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

Abstract

Background and methodsLoop 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). ResultsPrescribed 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 g roups. 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 (m M 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. ConclusionsFurosemide 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 g roups. Patients who died were prescribed higher furosemide doses and had g reater 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.Furosemide in the chronic treatment of heart failure Br J Clin Pharmacol 57 :5 623

Medication Adherence to Specific Drug Classes in Chronic Heart Failure

“…5,12,14,15,[19][20][21][22][23][24] Medication adherence can be assessed using direct and indirect methods, but no gold standard is widely accepted. Direct methods include the measurement of serum or urine drug levels and biologic markers, 25 providing information about the recent use of a drug; however, these depend on the variability in metabolism and have shortcomings to quantify adherence in the long term. 16 Medication adherence has been assessed indirectly in patients with HF using self-report, 26 pill counts, 27 prescription refill records, 10,17 and electronic-monitoring devices.…”

The Future of Pharmacogenetics in the Treatment of Heart Failure

“…Reasons why two clinically similar patients require widely differing loop diuretic doses evade us (59). One study looked at genetic variation in renal sodium transporters, measuring excretion of sodium, potassium, chloride and volume of urine in 97 healthy subjects taking bumetanide, torasemide and furosemide to identify differences related to genotype.…”

Contemporary Trends in the Pharmacological and Extracorporeal Management of Heart Failure

“…25 The definition of diuretic resistance has been problematic and hinders interpretation of the older literature: The natriuretic response to a loop diuretic such as furosemide can theoretically be defined by relating the amount of the drug in the urine to the sodium excretion in the same sample. 26 However, most clinical studies have used various diuretic doses (and/or urine volumes) as indices of resistance.…”