Abstract P146: Comparative Effectiveness Of Direct Oral Anticoagulants Versus Warfarin Among Medicare Beneficiaries With Atrial Fibrillation

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Shirin Ardeshirrouhanifard ◽  
Huijun An ◽  
Ravi Goyal ◽  
Mukaila Raji ◽  
Caleb Alexander ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Cancer Patients ◽  
Risk Model ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Competing Risk ◽  
Secondary Outcome ◽  
Systemic Embolism ◽  
Competing Risk Model

Objective: Post-hoc analysis of three pivotal clinical trials suggests no difference in risk of ischemic stroke or systemic embolism among cancer patients with atrial fibrillation treated with direct oral anticoagulants (DOACs) vs. warfarin. However, these studies were underpowered and also do not reflect the context of real-world use. We compared the effectiveness of DOACs versus warfarin for the risk of stroke or systemic embolism and all-cause death in patients with NVAF. Methods: We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 2009 to 2016 and included patients aged ≥66 years diagnosed with cancer (breast, bladder, colorectal, esophagus, lung, ovary, kidney, pancreas, prostate, stomach or uterus) and NVAF. We limited the cohort to patients who newly initiated warfarin or DOACs (from 2010 to 2016) with no history of ischemic stroke or systemic embolism. The primary outcome was hospitalization due to ischemic stroke or systemic embolism and the secondary outcome was all-cause death. We used Fine and Gray’s competing risk model, while treating death as a competing risk, to determine the association of oral anticoagulants with the incidence of stroke or systemic embolism. We also adjusted the analysis using inverse probability of treatment weighted (IPTW). Additionally, an IPTW-adjusted Cox proportional hazards regression model was constructed for all-cause death. Results: Of 1,028,784 patients with cancer, 158,744 (15.4%) were diagnosed with atrial fibrillation. After applying all inclusion criteria, the final study cohort included 7,334 cancer patients diagnosed with incident NVAF who newly initiated warfarin or DOACs, of which 3,194 (43.6%) used warfarin and 4,140 (56.4%) used DOACs. The unadjusted rate of stroke or systemic embolism was similar among warfarin and DOACs users (1.20 vs. 1.32 cases per 100 person-years, p=0.27). In the IPTW weighted competing risk model, the use of DOACs was not associated with an increased risk of stroke or systemic embolism compared with warfarin users (Hazard Ratio [HR] 1.41, 95% confidence intervals [CI] 0.90-2.20). However, DOACs users had a significantly lower risk of all-cause death compared with warfarin users (HR 0.82, CI 0.74-0.91). Conclusion: Among cancer patients diagnosed with NVAF, DOACs had a similar risk for stroke or systemic embolism compared to warfarin, although DOAC use was associated with reduced risk of all-cause mortality.

scholarly journals Early Initiation of Direct Oral Anticoagulants After Onset of Stroke and Short- and Long-Term Outcomes of Patients With Nonvalvular Atrial Fibrillation

Stroke ◽  
2020 ◽  
Vol 51 (3) ◽  
pp. 883-891 ◽  
Author(s):  
Tadataka Mizoguchi ◽  
Kanta Tanaka ◽  
Kazunori Toyoda ◽  
Sohei Yoshimura ◽  
Ryo Itabashi ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Hazard Ratio ◽  
Interquartile Range ◽  
Systemic Embolism ◽  
Nonvalvular Atrial Fibrillation ◽  
Ischemic Attack

Background and Purpose— We aimed to compare outcomes of ischemic stroke patients with nonvalvular atrial fibrillation between earlier and later initiation of direct oral anticoagulants (DOACs) after stroke onset. Methods— From data for 1192 nonvalvular atrial fibrillation patients with acute ischemic stroke or transient ischemic attack in a prospective, multicenter, observational study, patients who started DOACs during acute hospitalization were included and divided into 2 groups according to a median day of DOAC initiation after onset. Outcomes included stroke or systemic embolism, major bleeding, and death at 3 months, as well as those at 2 years. Results— DOACs were initiated during acute hospitalization in 499 patients in median 4 (interquartile range, 2–7) days after onset. Thus, 223 patients (median age, 74 [interquartile range, 68–81] years; 78 women) were assigned to the early group (≤3 days) and 276 patients (median age, 75 [interquartile range, 69–82] years; 101 women) to the late (≥4 days) group. The early group had lower baseline National Institutes of Health Stroke Scale score and smaller infarcts than the late group. The rate at which DOAC administration persisted at 2 years was 85.2% overall, excluding patients who died or were lost to follow-up. Multivariable Cox shared frailty models showed comparable hazards between the groups at 2 years for stroke or systemic embolism (hazard ratio, 0.86 [95% CI, 0.47–1.57]), major bleeding (hazard ratio, 1.39 [95% CI, 0.42–4.60]), and death (hazard ratio, 0.61 [95% CI, 0.28–1.33]). Outcome risks at 3 months also did not significantly differ between the groups. Conclusions— Risks for events including stroke or systemic embolism, major bleeding, and death were comparable whether DOACs were started within 3 days or from 4 days or more after the onset of nonvalvular atrial fibrillation–associated ischemic stroke or transient ischemic attack. Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT01581502.

Direct Oral Anticoagulants in Patients with Cancer

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 877-877 ◽  
Author(s):  
Surbhi Shah ◽  
Yvonne H Datta ◽  
Faye Norby ◽  
Alvaro Alonso
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Confidence Interval ◽  
Cancer Patients ◽  
Lower Risk ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Morbidity And Mortality ◽  
Severe Bleeding ◽  
Diagnostic Codes

Abstract Introduction Cancer patients are at high risk for morbidity and mortality due to thrombosis and bleeding, in addition they may also have pre-existing conditions, such as atrial fibrillation (AF) and prior venous thromboembolism (VTE), for which chronic anticoagulation may be indicated. Historically, warfarin was the most commonly prescribed anticoagulant for stroke prevention in AF patients. Since 2010, the US FDA has approved 4 alternative direct oral anticoagulants (DOACs) - dabigatran, rivaroxaban, apixaban, edoxaban to reduce the risk of stroke and systemic embolism in patients with AF. There is limited literature to support the use of DOACs in cancer patients, but they are being prescribed by medical professionals nonetheless. Therefore, additional research is necessary to determine the effectiveness of the DOACs in cancer patients, to quantify their bleeding risks, and to identify patients that are more likely to benefit from these new medications in comparison to warfarin. Large randomized clinical trials of DOACs compared to warfarin in cancer patients have not been performed. Our aim was to determine the effectiveness and associated risk of DOACs vs. warfarin in a large, real-world population of cancer patients with AF. Methods We identified 532,743 AF patients initiating oral anticoagulant use in 2010-2014 continuously enrolled in MarketScan databases. We selected 41,036 cancer patients with inpatient or outpatient ICD9 code 140.x-172.x and 174.x-209.x (excluded 173.x, non-melanoma skin cancer), and then identified a subset of cancer patients being actively treated at the time of anticoagulant initiation. Active cancer patients were defined by the use of chemotherapy, radiation therapy or cancer surgery within 6 months prior to the start of anticoagulation. Patients were categorized according to the first anticoagulant prescribed after AF diagnosis. DOAC users were matched with warfarin users by age (±3 years), sex, enrollment date (90 days), and anticoagulant initiation date (90 days). Study endpoints, including ischemic stroke, severe bleeding (intracranial hemorrhage, gastrointestinal bleeding), other bleeding (genitourinary bleeding, hemopericardium, hemarthrosis, epistaxis, hemoptysis and unspecified hemorrhage) and VTE were identified using inpatient diagnostic codes, and VTE was additionally identified from 2 outpatient diagnostic codes within the same year. Cox proportional hazards models were used to access the association between type of anticoagulant and outcomes adjusting for high-dimensional propensity score, age, sex, CHA2DS2-VASc score, and the prevalent outcome. Results The demographic profile of the patients included in the analysis are depicted in Table 1, and Table 2 summarizes the outcomes data. In this analysis there were 6,075 cancer patients with AF who were on DOACs (rivaroxaban 2808, dabigatran 2189, and apixaban 1078) compared to 10,021 on warfarin, with a mean age of 74 years, and a mean follow-up time of 1 year. Approximately 40% of the patients were woman, and breast cancer was the most common cancer in each cohort. We found that for rivaroxaban and dabigatran users, the adjusted hazard ratios for severe bleeding was non significantly different to warfarin users, however, apixaban users had a lower risk of severe bleeding compared to warfarin users, with a hazard ratio 0.37 (95% confidence interval 0.17-0.79, p=0.01). The risk of other bleeding was lower in dabigatran users compared to warfarin users with a hazard ratio 0.58 (95% confidence interval 0.41-0.84, p=0.003). The risk of ischemic stroke did not differ significantly amongst different anticoagulant users. Each of the DOACs was superior to warfarin in lowering the risk of incident VTE, with p values < 0.0001. Conclusion Based on this analysis the DOACs seem to be well tolerated in cancer patients in regard to the management of atrial fibrillation, with lower or similar rates of bleeding and stroke compared to warfarin users. Importantly, the DOAC users had a significantly lower risk of incident VTE. Given that VTE events contribute to significant morbidity and mortality in cancer patients, prescription of DOACs in place of warfarin can be considered in cancer patients with AF, while we are awaiting prospective data from randomized trials. Disclosures No relevant conflicts of interest to declare.

scholarly journals Comparative effectiveness of direct oral anticoagulants and warfarin in patients with cancer and atrial fibrillation

2018 ◽  
Vol 2 (3) ◽  
pp. 200-209 ◽  
Author(s):  
Surbhi Shah ◽  
Faye L. Norby ◽  
Yvonne H. Datta ◽  
Pamela L. Lutsey ◽  
Richard F. MacLehose ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Cancer Patients ◽  
Comparative Effectiveness ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Patients With Cancer ◽  
Key Points

Key Points In AF and cancer patients, rate of bleeding is lower with apixaban, similar in dabigatran and rivaroxaban users, compared to warfarin users. Ischemic stroke rates did not differ among anticoagulant users. Incident VTE risk was lower in all DOAC compared with warfarin users.

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.

Abstract 17301: Safety of Direct Oral Anticoagulants Compared to Warfarin for Atrial Fibrillation After Cardiac Surgery: A Systematic Review and Meta-Analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ali Hage ◽  
Daniel Dolan ◽  
Viviane G Nasr ◽  
Luis Castelo-Branco ◽  
Daniel Motta-Calderon ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trials ◽  
Cardiac Surgery ◽  
Hospital Readmission ◽  
Lower Risk ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Secondary Outcome ◽  
Systemic Embolization

Introduction: The evidence for use of direct oral anticoagulants (DOACs) in the management of post-operative cardiac surgery atrial fibrillation (POAF) is limited and mostly founded on clinical trials that excluded this patient population. Hypothesis: We performed a systematic review and meta-analysis of clinical trials and observational studies to evaluate the hypothesis that DOACs are safe compared to warfarin for the anticoagulation of patients with POAF. Methods: We searched PubMed, EMBASE, Web of Science, clinicaltrials.gov, and the Cochrane Library for clinical trials and observational studies comparing DOAC with warfarin in patients ≥18 years old who had post-cardiac surgery atrial fibrillation. Primary outcomes included stroke, systemic embolization, bleeding, and mortality, with secondary outcome of hospital readmission. We performed a random-effects meta-analysis. Results: We found 3 clinical trials, 1 prospective and 12 retrospective cohort studies eligible for inclusion with a total of 10,538 patients (3,207 DOAC patients and 7,331 warfarin patients). The meta-analysis for the primary outcomes showed significantly lower risk of stroke with DOAC use (6 studies, 7143 patients, RR 0.64; 95% CI 0.50 to 0.81, I2: 0.0%) compared to warfarin, a trend towards lower risk of systemic embolization (4 studies, 7289 patients, RR 0.64, 95% CI 0.41 to 1.01, I2: 31.99%) and similar risks of bleeding (14 studies, 10182 patients, RR 0.91; 95% CI 0.74 to 1.10, I2: 26.6%) and mortality (12 studies, 9843 patients, relative risk [RR] 1.01; 95% CI 0.74 to 1.37, I2: 26.5%) The secondary outcome of hospital readmission had similar risk between groups. Conclusions: Current evidence suggests that DOACs, compared to warfarin, in the management of atrial fibrillation after cardiac surgery is associated with lower risk of stroke and a strong trend for lower risk of systemic embolization, and no evidence of increased risk for hospital readmission, bleeding or mortality.

ANTICOAGULANT THERAPY IN CANCER PATIENTS WITH ATRIAL FIBRILLATION. CONSIDERING AGE FACTOR

2020 ◽  
pp. 99-106
Author(s):  
В. И. Потиевская ◽  
А. А. Ахобеков ◽  
М. Ф. Баллюзек
Keyword(s):  
Atrial Fibrillation ◽  
Cancer Patients ◽  
Anticoagulant Therapy ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Current Data ◽  
Related Factors ◽  
Age Related ◽  
Liver And Kidney ◽  
After Cancer

Рассматривается современное состояние вопроса выбора антикоагулянтной терапии при фибрилляции предсердий (ФП) у онкологических больных. Отмечается, что сложность выбора антикоагулянта при злокачественных новообразованиях (ЗНО) определяется такими факторами, как коморбидные сердечно-сосудистые заболевания, нарушения функции печени и почек, метаболические дисфункции, свойственные, прежде всего, пациентам старшей возрастной группы. Приводятся актуальные данные по оценке риска геморрагических и тромбоэмболических осложнений ФП при ЗНО в аспекте возраста. Обсуждаются возможные причины увеличения риска развития ФП во время и после лечения ЗНО, в том числе и в связи с возраст-ассоциированностью этих патологий. Рассмотрены вопросы выбора антикоагулянтов у пациентов, находящихся на активной противоопухолевой терапии, особенно на препаратах из группы прямых оральных антикоагулянтов (ПОАК). Согласно данным обсервационных исследований, именно ПОАК являются перспективным, относительно безопасным и эффективным выбором для онкологических пациентов с ФП, в связи с чем их применение должно активно изучаться в рандомизированных клинических исследованиях с учетом фактора возраста. Подчеркивается, что подбор схемы антикоагулянтной терапии у пациентов с ФП и ЗНО требует междисциплинарного участия кардиологов и онкологов, а часто и гериатров, чтобы индивидуализировать лечение и предложить наиболее эффективную терапию. The current issue of the choice of anticoagulant therapy of atrial fibrillation (AF) in cancer patients is considered. It is noted that the difficulty of choosing an anticoagulant in malignancies is largely determined by age-related factors, such as comorbid cardiovascular diseases, liver and kidney dysfunction, metabolic disorders common for in elderly patients. Current data on the risk assessment of hemorrhagic and thromboembolic complications of AF in cancer patients in the aspect of age presented. During and after cancer treatment, the risk of developing AF can increase, also in connection with the age-associated pathology. Possible reasons of it are discussed. The choice of different anticoagulants groups in patients treated with anticancer therapy, including direct oral anticoagulants (DOAC) is considered. According to available data from observational studies, it is the DOAC that is a promising, relatively safe and effective choice for cancer patients with AF, and therefore their use should be actively studied in randomized trials, considering the factor of age. It is particularly noted that solving this problem requires the interdisciplinary involvement of cardiologists, oncologists, and sometimes, geriatrics, to individualize treatment for each case and to offer the most effective therapy.

scholarly journals A new model to predict ischemic stroke in patients with atrial fibrillation using warfarin or direct oral anticoagulants

Heart Rhythm ◽  
2019 ◽  
Vol 16 (6) ◽  
pp. 820-826 ◽  
Author(s):  
J'Neka S. Claxton ◽  
Richard F. MacLehose ◽  
Pamela L. Lutsey ◽  
Faye L. Norby ◽  
Lin Y. Chen ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
New Model

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.

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