Nasal Spray Diuretic Evades Heart Failure Drug Flaw

CHICAGO — A nasal spray formulation of bumetanide, a diuretic drug, could help treat heart failure by preventing the resistance that can develop to oral forms of the drug, a preliminary safety and efficacy study in healthy volunteers showed.

Diuretic resistance is a common problem in patients with heart failure, said Eric Adler, MD, one of the study investigators and medical director of the Heart Transplant Program at the University of California, San Diego.

The congestion that occurs in heart failure also affects the gastrointestinal system, decreasing the effectiveness of drugs taken orally, including diuretics, which are a mainstay of heart failure treatment, he explained during his presentation of the study results — published simultaneously as a letter in Circulation — at the American Heart Association (AHA) Scientific Sessions 2024.

As diuretic resistance develops, the dose of diuretics is usually increased. And in many cases, the lack of diuretic efficacy leads to hospitalization, where diuretics are given intravenously. But this is often only temporarily or partially effective; an estimated 80% of patients are discharged with incomplete diuresis. As a result, “25% of patients who leave the hospital end up back in the hospital within 30 days of admission,” Adler reported.

Take It in the Nose

Nasal spray formulations are widely used for other classes of drugs, but this is the first time such a formulation is being tried for a diuretic drug.

“If we give an intranasal drug, whatever it may be, it accesses the capillary network to systemic circulation and bypasses the gastrointestinal system, getting quickly to our patients,” said Adler. It is hoped that this will prevent resistance and help better manage heart failure, he added.

The bumetanide nasal spray was compared with oral and intravenous formulations with the same pharmacological properties in a randomized, crossover study designed to confirm safety and tolerability. Data from 68 healthy volunteers showed equivalent urine output over the course of the study and the bioequivalence of the nasal spray and other formulations.

But this study is just a first step, said Eldrin Lewis, MD, a clinician-scientist in cardiovascular medicine at Stanford University in Palo Alto, California, who was not involved in the study.

“We really want to look at this in the population for whom it’s meant, and that’s patients with heart failure,” he said.

‘A Promissory Note’

This study was a “promissory note,” for future payback, however, that depends on the lack of side effects and the effectiveness panning out in patients with heart failure, Lewis explained.

It is possible that patients using the nasal spray for the long term might develop the same resistance as they develop to oral diuretics, he pointed out. There could also be risks to the nose or typical side effects associated with diuretics, such as muscle cramping, with repeated use.

But the nasal spray has potential value for patients discharged from the hospital after intravenous diuretic treatment, whose need for continuing diuretics is highly variable and sometimes leads to readmission. The nasal spray might help prevent readmission, Lewis said. It could also provide a rescue dose for patients on a stable dose of oral medication who experience a sudden change in fluid volume. And patients with both heart failure and stage III or IV chronic kidney disease often have greater diuretic resistance, so they may benefit from a nasal spray.

The formulation also widens the options for patients, he added. Some diuretics are available in a nebulizer, and some can be delivered subcutaneously. But some patients do not like nebulizers or needles and may prefer a nasal spray, he said.