Abstract
BackgroundDirect oral anticoagulants (DOACs) pharmacokinetics depends on estimated glomerular filtration rate (eGFR), whose estimation is crucial for optimal risk/benefit balance.AimsTo assess the concordance among different eGFR formulas and the potential impact on DOACs prescription appropriateness and bleeding risk in oldest hospitalized patients.MethodsPost hoc analysis of a single-centre prospective cohort study. eGFR was calculated by creatinine-based (MDRD, CKD-EPICr, BIS1) and creatinine–cystatin-C-based (CKD-EPIComb and BIS2) formulas. Patients were stratified according to eGFR [severely depressed (SD) 15–29; moderately depressed (MD) 30–49; preserved/mildly depressed (PMD): ≥ 50 ml/min/1.73 m2]. Concordance between the different equations was assessed by Cohen’s kappa coefficient.ResultsAmong AF patients, 841 (59.2% women, mean age 85.9 ± 6.5 years) received DOACs. By CKD-EPICr equation, 135 patients were allocated in the SD, 255 in the MD and 451 in the PMD group. The concordance was excellent only between BIS 2 and CKD-EPIComb and MDRD and CKD-EPICr, while was worse (from good to poor) between the other formulas. Indeed, by adding cystatin-C almost over 1/3 of the patients were reallocated to a worse eGFR class. Bleeding prevalence increased by 2–3% in patients with discordant eGFR between formulas, reallocated to a worse chronic kidney disease (CKD) stage, although without reaching statistical significance. CKD-EPIComb resulted the best predictor of bleeding events (AUROC 0.71, p = 0.03).DiscussionThis study highlights the variability in CKD staging according to different eGFR formulas, potentially determining inappropriate DOACs dosing. Although the cystatin-C derived CKDEPIComb equation is the most accurate for stratifying patients, BIS1 may represent a reliable alternative.
Highlights
Multimorbidity is a common problem in elderly population, especially above 85 years of age, leading to increased drug prescription and amount of adverse events, drug–drug and drug–disease interactions and inappropriate prescribing [1]
Since all directacting oral anticoagulants (DOACs) depend on renal excretion for elimination [7], an accurate glomerular filtration rate estimation is crucial, given that 43% of patients with atrial fibrillation (AF) and chronic kidney disease (CKD) resulted potentially overdosed with Direct oral anticoagulants (DOACs) [7, 8]
Among patients with AF, 926 received DOACs therapy at hospital discharge; cystatin-C was not measured in 85 of them, all the estimated glomerular filtration rate (eGFR) formulas were available in 841 patients: 287 (34.1%) received rivaroxaban, 278 (33.0%) apixaban, 252 (30.0%) dabigatran and 24 (2.9%) edoxaban
Summary
Multimorbidity is a common problem in elderly population, especially above 85 years of age, leading to increased drug prescription and amount of adverse events, drug–drug and drug–disease interactions and inappropriate prescribing [1]. We aimed at assessing the level of concordance among different eGFR estimating equations and the possible impact of discordant eGFR on DOACs prescription appropriateness and clinically relevant bleedings in older, hospitalized AF patients receiving DOACs. Direct oral anticoagulants (DOACs) pharmacokinetics depends on estimated glomerular filtration rate (eGFR), whose estimation is crucial for optimal risk/benefit balance. Aims To assess the concordance among different eGFR formulas and the potential impact on DOACs prescription appropriateness and bleeding risk in oldest hospitalized patients. Bleeding prevalence increased by 2–3% in patients with discordant eGFR between formulas, reallocated to a worse chronic kidney disease (CKD) stage, without reaching statistical significance. Discussion This study highlights the variability in CKD staging according to different eGFR formulas, potentially determining inappropriate DOACs dosing. The cystatin-C derived C KDEPIComb equation is the most accurate for stratifying patients, BIS1 may represent a reliable alternative
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