Risk of digoxin intoxication in heart failure patients exposed to digoxin–diuretic interactions: a population‐based study

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Increased frequency of electrolyte abnormalities and cardiac arrhythmias among patients exposed to digoxin–diuretic interactions has been well‐documented in numerous descriptive studies. • Nonetheless, a clear causal relationship has not been established in these studies. WHAT THIS STUDY ADDS • The risks of digoxin intoxication associated with use of digoxin in combination with any diuretic use, types of diuretics, combinations of diuretics, and individual diuretics were quantified using a population‐based nested case–control study design. • The combined therapy of digoxin with any diuretic is associated with a 3.08‐fold increase in the risk of digoxin intoxication. • Regarding diuretic class, the risk carried by loop diuretics is greater than that of thiazides or potassium–sparing diuretics, and the risk varies with different combinations of diuretic classes and individual diuretics. AIMS To quantify the digoxin intoxication risk associated with exposure to digoxin–diuretic interactions, and evaluate whether the risk varies by diuretic type, individually or in combination. METHODS This was a population‐based nested case–control study in which data from the National Health Insurance Research Database (NHIRD) in Taiwan were analysed. RESULTS The study cohort comprised 154 058 heart failure (HF) patients taking digoxin between 2001 and 2004, in whom digoxin intoxication requiring a hospitalization (ICD‐9 code 972.1) occurred in 595 cases. A total of 28 243 matched controls were also selected for analysis. Cases were 3.08 times (adjusted OR 3.08, 95% CI 2.50, 3.79) more likely to have been prescribed diuretic medication in the previous month than controls. Regarding the class of diuretics, loop diuretics carried the greatest risk (adjusted OR 2.97, 95% CI 2.35, 3.75), followed by thiazides (OR 2.36, 95% CI 1.70, 3.29) and potassium‐sparing diuretics (OR 1.72, 95% CI 0.83, 3.56). The risk was also observed to vary with different combinations of diuretics, and the loops/thiazides/potassium‐sparing diuretics combination carried the greatest risk (adjusted OR 6.85, 95% CI 4.93, 9.53). Among the individual diuretics examined, hydrochlorothiazide carried the greatest risk (adjusted OR 4.63, 95% CI 2.50, 8.57). CONCLUSIONS This study provided empirical evidence that digoxin–diuretic interactions increased the risk of hospitalization for digoxin intoxication in HF patients. The risk was particularly high for concomitant use of digoxin with a combination of loop diuretics, thiazide and potassium‐sparing diuretics. The combined use of digoxin and diuretics should be avoided if possible.

Correlation between Serum Digoxin Concentration and Impaired Renal or/and Hepatic Functions in Cardiac Patients

“…Therefore, as the serum potassium concentration is reduced for example by diuretics, the inhibition of the Na, K pump by digoxin is further facilitated (Katzung and Parmley, 2004). In consequence, the depletion of intracellular potassium might occur, and is connected digoxin-induced arrhythmia (Wang et al, 2010).…”

Risk of cancer in patients with heart failure who use digoxin: a 10-year follow-up study and cell-based verification

“…To ensure the study cohort consists of patients with a diagnosis of heart failure disease and digoxin consumption, patients were included if they had been prescribed DDDs of digoxin in 2000. Also, patients were considered as having continued digoxin therapy if less than 3 months had elapsed between prescriptions [ 31 ]. The digoxin included DIGOXIN INJECTION, LANOXIN DIGOXIN TABLETS, LANOXIN DIGOXIN INJECTION, or CARDIACIN ELIXIR [ 32 ].…”

Focus on digitalis intoxication in the elderly Report of a case treated with digoxin-specific Fab antibody fragments

“…L'interaction médicamenteuse à risque la plus fréquente chez le sujet âgé est la co-prescription d'un diurétique. Une étude taïwannaise a ainsi montré une augmentation du risque de surdosage chez les patients sous diurétiques : risque 3 fois plus élevé avec un diurétique de l'anse, 4,6 fois plus élevé avec l'hydrochlorothiazide et 3,8 fois plus élevée pour l'association de 2 classes de diurétiques [17]. De plus, un diurétique kaliurétique peut entraîner une hypokaliémie, dont nous verrons qu'elle s'associe à un risque accru de torsade de pointe dans le cas d'une intoxication digitalique.…”

“…Un épisode de surdosage, toutes gravités confondues, surviendrait dans 6 à 23 % des traitements prolongés [5]. Le surdosage au cours d'un traitement chronique représentait 86 % des cas dans une cohorte de 838 patients pris en charge pour une intoxication digitalique en 1999-2000 [17]. Dans une cohorte nord-américaine de 1991, 71 % des 717 cas d'intoxications sévères étaient sous traitement au long cours [19].…”

“…À l'inverse, une hypokaliémie peut être délétère car associée à un risque plus élevé de torsade de pointe. Elle n'est évidemment pas directement liée à l'intoxication digitalique, mais peut se voir en cas de traitement diurétique associé ; elle explique d'ailleurs une part du risque vital de l'interaction médicamenteuse entre digoxine et diurétique [17].…”