Correction to: The impact on renal function after longterm use of anticoagulants in atrial fibrillation patients

Abstract Introduction Rivaroxaban is recommended as an option for anticoagulation in patients with nonvalvular atrial fibrillation (AF) with one or more risk factors for stroke. The approved/recommended rivaroxaban dose for stroke prevention in patients with atrial fibrillation (AF) is solely based on renal function: 20 mg once daily (od) for patients with a creatinine clearance [CrCl] ≥50 ml/min and 15 mg od in patients with CrCl 15–49 mL/min). Purpose To assess the patterns of rivaroxaban prescription as per the creatinine clearances levels and to assess the impact of the rivaroxaban dosing on the rate of events at 2-year follow-up in patients with AF. Methods RIVaroxaban Evaluation in Real Life setting (RIVER) is a prospective international registry of patients with newly diagnosed non-valvular AF treated with rivaroxaban for the prevention of thromboembolic stroke and at least one investigator-determined risk factor for stroke. Adjusted hazard ratios (HRs) were obtained through Cox proportional-hazard model. Results Among 3402 patients with normal renal function (CrCl ≥50 mL/min), 82.1% were prescribed the recommended rivaroxaban dose of 20 mg (od) at baseline. Among 524 patients with moderate or severe renal impairment (CrCl 15–50 mL/min), 55.3% patients received rivaroxaban 15 mg (od), 39.9% received 20 mg (od) and 4.2% 10 mg (od). Non-recommended dosing was rare in patients younger than 70 (13.5%) but more frequent in older patients (28.8%). Non-recommended low dosing was more frequent in Asians (38.9%), compared to non-Asian patients (13.8%). Regarding clinical outcomes, adjusted hazards ratios (HR, presented with 95% confidence intervals) showed that the non-recommended low dosing (<20 mg od) was associated with higher risk of non-cardiovascular mortality (HR 2.09 (1.16–3.77)) in patients with normal renal function. The non-recommended high dosing (>15 mg od) was associated with lower risk of all-cause mortality (HR 0.63 (0.42–0.93)) and cardiovascular mortality (HR 0.32 (0.13–0.77)) and higher risk of major bleeding (HR 2.86 (1.49–5.50)) in patients with moderate to severe renal impairment (figure 1 and 2). Conclusion In patients with normal renal function, non-recommended low dose rivaroxaban was associated with increased cardiovascular mortality without reducing the risk of major bleeding compared to recommended dosing. In patients with CrCl <50 ml/min, non-recommended high dose rivaroxaban was associated with reduced cardiovascular mortality but at the cost of increased major bleeding. These observational data largely support the reduction of rivaroxaban dosing according to renal function but educational strategies are needed to ensure that rivaroxaban is used appropriately. FUNDunding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This work was supported by an unrestricted research grant from Bayer AG, Berlin, Germany, to TRI, London, UK, which sponsors the RIVER registry. This work is supported by KANTOR CHARITABLE FOUNDATION for the Kantor-Kakkar Global Centre for Thrombosis Science.

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Fluctuating renal function and the risk of incident atrial fibrillation: a nationwide population-based study

Scientific Reports ◽

10.1038/s41598-019-54528-w ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Soonil Kwon ◽

So-Ryoung Lee ◽

Eue-Keun Choi ◽

Kyung-Do Han ◽

Seokhun Yang ◽

...

Keyword(s):

Atrial Fibrillation ◽

Renal Function ◽

Population Based ◽

Incidence Rates ◽

Population Based Study ◽

Increased Risk ◽

Study Population ◽

Multiple Variables ◽

The Impact

AbstractAlthough chronic kidney disease is known to increase the risk of atrial fibrillation (AF), the impact of the variability of renal function on the risk of incident AF is unknown. We aimed to evaluate the association between variability of renal function and the risk of developing AF among the general population. We evaluated a total of 3,551,249 adults who had three annual health check-ups provided by the National Health Insurance Service. The variability of renal function was defined as GFR-VIM, which is variability independent of the mean (VIM) of creatinine-based estimated glomerular filtration rate (eGFR). The study population was divided into four groups (Q1-4) based on the quartiles of GFR-VIM, and the risks of incident AF by each group were compared. During a mean of 3.2 ± 0.5 years follow-up, incident AF occurred in 15,008 (0.42%) subjects. The incidence rates of AF increased from Q1 to Q4 (0.98, 1.42, 1.27, and 1.63 per 1,000 person-years, respectively). Adjusting with multiple variables, Q4 showed an increased risk of incident AF compared to Q1 (hazard ratio (HR) 1.125, 95% confidence interval (CI) 1.071–1.181). Variability of serum creatinine or other definitions of variability showed consistent results. On subgroup analyses, Q4 in males or those with a decreasing trend of eGFR had significantly increased risks of incident AF compared to Q1 (HR 1.127, 95% CI 1.082–1.175; and HR 1.115, 95% CI 1.059–1.173, respectively). High variability of eGFR was associated with an increased risk of incident AF, particularly in males or those with decreasing trends of eGFR during follow-up.

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Prognostic impact of renal function trajectories and temporal variability amongst anticoagulated atrial fibrillation patients: a subgroup analysis of the SPORTIF III and V trials

European Heart Journal ◽

10.1093/ehjci/ehaa946.0681 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

M Proietti ◽

J Gumprecht ◽

G.F Romiti ◽

G.Y.H Lip

Keyword(s):

Atrial Fibrillation ◽

Renal Function ◽

Creatinine Clearance ◽

Major Bleeding ◽

Temporal Variability ◽

Adverse Outcomes ◽

Prognostic Impact ◽

Increased Risk ◽

The Impact

Abstract Background Renal function is a major determinant of major adverse outcomes in patients with atrial fibrillation (AF). Scarce data are available about the impact of renal function trajectories and creatinine clearance (CrCl) temporal variability, on prognosis. Aim To evaluate the progression and impact of renal function impairment and variability on outcomes over a long-term follow-up observation in a cohort of anticoagulated AF patients. Methods We included warfarin-treated AF patients in SPORTIF trials with available creatinine clearance (according to Cockroft-Gault) at baseline and at least 4 evaluations throughout their follow-up. Patients with a BMI ≥45 kg/m2 were excluded from the analysis. Average successive variability (ASV) was used as measure of variability. Results Among 3665 original patients, 3366 (91.8%) were included in this analysis. Median [IQR] CHA2DS2-VASc score was 3 [2–4] and HAS-BLED was 3 [2–4]. At baseline, 876 (26.0%) patients had CKD (CrCl <60 mL/min), with 14 (0.4%) patients having severe CKD (<30 mL/min), with a mean (SD) CrCl of 86.7 (47.4) mL/min. Over a mean (SD) 577.1 (122.1) days of follow-up, a total of 521 new CKD cases were found with an overall incidence of 13.1 per 100 patient-years, with 91 new severe CKD cases (1.71 per 100 patient-years). Across follow-up, prevalence of CKD and severe CKD increased progressively (both p<0.001) [Figure]. Mean (SD) AVS was −0.567 (±2.803) mL/min. According to AVS, patients were divided into quartiles: i) Q1: +34.012/+0.450; ii) Q2: +0.449/−0.443; iii) Q3: −0.443/−1.503; Q4: −1.505/−19.750. While no difference was found in stroke/systemic embolism, rate of major bleeding was higher in Q4 (4.5%) and Q1 (4.0%) than in other quartiles (Q2 2.5%, Q3 2.0%; p=0.009) as well as all-cause death (Q4: 6.7%; p=0.003 compared to other quartiles). A Cox multivariate adjusted model documented that AVS Q1 and Q4 were independently associated with a higher risk of major bleeding, while Q4 was associated with a higher risk of all-cause death (Table). Conclusion In a cohort of AF patients treated with warfarin, characterized by a progressive increase in the proportion with CKD and severe CKD, the largest reduction in CrCl throughout follow-up was associated to an increased risk of major bleeding and all-cause death. Renal Function Trajectories Funding Acknowledgement Type of funding source: None

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The Impact of Body Weight and Renal Function on the Risk of Bleeding With Direct Oral Anticoagulants in Atrial Fibrillation

Annals of Pharmacotherapy ◽

10.1177/1060028021995201 ◽

2021 ◽

pp. 106002802199520

Author(s):

Hannah Whittemore ◽

Andrew K. Posen ◽

Erika L. Hellenbart ◽

Vicki Groo ◽

Eric Wenzler ◽

...

Keyword(s):

Atrial Fibrillation ◽

Renal Function ◽

Body Weight ◽

Renal Dysfunction ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Bleeding Events ◽

Risk Of Bleeding ◽

Increased Risk ◽

The Impact

Background: Atrial fibrillation (AF) increases the risk of stroke and direct oral anticoagulants (DOACs) are first-line agents for prevention. Gaps in the literature cause reluctance in prescribing DOACs for patients with renal dysfunction and/or extremes in body weight. Objective: To evaluate the impact body weight and renal function have on major and clinically relevant nonmajor (CRNM) bleeding events and ischemic strokes in AF patients receiving a DOAC. Methods: This retrospective cohort study included adults with nonvalvular atrial fibrillation (NVAF) or atrial flutter (AFL) receiving a DOAC ≥12 months. The primary outcome was a composite of major and CRNM bleeding events. Secondary outcomes included ischemic stroke and risk factors for bleeding events. Results: Of the 233 patients analyzed, 25 patients experienced a bleeding event. Patients who bled weighed 10 kg less ( P = 0.043) than those who did not and had a higher HASBLED score ( P = 0.003). Multivariate logistic regression identified weight ( P = 0.048), serum creatinine (SCr; P = 0.027), and HASBLED score ( P = 0.024) as the significant predictors for experiencing a bleed. Three patients experienced a stroke. Conclusion and Relevance: This study demonstrates an association between higher baseline SCr, elevated HASBLED score, and lower weight, with an increased risk of bleeding in patients with NVAF or AFL receiving a DOAC. These findings add to prescribing considerations when initiating DOACs. Closer monitoring is advised for patients with significant renal dysfunction and/or low body weight, even with renal dose adjustments.

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Renal Function, Time in Therapeutic Range and Outcomes in Warfarin-Treated Atrial Fibrillation Patients: A Retrospective Analysis of Nationwide Registries

Thrombosis and Haemostasis ◽

10.1160/th17-03-0198 ◽

2017 ◽

Vol 117 (12) ◽

pp. 2291-2299 ◽

Cited By ~ 11

Author(s):

Anders Bonde ◽

Gregory Lip ◽

Anne-Lise Kamper ◽

Laila Staerk ◽

Christian Torp-Pedersen ◽

...

Keyword(s):

Atrial Fibrillation ◽

Renal Function ◽

Therapeutic Range ◽

Cox Regression ◽

International Normalized Ratio ◽

Adverse Outcomes ◽

Time In Therapeutic Range ◽

Anticoagulation Control ◽

The Impact ◽

Reduced Renal Function

AbstractPatients with severely reduced renal function have been excluded from randomized controlled trials of oral anticoagulation in atrial fibrillation (AF). Warfarin treatment in this population is controversial and data on anticoagulation control and the impact on adverse outcomes are needed. By individual-level linkage of nationwide registries, we identified all patients discharged from hospitals with AF in Denmark between 1997 and 2011. Patients with available serum creatinine tests were categorized according to the estimated glomerular filtration rate (eGFR). Time in therapeutic range (TTR) was calculated using the Rosendaal method. The risk of stroke and bleeding was estimated using multivariable Cox regression analyses with eGFR and TTR estimated time dependently throughout follow-up. We identified 10,423 warfarin-treated AF patients with available international normalized ratio and creatinine tests; 5,527 with eGFR > 60 mL/min/1.73 m2, 4,524 with eGFR 30–60 mL/min/1.73 m2 and 372 with eGFR < 30 mL/min/1.73 m2. Median TTR was 66.7, 61.2 and 49.7% in patients with eGFR > 60, 30–59 and <30 mL/min/1.73 m2, respectively. A TTR < 70% was associated with a higher risk of stroke/thromboembolism (hazard ratio [HR]: 1.39; 95% confidence interval [CI]: 1.20–1.60) and bleeding (HR: 1.22; 95% CI: 1.05–1.42) among patients with eGFR of 30 to 59 and a trend towards higher risk of stroke/thromboembolism (HR: 1.24; 95% CI: 0.86–1.80) and bleeding (HR: 1.17; 95% CI: 0.83–1.65) among patients with eGFR < 30 mL/min/1.73 m2. In conclusion, warfarin-treated AF patients with reduced renal function have suboptimal anticoagulation control which was related to the risk of adverse outcomes.

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The impact on renal function after long-term use of anticoagulants in atrial fibrillation patients

Thrombosis Journal ◽

10.1186/s12959-021-00351-1 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Wei-Chieh Lee ◽

Pai-Wei Lee ◽

Po-Jui Wu ◽

Yen-Nan Fang ◽

Huang-Chung Chen ◽

...

Keyword(s):

Atrial Fibrillation ◽

Renal Function ◽

Propensity Score ◽

Propensity Score Matching ◽

Observation Time ◽

Study Endpoint ◽

The Mean ◽

The Impact

Abstract Objective Long-term oral anticoagulant should be considered or recommended in patients with atrial fibrillation (AF) and CHA2DS2VASc score ≥ 1 for stroke prevention. Warfarin and different direct oral anticoagulants (DOACs) are metabolized differently by the kidney. The impact on renal function after long-term use of anticoagulants in the patients with AF remains unclear. This study aimed to compare DOACs and warfarin’s impact on the decline in renal function from a large cohort with AF. Methods This study included patients with nonvalvular AF from 2000 to 2018, mainly through the medical history (ICD code) of the Chang Gung Research Database. Baseline estimated glomerular filtration rate (eGFR), follow-up eGFR and the change in eGFR between 2-year eGFR and baseline eGFR were compared between different DOACs and warfarin after propensity score matching. The primary study endpoint was acute kidney injury (AKI). Results 3657 patients were enrolled in this study and the mean observation time was 3.3 ± 0.9 years. During the observation period, there was a significantly higher incidence of AKI during follow-up in the warfarin group than in the different DOAC groups before and after propensity score matching (before: warfarin vs. DOAC: 9.2% vs. 5.2%, p < 0.001; after: warfarin vs. DOAC: 8.9% vs. 4.4%, p < 0.001). There was no difference in the incidence of AKI between dabigatran group and anti-factor Xa inhibitor group after propensity score matching. The incidence of AKI was similar among rivaroxaban, apixaban and edoxaban groups after propensity score matching. The change in eGFR between 2-year eGFR and baseline eGFR did not differ between the warfarin and DOAC groups after propensity score matching (warfarin vs. DOAC: − 1.27 ± 20.32 vs. -1.94 ± 17.24 mL/min/1.73 m2, p = 0.461). Conclusions During the mean observation time of 3.3 ± 0.9 years, warfarin was associated with a higher incidence of AKI compared with DOACs. The decline in renal function did not differ among warfarin and different DOAC groups.

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