scholarly journals Relationship between the Renal Function and Adverse Clinical Events in Patients with Atrial Fibrillation: A Japanese Multicenter Registry Substudy

2020 ◽  
Vol 9 (1) ◽  
pp. 167
Author(s):  
Yasuhumi Yuzawa ◽  
Keiichiro Kuronuma ◽  
Yasuo Okumura ◽  
Katsuaki Yokoyama ◽  
Naoya Matsumoto ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Renal Function ◽  
Major Bleeding ◽  
Normal Renal Function ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Real World Data ◽  
Clinical Events ◽  
Gault Formula

Background: Atrial fibrillation (AF) and chronic kidney disease (CKD) often coexist, but the real-world data after approval of direct oral anticoagulants (DOACs) are still lacking in Japan. We investigated the association of the baseline renal function and adverse clinical events and risk of adverse clinical events with DOACs compared to warfarin for each renal functional level in Japanese AF patients. Methods: The present substudy was based on the SAKURA AF Registry, a Japanese multicenter observational registry (median follow-up period: 39 months). The creatinine clearance (CrCl) values were estimated by the Cockcroft–Gault formula, and divided into normal renal function, and mild and moderate-severe CKD (CrCl ≥ 80, 50–79, <50 mL/min). Results: In the SAKURA AF Registry, the baseline CrCl data were available for 3242 patients (52% for DOAC and 48% for warfarin user). The relative risk of adverse clinical events was significantly higher in the patients with a CrCl < 50 mL/min as compared to those with a CrCl ≥ 80 mL/min (adjusted HRs: 2.53 for death, 2.53 for cardiovascular [CV] events, 2.13 for strokes, and 1.83 for major bleeding). Risks of all adverse clinical events were statistically even between DOAC and warfarin users for each renal function level. Conclusion: Moderate–severe CKD was associated with a higher mortality, CV events, strokes, and major bleeding than normal renal function. The safety and effectiveness of DOACs over warfarin were similar for each renal function level. By a worsening renal function, the incidence of adverse clinical events increased, especially deaths and CV events as compared to strokes and major bleeding.

scholarly journals The Number of Concomitant Drugs and the Safety of Direct Oral Anticoagulants in Routine Care Patients with Atrial Fibrillation

TH Open ◽  
2020 ◽  
Vol 04 (04) ◽  
pp. e417-e426
Author(s):  
Carline J. van den Dries ◽  
Sander van Doorn ◽  
Patrick Souverein ◽  
Romin Pajouheshnia ◽  
Karel G.M. Moons ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Routine Care ◽  
P Value ◽  
Risk Of Mortality ◽  
Mortality Effect

Abstract Background The benefit of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) on major bleeding was less prominent among atrial fibrillation (AF) patients with polypharmacy in post-hoc randomized controlled trials analyses. Whether this phenomenon also exists in routine care is unknown. The aim of the study is to investigate whether the number of concomitant drugs prescribed modifies safety and effectiveness of DOACs compared with VKAs in AF patients treated in general practice. Study Design Adult, nonvalvular AF patients with a first DOAC or VKA prescription between January 2010 and July 2018 were included, using data from the United Kingdom Clinical Practice Research Datalink. Primary outcome was major bleeding, secondary outcomes included types of major bleeding, nonmajor bleeding, ischemic stroke, and all-cause mortality. Effect modification was assessed using Cox proportional hazard regression, stratified for the number of concomitant drugs into three strata (0–5, 6–8, ≥9 drugs), and by including the continuous variable in an interaction term with the exposure (DOAC vs. VKA). Results A total of 63,600 patients with 146,059 person-years of follow-up were analyzed (39,840 person-years of DOAC follow-up). The median age was 76 years in both groups, the median number of concomitant drugs prescribed was 7. Overall, the hazard of major bleeding was similar between VKA-users and DOAC-users (hazard ratio [HR] 0.98; 95% confidence interval [CI] 0.87–1.11), though for apixaban a reduction in major bleeding was observed (HR 0.81; 95% CI 0.68–0.98). Risk of stroke was comparable, while risk of nonmajor bleeding was lower in DOAC users compared with VKA users (HR 0.92; 95% CI 0.88–0.97). We did not observe any evidence for an impact of polypharmacy on the relative risk of major bleeding between VKA and DOAC across our predefined three strata of concomitant drug use (p-value for interaction = 0.65). For mortality, however, risk of mortality was highest among DOAC users, increasing with polypharmacy and independent of the type of DOAC prescribed (p-value for interaction <0.01). Conclusion In this large observational, population-wide study of AF patients, risk of bleeding, and ischemic stroke were comparable between DOACs and VKAs, irrespective of the number of concomitant drugs prescribed. In AF patients with increasing polypharmacy, our data appeared to suggest an unexplained yet increased risk of mortality in DOAC-treated patients, compared with VKA recipients.

scholarly journals Adverse outcomes after worsening renal function in patients with atrial fibrillation: the Fushimi AF Registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Ogawa ◽  
Y An ◽  
S Ikeda ◽  
Y Aono ◽  
K Doi ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Renal Function ◽  
Oral Anticoagulants ◽  
Adverse Outcomes ◽  
Funding Source ◽  
Worsening Renal Function ◽  
Gault Formula ◽  
Bayer Healthcare ◽  
Artery Disease

Abstract Background Patients with atrial fibrillation (AF) commonly coexist with chronic kidney disease (CKD). Non-vitamin K antagonist oral anticoagulants (NOAC) are recommended for stroke prevention in patients with non-valvular atrial fibrillation (AF), and worsening renal function (WRF) as well as CKD is an important issue in using NOAC. However, little is known about the clinical outcomes of patients after WRF. Purpose We aimed to investigate outcomes after WRF in AF patients. Methods The Fushimi AF Registry is a community-based prospective survey of the AF patients in our city. Follow-up data including prescription status were available for 4,441 patients. Of them, 1,890 patients who have baseline and at least 1 follow-up creatinine clearance (CrCl) measurements, estimated by the Cockcroft-Gault formula, were analyzed in the present study. WRF was defined as a decrease of ≥20% from baseline CrCl measurement at any time point during follow-up. We evaluated demographics and outcomes after WRF in AF patients. Results During the median follow-up period of 2,194 days, mean CrCl decrease of 2.2 ml/min/year was observed and WRF occurred in 981 patients (51.9%). Patients with WRF were significantly more often female (with vs. without WRF; 40.3% vs. 35.4%; p=0.03), older (73.4 vs. 71.1 years of age; p&lt;0.01), more often paroxysmal type (49.9% vs. 47.1%; p&lt;0.01), and more likely to have prior stroke (17.9% vs. 12.7%; p&lt;0.01), heart failure (30.8% vs. 24.8%; p&lt;0.01), diabetes (31.7% vs. 27.1%; p=0.03), and coronary artery disease (19.9% vs. 12.1%; p&lt;0.01) than those without WRF. Co-existing of CKD and mean CrCl at baseline were comparable (37.4% vs. 36.9%; p=0.82, 65.3 vs. 63.5 ml/min; p=0.66, respectively). Mean CHA2DS2-VASc score was significantly higher in WRF patients (3.55 vs. 3.03; p&lt;0.01). On landmark analysis, all-cause mortality occurred in 135 patients (8.6 /100 person-years) after WRF and 82 patients (1.7 /100 person-years) without WRF, with an adjusted hazard ratio (HR) of 6.33 (95% confidence interval [CI], 4.33–9.50; p&lt;0.01), adjusted by sex, age, body weight, serum creatinine, type of AF, oral anticoagulant prescription and comorbidities. Stroke or systemic embolism occurred in 45 patients after WRF (3.0 /100 person-years) and 78 (1.7 /100 person-years) patients without WRF (adjusted HR 1.60 [95% CI, 1.04–2.49; p=0.03]) (Figure). Conclusions AF patients after WRF had higher incidence of various adverse events. Incidence of Adverse Outcomes Funding Acknowledgement Type of funding source: Other. Main funding source(s): The Practical Research Project for Life-Style related Diseases including Cardiovascular Diseases and Diabetes Mellitus from Japan Agency for Medical Research and Development. Boehringer Ingelheim, Bayer Healthcare, Pfizer, Bristol-Myers Squibb, Astellas Pharma, AstraZeneca, Daiichi-Sankyo, Novartis Pharma, MSD, Sanofi-Aventis, and Takeda Pharmaceutical.

scholarly journals 122 Are We Effective Prescribers? A Retrospective Audit of DOAC Prescribing Post Embolic Stroke for Non Valvular Atrial Fibrillation

2019 ◽  
Vol 48 (Supplement_3) ◽  
pp. iii17-iii65
Author(s):  
Karen Dennehy ◽  
Joseph Morris ◽  
Diarmaid Hughes ◽  
Kate Donlon ◽  
Thomas Walsh
Keyword(s):  
Atrial Fibrillation ◽  
Renal Function ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Embolic Stroke ◽  
Haemorrhagic Transformation ◽  
Retrospective Audit ◽  
Online Laboratory ◽  
Number Of Patients

Abstract Background Direct oral anticoagulants (DOAC) are indicated for stroke prophylaxis in non-valvular atrial fibrillation, which is responsible for up to 20% of all ischaemic strokes(1). We performed a retrospective audit of all consecutive stroke patients in an Irish teaching hospital over a 1-year period to investigate the rate of incorrect dosing and any risk factors for this occurring. Methods We assessed our hospital stroke database from January to December 2017. Our research focused on DOAC prescribing in non valvular atrial fibrillation post embolic stroke. We collected data on baseline characteristics, choice of anticoagulation, dosing, and assessment of renal function, with follow up renal function if available. We reviewed electronic discharge summaries, online laboratory systems and completed a chart review. Results There was a total of 116 people with atrial fibrillation who developed an embolic stroke in our centre, of which 68 were eligible for anticoagulation using a DOAC (59). The main reasons for omission were CKD and haemorrhagic transformation. Patients were discharged on either Apixaban (32 patients), Rivaroxoban (32 patients), or Dabigatran (4 patients). Following our review, we established that 54/68 (79%) of patients were correctly anticoagulated. Over 20% of patients were incorrectly dosed and there was a clear tendency to under-dose 13/14 (93%). There were significant differences between the correct and incorrect dosing groups, with the latter group of patients being older and more at risk of polypharmacy. Renal function did not differ significantly between the groups at discharge or follow up and none of the incorrectly dosed patients were on a concurrent anti platelet. Conclusion A significant number of patients prescribed DOAC in hospital were not appropriately anticoagulated (21%), a majority of which were under-dosed. The patients who were under-dosed were older and more likely to be on 5 or more medications.

Abstract 17126: Efficacy and Safety of Dabigatran Compared With Warfarin in Patients With Atrial Fibrillation and Normal Renal Function Over Time: Insights From the RE-LY Trial

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Ziad Hijazi ◽  
Stefan H Hohnloser ◽  
Jonas Oldgren ◽  
Ulrika Andersson ◽  
Stuart J Connolly ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Renal Function ◽  
Relative Risk ◽  
Major Bleeding ◽  
Normal Renal Function ◽  
Cox Regression ◽  
Factor Xa ◽  
Renal Elimination ◽  
Efficacy And Safety

Background: In patients with atrial fibrillation (AF) and normal renal function it has been reported that one oral factor-Xa inhibitor is associated with decreased efficacy compared to warfarin. In the RE-LY trial of patients with AF dabigatran, with approximately 80% renal elimination, was superior to warfarin for prevention of stroke and systemic embolism (SEE) with the 150 mg dose and non-inferior with the 110 mg dose and associated with significantly less major bleeding with the 110 mg dose. This is a post hoc analysis of the efficacy and safety of dabigatran vs. warfarin treatment in patients with normal renal function during the study. Methods: In the RE-LY trial among patients who received at least one dose of study medication, 17882 had creatinine measurements available at baseline, out of which 91% also had measurements after randomization. There were a total of 382 stroke/SEE, 280 ischemic strokes, and 1018 major bleed events during median follow-up of 1.8 years. The relations between outcomes, treatment, and renal function (Cockcroft-Gault estimated glomerular filtration rate (eGFR)) during follow-up were evaluated using Cox regression including treatment, eGFR as a continuous time dependent covariate, fitted using restricted cubic splines, and interaction. Hazard ratios (95% CI) comparing treatment effects were analyzed according to eGFR level. Results: In patients with normal renal function the relative risk of stroke/SEE was consistently lower in those treated with dabigatran as compared with warfarin. The patterns were similar for major bleeding with a trend of greater relative risk reduction with dabigatran as compared to warfarin at normal renal function. Conclusions: In patients with AF and normal renal function during treatment the efficacy of dabigatran compared to warfarin was consistent with the overall result of the RELY study. Both dabigatran doses were associated with lower risk of major bleeding in patients with normal renal function.

P4753Impact of renal function on bleeding risk in patients with non-valvular atrial fibrillation treated with direct oral anticoagulants: Subanalysis of the DIRECT registry

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Hirata ◽  
Y Sotomi ◽  
T Kobayashi ◽  
R Amiya ◽  
A Hirayama ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Renal Function ◽  
Renal Dysfunction ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Risk ◽  
Rank Test ◽  
Log Rank Test ◽  
Kaplan Meier

Abstract Background Renal dysfunction is one of the high bleeding risk factors in patients with atrial fibrillation as presented in the HAS-BLED score. The impact of renal function on bleeding risk is, however, still to be investigated in the era of direct oral anticoagulants (DOAC). Methods We conducted a single-center prospective observational registry of NVAF patients with DOACs: the DIRECT registry (UMINehz745.112933283). All patients with NVAF (N=2216) who were users of dabigatran (N=648), rivaroxaban (N=538), apixaban (N=599), or edoxaban (N=431) from 2011 to 2017 were enrolled (71.6±10.8 years, mean follow-up duration: 407.2±388.3 days). In the present substudy, all patients were stratified by renal function. Creatinine clearance (CCr) was estimated with the Cockcroft-Gault equations with available creatinine at baseline. Patients were divided into 4 groups based on CCr. (CCr>80, CCr50–80, CCr30–50, and CCr<30). The primary endpoint was major bleeding according to the ISTH criteria. Clinical endpoints were compared between the groups (Kaplan-Meier analysis, Log-rank test). The influence of DOAC type in patients with renal dysfunction was also assessed for the primary endpoints of major bleeding. Results Kaplan-Meier estimated 2-year major bleeding rate significantly increased as renal function decreased (CCr>80 2.5%, CCr50–80 4.2%, CCr30–50 4.2%, CCr<30 7.8%, Log-rank test p<0.001). However, in patients with apixaban (low CCr 59.6±25.9ml), major bleeding does not appear to increase as renal function decreased.(CCr >80 9.2%, CCr 50–80 8.0%, CCr 30–50 10.3%, CCr<30 7.3%, Log-rank test p=0.97). Kaplan-Meier Analysis Conclusions Renal dysfunction increased bleeding risks in NVAS patients with DOACs. Apixaban might be safely used for patients with renal dysfunction.

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

2019 ◽  
Vol 8 (12) ◽  
pp. 2034 ◽  
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.

Abstract 12404: Efficacy and Safety of Apixaban Compared With Warfarin in Patients With Atrial Fibrillation and Normal Renal Function over Time: Insights From the ARISTOTLE Trial

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Ziad Hijazi ◽  
Stefan H. H Hohnloser ◽  
Ulrika Andersson ◽  
John H Alexander ◽  
Christopher B Granger ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Renal Function ◽  
Major Bleeding ◽  
Normal Renal Function ◽  
Cox Regression ◽  
Factor Xa ◽  
Efficacy And Safety ◽  
Major Bleed ◽  
Over Time

Introduction: It has been recently observed that one oral factor-Xa inhibitor (at the dose studied) might be associated with decreased efficacy in patients with atrial fibrillation (AF) and normal renal function. In the ARISTOTLE trial, apixaban compared to warfarin reduced stroke, mortality, and major bleeding irrespective of renal function at baseline. Our aim was to evaluate the efficacy and safety of apixaban vs. warfarin in patients with normal renal function over time. Methods: In ARISTOTLE, 16,971 patients had serial creatinine measurements available after randomization. There were a total of 397 stroke or systemic embolic events, 286 ischemic or unspecified strokes, and 712 major bleed events during median follow-up of 1.8 years. Normal renal function was predefined as an estimated glomerular filtration rate (eGFR) >80 mL/min. The relations between renal function, treatment, and outcomes were investigated by using Cox regression with renal function as a continuous time dependent covariate, fitted using restricted splines. Hazard ratios with 95% confidence intervals (CI) were analyzed based on continuous eGFR level during follow-up using both the Cockcroft-Gault and CKD-EPI equations. Results: The relative risk of stroke or systemic embolism was consistently lower in participants randomized to apixaban compared with warfarin. The patterns were similar for the ischemic or unspecified stroke outcome as well as for major bleeding (Table). Conclusions: Apixaban, relative to warfarin, demonstrated preserved efficacy and safety in AF patients with normal renal function over time.

scholarly journals A Systematic Review of the Efficacy and Safety of Direct Oral Anticoagulants in Atrial Fibrillation Patients with Diabetes Using a Risk Index

2021 ◽  
Vol 10 (13) ◽  
pp. 2924
Author(s):  
Domenico Acanfora ◽  
Marco Matteo Ciccone ◽  
Valentina Carlomagno ◽  
Pietro Scicchitano ◽  
Chiara Acanfora ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Risk Index ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Efficacy Rate ◽  
Cochrane Central Register ◽  
Efficacy And Safety

Diabetes mellitus (DM) represents an independent risk factor for chronic AF and is associated with unfavorable outcomes. We aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF), with and without diabetes mellitus (DM), using a new risk index (RI) defined as: RI =Rate of EventsRate of Patients at Risk. In particular, an RI lower than 1 suggests a favorable treatment effect. We searched MEDLINE, MEDLINE In-Process, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials. The risk index (RI) was calculated in terms of efficacy (rate of stroke/systemic embolism (stroke SEE)/rate of patients with and without DM; rate of cardiovascular death/rate of patients with and without DM) and safety (rate of major bleeding/rate of patients with and without DM) outcomes. AF patients with DM (n = 22,057) and 49,596 without DM were considered from pivotal trials. DM doubles the risk index for stroke/SEE, major bleeding (MB), and cardiovascular (CV) death. The RI for stroke/SEE, MB, and CV death was comparable in patients treated with warfarin or DOACs. The lowest RI was in DM patients treated with Rivaroxaban (stroke/SEE, RI = 0.08; CV death, RI = 0.13). The RIs for bleeding were higher in DM patients treated with Dabigatran (RI110 = 0.32; RI150 = 0.40). Our study is the first to use RI to homogenize the efficacy and safety data reported in the DOACs pivotal studies against warfarin in patients with and without DM. Anticoagulation therapy is effective and safe in DM patients. DOACs appear to have a better efficacy and safety profile than warfarin. The use of DOACs is a reasonable alternative to vitamin-K antagonists in AF patients with DM. The RI can be a reasonable tool to help clinicians choose between DOACs or warfarin in the peculiar set of AF patients with DM.

scholarly journals Prescribing Errors With Direct Oral Anticoagulants and Their Impact on the Risk of Bleeding in Patients With Atrial Fibrillation

2021 ◽  
pp. 107424842110196
Author(s):  
Bruria Hirsh Raccah, PharmD, PhD ◽  
Yevgeni Erlichman ◽  
Arthur Pollak ◽  
Ilan Matok ◽  
Mordechai Muszkat
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Negative Impact ◽  
Conditional Logistic Regression ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Drug Dose ◽  
Prescribing Errors ◽  
Duration Of Treatment ◽  
Inappropriate Treatment

Introduction: Anticoagulants are associated with significant harm when used in error, but there are limited data on potential harm of inappropriate treatment with direct oral anticoagulants (DOACs). We conducted a matched case-control study among atrial fibrillation (AF) patients admitting the hospital with a chronic treatment with DOACs, in order to assess factors associated with the risk of major bleeding. Methods: Patient data were documented using hospital’s computerized provider order entry system. Patients identified with major bleeding were defined as cases and were matched with controls based on the duration of treatment with DOACs and number of chronic medications. Appropriateness of prescribing was assessed based on the relevant clinical guidelines. Conditional logistic regression was used to evaluate the potential impact of safety-relevant prescribing errors with DOACs on major bleeding. Results: A total number of 509 eligible admissions were detected during the study period, including 64 cases of major bleeding and 445 controls. The prevalence of prescribing errors with DOACs was 33%. Most prevalent prescribing errors with DOACs were “drug dose too low” (16%) and “non-recommended combination of drugs” (11%). Safety-relevant prescribing errors with DOACs were associated with major bleeding [adjusted odds ratio (aOR) 2.17, 95% confidence interval (CI) 1.14-4.12]. Conclusion: Prescribers should be aware of the potential negative impact of prescribing errors with DOACs and understand the importance of proper prescribing and regular follow-up.

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