Effectiveness and Safety of Non–Vitamin K Oral Anticoagulants in Comparison to Phenprocoumon: Data from 61,000 Patients with Atrial Fibrillation

2018 ◽  
Vol 118 (03) ◽  
pp. 526-538 ◽  
Author(s):  
Stefan Hohnloser ◽  
Edin Basic ◽  
Christopher Hohmann ◽  
Michael Nabauer
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Standard Dose ◽  
Oral Anticoagulants ◽  
Proportional Hazard ◽  
Systemic Embolism ◽  
Cox Proportional Hazard ◽  
Hazard Ratios ◽  
Cox Proportional Hazard Models ◽  
Baseline Characteristics

AbstractAll pivotal trials have evaluated non–vitamin K oral antagonists (NOACs) against warfarin. However, in some regions of the world, phenprocoumon is the most widely used vitamin K antagonist (VKA). There is little evidence documenting effectiveness and safety of NOACs compared with phenprocoumon in atrial fibrillation (AF). A retrospective cohort study using a German claims database was conducted to assess effectiveness (stroke, systemic embolism [SE]) and safety (bleeding leading to hospitalization) during therapy with NOACs and phenprocoumon in 61,205 AF patients. Hazard ratios (HRs) for effectiveness and safety outcomes were derived from Cox proportional hazard models, adjusting for baseline characteristics. Propensity score matching was performed as a sensitivity analysis. As a prespecified subgroup analysis, the effects of reduced NOAC dosing were compared with phenprocoumon. A total of 61,205 patients were identified in whom phenprocoumon (n = 23,823, 38.9%), apixaban (n = 10,117, 16.5%), dabigatran (n = 5,122, 8.4%), or rivaroxaban (n = 22,143, 36.2%) was initiated. After adjusting for baseline confounders, all three NOACs tested had significantly lower risks of stroke/SE compared with phenprocoumon (apixaban—HR: 0.77, 95% CI: 0.66–0.90; dabigatran—HR: 0.74, 95% CI: 0.60–0.91; rivaroxaban—HR: 0.86, 95% CI: 0.76–0.97). Apixaban (HR: 0.58, 95% CI: 0.49–0.69) and dabigatran (HR: 0.64, 95% CI: 0.50–0.80) were associated with lower bleeding risks than phenprocoumon, whereas the risk was similar for rivaroxaban and phenprocoumon. All three NOACs showed reduced risk of intracranial bleeding compared with phenprocoumon. Reduced doses of NOACs were predominantly used in patients with advanced age and comorbidities with generally similar effectiveness and safety benefits compared with phenprocumon as standard-dose NOACs.

P3470Comparative effectiveness and safety of non-vitamin K oral anticoagulants and warfarin in non-valvular atrial fibrillation - a cohort study in 3 Nordic countries

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Johnsen ◽  
M Madsen ◽  
M Linder ◽  
G Sulo ◽  
W Ghanima ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Cohort Study ◽  
Vitamin K ◽  
Oral Anticoagulants ◽  
Cox Proportional Hazards ◽  
Nordic Countries ◽  
Systemic Embolism ◽  
Hazard Ratios ◽  
Warfarin Treatment

Abstract Background Non-vitamin K oral anticoagulants (NOACs) are an alternative to warfarin in the prevention of stroke in non-valvular atrial fibrillation (NVAF). Nordic countries have high quality of warfarin treatment, making them an especially suitable setting for assessing effectiveness and safety of NOACs against warfarin. Purpose The BEYOND Pooled (BEnefit of NOACs studY of nOn-valvular AF patieNts in NorDic countries) study compared risks of ischaemic or haemorrhagic stroke/systemic embolism (S/SE), and risk of bleeding with acute hospitalisation with an overnight stay (bleeding) in NVAF patients treated with apixaban, dabigatran or rivaroxaban, each compared with warfarin treatment. Methods A cohort study of treatment-naïve adult NVAF patients dispensed apixaban, dabigatran, rivaroxaban or warfarin was identified from 01 Jan 2013 to 31 Dec 2016. The population and study variables were identified from national registries in Denmark, Norway and Sweden. After 1:1 propensity score (PS) matching for each NOAC-warfarin comparison, individual-level data were pooled across the countries. Cox proportional-hazards regression was used to estimate adjusted hazard ratios (aHRs) of the endpoints. Results PS matched NOAC cohort sizes were: apixaban (55,696) dabigatran (28,526) and rivaroxaban (30,701), and the total follow-up in the PS-matched population was 291,171 years (mean 1.3 years). During the follow-up, 35,450 oral anticoagulation (OAC) patients had a S/SE and 38,620 OAC patients had bleeding. Adjusted HRs for the two endpoints are presented in the table. PH assumption has not been formally tested but cum incidence curves did not indicate substantial differences in the effects over time. Table 1. Adjusted hazard ratios (aHR) of stroke/systemic embolism and bleeding for non-vitamin K oral anticoagulants versus warfarin Endpoint Apixaban vs Warfarin: aHR (95% CI) Dabigatran vs Warfarin: aHR (95% CI) Rivaroxaban vs Warfarin: aHR (95% CI) Stroke/SE 0.93 (0.85–1.03) 0.89 (0.80–1.00) 0.97 (0.88–1.08) Bleeding 0.72 (0.67–0.77) 0.87 (0.80–0.95) 1.12 (1.04–1.20) Conclusions Relative to warfarin, apixaban and dabigatran were associated with lower rates of bleeding whereas rivaroxaban was associated with a higher rate. The three NOACs had comparable rates of stroke and systemic embolism relative to warfarin. Acknowledgement/Funding This study was funded by the Pfizer/Bristol-Myers Squibb Alliance.

Effectiveness and safety of oral anticoagulants among non-valvular atrial fibrillation patients with polypharmacy

2020 ◽  
Author(s):  
Gregory Y H Lip ◽  
Allison Keshishian ◽  
Amiee Kang ◽  
Amol D Dhamane ◽  
Xuemei Luo ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Lower Risk ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Proportional Hazard ◽  
Effective Management ◽  
Cox Proportional Hazard ◽  
Cox Proportional Hazard Models ◽  
Concomitant Medications ◽  
Potential Issue

Abstract Aims Polypharmacy is prevalent among non-valvular atrial fibrillation (NVAF) patients and presents a potential issue for the effective management of NVAF. This study compared the risk of stroke/systemic embolism (SE) and major bleeding (MB) among NVAF patients with polypharmacy newly prescribed oral anticoagulants (OACs). Methods and results A retrospective study of NVAF patients with polypharmacy who initiated OACs from 01 January 2013 to 30 September 2015 was conducted using US CMS Medicare and four commercial databases. Polypharmacy was defined as ≥6 concomitant medications on the index date. Propensity score matching was conducted to compare non-vitamin K antagonists OACs (NOACs) to warfarin as well as between NOACs. Cox proportional hazard models were used to evaluate the risk of stroke/SE and MB. A total of 188 893 patients with polypharmacy were included, with an average of 8 concomitant medications (interquartile range 6–9). Compared to warfarin, apixaban [hazard ratio (HR): 0.59, 95% confidence interval (CI): 0.52–0.68], and rivaroxaban (HR: 0.75, 95% CI: 0.69–0.83) were associated with a lower risk of stroke/SE. Apixaban (HR: 0.57, 95% CI: 0.54–0.61) and dabigatran (HR: 0.76, 95% CI: 0.66–0.88) were associated with a decreased risk of MB compared with warfarin. Compared with dabigatran and rivaroxaban, apixaban was associated with a lower risk of stroke/SE and MB. Dabigatran was associated with lower risk of MB compared with rivaroxaban. Conclusions In this observational study of anticoagulated NVAF patients with polypharmacy, effectiveness and safety profiles are more favourable for NOACs vs. warfarin. Our observations are hypothesis generating and may help inform future clinical trials regarding appropriate OAC treatment selection in polypharmacy patients.

scholarly journals Anticoagulation Challenges in Hematogeriatrics: Effectiveness and Safety of Direct Oral Anticoagulants Vs Vitamin k Antagonist in Elderly with Atrial Fibrillation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1162-1162
Author(s):  
Desirée Campoy ◽  
Gonzalo Artaza ◽  
César A Velasquez ◽  
Tania Canals ◽  
Erik A Johansson ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Elderly Patients ◽  
Vitamin K ◽  
Major Bleeding ◽  
Frail Elderly ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Systemic Embolism ◽  
Bleeding Events

BACKGROUND Direct oral anticoagulants (DOAC) are increasingly used in patients with Non Valvular Atrial Fibrillation (NVAF) for stroke prevention. However, Follow-Up (FU) and dosing these agents in the elderly can be challenging due to different factors, such as chronic kidney disease, frailty, falls, multifactorial anemia and concomitant polypharmacy. These factors in elderly patients predisposes to both thromboembolic and bleeding events once atrial fibrillation occurs. Therefore, balancing risks and benefits of antithrombotic strategies in older populations is crucial. Despite recent increases in DOAC use in NVAF, there are still limited data regarding DOACs effectiveness and safety in frail elderly patients. AIM To assess the effectiveness and safety according to DOAC or Vitamin K Antagonist (VKA) in a cohort of elderly patients with NVAF. METHODS From April 2016 to April 2019, we consecutively included NVAF elderly patients (≥80 years-old) treated with DOAC or VKA in a prospective multicenter registry. Demographic, laboratory, frailty risk stratification and antithrombotic therapy data were collected. Patients had a minimum FU of 6 months. VKA patients had a standard FU through digital international normalized ratio (INR) control and the efficacy of therapy was determined by the time in therapeutic range (TTR) values from the preceding 6 months of treatment using Rosendaal's method. FU in DOAC patients was performed through structured and integral assessment following the Tromboc@t Working Group recommendations for management in patients receiving DOAC (Olivera et al, Med Clin 2018). Key practical management aspects are listed in the flow chart (Figure 1). Clinical Frailty Scale (CFS score) was assigned to each patient at the beginning and during the FU; patients were classified into three categories: non-frail (CFS 1-4), mild-to-moderately frail (CFS 5-6), and severely frail (CFS 7-9). RESULTS From a total of 1040 NVAF patients, 690 (63.5%) were treated with DOAC (61 dabigatran, 95 rivaroxaban, 254 edoxaban and 280 apixaban) and 350 with VKA. In the VKA group, the mean TTR was 52.8%. Demographic characteristics and CFS score are summarized in table 1. Kaplan-Meier analysis (median FU: 16.5 months) showed a significantly high incidence of stroke/systemic embolism among VKA patients vs DOAC patients (4.2 vs 0.5 events per 100 patient-years, p<0.001). Major bleeding in the DOAC group was significantly infrequent compared with VKA group (2.2 vs 8.9 events, p=0.001). In the DOAC group, 90% (n=20/22) of the major bleedings were gastrointestinal [16 rivaroxaban and 4 edoxaban]. However, in the VKA group 64% (n = 20/31) were gastrointestinal, 25.8% (n= 8/31) intracranial and 9.7% (n = 3/31) urogenital bleedings. We identified 365 very elderly patients (aged ≥ 90 years) of which 270 (39.1%) were DOAC patients and 95 (27.1%) VKA patients. In this subgroup of patients, after a multivariate regression analysis, the stroke/systemic embolism incidence was similar in both treatment groups regardless of the age, but major bleeding decreased significantly in DOAC group (adjusted HR 0.247, 95% CI 0.091-0.664). CONCLUSIONS Our data indicate that DOACs can be a good therapeutic option for stroke/systemic embolism prevention in frail elderly patients, showing low rates of stroke as well as bleeding events when a structured and integral FU is applied to anticoagulated patients. Further investigations are necessary to analyze the impact in the quality of life and net clinical benefit of anticoagulant therapy when a FU program is applied in elderly patients. Disclosures Sierra: Novartis: Honoraria, Research Funding, Speakers Bureau; Astellas: Honoraria; Pfizer: Honoraria; Daiichi-Sankyo: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; Roche: Honoraria; Jazz Pharmaceuticals: Honoraria.

6072Risk of stroke in hypertensive patients with atrial fibrillation treated with oral anticoagulants

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
R E Harskamp ◽  
W A M Lucassen ◽  
R D Lopes ◽  
H C Van Weert
Keyword(s):  
Atrial Fibrillation ◽  
Blood Pressure ◽  
Vitamin K ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Haemorrhagic Stroke ◽  
Uncontrolled Hypertension ◽  
P Value ◽  
Systemic Embolism ◽  
History Of

Abstract Background Hypertension is common in patients with atrial fibrillation (AF) and carries an additional risk for complications, most notably stroke and bleeding. We assessed the history of hypertension, level of blood pressure control, and an interaction with the choice of oral anticoagulants on clinical outcomes. Purpose To gain insights into the risks of hypertension in the setting of AF and explore possible interactions with the safety and efficacy of non-vitamin K oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs). Methods We performed a systematic review and meta-analysis of studies that randomised patients to NOACs or VKAs and reported outcomes stratified by presence of hypertension. Collected outcomes included: ischaemic stroke or systemic embolism (SE), death from any cause, hemorrhagic stroke, major bleeding, and intracranial hemorrhage. Log adjusted hazard ratios (HR) and corresponding standard error were calculated, and HRs were compared using Mantel-Haenszel random effects. Quality of the evidence was assessed with Cochrane risk of bias tool. Results Five high-quality studies were eligible, including 71,602 participants who received NOACs (apixaban, dabigatran, edoxaban, rivaroxaban) or VKAs, with median follow-up of 1.8–2.8 years. 89.2% of participants had a history of hypertension. Compared with patients without hypertension, those with controlled and uncontrolled hypertension had higher risk for stroke/SE (HR: 1.21 [1.04–1.41] and HR: 1.50 [1.12–2.01], respectively) and haemorrhagic stroke (HR: 1.78 [1.06, 3.00] and HR: 1.66 [0.99–4.01], respectively). On a continuous scale, the risk of stroke increased 7% per 10mmHg increase in systolic blood pressure. As shown in the Table, no interactions were found between hypertension status and the efficacy or safety of NOACs versus VKAs. Table 1. Interaction of presence of hypertension on the comparative efficacy and safety of NOAC versus VKA Hypertension (n=63,869) No hypertension (n=7,733) P-value (int) Adjusted HR, 95% CI Adjusted HR, 95% CI Stroke or systemic embolism 080, 0.72–0.89 0.79, 0.53–1.19 0.98 Haemorrhagic stroke 0.55, 0.41–0.74 0.24, 0.04–1.37 0.36 Death from any cause 0.91, 0.84–0.98 0.89, 0.76–1.04 0.82 Major bleeding 0.90, 0.76–1.07 0.84, 0.69–1.01 0.57 Intracranial haemorrhage 0.41, 0.24-.068 0.48, 0.14–1.69 0.81 Major or clinically relevant non-major bleed 0.90, 0.68–1.18 0.91, 0.55–1.53 0.96 Conclusions Adequate blood pressure management is vital to optimally reduce the risk of stroke in patients with atrial fibrillation. The benefits of NOACs over VKAs, also apply to patients with elevated blood pressure.

scholarly journals Farming tasks and the development of rheumatoid arthritis in the agricultural health study

2019 ◽  
pp. oemed-2018-105361 ◽  
Author(s):  
Christine G Parks ◽  
Armando Meyer ◽  
Laura E Beane Freeman ◽  
Jonathan Hofmann ◽  
Dale P Sandler
Keyword(s):  
Rheumatoid Arthritis ◽  
Self Report ◽  
Health Study ◽  
Proportional Hazard ◽  
Agricultural Health ◽  
Cox Proportional Hazard ◽  
Hazard Ratios ◽  
Cox Proportional Hazard Models ◽  
Agricultural Health Study

ObjectivesFarming has been associated with rheumatoid arthritis (RA). Some studies have evaluated the effects of pesticides, but other agricultural exposures may also affect immune response.MethodsWe investigated non-pesticide agricultural exposures in relation to RA in licensed pesticide applicators (n=27 175, mostly male farmers) and their spouses (n=22 231) in the Agricultural Health Study (AHS) cohort (1993–1997) who completed at least one follow-up survey through 2015. Incident RA cases (n=229 applicators and 249 spouses) were identified based on self-report confirmed by use of disease-modifying antirheumatic drugs or medical records. Hazard Ratios (HRs) and 95% Confidence Intervals (CIs) were estimated by Cox proportional hazard models adjusting for applicator status, state, smoking, education and specific pesticide use, allowing estimates to vary by median age when hazards assumptions were not met.ResultsOverall, RA was associated with regularly applying chemical fertilisers (HR=1.50; 95% CI 1.11 to 2.02), using non-gasoline solvents (HR=1.40; 95% CI 1.09 to 1.80), and painting (HR=1.26; 95% CI 1.00 to 1.59). In older applicators (>62 years), RA was associated with driving combines (HR=2.46; 95% CI 1.05 to 5.78) and milking cows (HR=2.56; 95% CI 1.01 to 6.53). In younger participants (≤62 years), RA was inversely associated with raising animals as well as crops (HR=0.68; 95% CI 0.51 to 0.89 vs crops only). Associations with specific crops varied by age: some (eg, hay) were inversely associated with RA in younger participants, while others (eg, alfalfa) were associated with RA in older participants.ConclusionThese findings suggest several agricultural tasks and exposures may contribute to development of RA.

scholarly journals HAS FRAILTY SCORE AND FRAILTY LETHALITY CHANGED OVER TIME? HARMONIZATION OF NHANES COHORTS FROM 1999 TO 2016

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S682-S682
Author(s):  
Joanna M Blodgett ◽  
Kenneth Rockwood ◽  
Olga Theou
Keyword(s):  
Multilevel Models ◽  
Healthcare Access ◽  
Frailty Index ◽  
Age Groups ◽  
Proportional Hazard ◽  
Health And Nutrition ◽  
Cox Proportional Hazard ◽  
Hazard Ratios ◽  
Cox Proportional Hazard Models ◽  
Over Time

Abstract Positive advances in life expectancy, healthcare access and medical technology have been accompanied by an increased prevalence of chronic diseases and substantial population ageing. How this impacts changes in both frailty level and subsequent mortality in recent decades are not well understood. We aimed to investigate how these factors changed over an 18-year period. Nine waves of the National Health and Nutrition Examination Survey (1999-2016) were harmonized to create a 46-item frailty index (FI) using self-reported and laboratory-based health deficits. Individuals aged 20+ were included in analyses (n=44086). Mortality was ascertained in December 2015. Weighted multilevel models estimated the effect of cohort on FI score in 10-year age-stratified groups. Cox proportional hazard models estimated if two or four-year mortality risk of frailty changed across the 1999-2012 cohorts. Mean FI score was 0.11±0.10. In the five older age groups (&gt;40 years), later cohorts had higher frailty levels than did earlier cohorts. For example, in people aged 80+, each subsequent cohort had an estimated 0.007 (95%CI: 0.005, 0.009) higher FI score. However, in those aged 20-29, later cohorts had lower frailty [β=-0.0009 (-0.0013, -0.0005)]. Hazard ratios and cohort-frailty interactions indicated that there was no change in two or four-year lethality of FI score over time (i.e. two-year mortality: HR of 1.069 (1.055, 1.084) in 1999-2000 vs 1.061 (1.044, 1.077) in 2011-2012). Higher frailty levels in the most recent years in middle and older aged adults combined with unchanged frailty lethality suggests that the degree of frailty may continue to increase.

scholarly journals Comparison of dabigatran, rivaroxaban, and apixaban for effectiveness and safety in atrial fibrillation: a nationwide cohort study

2020 ◽  
Vol 6 (2) ◽  
pp. 75-85 ◽  
Author(s):  
Ole-Christian W Rutherford ◽  
Christian Jonasson ◽  
Waleed Ghanima ◽  
Fabian Söderdahl ◽  
Sigrun Halvorsen
Keyword(s):  
Atrial Fibrillation ◽  
Cohort Study ◽  
Major Bleeding ◽  
Lower Risk ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Routine Clinical Practice ◽  
Systemic Embolism ◽  
Nationwide Study ◽  
Hazard Ratios

Abstract Aims The aim of this study was to compare the risk of stroke or systemic embolism (SE) and major bleeding in patients with atrial fibrillation (AF) using dabigatran, rivaroxaban, and apixaban in routine clinical practice. Methods and results Using nationwide registries in Norway from January 2013 to December 2017, we established a cohort of 52 476 new users of non-vitamin K antagonist oral anticoagulants (NOACs) with AF. Users of individual NOACs were matched 1:1 on the propensity score to create three pairwise-matched cohorts: dabigatran vs. rivaroxaban (20 504 patients), dabigatran vs. apixaban (20 826 patients), and rivaroxaban vs. apixaban (27 398 patients). Hazard ratios (HRs) for the risk of stroke or SE and major bleeding were estimated. In the propensity-matched comparisons of the risk of stroke or SE, the HRs were 0.88 [95% confidence interval (CI) 0.76–1.02] for dabigatran vs. rivaroxaban, 0.88 (95% CI 0.75–1.02) for dabigatran vs. apixaban, and 1.00 (95% CI 0.89–1.14) for apixaban vs. rivaroxaban. For the risk of major bleeding, the HRs were 0.75 (95% CI 0.64–0.88) for dabigatran vs. rivaroxaban, 1.03 (95% CI 0.85–1.24) for dabigatran vs. apixaban, and 0.79 (95% CI 0.68–0.91) for apixaban vs. rivaroxaban. Conclusion In this nationwide study of patients with AF in Norway, we found no statistically significant differences in risk of stroke or SE in propensity-matched comparisons between dabigatran, rivaroxaban, and apixaban. However, dabigatran and apixaban were both associated with significantly lower risk of major bleeding compared with rivaroxaban.

scholarly journals MicroRNAs as biomarkers for prostate cancer prognosis: a systematic review and a systematic reanalysis of public data

2022 ◽  
Author(s):  
Sharmila Rana ◽  
Gabriel N. Valbuena ◽  
Ed Curry ◽  
Charlotte L. Bevan ◽  
Hector C. Keun
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Cancer Prognosis ◽  
Prognostic Biomarkers ◽  
Random Effects Model ◽  
Proportional Hazard ◽  
Cox Proportional Hazard ◽  
Hazard Ratios ◽  
Public Data ◽  
Cox Proportional Hazard Models

Abstract Background Reliable prognostic biomarkers to distinguish indolent from aggressive prostate cancer (PCa) are lacking. Many studies investigated microRNAs (miRs) as PCa prognostic biomarkers, often reporting inconsistent findings. We present a systematic review of these; also systematic reanalysis of public miR-profile datasets to identify tissue-derived miRs prognostic of biochemical recurrence (BCR) in patients undergoing radical prostatectomy. Methods Independent PubMed searches were performed for relevant articles from January 2007 to December 2019. For the review, 128 studies were included. Pooled-hazard-ratios (HRs) for miRs in multiple studies were calculated using a random-effects model (REM). For the reanalysis, five studies were included and Cox proportional-hazard models, testing miR association with BCR, performed for miRs profiled in all. Results Systematic review identified 120 miRs as prognostic. Five (let-7b-5p, miR-145-5p, miR152-3p, miR-195-5p, miR-224-5p) were consistently associated with progression in multiple cohorts/studies. In the reanalysis, ten (let-7a-5p, miR-148a-3p, miR-203a-3p, miR-26b-5p, miR30a-3p, miR-30c-5p, miR-30e-3p, miR-374a-5p, miR-425-3p, miR-582-5p) were significantly prognostic of BCR. Of these, miR-148a-3p (HR = 0.80/95% CI = 0.68-0.94) and miR-582-5p (HR = 0.73/95% CI = 0.61-0.87) were also reported in prior publication(s) in the review. Conclusions Fifteen miRs were consistently associated with disease progression in multiple publications or datasets. Further research into their biological roles is warranted to support investigations into their performance as prognostic PCa biomarkers.

P4758Label adherence of non-vitamin K antagonist oral anticoagulants and clinical outcomes in patients with atrial fibrillation: A nationwide study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H T Yu ◽  
P S Yang ◽  
E Jang ◽  
T H Kim ◽  
J S Uhm ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Practice ◽  
Clinical Outcomes ◽  
Vitamin K ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Systemic Embolism ◽  
Increased Risk ◽  
All Cause Mortality

Abstract Background Dose adjustment of non-vitamin K antagonist oral anticoagulants (NOACs) is indicated in some patients with atrial fibrillation (AF), based on selected patient factors or concomitant medications. Purpose We assessed the frequency of label adherence of NOAC dosing among AF patients and the associations between off-label NOAC dosing and clinical outcomes in real-world clinical practice. Methods We evaluated 53,649 AF patients treated with a NOAC using Korean National Health Insurance Service database during the period from January 2013 to December 2016. NOAC doses were classified as either underdosed or overdosed, consistent with U.S. Food and Drug Administration labeling. Cox proportional hazards regression was performed to investigate the effectiveness and safety outcomes including stroke or systemic embolism, major bleeding, and all-cause mortality. Results Overall, 16,757 NOAC-treated patients (31.2%) were underdosed, 4,492 were overdosed (8.4%), and 32,400 (60.4%) were dosed appropriately according to drug labeling. Compared with patients with label adherence, those who were underdosed or overdosed were older (71±8 and 75±7 years of age vs. 70±9 years of age, respectively; p<0.001), more likely female (39% and 53% vs. 38%, respectively; p<0.001), and had higher CHA2DS2-VASc scores (4.6±1.7 and 5.3±1.7 vs. 4.5±1.8, respectively; p<0.001). NOAC overdosing was associated with increased risk for stroke or systemic embolism (5.76 vs. 4.03 events/100 patient-years, p<0.001), major bleeding (4.77 vs. 2.94 events/100 patient-years, p<0.001), and all-cause mortality (5.43 vs. 3.05 events/100 patient-years, p<0.001) compared with label-adherent use. Figure 1 Conclusion In routine clinical practice, a significant proportion (almost 2 in 5) of AF patients received NOAC doses inconsistent with drug labeling. NOAC overdosing is associated with increased risk for stroke or systemic embolism, major bleeding, and all-cause mortality in Asian patient with AF.

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