical Center/ Tufts University School of Medicine, Brighton, MA 02135, USA 2 Department of Medicine, St Elizabeth’ s Medical Center/ Tufts University School of Medicine, Brighton, MA 02135, USA Heart Failure Reviews https://doi.org/10.1007/s10741-018-9760-6