Furosemide responsiveness, non-adherence and resistance during the chronic treatment of heart failure: a longitudinal study

BACKGROUND AND METHODS: Loop diuretic therapy is an essential part of chronic systolic heart failure (CH)F management, yet response to treatment can be variable. We analysed diuretic responsiveness in 39 stable patients with CHF in the community over 2 years. We measured serum ACE as a marker of adherence to ACE inhibitor therapy and urinary furosemide as a marker of diuretic adherence and action. Patients' clinical outcome was stable and not hospitalized (Group 0); alive but hospitalized (Group 1); or dead during follow up (Group 2). RESULTS: Prescribed furosemide dose was variable (range 20-370 mg generally once daily) and progressive dose increments were common. Failed furosemide adherence (defined as < 10% of a dose excreted in 24 h urine where normal average excretion = 50% of an oral dose) during static prescribed dosing was infrequent relative to all days of therapy; yet was equally common across all outcome groups. Furosemide non-adherence appeared to be independent of non-adherence with ACE inhibitor (as marked by serum ACE activity > 20 U l(-1)) treatment. Furosemide responsiveness (mm of sodium excreted per mg furosemide in urine) showed no relationship to prescribed dose and paradoxically tended to rise in patients with higher basal aldosterone concentrations. Furosemide responsiveness fell by outcome class despite increased dose. Within-patient responsiveness remained relatively constant although highly variable between individuals. CONCLUSIONS: Furosemide responsiveness varied greatly between individuals but was constant within an individual. Non-adherence with furosemide was less common among those who died and appeared to occur at different time points from non-adherence with ACE inhibitor treatment, which was slightly more common in all outcome groups. Patients who died were prescribed higher furosemide doses and had greater furosemide excretion yet had similar sodium excretion. The main factor in response to chronic furosemide therapy was intrarenal diuretic resistance. Gross non-adherence was less important.