Letter to the Editor: Using Randomized Controlled Trials to Evaluate the Effectiveness of Subcutaneous Furosemide in Advanced Heart Failure Patients With Palliative Care Needs

Introduction

Patients with advanced heart failure develop symptoms such as breathlessness and peripheral edema and have a progressive disease trajectory as well as a substantial symptom burden. ¹ Therefore, developing cost-effective interventions that avoid unnecessary hospitalization are necessary. Administering furosemide subcutaneously (SC) is one such intervention, due to the ability to manage patients in the community, which may reduce costs and improve outcomes. A recent systematic review investigating the effectiveness of SC diuretics for symptom control identified a paucity of evidence. The review recommended that randomized controlled trials (RCTs) are needed to understand where, to whom, and in what context, SC furosemide should be administered. ²

Strengths

High-quality RCTs are considered to be the gold standard for evaluating the efficacy and effectiveness of new health care interventions. In research there are numerous sources of potential error, with the most significant being bias, confounding, and chance. A competently designed RCT can reduce these sources of error. RCTs have the potential to be an appropriate approach to evaluate the effectiveness of SC furosemide in advanced heart failure patients.

This is due to the fact that there is both evidence and uncertainty with regard to the efficacy and effectiveness of this intervention, which, therefore, justifies the exposure of the intervention to some patients, whereas withholding from others. In addition, it is also possible to randomize and blind study participants receiving this intervention, which is not possible with all palliative care interventions. A small pilot crossover trial has evaluated the efficacy of SC furosemide in heart failure patients, which shows the potential for this study design to be used in future trials at a larger scale and in the advanced disease population specifically. ³

Limitations

Patients with advanced heart failure are a vulnerable cohort of patients and obtaining valid consent to include these patients in RCTs can be difficult. This leads to difficulties with enrolling adequate patient numbers into RCTs, which is exemplified in the Subcutaneous Furosemide in Acute Decompensated Heart Failure (SUBQ-HF) parallel RCT, which was terminated in 2019 due to slow enrollment. ⁴ The study was a pragmatic RCT that planned to determine whether SC furosemide improved outcomes within 30 days of randomization in advanced heart failure patients and would have contributed to the current evidence base. Suitable numbers of participants analyzed in palliative care studies are also affected by attrition, retention, and follow-up, and is one of the reasons SC furosemide has become commonplace without proven efficacy and effectiveness. Finally, there is currently insufficient funding in palliative care research that must be addressed if more high-quality RCTs are to be conducted in this field moving forward.

Conclusion

An RCT is both a suitable and viable study design to investigate this research question and, therefore, RCTs should be conducted moving forward to provide sufficient evidence to either justify or refute the use of SC furosemide in advanced heart failure patients. If this is to be the case, then considerable planning, methodological rigor, and funding are critical to ensure meaningful results are obtained, which can then be used to improve clinical practice.