Predictive performance of serum digoxin concentration in patients with congestive heart failure by a hyperbolic model based on creatinine clearance

Konishi, Hiroki; Shimizu, Shoko; Chiba, Momoko; Minouchi, Tokuzo; Koida, Masao; Yamaji, Akihiro

doi:10.1046/j.1365-2710.2002.00418.x

Cited by 17 publications

(23 citation statements)

References 27 publications

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“…It was also shown that although there was a significant correlation between CL and Ccr in the group overall, correlations within the different stages of renal function were not evident (Figure 3). These results are the same as those reported by Konishi5 and Muzzarelli14 in all inclusion patients. However, when considering the effect of renal function, the results of correlation between predicted and measured SDC were largely nonsignificant, only significant in stage 3 patients.…”

Section: Discussionsupporting

confidence: 92%

“…Assuming no clinically significant interindividual difference in nonrenal digoxin CL owing to the lack of a compensatory increase in metabolic clearance with a decrease in the renal clearance, Konishi developed a predictive model in order to apply the equation in clinical practice for accurate and rapid determination of digoxin concentration 5. However, in subsequent research, it was found that only 26% of interindividual variability in digoxin CL can be explained by changes in Ccr 13.…”

Section: Discussionmentioning

confidence: 99%

“…A number of equations have been developed to calculate the digoxin dosage in order to avoid the adverse effects of overexposure to the drug, but most have targeted higher SDCs than those now recommended due to safety concerns. Konishi5 formulated an equation to determine the daily dose of digoxin based only on creatinine clearance rate (Ccr) and SDC. However, this equation has not been tested in Chinese patients.…”

Section: Introductionmentioning

confidence: 99%

“…The aim of this study was to evaluate the correlation between SDC predicted by the Konishi equation,5 ie, L (ng/mL) = D (μg/day)/[2.22*Ccr + 25.7], and the actual SDC measured in Chinese patients at different stages of renal disease, with Ccr values estimated by the Cockcroft–Gault equation in mL per minute 6…”

Section: Introductionmentioning

confidence: 99%

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Efficiency of individual dosage of digoxin with calculated concentration

Zhao

Yang

et al. 2014

CIA

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BackgroundDigoxin is a frequently prescribed drug, particularly in the elderly population, in which there is an increased prevalence of atrial fibrillation and cardiac failure. With its complex pharmacokinetic profile and narrow therapeutic index, use of digoxin requires regular monitoring of blood levels. Recent evidence suggests that a lower concentration range (0.4–1.0 ng/mL) is preferable in patients with congestive heart failure and a higher range (0.8–2.0 ng/mL) is needed in patients with atrial tachyarrhythmia. The Konishi equation is widely used to predict the serum digoxin concentration (SDC) in Japan. This study assessed the correlation between SDC predicted by the Konishi equation and that actually measured in Chinese patients and investigated the impact of renal function on SDC.MethodsThe study subjects comprised 72 patients with cardiac failure or/and atrial tachyarrhythmia seen at our hospital from January 2012 to December 2013. The patients were divided into five groups according to Kidney Diseases Outcome Quality Initiative guidelines. SDCs were measured using the Abbott Architect i1000 immunology analyzer. The correlations between measured SDCs and calculated SDCs and between clearance of digoxin and creatinine clearance rate were assessed retrospectively.ResultsThe correlation between measured and predicted SDC calculated by the Konishi equation was significant (r=0.655, P<0.001) for the 72 patients overall; however, correlations within the different stages of renal function were nonsignificant, with a correlation found only in patients with stage 3 (30 mL per minute < creatinine clearance <60 mL per minute). With regard to the correlation between clearance of digoxin and creatinine clearance, our results show that although there was a significant correlation between clearance of digoxin and creatinine clearance in the group overall, correlations were not evident within the different stages of renal function.ConclusionThe results of this study indicate that clearance of digoxin and the creatinine clearance rate cannot be explained by renal function alone and that the validity of the Konishi equation for individualizing the digoxin dosage in Chinese patients is limited, being applicable only in stage 3 renal disease. Further research in larger numbers of patients across all stages of renal function will be required in the future to verify the original Konishi model.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Efficiency of individual dosage of digoxin with calculated concentration

Zhao

Yang

et al. 2014

CIA

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“…Previous studies have employed statistical models [1, 2, 20, 22, 25] and pharmacokinetics [18, 21, 23, 26, 28, 29, 31–36], and data mining and machine learning techniques have only recently been adopted to improve model predictability [8, 24]. This study investigated decision tree-based approaches, which were identified to exhibit an average performance superior to that of other techniques.…”

Section: Discussionmentioning

confidence: 99%

Improvement of Adequate Digoxin Dosage: An Application of Machine Learning Approach

Tai

Tsai

et al. 2018

Journal of Healthcare Engineering

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Digoxin is a high-alert medication because of its narrow therapeutic range and high drug-to-drug interactions (DDIs). Approximately 50% of digoxin toxicity cases are preventable, which motivated us to improve the treatment outcomes of digoxin. The objective of this study is to apply machine learning techniques to predict the appropriateness of initial digoxin dosage. A total of 307 inpatients who had their conditions treated with digoxin between 2004 and 2013 at a medical center in Taiwan were collected in the study. Ten independent variables, including demographic information, laboratory data, and whether the patients had CHF were also noted. A patient with serum digoxin concentration being controlled at 0.5–0.9 ng/mL after his/her initial digoxin dosage was defined as having an appropriate use of digoxin; otherwise, a patient was defined as having an inappropriate use of digoxin. Weka 3.7.3, an open source machine learning software, was adopted to develop prediction models. Six machine learning techniques were considered, including decision tree (C4.5), k-nearest neighbors (kNN), classification and regression tree (CART), randomForest (RF), multilayer perceptron (MLP), and logistic regression (LGR). In the non-DDI group, the area under ROC curve (AUC) of RF (0.912) was excellent, followed by that of MLP (0.813), CART (0.791), and C4.5 (0.784); the remaining classifiers performed poorly. For the DDI group, the AUC of RF (0.892) was the best, followed by CART (0.795), MLP (0.777), and C4.5 (0.774); the other classifiers' performances were less than ideal. The decision tree-based approaches and MLP exhibited markedly superior accuracy performance, regardless of DDI status. Although digoxin is a high-alert medication, its initial dose can be accurately determined by using data mining techniques such as decision tree-based and MLP approaches. Developing a dosage decision support system may serve as a supplementary tool for clinicians and also increase drug safety in clinical practice.

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A perspective on re‐evaluating digoxin's role in the current management of patients with chronic systolic heart failure: targeting serum concentration to reduce hospitalization and improve safety profile

Ghali

Patterson

Stough

et al. 2014

European J of Heart Fail

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Digoxin improves exercise tolerance and reduces hospitalizations in patients with systolic heart failure, but its use has declined progressively for the past two decades. The Digitalis Investigation Group trial showed that digoxin reduced hospitalizations but had a neutral effect on total mortality. There was evidence that mortality caused by worsening heart failure was less, but there was also a signal suggesting an increase in other cardiac (presumed arrhythmic) death. Use of digoxin has declined substantially and recent guideline recommendations have significantly de-emphasized the importance of this drug in the management of heart failure. Two developments suggest that re-evaluation of the contemporary role of digoxin in the management of heart failure with reduced ejection fraction is warranted. First, heart failure remains progressive, characterized by chronic debility, exercise intolerance, and frequent and costly hospitalizations, despite evidence-based drug and device therapies that prolong survival. Health economics have made reducing hospitalizations in patients with heart failure a major priority. Second, a strong association has emerged between serum concentration and the safety and efficacy of digoxin, which indicates a change in our approach to dosing this agent is needed. Experimental and clinical results suggest that optimizing therapeutic benefit and avoiding harm means dosing to achieve low serum digoxin concentrations (0.5-0.9 ng/mL). Digoxin is an inexpensive agent and the totality of evidence indicates that it reduces hospitalizations and improves symptoms safely when dosed to achieve low serum concentrations. These findings suggest digoxin should have a more prominent therapeutic role in patients with heart failure and reduced ejection fraction.

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Predictive performance of serum digoxin concentration in patients with congestive heart failure by a hyperbolic model based on creatinine clearance

Cited by 17 publications

References 27 publications

Efficiency of individual dosage of digoxin with calculated concentration

Efficiency of individual dosage of digoxin with calculated concentration

Improvement of Adequate Digoxin Dosage: An Application of Machine Learning Approach

A perspective on re‐evaluating digoxin's role in the current management of patients with chronic systolic heart failure: targeting serum concentration to reduce hospitalization and improve safety profile

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