Comparison of Renal Function Estimation Formulae for Dosing Direct Oral Anticoagulants in Patients with Atrial Fibrillation

The Cockcroft-Gault (CG) formula is recommended to guide clinicians in the choice of the appropriate dosage for direct oral anticoagulants (DOACs). However, the performance of the CG formula varies depending on the patient’s age, weight, and degree of renal function. We aimed to compare the validity of the CG formula with that of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) formulae for dosing DOACs. A total of 6268 consecutive patients on anticoagulants for atrial fibrillation (AF) were retrospectively investigated. Among underweight and elderly patients, the CG formula underestimated renal function compared with the non-CG formulae. However, the concordant rate of drug indications between the CG and the non-CG formulae was approximately 94%. On-label uses under the three formulae were associated with a lower risk of major bleeding (but not thromboembolism) compared to warfarin. Although we found differences in estimating renal function and the proportions of drug indications between the CG and non-CG formulae, the risks of thromboembolism and major bleeding were similar to those with warfarin regardless of which formula was used.

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Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Renal Dysfunction

Rational Pharmacotherapy in Cardiology ◽

10.20996/1819-6446-2021-02-03 ◽

2021 ◽

Vol 17 (1) ◽

pp. 62-72

Author(s):

Z. D. Kobalava ◽

A. A. Shavarov ◽

M. V. Vatsik-Gorodetskaya

Keyword(s):

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Renal Function ◽

Kidney Disease ◽

Renal Dysfunction ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Disease Epidemiology ◽

Increased Risk ◽

Estimate Glomerular Filtration Rate

Atrial fibrillation and renal dysfunction often coexist, each disorder may predispose to the other and contribute to worsening prognosis. Both atrial fibrillation and chronic kidney disease are associated with increased risk of stroke and thromboembolic complications. Oral anticoagulation for stroke prevention is therefore recommended in patients with atrial fibrillation and decreased renal function. Each direct oral anticoagulant has unique pharmacologic properties of which clinician should be aware to optimally manage patients. The doses of direct oral anticoagulants require adjustment for renal function. There is debate regarding which equation, the Chronic Kidney Disease Epidemiology (CKD-EPI) equation vs. the Cockcroft-Gault equation, should be used to estimate glomerular filtration rate in patients with atrial fibrillation treated with direct oral anticoagulants. Our review tries to find arguments for benefit of direct oral anticoagulants in patients with renal dysfunction.

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Bleeding Risk of Direct Oral Anticoagulants in Patients With Heart Failure And Atrial Fibrillation

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.120.007230 ◽

2021 ◽

Vol 14 (2) ◽

Author(s):

Cynthia A. Jackevicius ◽

Lingyun Lu ◽

Zunera Ghaznavi ◽

Alberta L. Warner

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Renal Function ◽

Kidney Disease ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Risk ◽

Hazard Ratio ◽

Patients With Heart Failure

Background: Patients with heart failure and atrial fibrillation are an important atrial fibrillation subgroup in which direct oral anticoagulants (DOACs) have not been adequately studied in real-world settings. Since DOACs rely on renal elimination and renal dysfunction is prevalent in patients with heart failure, their use may increase bleeding risk, negating some of their advantage over warfarin. Methods: We conducted a retrospective cohort study using linked Veterans Administration databases of patients with heart failure newly started on warfarin or DOACs for atrial fibrillation from October 2010 to August 2017 (23 635 warfarin, 25 823 DOAC). Outcomes included time to first bleeding, stroke, and death using Cox proportional hazards models with inverse probability of treatment weighting. Results: Total bleeding (hazard ratio, 0.62 [95% CI, 0.56–0.68]), major bleeding (hazard ratio, 0.49 [95% CI, 0.40–0.61]), and death (hazard ratio, 0.74 [95% CI, 0.71–0.78]) were lower with DOAC than warfarin, and with apixaban and dabigatran, but not rivaroxaban. Moderate/severe chronic kidney disease was common (48.7%); moderate chronic kidney disease was associated with increased bleeding with DOACs but not warfarin. However, death and bleeding remained lower with DOACs than warfarin across all renal function levels and clinical subgroups. A >20% transient/persistent decline in renal function occurred in 53% of DOAC-treated patients at some point during follow-up, would have required dose reduction in 10.5% of patients, and was associated with increased bleeding. Dose adjustments were made more often, and bleeding and death were lower in patients seen by pharmacists or anticoagulation clinics. There were significant between-site variations in DOAC dosing. Conclusions: DOACs overall, apixaban, and dabigatran, but not rivaroxaban, were associated with less total bleeding and death than warfarin in patients with heart failure and atrial fibrillation at all levels of renal function. Renal function decline resulted in increased bleeding in patients with DOACs. DOAC dose adjustment was often indicated, associated with increased bleeding when not adjusted, emphasizing the need for closer monitoring in these patients.

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How do direct oral anticoagulants compare with warfarin for preventing stroke and systemic embolic events in adults with atrial fibrillation and chronic kidney disease?

Cochrane Clinical Answers ◽

10.1002/cca.2014 ◽

2018 ◽

Author(s):

Jane Burch ◽

Juliana Ester Martin-Lopez

Keyword(s):

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants

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Non-vitamin K antagonist oral anticoagulants vs. vitamin-K antagonists in patients with atrial fibrillation and chronic kidney disease: a nationwide cohort study

Thrombosis Journal ◽

10.1186/s12959-019-0211-y ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 2

Author(s):

Emma Kirstine Laugesen ◽

Laila Staerk ◽

Nicholas Carlson ◽

Anne-Lise Kamper ◽

Jonas Bjerring Olesen ◽

...

Keyword(s):

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Vitamin K ◽

Major Bleeding ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Vitamin K Antagonist ◽

All Cause Mortality ◽

Comparable Population

Abstract Background We aimed to compare effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin-K antagonists (VKA) in atrial fibrillation (AF) patients with chronic kidney disease (CKD) not receiving dialysis. Methods By using personal identification numbers, we cross-linked individual-level data from Danish administrative registries. We identified every citizen with a prior diagnosis of AF and CKD who initiated NOAC or VKA (2011–2017). An external analysis of 727 AF patients with CKD (no dialysis) was performed to demonstrate level of kidney function in a comparable population. Study outcomes included incidents of stroke/thromboembolisms (TEs), major bleedings, myocardial infarctions (MIs), and all-cause mortality. We used Cox proportional hazards models to determine associations between oral anticoagulant treatment and outcomes. Results Of 1560 patients included, 1008 (64.6%) initiated VKA and 552 (35.4%) initiated NOAC. In a comparable population we found that 95.3% of the patients had an estimated glomerular filtration rate (eGFR) < 59 mL/min. Patients treated with NOAC had a significantly decreased risk of major bleeding (hazard ratio (HR): 0.47, 95% confidence interval (CI): 0.26–0.84) compared to VKA. There was not found a significant association between type of anticoagulant and risk of stroke/TE (HR: 0.83, 95% CI: 0.39–1.78), MI (HR: 0.45, 95% CI: 0.18–1.11), or all-cause mortality (HR: 0.99, 95% CI: 0.77–1.26). Conclusion NOAC was associated with a lower risk of major bleeding in patients with AF and CKD compared to VKA. No difference was found in risk of stroke/TE, MI, and all-cause mortality.

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Direct Oral Anticoagulants in Atrial Fibrillation Patients With Concomitant Hyperthyroidism

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa050 ◽

2020 ◽

Vol 105 (9) ◽

pp. 2893-2904

Author(s):

Yi-Hsin Chan ◽

Lung-Sheng Wu ◽

Lai-Chu See ◽

Jia-Rou Liu ◽

Shang-Hung Chang ◽

...

Keyword(s):

Atrial Fibrillation ◽

Major Bleeding ◽

Lower Risk ◽

Randomized Clinical Trials ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Study Groups ◽

Research Database ◽

Nonvalvular Atrial Fibrillation ◽

Asian Patients

Abstract Objective Patients with hyperthyroidism were excluded from the randomized clinical trials of direct oral anticoagulants (DOACs) for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). Methods We performed a nationwide retrospective cohort study using data from the Taiwan National Health Insurance Research Database. We enrolled 3213 and 1181 NVAF patients with hyperthyroidism who were taking DOACs and warfarin, respectively, from June 1, 2012 to December 31, 2017. We also enrolled 53 591 and 16 564 NVAF patients without hyperthyroidism, taking DOACs and warfarin, respectively. We used propensity score stabilized weights (PSSWs) to balance covariates across the study groups. We also used 1:4 matching on both taking DOACs, with (n = 3213) and without hyperthyroidism (n = 12 852); and both taking warfarin, with (n = 1181) and without hyperthyroidism (n = 4724). Results After PSSW, DOAC had a comparable risk of ischemic stroke/systemic embolism (IS/SE) and a lower risk of major bleeding (hazard ratio [HR] 0.65; 95% confidential interval [CI], 0.44–0.96; P = 0.0295) than warfarin among patients with hyperthyroidism. There were comparable risks of IS/SE and major bleeding between those patients with and without hyperthyroidism. However, among patients taking warfarin, those with hyperthyroidism had a lower risk of IS/SE than those without hyperthyroidism (HR 0.61; 95% CI, 0.43–0.86; P = 0.0050). Conclusion Among NVAF Asian patients with concomitant hyperthyroidism, DOACs may be an effective and safer alternative to warfarin. Thromboprophylaxis with DOACs may be considered for such patients, and it is important to validate this finding in further prospective study.

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Apixaban vs. Warfarin in Atrial Fibrillation Patients With Chronic Kidney Disease

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.752468 ◽

2021 ◽

Vol 8 ◽

Author(s):

Chung-Ming Fu ◽

Lung-Chih Li ◽

Yueh-Ting Lee ◽

Shih-Wei Wang ◽

Chien-Ning Hsu

Keyword(s):

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Kidney Function ◽

Major Bleeding ◽

Lower Risk ◽

Standard Dose ◽

Healthcare Delivery ◽

Real World Evidence ◽

Record Data

Background and Objectives: Real-world evidence of apixaban treatment in patients with chronic kidney disease remains scarce. This study aimed to compare the relative risk of stroke or systemic embolism (SE) and major bleeding between apixaban and warfarin in atrial fibrillation (AF) patients with different degrees of kidney function.Design, Setting, Participants, and Measurements: We evaluated newly diagnosed AF patients between 2004 and 2018, who were receiving apixaban or warfarin. Electronic medical record data were collected from a large healthcare delivery network in Taiwan. The outcomes of hospitalization for stroke/SE and major bleeding were compared with propensity-score matched apixaban and warfarin cohorts. Stratified analyses according to initial apixaban dose (standard dose of 10 mg/day vs. lower dose of 2.5–5.0 mg/day) and baseline estimated glomerular filtration rate were performed.Results: Each cohort involved 1,625 matched patients. Apixaban was significantly associated with a lower risk of stroke/SE (adjusted hazard ratio [aHR]: 0.74; 95% confidence interval [CI]:0.57–0.97; p = 0.03). The risk of major bleeding was not increased whether in standard doses (aHR: 0.66; 95% CI: 0.45–0.96; p = 0.03) or reduced doses (aHR, 0.84; 95% CI, 0.63–1.12; p = 0.23) of apixaban. Regarding kidney function, apixaban reduced the risk of stroke/SE by 37% in those with an eGFR of <30 ml/min/1.73 m2 (aHR: 0.63; 95% CI: 0.40–0.98; p = 0.04).Conclusions: Compared to warfarin, apixaban is associated with a reduced risk of stroke/SE and is consistent with a subset of AF patients with eGFR <30 ml/min/1.73 m2. Both standard and reduced doses of apixaban showed lower risk of major bleeding than those of warfarin.

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P2529Efficacy and safety of oral anticoagulation in nonagenarian patients with atrial fibrillation

European Heart Journal ◽

10.1093/eurheartj/ehz748.0858 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

L Dominguez Rodriguez ◽

S Raposeiras Roubin ◽

D Alonso Rodriguez ◽

S J Camacho Freire ◽

E Abuassi ◽

...

Keyword(s):

Atrial Fibrillation ◽

Major Bleeding ◽

Oral Anticoagulation ◽

Lower Risk ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Events ◽

The Impact ◽

Similar Risk

Abstract Introduction Embolic prevention with oral anticoagulation is the cornerstone for the management of patients with atrial fibrillation (AF). However, data about the efficacy and safety of oral anticoagulation in nonagenarian patients are limited. We aimed to analyze the impact of oral anticoagulation in mortality, embolic and hemorrhagic events, in patients ≥90 years with non-valvular AF. Methods We used data from a multicentric registry of 1,750 consecutive nonagenarian patients diagnosed of AF between 2013 and 2018. A propensity-matched analysis was performed to match the baseline characteristics of patients treated or not with oral anticoagulants, and for those treated with vitamin K antagonists (VKAs) vs direct oral anticoagulants (DOACs). The impact of oral anticoagulation in the embolic and hemorrhagic risk was assessed by a competitive risk analysis, using a Fine and Gray regression model, with death being the competitive event. For embolic risk, we have considered a stroke, pulmonary or peripheral embolism. For bleeding risk, we have considered any bleeding requiring hospital admission. Results The mean of CHA2DS2-VASC and HASBLED scores was 4.5±1.3 and 2.8±1.0 points, respectively. Most of patients were anticoagulated (70.1%; n=1,256). DOACs were used in 709 patients, and VKAs in 517 patients. During a median follow-up of 25.2 months (IQR 12.2–44.3 months), 988 patients died (56.5%), 180 presented embolic events (10.3%), 186 had bleeding events (10.6%), and 29 had intracranial hemorrhage (ICH, 1.7%). After propensity-score matching, anticoagulation (versus non anticoagulation) was associated with lower mortality rate (HR 0.73, 95% CI 0.60–0.89; p=0.002), less mortality and embolic events (HR 0.77, 95% CI 0.64–0.92; p=0.005), but more bleeding events (HR 2.05, 95% CI 1.25–3.35; p=0.004). In comparison with VKAs, DOACs showed similar risk of mortality and embolic events (HR 1.14, 95% CI 0.88–1.47; p=0.337), and similar risk of bleeding events (HR 0.75, 95% CI 0.43–1.28; p=0.287), although a trend to lower risk of ICH was found (HR 0.17, 95% CI 0.02–1.39; p=0.097). Conclusions Among nonagenarian patients with AF, oral anticoagulation was associated with lower all-cause mortality. Although survival free of embolic events was significantly higher in patients with anticoagulation, the risk of major bleeding was twice than in non-anticoagulated patients. There was not differences between VKAs and DOACs in terms of embolic events and total major bleeding. However, compared with VKAs, DOACs were showed a trend to lower risk of ICH.

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