Incidence of thromboembolic stroke and of major bleeding in patients with atrial fibrillation and chronic kidney disease treated with and without warfarin

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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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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Stroke and Major Bleeding when Switching from Warfarin to Apixaban in Patients with Advanced Chronic Kidney Disease and Prevalent Atrial Fibrillation

10.21203/rs.3.rs-144190/v1 ◽

2021 ◽

Author(s):

Katherine Garlo ◽

Thomas Mavrakanas ◽

Wei Wang ◽

Elisabeth Burdick ◽

David Charytan

Keyword(s):

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Major Bleeding ◽

The United States ◽

Bleeding Events ◽

Part D ◽

Stage 4 ◽

Ischemic Attack

Abstract Background Apixaban is the most widely used direct oral anticoagulant in patients with chronic kidney disease (CKD). Data on the incidence of stroke and major bleeding after switching from warfarin to apixaban in patients with prevalent atrial fibrillation (AF) and CKD are limited.Methods Warfarin users with stage 4-5 CKD not on dialysis and non-valvular AF prior to Jan 1,2012 were identified from the United States Data Renal System CKD dataset and individuals switching to apixaban from Jan 1,2012 -Dec 31, 2015 were identified. The incidence of stroke (ischemic or hemorrhagic), transient ischemic attack, or systemic thromboembolism and major bleeding events were estimated. Outcomes were compared between individuals switching to apixaban and those continuing warfarin using survival analyses with inverse probability treatment weighting. Individuals were censored at the time of anticoagulation discontinuation, loss of Medicare part D coverage, dialysis, kidney transplant, a 2nd switch in anticoagulant class, or death. Results 1762 individuals with advanced CKD and AF were initially on warfarin; 71 (4.0%) switched to apixaban (57.8% male, mean age 78.2 years (SD ±6.6), 78.9% white, mean CHA2DS2-VASc 5.0 (SD ±1.5), mean HAS-BLED 2.2 (SD ±0.5) and 1691 (96.0%) continued warfarin (47.6% male, mean age 80.1 years (SD ±8.7), 87.9% white, mean CHA2DS2-VASc 5.5 (SD ±1.6), mean HAS-BLED 2.5 (SD ±0.8). The incidence of stroke in the apixaban switch and warfarin continuation groups were 0.02/patient-year (95%CI 0.002-0.12) and 0.06/patient-year (95%CI 0.05-0.07) (p=0.21). Incidence of major bleeding were 0.02/patient-year (95% CI 0.002-0.13) and 0.06 (95% CI 0.03-0.04) (p =0.44) in the switch and warfarin groups, respectively. In adjusted models, the risk of stroke (HR 0.27 (95% CI 0.04-1.99)) and major bleeding (HR 0.41 (95% CI 0.06-3.02)) trended lower in the apixaban switch compared to the warfarin continuation group.Conclusions The incidence and risk of stroke and major bleeding trended lower in individuals with stage 4-5 CKD and prevalent AF who switched from warfarin to apixaban than individuals continuing warfarin. Our findings support a strategy of switching prevalent AF patients with late stage CKD from warfarin to apixaban. Additional studies including a larger number of events with a longer-duration of follow-up are needed to refine effect estimates.

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Longitudinal kidney function trajectories predict major bleeding, hospitalization and death in patients with atrial fibrillation and chronic kidney disease

International Journal of Cardiology ◽

10.1016/j.ijcard.2019.01.089 ◽

2019 ◽

Vol 282 ◽

pp. 47-52

Author(s):

Florian Posch ◽

Cihan Ay ◽

Herbert Stöger ◽

Reinhold Kreutz ◽

Jan Beyer-Westendorf

Keyword(s):

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Kidney Function ◽

Major Bleeding

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Reclassification, Thromboembolic, and Major Bleeding Outcomes Using Different mates of Renal Function in Anticoagulated Patients With Atrial Fibrillation: Insights From the PREFER-in-AF and PREFER-in-AF Prolongation Registries

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.120.006852 ◽

2021 ◽

Author(s):

Miklos Rohla ◽

Ladislav Pecen ◽

Roberto Cemin ◽

Giuseppe Patti ◽

Jolanta M. Siller-Matula ◽

...

Keyword(s):

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Dose Reduction ◽

Major Bleeding ◽

Odds Ratio ◽

Thromboembolic Events ◽

Bleeding Events ◽

Disease Epidemiology ◽

Anticoagulated Patients

Background: The Cockcroft-Gault formula is recommended to determine a renal indication for dose reduction of dabigatran, edoxaban, and rivaroxaban. Nephrology guidelines now recommend the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulae as more accurate estimates of glomerular filtration rate. Methods: We analyzed anticoagulated patients with atrial fibrillation who were enrolled in the Prevention of Thromboembolic Events – European Registry in Atrial Fibrillation (PREFER in AF). The proportion of patients with dissimilar renal dosing indications was assessed when applying Cockcroft-Gault, MDRD, or CKD-EPI. Thromboembolic and major bleeding events at 1 year were compared in patients in whom Cockcroft-Gault and CKD-EPI provided concordant or discordant results around a threshold of 50 mL/minute. Results: Out of 1288 patients with atrial fibrillation with chronic kidney disease in whom Cockcroft-Gault suggested a dose reduction of dabigatran, edoxaban, or rivaroxaban (creatinine clearance ≤50 mL/minutes), 19% and 16% were reclassified to the respective higher doses, and 24% and 23% to the respective lower doses by applying the MDRD and CKD-EPI formulae, respectively. In patients potentially receiving a different dose of dabigatran, edoxaban, or rivaroxaban when using CKD-EPI, we observed an excess of thromboembolic events (4.1% versus 0.8%; odds ratio, 5.5 [95% CI, 1.5–20.8]; P =0.01). Major bleeding rates were nonsignificantly different in the discordance versus concordance group (5.7% versus 2.7%; odds ratio, 2.2 [95% CI, 0.9–5.6]; P =0.09). Conclusions: The MDRD and CKD-EPI formulae suggest a different dosing in up to a quarter of anticoagulated patients with atrial fibrillation. This seems to impact hard outcomes.

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Abstract P682: Risk of All Cause Stroke and Major Bleeding Events When Switching From Warfarin to Apixaban in Patients With Advanced Chronic Kidney Disease and Prevalent Atrial Fibrillation

Stroke ◽

10.1161/str.52.suppl_1.p682 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Katherine Garlo ◽

Thomas Mavrakanas ◽

Elisabeth Burdick ◽

Wei Wang ◽

David Charytan

Keyword(s):

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Major Bleeding ◽

The United States ◽

Bleeding Events ◽

Part D ◽

Major Bleeding Events ◽

Ischemic Attack ◽

Direct Acting

Introduction: Apixaban is the preferred direct acting oral anticoagulant in patients with chronic kidney disease (CKD). Reporting on the incidence of all cause stroke and major bleeding after switching from warfarin to apixaban in patients with prevalent atrial fibrillation (AF) and CKD are limited. Methods: Individuals with stage 4-5 CKD not on dialysis and prevalent non valvular AF on warfarin who switched to apixaban were identified from the United States Data Renal System from Jan 1,2012-Dec 31, 2015. The incidences of combined all cause stroke, transient ischemic attack, or systemic thromboembolism and major bleeding events were estimated. Outcomes were compared between individuals switching to apixaban and continuing on warfarin using logistic regression and survival analyses adjusted with inverse probability treatment weighting. Individuals were censored at anticoagulation discontinuation, discontinuous Medicare part D, dialysis, kidney transplant, a 2 nd switch in anticoagulant, or death. Results: 1762 individuals with advanced CKD with AF were on warfarin; 71 (4.0%) switched to apixaban (57.8% male, mean age 78.2 years (SD ±6.6), 78.9% white, mean CHA 2 DS 2 -VASc 5.0 (SD ±1.5), mean HAS-BLED 2.2 (SD ±0.5) and 1691 (41.3%) continued warfarin (47.6% male, mean age 80.1 years (SD ±8.7), 87.9% white, mean CHA 2 DS 2 -VASc 5.5 (SD ±1.6), mean HAS-BLED 2.5 (SD ±0.8). Incidence of all cause stroke in the apixaban switch and warfarin continuation groups were 0.020/patient year (95%CI 0.002- 0.123) and 0.061/patient year (95%CI 0.054-0.068) (p=0.211). Incidence of major bleeding in the two groups were 0.018/patient year (95% CI 0.002 - 0.125) and 0.045 (95% CI 0.033 - 0.044) (p =0.438). The risk of all cause stroke (OR 0.06; 95% CI 0.01-0.45; HR 0.18 (95%CI 0.03-1.35)) and major bleeding (OR 0.09; 95%CI 0.01-0.68; HR is 0.31 95%CI (0.04-2.27)) were lower in the apixaban switch compared to the warfarin continuation group. Conclusions: The incidence and risk of all cause stroke and major bleeding are lower in individuals with stage4-5 CKD and prevalent AF who switch from warfarin to apixaban versus continuing on warfarin. Data are limited by few events and short duration on apixaban.

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Direct-Acting Oral Anticoagulants Versus Warfarin in Medicare Patients With Chronic Kidney Disease and Atrial Fibrillation

Stroke ◽

10.1161/strokeaha.120.028934 ◽

2020 ◽

Vol 51 (8) ◽

pp. 2364-2373 ◽

Cited By ~ 7

Author(s):

James B. Wetmore ◽

Nicholas S. Roetker ◽

Heng Yan ◽

Jorge L. Reyes ◽

Charles A. Herzog

Keyword(s):

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Major Bleeding ◽

Oral Anticoagulants ◽

Systemic Embolism ◽

Intention To Treat ◽

Hazard Ratios ◽

Direct Acting ◽

Direct Acting Oral Anticoagulants

Background and Purpose: The comparative effectiveness of direct-acting oral anticoagulants, compared with warfarin, for risks of stroke/systemic embolism, major bleeding, or death have not been studied in Medicare beneficiaries with atrial fibrillation and nondialysis-dependent chronic kidney disease. Methods: Medicare data from 2011 to 2017 were used to identify patients with stages 3, 4, or 5 chronic kidney disease and new atrial fibrillation who received a new prescription for warfarin, apixaban, rivaroxaban, or dabigatran. We estimated marginal hazard ratios with 95% CIs for the association of each direct-acting oral anticoagulant, compared with warfarin, for the outcomes of interest using inverse-probability-of-treatment weighted Cox proportional hazards models in as-treated and intention-to-treat analyses. Results: A total of 22 739 individuals met criteria (46.3% warfarin, 29.6% apixaban, 17.2% rivaroxaban, 6.9% dabigatran). Across the groups of anticoagulant users, mean age was 78.4 to 79.0 years; 50.3% to 51.4% were women, and 80.3% to 82.8% had stage 3 chronic kidney disease. In the as-treated analysis, for stroke/systemic embolism, hazard ratios, all compared with warfarin, were 0.70 (0.51–0.96) for apixaban, 0.80 (0.54–1.17) for rivaroxaban, and 1.15 (0.69–1.94) for dabigatran. For major bleeding, analogous hazard ratios were 0.47 (0.37–0.59) for apixaban, 1.05 (0.85–1.30) for rivaroxaban, and 0.95 (0.70–1.31) for dabigatran. There was no difference in the risk of all-cause mortality between the direct-acting oral anticoagulants and warfarin. Results of the intention-to-treat analysis were similar. Conclusions: Apixaban, compared with warfarin, was associated with decreased risk of stroke/systemic embolism and major bleeding; risks for both outcomes with rivaroxaban and dabigatran did not differ from risks with warfarin.

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

Journal of Clinical Medicine ◽

10.3390/jcm8122034 ◽

2019 ◽

Vol 8 (12) ◽

pp. 2034 ◽

Cited By ~ 1

Author(s):

Kwang-No Lee ◽

Jong-Il Choi ◽

Yun Gi Kim ◽

Ki Yung Boo ◽

Do Young Kim ◽

...

Keyword(s):

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Renal Function ◽

Kidney Disease ◽

Major Bleeding ◽

Lower Risk ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Function Estimation ◽

Disease Epidemiology

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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