Use of rivaroxaban in patients attending a hematology unit in clinical practice

Aim: To determine drug persistence and rates of events among patients treated with rivaroxaban in a hematology unit. Methods: Retrospective study of patients that started treatment with rivaroxaban, in the hematology unit of a tertiary hospital. Results: A total of 161 patients were included, of whom 83.9% had atrial fibrillation and 11.2% venous thromboembolism, and 76.4% of patients were taking rivaroxaban 20 mg, 22.4% 15 mg and 1.2% 10 mg. After a follow-up of 1.8 ± 1.1 years, only four patients (2.5%) discontinued treatment. Rates of thromboembolic events, major bleeding/clinically relevant nonmajor bleeding and intracranial hemorrhage were 1.1, 2.8, 0.3 events per 100 patient-years, respectively. Conclusion: In patients attended in a hematology unit, medication persistence was high, and the incidence of outcomes low.

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Abstract 17152: Frequency and Management of Major Bleeding in Atrial Fibrillation Patients Treated With Warfarin and Non-vitamin K Oral Anticoagulants in Community Practice: Results From the ORBIT-AF II Registry

Circulation ◽

10.1161/circ.132.suppl_3.17152 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Benjamin A Steinberg ◽

DaJuanicia N Simon ◽

Laine Thomas ◽

Jack Ansell ◽

Gregg C Fonarow ◽

...

Keyword(s):

Atrial Fibrillation ◽

Clinical Practice ◽

Vitamin K ◽

Major Bleeding ◽

Oral Anticoagulants ◽

Recurrent Bleeding ◽

Bleeding Events ◽

Reversal Agents ◽

Major Bleeding Events

Background: Non-vitamin K oral anticoagulants (NOACs) are effective at preventing stroke in patients with atrial fibrillation (AF). However, little is known about the frequency of major bleeds on NOACs and how these events are managed in clinical practice. Methods: We assessed the rates, management, and outcomes of ISTH major bleeding events among AF patients in the ORBIT-AF II registry (mean follow-up 213 days). Results: Overall, 103 patients experienced 110 major bleeding events during follow-up n=90/4986 (1.8%) on NOAC, and n=20/1320 (1.5%) on warfarin. Patients with bleeding events on NOAC were slightly younger than those on warfarin (median age 76 vs. 80; p=0.2). Among mutually-exclusive bleeding types, intracranial bleeding was more common in warfarin treated patients than NOAC-treated (15% vs 6.7%), whereas GI bleeding was more common on NOACs (56% vs. 40%, overall p=0.1 for bleeding type). Management of bleeding differed by anticoagulation type: blood products and reversal agents were more commonly used in patients on warfarin (Table). No patient received prothrombin complexes, recombinant factor VIIa, aminocaproic acid, tranexamic acid, aprotinin, or desmopressin. Out of 90 major bleeding events in NOAC patients, only 1 was fatal (1%). Within 30 days following bleeding, there were no strokes and 1 TIA (NOAC). Following a major bleed, the recurrent bleeding rate in NOAC patients in the next 30-days was 4% and the death rate was 4%. Conclusions: Rates of major bleeding with NOACs in clinical practice are comparable to those reported in clinical trials. Compared with warfarin, bleeding among NOAC users was less likely intracranial and more likely to be GI. Management of bleeding in the setting of NOAC rarely includes reversal agents.

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3054Efficacy and safety of non-vitamin K oral anticoagulants in patients with atrial fibrillation and cancer

European Heart Journal ◽

10.1093/eurheartj/ehz745.0021 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

I Cavallari ◽

G Verolino ◽

G Patti

Keyword(s):

Atrial Fibrillation ◽

Venous Thromboembolism ◽

Intracranial Hemorrhage ◽

Major Bleeding ◽

Meta Analysis ◽

Oral Anticoagulants ◽

Efficacy And Safety ◽

Systemic Embolism ◽

Patients With Cancer ◽

All Cause Mortality

Abstract Background Anticoagulation in patients with cancer and atrial fibrillation (AF) is particularly challenging given the higher risk of both thrombotic and bleeding complications in this setting. Data regarding the efficacy and safety of non-vitamin K oral anticoagulants (NOACs) in AF patients with malignancy remain unclear. Purpose In the present meta-analysis we further investigate the efficacy and safety of NOACs compared to warfarin in patients with AF and cancer assuming that available studies may be individually underpowered for endpoints at low incidence, i.e. stroke, major and intracranial bleeding. Methods We performed a systematic review and meta-analysis of studies comparing the use of NOACs vs. warfarin in AF patients with cancer. Efficacy outcome measures included stroke or systemic embolism, venous thromboembolism and mortality. Safety outcome measures were major bleeding and intracranial hemorrhage. Results We pooled data from 6 identified studies enrolling a total of 31,756 AF patients with cancer. Mean follow-up was 1.7 years. Patients with cancer had significantly increased annualized rates of venous thromboembolism (1.38% vs. 0.74%), major bleeding (9.01% vs. 5.13%), in particular major gastrointestinal bleeding (2.38% vs. 1.60%), and all-cause mortality (17.73% vs. 8.50%) vs. those without (all P values <0.001), whereas the incidence of stroke or systemic embolism and intracranial hemorrhage did not differ. Compared with warfarin, treatment with NOACs nominally decreased the risk of stroke or systemic embolism (5.41% vs. 2.70%; odds ratio, OR; 95% confidence intervals, CI 0.51, 0.26–1.01; P=0.05; Figure), mainly of ischemic stroke (OR 0.56; 95% CI 0.35–0.89; P=0.01), and the risk of venous thromboembolism (OR 0.51; 95% CI 0.42–0.61; P<0.001). In cancer patients receiving NOACs there was a significant reduction of major bleeding (3.95% vs. 4.66%; OR 0.66, 95% CI 0.46–0.94; P=0.02; Figure) and intracranial hemorrhage (0.26% vs. 0.66%; OR 0.25, 95% CI 0.08–0.82; P=0.02) vs. warfarin, with no difference in gastrointestinal major bleeding rates. Conclusion AF patients on oral anticoagulation and concomitant cancer are at higher risk of venous thromboembolism, major bleeding and all-cause mortality. NOACs may represent a safer and more effective alternative to warfarin also in this setting of patients.

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Temporal trend of clinical events in patients with atrial fibrillation on edoxaban therapy: results from the non-interventional global ETNA-AF program

European Heart Journal ◽

10.1093/eurheartj/ehab724.2979 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

L Dinshaw ◽

C Chen ◽

R De Caterina ◽

W Jiang ◽

Y.-H Kim ◽

...

Keyword(s):

Atrial Fibrillation ◽

Clinical Practice ◽

Ischaemic Stroke ◽

Major Bleeding ◽

Temporal Trend ◽

Routine Clinical Practice ◽

Clinical Event ◽

Clinical Events ◽

Baseline Characteristics

Abstract Background Patients with atrial fibrillation (AF) who initiated vitamin K antagonist (VKA) were at highest risk of stroke and bleeding in the first few months of therapy. Understanding of the temporal trend of clinical events in AF patients on non-VKA oral anticoagulant (NOAC) therapy should aid therapeutic decisions. Purpose To evaluate the temporal trend of clinical events in AF patients receiving edoxaban in routine clinical practice in the Global ETNA-AF program. Methods Global ETNA-AF is a multicentre, prospective, noninterventional program evaluating the safety and effectiveness of edoxaban in patients from European and Asian countries. Thromboembolic, bleeding and death events were analysed separately for the 1st and 2nd year of the follow-up period, using a time-to-first-event estimation of cumulative incidence and annual rate via Kaplan-Meier method. Results A total of 27,617 patients were included in this analysis, 48.6% from Europe and 51.4% from Japan, Korea, and Taiwan. Baseline characteristics were consistent with typical AF population in real world studies (Table 1). Approximately 83% of patients received the recommended edoxaban dose. Annualized rates of ischaemic stroke and major bleeding (ISTH) were lower in the 2nd year than in the 1st year: ischaemic stroke 0.59% (95% CI, 0.50–0.70) vs 0.86% (95% CI, 0.75–0.98), p=0.015; major bleeding 0.87% (95% CI, 0.75–1.00) vs 1.15% (95% CI, 1.02–1.29), p=0.036. The trend toward lower rates of ischaemic stroke and major bleeding in the 2nd year was consistent across regions. All-cause mortality increased slightly from the 1st year to the 2nd year, which was not statistically significant and was not driven by cardiovascular (CV) mortality (Table 2). Conclusion In routine clinical practice in the Global ETNA-AF program, major bleeding and ischaemic stroke rates in >27,000 patients on edoxaban therapy declined from 1st year to 2nd year. Further analyses will investigate whether such trend is influenced by selection for healthier patients over time. Longer follow-up is needed to better understand long-term trends. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Table 1. Baseline characteristics Table 2. Annualised clinical event rates

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Natural Course of New‐Onset Postoperative Atrial Fibrillation after Noncardiac Surgery

Journal of the American Heart Association ◽

10.1161/jaha.120.018548 ◽

2021 ◽

Author(s):

Junho Hyun ◽

Min Soo Cho ◽

Gi‐Byoung Nam ◽

Minsoo Kim ◽

Ungjeong Do ◽

...

Keyword(s):

Atrial Fibrillation ◽

Major Bleeding ◽

Anticoagulation Therapy ◽

Noncardiac Surgery ◽

Natural Course ◽

Postoperative Atrial Fibrillation ◽

Thromboembolic Events ◽

Af Recurrence ◽

New Onset

Background Postoperative atrial fibrillation (POAF) is common after cardiac surgery, but little is known about its incidence and natural course after noncardiac surgery. We evaluated the natural course and clinical impact of POAF and the long‐term impact of anticoagulation therapy in patients without a history of atrial fibrillation (AF) undergoing noncardiac surgery. Methods and Results We retrospectively analyzed the database of Asan Medical Center (Seoul, Korea) to identify patients who developed new‐onset POAF after undergoing noncardiac surgery between January 2006 and January 2016. The main outcomes were AF recurrence, thromboembolic event, and major bleeding during follow‐up. Of 322 688 patients who underwent noncardiac surgery, 315 patients (mean age, 66.4 years; 64.4% male) had new‐onset POAF with regular rhythm monitoring after discharge. AF recurred in 53 (16.8%) during 2 years of follow‐up. Hypertension (hazard ratio, 2.12; P =0.02), moderate‐to‐severe left atrial enlargement (hazard ratio, 2.33; P =0.007) were independently associated with recurrence. Patients with recurrent AF had higher risks of thromboembolic events (11.2% versus 0.8%; P <0.001) and major bleeding (26.9% versus 4.1%; P <0.001) than those without recurrence. Patients with recurrent AF and without anticoagulation were especially predisposed to thromboembolic events ( P <0.001). Overall, anticoagulation therapy was not significantly associated with thromboembolic events (1.4% versus 2.5%, P =0.95). Conclusions AF recurred in 16.8% of patients with POAF after noncardiac surgery. AF recurrence was associated with higher risks of adverse clinical outcomes. Considering the high risk of anticoagulation‐related bleeding, the benefits of routine anticoagulation should be carefully weighed in this population. Active surveillance for AF recurrence is warranted.

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Effectiveness and Safety of Apixaban versus Warfarin as Outpatient Treatment of Venous Thromboembolism in U.S. Clinical Practice

Thrombosis and Haemostasis ◽

10.1055/s-0038-1673689 ◽

2018 ◽

Vol 118 (11) ◽

pp. 1951-1961 ◽

Cited By ~ 10

Author(s):

Derek Weycker ◽

Xiaoyan Li ◽

Gail DeVecchis Wygant ◽

Theodore Lee ◽

Melissa Hamilton ◽

...

Keyword(s):

Clinical Practice ◽

Venous Thromboembolism ◽

Major Bleeding ◽

Outpatient Treatment ◽

Large Scale ◽

Frailty Models ◽

Shared Frailty ◽

Recurrent Vte ◽

Bridge Therapy

AbstractIn the AMPLIFY clinical trial, apixaban was non-inferior to warfarin plus subcutaneous enoxaparin bridge therapy in the treatment of acute venous thromboembolism (VTE) and was associated with significantly less bleeding. This study evaluated their comparative effectiveness and safety in routine clinical practice. A matched-cohort design and data from four U.S. private health care claims databases were employed. Study population comprised patients who initiated outpatient treatment with apixaban versus warfarin (plus parenteral anticoagulant bridge therapy) within 30 days of their initial VTE episode; apixaban and warfarin patients were matched on age, characteristics of VTE episode, study database and propensity score. Major bleeding, clinically relevant non-major (CRNM) bleeding and recurrent VTE during the 180-day (maximum) follow-up period were compared using shared frailty models. During mean follow-up of 143 days among apixaban patients (n = 17,878) and 152 days among warfarin patients (n = 17,878), incidence proportions for apixaban versus warfarin, respectively, were 1.7% versus 2.3% for major bleeding, 7.0% versus 9.4% for CRNM bleeding and 2.3% versus 2.9% for recurrent VTE. In shared frailty models, risks of major bleeding (hazard ratio [HR] = 0.75, 95% confidence interval [CI] = 0.64–0.87), CRNM bleeding (HR = 0.77, 95% CI = 0.71–0.83) and recurrent VTE (HR = 0.80, 95% CI = 0.70–0.91) were lower for apixaban versus warfarin. In this large-scale evaluation of VTE patients receiving outpatient treatment with apixaban or warfarin in U.S. clinical practice, risks of major bleeding, CRNM bleeding and recurrent VTE were significantly lower among patients who received apixaban.

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Patterns of oral anticoagulation use with cardioversion in clinical practice

Heart ◽

10.1136/heartjnl-2019-316315 ◽

2020 ◽

pp. heartjnl-2019-316315

Author(s):

Kyle Geurink ◽

DaJuanicia Holmes ◽

Michael D Ezekowitz ◽

Karen Pieper ◽

Gregg Fonarow ◽

...

Keyword(s):

Atrial Fibrillation ◽

Clinical Practice ◽

Major Bleeding ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Inclusion Criteria ◽

Related Hospitalisation ◽

Informed Treatment ◽

Ischaemic Attack

BackgroundCardioversion is common among patients with atrial fibrillation (AF). We hypothesised that novel oral anticoagulants (NOAC) used in clinical practice resulted in similar rates of stroke compared with vitamin K antagonists (VKA) for cardioversion.MethodsUsing the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II, patients with AF who had a cardioversion, follow-up data and an AF diagnosis within 6 months of enrolment were identified retrospectively. Clinical outcomes were compared for patients receiving a NOAC or VKA for 1 year following cardioversion.ResultsAmong 13 004 patients with AF, 2260 (17%) underwent cardioversion. 1613 met the inclusion criteria for this analysis. At the time of cardioversion, 283 (17.5%) were receiving a VKA and 1330 (82.5%) a NOAC. A transoesophageal echocardiogram (TOE) was performed in 403 (25%) cardioversions. The incidence of stroke/transient ischaemic attack (TIA) at 30 days was the same for patients having (3.04 per 100 patient-years) or not having (3.04 per 100 patient-years) a TOE (p=0.99). There were no differences in the incidence of death (HR 1.19, 95% CI 0.62 to 2.28, p=0.61), cardiovascular hospitalisation (HR 1.02, 95% CI 0.76 to 1.35, p=0.91), stroke/TIA (HR 1.18, 95% CI 0.30 to 4.74, p=0.81) or bleeding-related hospitalisation (HR 1.29, 95% CI 0.66 to 2.52, p=0.45) at 1 year for patients treated with either a NOAC or VKA.ConclusionsCardioversion was a low-risk procedure for patients treated with NOAC, and there were statistically similar rates of stroke/TIA 30 days after cardioversion as for patients treated with VKA. There were no statically significant differences in death, stroke/TIA or major bleeding at 1 year among patients treated with NOAC compared with VKA after cardioversion.

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Low bleeding and stroke rates with minor age-dependent increase confirm the safety and effectiveness of edoxaban in patients with atrial fibrillation across age groups: Two-year results from ETNA-AF

EP Europace ◽

10.1093/europace/euab116.272 ◽

2021 ◽

Vol 23 (Supplement_3) ◽

Author(s):

D Morrone ◽

M Unverdorben ◽

C Chen ◽

L Dinshaw ◽

W Jiang ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Intracranial Hemorrhage ◽

Major Bleeding ◽

Age Groups ◽

Mortality Data ◽

Clinical Events ◽

Program Support ◽

The Impact

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Background Age is a risk factor for ischemic stroke and bleeding in patients with atrial fibrillation (AF). The large dataset from the global prospective, noninterventional ETNA-AF program allows for analysis of the impact of age on clinical events in AF patients treated with edoxaban. Purpose Evaluate the safety and effectiveness of edoxaban by age subgroups and the impact of age on clinical events. Methods Baseline patient characteristics, thromboembolic and bleeding events, and mortality data were collected from patients with 2-year follow-up in ETNA-AF program and analyzed in defined age subgroups. Cox regression analysis was conducted using age as a continuous variable and clinical events as outcome variables. Results A total of 27,617 patients were categorized into four age subgroups: <65, 65-74, 75-84 and ≥85 years. Patient demographics and baseline characteristics are shown in the Table. Percentage of male, mean body weight, and mean creatinine clearance decreased with age, whereas percentages of patients with heart failure, patients on reduced dose edoxaban 30 mg, mean stroke and bleeding risk scores increased with age. The annualized rates of ischemic stroke and major bleeding increased with age, yet remained low. Importantly, the rate of intracranial hemorrhage was low across age groups, including the ≥85 years group. The hazard ratio (HR) for ischemic stroke was 1.041 (95%CI 1.028-1.053), ie. with a 1-year increase in age, the risk of ischemic stroke increased by 4.1%. The HRs for other clinical events were: major bleeding 1.044 (95%CI 1.033-1.055), intracranial hemorrhage 1.027 (95%CI 1.007-1.046), major gastrointestinal bleeding 1.065 (95%CI 1.048-1.081), all-cause mortality 1.086 (95%CI 1.079-1.093). Conclusion Two-year follow-up data from the global ETNA-AF program support the use of edoxaban as a safe and effective treatment for AF patients across all age groups, including the very elderly, in routine clinical care. The impact of age on the risk of ICH was smaller than that of ischemic stroke and major bleeding. <65 yr(N = 4,278) ≥65-74 yr(N = 9,396) ≥75-84 yr(N = 10,728) ≥85 yr(N = 3,214) Age [years], mean (SD)Male, %Weight [kg], mean (SD) 57.3 (6.6)72.580.6 (20.3) 69.9 (2.9)61.973.0 (17.7) 79.1 (2.8)53.968.0 (16.0) 87.9 (2.8)42.260.1 (14.9) CrCL [mL/min], mean (SD)CHA2DS2-VASc, mean (SD)Mod. HAS-BLED≠, mean (SD) 101.8 (33.7)1.6 (1.1)1.4 (1.0) 75.3 (22.3)2.8 (1.2)2.5 (1.1) 57.9 (18.1)4.1 (1.2)2.7 (1.0) 42.5 (14.3)4.4 (1.3)2.7 (1.0) 2-year clinical events Major Bleeding (ISTH)%/yr [95% CI] Intracranial Hemorrhage%/yr [95% CI] Major GI Bleeding%/yr [95% CI] 0.49 [0.35; 0.68] 0.18 [0.09; 0.30] 0.22 [0.13; 0.36] 0.84 [0.70; 0.99] 0.26 [0.18; 0.34] 0.34 [0.26; 0.44] 1.16 [1.00; 1.32] 0.31 [0.23; 0.40]0.60 [0.49; 0.72] 1.88 [1.51; 2.30] 0.46 [0.29; 0.69]1.19 [0.90; 1.53] Any Stroke%/yr [95% CI]Ischemic Stroke%/yr [95% CI]Hemorrhagic Stroke%/yr [95% CI] 0.54 [0.38; 0.73]0.38[0.26; 0.56]0.12[0.06; 0.23] 0.79 [0.66; 0.94]0.59[0.47; 0.71]0.19[0.13; 0.27] 1.15 [1.00; 1.32]0.89[0.76; 1.04]0.23[0.16; 0.31] 1.53 [1.21; 1.92]1.21[0.92; 1.56]0.320.18; 0.52] All-cause Death%/yr [95% CI]CV Death (sensitivity)%/yr [95% CI] 1.05 [0.83; 1.32]0.51[0.36; 0.70] 1.82 [1.62; 2.04]0.83[0.69; 0.98 3.51 [3.25; 3.80]1.65[1.47; 1.84] 9.08 [8.27; 9.96]4.16[3.62; 4.77] ≠Excluding labile INR.

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Safety and Effectiveness of Edoxaban in Atrial Fibrillation Patients in Routine Clinical Practice: One-Year Follow-Up from the Global Noninterventional ETNA-AF Program

Journal of Clinical Medicine ◽

10.3390/jcm10040573 ◽

2021 ◽

Vol 10 (4) ◽

pp. 573

Author(s):

Raffaele De Caterina ◽

Young-Hoon Kim ◽

Yukihiro Koretsune ◽

Chun-Chieh Wang ◽

Takeshi Yamashita ◽

...

Keyword(s):

Atrial Fibrillation ◽

Clinical Practice ◽

Major Bleeding ◽

Stroke Prevention ◽

Oral Anticoagulants ◽

Routine Clinical Practice ◽

Bleeding Events ◽

Major Bleeding Events ◽

One Year

Non-vitamin K antagonist oral anticoagulants such as edoxaban are the standard of care for stroke prevention in patients with atrial fibrillation (AF). The Global Edoxaban Treatment in routiNe clinical prActice (ETNA)-AF program integrates prospective, observational, noninterventional regional studies from Europe, Japan, and other Asian countries, collecting data on patient characteristics and clinical outcomes in unselected patients treated with edoxaban for stroke prevention in AF. Overall, 26,823 patients completed a 1-year follow-up and were treated with edoxaban; either 60 or 30 mg once daily. The majority (82.6%) of patients received the recommended doses according to the local label. At baseline, the median (interquartile range) age was 75 (68, 80) years, the CHA2DS2-VASc score was 3.0 (2.0, 4.0), and the hypertension, abnormal renal and liver function, stroke, bleeding, labile international normalized ratio, elderly, drugs, or alcohol (HAS-BLED) score was 2.0 (2.0, 3.0). At one year, there were 273 (1.12%/year) major bleeding events, including 75 (0.31%/year) intracranial hemorrhages and 140 (0.57%/year) major gastrointestinal (GI) bleeds. There were 214 ischemic strokes (0.87%/year). Mortality was 3.03%/year (745 deaths), and cardiovascular mortality accounted for 40% of all deaths (1.22%/year, 299 cardiovascular deaths). In conclusion, stroke, intracranial hemorrhage, and other major bleeding events were low in patients with AF treated with edoxaban in routine care. Even on anticoagulation, cardiovascular death remained common.

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Edoxaban treatment of elderly patients with atrial fibrillation in routine clinical practice: 1-year results of the non-interventional Global ETNA-AF program

European Heart Journal ◽

10.1093/ehjci/ehaa946.0663 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

T Yamashita ◽

C.C Wang ◽

Y.-H Kim ◽

R De Caterina ◽

P Kirchhof ◽

...

Keyword(s):

Atrial Fibrillation ◽

Clinical Practice ◽

Major Bleeding ◽

Intracranial Haemorrhage ◽

Clinical Care ◽

Oral Anticoagulants ◽

Clinical Event ◽

Funding Source ◽

Private Company ◽

All Cause Mortality

Abstract Background The prevalence of atrial fibrillation (AF) and the need for appropriate anticoagulation increase with age. The benefit/risk profile of direct oral anticoagulants such as edoxaban in elderly population with AF in regular clinical practice is therefore of particular interest. Purpose Analyses of Global ETNA-AF data were performed to report patient characteristics, edoxaban treatment, and 1-year clinical events by age subgroups. Methods Global ETNA-AF is a multicentre, prospective, noninterventional program conducted in Europe, Japan, Korea, Taiwan, and other Asian countries. Demographics, baseline characteristics, and 1-year clinical event data were analysed in four age subgroups. Results Of 26,823 patients included in this analysis, 50.4% were ≥75 years old and 11.6% were ≥85 years. Increase in age was generally associated with lower body weight, lower creatinine clearance, higher CHA2DS2-VASc and HAS-BLED scores, and a higher percentage of patients receiving the reduced dose of 30 mg daily edoxaban. At 1-year, rates of ISTH major bleeding and ischaemic stroke were generally low across all age subgroups. The proportion of intracranial haemorrhage within major bleeding events was similar across age groups. All-cause mortality increased with age more than cardiovascular mortality. Conclusion Data from Global ETNA-AF support the safety and effectiveness of edoxaban in elderly AF patients (including ≥85 years) in routine clinical care with only a small increase in intracranial haemorrhage. The higher all-cause mortality with increasing age is not driven by cardiovascular causes. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Daiichi Sankyo

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

TH Open ◽

10.1055/s-0040-1721499 ◽

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.

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