scholarly journals Effectiveness and safety of non-vitamin K antagonist oral anticoagulants among nonvalvular atrial fibrillation patients with prior bleeding events

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
G.Y.H Lip ◽  
A Keshishian ◽  
A Kang ◽  
X Luo ◽  
N Atreja ◽  
...  

Abstract Background Among non-valvular atrial fibrillation (NVAF) patients with a history of bleeding, there is a reluctance to use oral anticoagulants (OACs) due to concerns about the risk of bleeding associated with OACs. However, lack of OAC treatments for NVAF patients is associated with a higher risk of stroke and mortality. Non-vitamin K antagonist OAC (NOACs) have been approved for the prevention of stroke in NVAF patients. There are limited data comparing the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) between patients prescribed NOACs and with a history of bleeding. Purpose This study used multiple United States data sources to evaluate the risk of S/SE and MB among NVAF patients with prior bleeding events who were prescribed NOACs. Methods This retrospective observational study used data from CMS Medicare and four commercial databases–covering >180 million beneficiaries. The study selected adult NVAF patients who were prescribed apixaban, dabigatran, or rivaroxaban (01JAN2013–30JUN2019) and had a prior bleeding event which was defined as a hospitalization with a bleeding diagnosis (intracranial hemorrhage [ICH], gastrointestinal [GI] bleeding, or other bleeding sites) prior to or during the index treatment episode. After 1:1 propensity-score-matched (PSM) in each database between NOACs (apixaban-dabigatran, apixaban-rivaroxaban, and dabigatran-rivaroxaban), the resulting patient records were pooled. S/SE and MB (identified by inpatient claims) were captured during the follow-up period, which was defined as the time between the day after the index treatment date and treatment discontinuation or switch, death, end of study period, or end of medical and pharmacy enrollment. Hazard ratios of S/SE and MB were calculated using Cox proportional hazards models. Results Of the overall NVAF population treated with NOACs, 6.2% had a prior bleeding event (ICH: 13.5%; GI: 61.8%; Other: 24.6%). After PSM, a total of 11,106 apixaban-dabigatran, 30,665 apixaban-rivaroxaban, and 11,148 dabigatran-rivaroxaban pairs were matched. Apixaban was associated with a lower risk of S/SE compared to dabigatran and rivaroxaban, and dabigatran was associated with a similar risk of S/SE compared to rivaroxaban. Apixaban was associated with a lower risk of MB compared to dabigatran and rivaroxaban, and dabigatran was associated with a lower risk of MB compared to rivaroxaban (Figure). Conclusions In this subgroup of NVAF patients with a history of bleeding, apixaban was associated with a lower risk of S/SE and MB compared to dabigatran and rivaroxaban. Dabigatran was associated with a lower risk of MB compared to rivaroxaban. These results are informative for understanding the impact of NOAC treatment in NVAF patients with prior bleeding events. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bristol-Myers Squibb Company and Pfizer, Inc.

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
G.Y.H Lip ◽  
A Keshishian ◽  
A Kang ◽  
X Luo ◽  
N Atreja ◽  
...  

Abstract Background Patients with non-valvular atrial fibrillation (NVAF) use oral anticoagulants such as warfarin or non-vitamin K antagonist oral anticoagulants (NOACs) for the prevention of stroke. However, the effectiveness and safety of warfarin and NOACs can be influenced by pre-existing patient comorbidities, such as a history of bleeding, and limited evidence are available to inform the choice of the most appropriate anticoagulant treatment for NVAF patients with bleeding history. Purpose This study used five United States insurance claims databases to evaluate the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) among NVAF patients with prior bleeding events who were prescribed NOACs versus warfarin. Methods This retrospective observational study used data from 5 databases (CMS Medicare and four commercial databases, covering >180 million beneficiaries) to select adult NVAF patients who were treated with apixaban, dabigatran, rivaroxaban, or warfarin (01JAN2013–30JUN2019). Patients were required to have a prior bleeding event, defined as a hospitalization with a diagnosis for intracranial hemorrhage (ICH), gastrointestinal (GI) bleeding or bleeding at other key sites prior to or during the index treatment episode. In each database, three 1:1 NOAC-warfarin propensity-score-matched (PSM) cohorts were created before pooling the results. Outcome measures were time to first stroke/SE, (ischemic stroke, hemorrhagic stroke, and SE), and time to first MB (gastrointestinal bleeding, intracranial hemorrhage, and MB at other key sites), and were measured from the index treatment episode to treatment discontinuation or switch, death, health plan disenrollment, or end of study period. Hazard ratios of S/SE and MB were calculated using Cox proportional hazards models. Results Among the eligible NVAF population, 8.2% of patients had a prior bleeding event (ICH: 12.3%; GI: 60.7%; Other: 27.0%). After PSM, a total of 43,092 apixaban-warfarin, 11,295 dabigatran-warfarin, and 32,723 rivaroxaban-warfarin patient pairs with prior bleeding were selected with a mean follow-up of 8–9 months. Apixaban and rivaroxaban were associated with a lower risk of S/SE, and dabigatran was associated with a similar risk of S/SE when compared to warfarin. Apixaban and dabigatran were associated with a lower risk of MB, and rivaroxaban was associated with a similar risk of MB, compared to warfarin (Figure). Conclusion Among NVAF patients with prior bleeding events, NOACs were associated with varying risks of S/SE and MB compared to warfarin. These results can help inform healthcare providers concerning the impact of OAC treatment in NVAF patients with history of bleeding. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bristol-Myers Squibb Company and Pfizer, Inc.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1162-1162
Author(s):  
Desirée Campoy ◽  
Gonzalo Artaza ◽  
César A Velasquez ◽  
Tania Canals ◽  
Erik A Johansson ◽  
...  

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.


Author(s):  
Hsin-Fu Lee ◽  
Lai-Chu See ◽  
Pei-Ru Li ◽  
Jia-Rou Liu ◽  
Tze-Fan Chao ◽  
...  

Abstract Aims  To investigate the effectiveness, safety, and outcomes of lower limb events for non-vitamin K antagonist oral anticoagulants (NOACs) vs. warfarin among atrial fibrillation (AF) patients with concomitant peripheral artery disease (PAD). Methods and results In this nationwide retrospective cohort study collected from Taiwan National Health Insurance Research Database, a total of 5768 and 2034 consecutive AF patients with PAD patients taking NOACs or warfarin were identified from 1 June 2012 to 31 December 2017, respectively. We used propensity score stabilized weighting to balance covariates across study groups. In the cohort, there were 89% patients were taking low-dose NOAC (dabigatran 110 mg twice daily, rivaroxaban 10–15 mg daily, apixaban 2.5 mg twice daily, or edoxaban 30 mg daily). Non-vitamin K antagonist oral anticoagulant was associated with a comparable risk of ischaemic stroke, and a lower risk of acute myocardial infarction [hazard ratio (HR): 0.61, 95% confidence interval (CI): 0.42–0.87; P = 0.007], lower extremity thromboembolism (HR: 0.56, 95% CI: 0.44–0.72; P &lt; 0.0001), revascularization procedure (HR: 0.58, 95% CI: 0.47–0.72; P &lt; 0.0001), lower limb amputation (HR: 0.32, 95% CI: 0.23–0.46; P &lt; 0.0001), and all major bleeding (HR: 0.64, 95% CI: 0.50–0.80; P = 0.0001) than warfarin after weighting. The advantage of NOACs over warfarin persisted in high-risk subgroups including patients of ≥75 years of age, diabetes, renal impairment, or use of concomitant antiplatelet agent. Conclusion  This population-based study indicated that NOACs were associated with a comparable risk of ischaemic stroke, and a significantly lower risk of major adverse limb events and major bleeding than warfarin among AF patients with concomitant PAD. Therefore, thromboprophylaxis with NOACs may be considered for such patients.


2019 ◽  
Vol 6 (3) ◽  
pp. 147-154 ◽  
Author(s):  
Chun-Li Wang ◽  
Victor Chien-Chia Wu ◽  
Kuo-Hsuan Chang ◽  
Hui-Tzu Tu ◽  
Chang-Fu Kuo ◽  
...  

Abstract Aims This study compared the risk of major bleeding between atrial fibrillation (AF) patients who took non-vitamin K antagonist oral anticoagulants (NOACs) and antiepileptic drugs (AEDs) concurrently and those who took only NOACs. Methods and results We performed a retrospective cohort study using Taiwan National Health Insurance database and included AF patients who received NOAC prescriptions from 1 June 2012 to 31 December 2017. The major bleeding risks of person-quarters exposed to NOAC and 11 concurrent AEDs (carbamazepine, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, pregabalin, topiramate, valproic acid, and zonisamide) were compared with person-quarters exposed to NOAC alone. Adjusted incidence rate differences between NOAC with or without concurrent AEDs were estimated using Poisson regression models weighted by the inverse probability of treatment. Among 104 319 patients (age 75.0 ± 10.3 years; men, 56.2%), 8546 major bleeding events occurred during 731 723 person-quarters with NOAC prescriptions. Concurrent AED use was found in 15.3% of NOAC-treated patients. Concurrent use of NOAC with valproic acid, phenytoin, or levetiracetam increased adjusted incidence rates per 1000 person-years of major bleeding more significantly than NOAC alone: 153.49 for NOAC plus valproic acid vs. 55.06 for NOAC alone [difference 98.43, 95% confidence interval (CI) 82.37–114.49]; 135.83 for NOAC plus phenytoin vs. 54.43 for NOAC alone (difference 81.4, 95% CI 60.14–102.66); and 132.96 for NOAC plus levetiracetam vs. 53.08 for NOAC alone (difference 79.88, 95% CI 64.47–95.30). Conclusion For AF patients, the concurrent use of NOACs and valproic acid, phenytoin, or levetiracetam was associated with a higher risk of major bleeding.


2020 ◽  
Author(s):  
Yi-Hsin Chan ◽  
Hsin-Fu Lee ◽  
Pei-Ru Li ◽  
Jia-Rou Liu ◽  
Tze-Fan Chao ◽  
...  

Abstract Background: Evidence of adverse clinical outcomes for non-vitamin K antagonist oral anticoagulant (NOACs) and warfarin in patients with atrial fibrillation (AF) and diabetes mellitus are limited. We investigated the effectiveness, safety, and major adverse limb events for NOACs versus warfarin among diabetic AF patients. Methods: In this nationwide retrospective cohort study collected from Taiwan National Health Insurance Research Database, we identified a total of 20,967 and 5,812 consecutive AF patients with diabetes taking NOACs and warfarin from June 1, 2012, to December 31, 2017, respectively. We used propensity-score stabilized weighting to balance covariates across study groups. Results: NOAC was associated with a lower risk of major adverse cardiovascular events (MACE) (adjusted hazard ratio (aHR):0.88; [95% confidential interval (CI):0.78-0.99]; P =0.0283), major adverse limb events (aHR:0.72;[95%CI:0.57-0.92]; P =0.0083), and major bleeding (aHR:0.67;[95%CI:0.59-0.76]; P <.0001) compared to warfarin. NOACs decreased MACE in patients of 75 but not in those aged <75 years ( P interaction=0.01), and in patients with ischemic heart disease (IHD) compared to those without IHD ( P interaction<0.01). For major adverse limb events, the advantage of risk reduction for NOAC over warfarin persisted in high risk subgroups including age 75 years, chronic kidney disease, IHD, peripheral artery disease, or use of concomitant antiplatelet drugs. Conclusion: NOACs were associated with a lower risk of effectiveness, safety, and major adverse limb events than warfarin among diabetic AF patients. Thromboprophylaxis with NOACs should be considered in the diabetic AF population with a high atherosclerotic burden.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
S Deitelzweig ◽  
A Keshishian ◽  
A Kang ◽  
A Jenkins ◽  
N Atreja ◽  
...  

Abstract Background Clinical trials and real-world database studies have shown the benefits of non-vitamin K antagonist oral anticoagulants (NOACs) compared to warfarin; however, measures of functional outcomes are critical in evaluating a patient's quality of life. Previous measures of time spent out of hospital in a home setting and time spent receiving disease-related care among non-valvular atrial fibrillation (NVAF) patients are lacking in the current literature. Purpose This analysis was based on the previously published ARISTOPHANES study, and used multiple data sources to evaluate the amount of time spent at a patient's home among NVAF patients who were prescribed NOACs versus warfarin. Methods This retrospective observational study used US data from CMS Medicare and four commercial databases to select adult NVAF patients who initiated apixaban, dabigatran, rivaroxaban, or warfarin (01JAN2013–30SEP2015). Time at home and time at home without external AF-related care were measured during the 180 days after the index date (OAC prescription). Time at home was defined as days from index date without any of the following: an inpatient, skilled nursing facility or nursing facility, hospice, or inpatient rehabilitation facility admission. Time at home and without external AF-related care was defined as days away from home and days with a claim for bleeding, stroke/systemic embolism, AF, or an INR test. Each day a claim was observed was counted as one day. In each database, three 1:1 NOAC-warfarin propensity-score-matched (PSM) cohorts were created before pooling the results. After PSM, a subgroup of patients who were alive and had ≥180 days of follow-up was created. Poisson regression was conducted in each NOAC-warfarin matched cohort to compare time at home and time at home without external AF-related care. Results After matching, a total of 100,977 apixaban-warfarin, 36,990 dabigatran-warfarin, and 125,068 rivaroxaban-warfarin patient pairs were selected. Of those patients, 38–46% had 180 days of follow-up available. Across treatment cohorts, approximately 75% of patients were at home for the 180-day follow-up. Apixaban, dabigatran, and rivaroxaban patients had 1.3, 0.9, and 0.8 more days at home, respectively, compared to warfarin patients. Patients treated with apixaban had 13.4 more days at home without AF-related care compared to warfarin, while dabigatran and rivaroxaban had 11.6 and 11.7 more days at home without AF-related care compared to warfarin. A greater proportion of warfarin patients than NOAC patients had an INR test (81–82% vs 14–21%), and days with INR testing were the main driver for external AF-related care for warfarin patients. Conclusion Among NVAF patients treated with OACs, NOACs were associated with a longer time at home and time at home without external AF-related care compared to warfarin. These results can help inform healthcare providers and patients regarding the impact of NOAC treatment in NVAF patients. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bristol-Myers Squibb Company and Pfizer Inc.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
L Dominguez Rodriguez ◽  
S Raposeiras Roubin ◽  
D Alonso Rodriguez ◽  
S J Camacho Freire ◽  
E Abuassi ◽  
...  

Abstract Introduction Embolic prevention with oral anticoagulation is the cornerstone for the management of patients with atrial fibrillation (AF). However, data about the efficacy and safety of oral anticoagulation in nonagenarian patients are limited. We aimed to analyze the impact of oral anticoagulation in mortality, embolic and hemorrhagic events, in patients ≥90 years with non-valvular AF. Methods We used data from a multicentric registry of 1,750 consecutive nonagenarian patients diagnosed of AF between 2013 and 2018. A propensity-matched analysis was performed to match the baseline characteristics of patients treated or not with oral anticoagulants, and for those treated with vitamin K antagonists (VKAs) vs direct oral anticoagulants (DOACs). The impact of oral anticoagulation in the embolic and hemorrhagic risk was assessed by a competitive risk analysis, using a Fine and Gray regression model, with death being the competitive event. For embolic risk, we have considered a stroke, pulmonary or peripheral embolism. For bleeding risk, we have considered any bleeding requiring hospital admission. Results The mean of CHA2DS2-VASC and HASBLED scores was 4.5±1.3 and 2.8±1.0 points, respectively. Most of patients were anticoagulated (70.1%; n=1,256). DOACs were used in 709 patients, and VKAs in 517 patients. During a median follow-up of 25.2 months (IQR 12.2–44.3 months), 988 patients died (56.5%), 180 presented embolic events (10.3%), 186 had bleeding events (10.6%), and 29 had intracranial hemorrhage (ICH, 1.7%). After propensity-score matching, anticoagulation (versus non anticoagulation) was associated with lower mortality rate (HR 0.73, 95% CI 0.60–0.89; p=0.002), less mortality and embolic events (HR 0.77, 95% CI 0.64–0.92; p=0.005), but more bleeding events (HR 2.05, 95% CI 1.25–3.35; p=0.004). In comparison with VKAs, DOACs showed similar risk of mortality and embolic events (HR 1.14, 95% CI 0.88–1.47; p=0.337), and similar risk of bleeding events (HR 0.75, 95% CI 0.43–1.28; p=0.287), although a trend to lower risk of ICH was found (HR 0.17, 95% CI 0.02–1.39; p=0.097). Conclusions Among nonagenarian patients with AF, oral anticoagulation was associated with lower all-cause mortality. Although survival free of embolic events was significantly higher in patients with anticoagulation, the risk of major bleeding was twice than in non-anticoagulated patients. There was not differences between VKAs and DOACs in terms of embolic events and total major bleeding. However, compared with VKAs, DOACs were showed a trend to lower risk of ICH.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S.R Lee ◽  
E.K Choi ◽  
S.H Park ◽  
K.D Han ◽  
S Oh ◽  
...  

Abstract Background Atrial fibrillation (AF) is a risk factor for dementia and oral anticoagulant (OAC) use is associated with a decreased risk of dementia in patients with AF. Objective We sought to find whether the risk of dementia would be different between patients treated with non-vitamin K antagonist oral anticoagulants (NOACs) and those treated with warfarin. Methods Using the Korean National Health Insurance database from January 2014 to December 2017, we identified OAC naïve non-valvular AF patients aged 40 years or older. For the comparison, warfarin and NOAC groups were balanced using the inverse probability of treatment weighting method (IPTW). The primary outcome was incident dementia. Patients were censored at the occurrence of dementia, discontinuation of index treatment, or the end of the study period (December 31, 2018). Results Among 72,846 of total study patients, 25,948 were treated with warfarin and 46,898 were treated with NOAC (17,193 with rivaroxaban, 9,882 with dabigatran, 11,992 with apixaban, and 7,831 with edoxaban). Crude incidence of dementia was 4.65 per 100 person-years in warfarin group and 4.98 per 100 person years in NOAC group. Baseline characteristics were well-balanced after IPTW (mean age 72 years, 93% CHA2DS2-VASc ≥2, 58% men). Compared to warfarin, NOAC showed a comparable risk of dementia (hazard ratio [HR] 0.944, 95% confidence interval [CI] 0.934–1.059), vascular dementia (HR 0.921, 95% CI 0.814–1.043) and Alzheimer dementia (HR 1.101, 95% CI 1.019–1.191). When comparing individual NOACs with warfarin, edoxaban was associated with a lower risk of dementia (HR 0.830, 95% CI 0.740–0.931). Rivaroxaban (HR 0.767, 95% CI 0.648–0.907) and edoxaban (HR 0.786, 95% CI 0.620–0.996) were associated with a lower risk of vascular dementia than warfarin. In subgroup analyses, NOAC was associated with a lower incidence of dementia than warfarin particularly in patients with prior stroke (HR 0.891, 95% CI 0.820–0.968) and in patients aged 65–74 years (HR 0.815, 95% CI 0.709–0.936). Conclusion In this large Asian population with AF, NOAC showed a comparable result with warfarin on the risk of dementia. Edoxaban was associated with a lower risk of dementia. NOAC appeared more beneficial especially in those with AF who had a history of prior stroke and aged 65–74 years. Funding Acknowledgement Type of funding source: None


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