onventional diuretics, including loop diuretics, are commonly
prescribed for heart failure (HF) patients with
volume overload.1–6 Loop diuretics are clinically useful
to reduce volume overload, but patients sometimes have an
insufficient response. In the Acute Decompensated Heart Failure
Registry (ADHERE), diuretic resistance was observed in approximately
30% of patients.7 A few therapeutic strategies, including
salt restriction, intravenous administration of loop diuretics,
and combination therapy with loop and thiazide diuretics,
have been developed to reduce resistance to loop diuretics, but
often result in unsatisfactory resolution. Moreover, administration
of high-dose loop diuretics is recognized as inducing several
adverse events, including renal impairment and hyponatremia,
with higher mortality.5,8–11 Despite this unmet medical need,
no new oral diuretics have been developed over the past decade.
C