Non-vitamin K Antagonist Oral Anticoagulants Treatment Research Articles

Optimal adherence threshold to non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation to reduce the risk of thromboembolism and death

Abstract Background Poor adherence to non-vitamin K antagonist oral anticoagulants (NOACs) may raise thromboembolic risks in patients with atrial fibrillation (AF). However, the minimal adherence to maintain the protective effects of NOACs is currently unknown. Purpose To investigate thresholds of NOAC adherence in association with thromboembolic and mortality risks. Methods Using two Belgian nationwide healthcare databases, AF patients ≥45 years old with ≥1 NOAC prescription claim between January 1st, 2013 and January 1st, 2019 were identified. Patients were followed from NOAC initiation until the first occurrence of the investigated outcome, treatment discontinuation (>60-day supply gap), switch to VKAs, death, emigration or end of the study period. Adherence was measured using the proportion of days covered (PDC) after one year of treatment. Inverse probability weighted Cox regression (adjusting for 39 confounding covariates) was used to investigate outcomes (identified using International Classification of Diseases-coded hospital discharge diagnoses and medical procedure codes) between NOAC users with a one-year PDC of 100% (reference group) and NOAC users with lower PDCs. Results A total of 92,111 newly-treated AF patients were included during a mean follow-up of 2.7 ± 1.4 years (250,750 person-years of on-treatment follow-up). The proportions of persistent NOAC users with a PDC of 100%, 95-99%, 90-94%, 85-89%, 80-84% and <80% after one year of treatment were 62.7%, 17.4%, 9.5%, 5.1%, 2.8% and 2.5%, respectively. Compared to NOAC users with a one-year PDC of 100%, significantly higher risks of stroke or systemic embolism were observed among NOAC users with PDCs of 85-89% (adjusted hazard ratio (aHR) 1.35, 95% confidence interval (CI) (1.19-1.54)), 80-84% (aHR 1.31, 95%CI (1.08-1.58)) and <80% (aHR 1.64, 95%CI (1.34-2.01)), while no significant differences were observed among NOAC users with one-year PDCs of 95-99% (aHR 1.02, 95%CI (0.94-1.12)) or 90-94% (aHR 1.06, 95%CI (0.95-1.18)) after multivariable adjustment. Significantly higher risks of all-cause mortality (aHR 1.09, 95%CI (1.01-1.17) and major or clinically relevant non-major bleeding (aHR 1.10, 95%CI (1.04-1.16) were observed with decreasing levels of NOAC adherence, starting from NOAC users with a one-year PDC of 90-94% versus 100%. Findings were similar with once-daily and twice-daily dosed NOACs. Conclusion Lower adherence to NOAC treatment is associated with increased risks of thromboembolism, all-cause mortality and bleeding. For adequate stroke prevention in AF, the optimal adherence threshold to NOAC treatment should be at least 90%, irrespective of the dosing regimen of NOACs.Figure 1

Pharmacodynamic Drug-Drug Interactions and Bleeding Outcomes in Patients with Atrial Fibrillation Using Non-Vitamin K Antagonist Oral Anticoagulants: a Nationwide Cohort Study.

Pharmacodynamic drug-drug interactions (PD DDIs) may influence the safety of non-vitamin K antagonist oral anticoagulants (NOACs), but the extent to which PD DDIs increase bleeding risks, remains unclear. Therefore, the impact of PD DDIs on bleeding outcomes in NOAC-treated patients with atrial fibrillation (AF) was investigated. Using Belgian nationwide data, NOAC-treated AF patients were included between 2013-2019. Concomitant use of PD interacting drugs when initiating NOAC treatment was identified. Among 193,072 patients, PD DDIs were identified in 114,122 (59.1%) subjects. After multivariable adjustment, concomitant use of PD interacting drugs was associated with significantly higher risks of major or clinically-relevant non-major bleeding (adjusted hazard ratio (aHR) 1.19, 95% confidence interval (CI) (1.13-1.24)), gastrointestinal (aHR 1.12, 95%CI (1.03-1.22)), urogenital (aHR 1.21, 95%CI (1.09-1.35)) and other bleeding (aHR 1.28, 95%CI (1.20-1.36)), compared to NOAC-treated AF patients without PD interacting drug use. Increased bleeding risks were most pronounced with P2Y12 inhibitors (aHR 1.62, 95%CI (1.48-1.77)) and corticosteroids (aHR 1.53, 95%CI (1.42-1.66)), followed by selective serotonin or serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI, aHR 1.26, 95%CI (1.17-1.35)), low-dose aspirin (aHR 1.14, 95%CI (1.08-1.20)) and non-steroidal anti-inflammatory drugs (NSAID, aHR 1.10, 95%CI (1.01-1.21)). Significantly higher intracranial bleeding risks in NOAC users were observed with SSRI/SNRIs (aHR 1.50, 95%CI (1.25-1.81)) and corticosteroids (aHR 1.49, 95%CI (1.21-1.84)). Concomitant use of PD interacting drugs, especially P2Y12 inhibitors and corticosteroids, was associated with higher major, gastrointestinal, urogenital, and other bleeding risks in NOAC-treated AF patients. Remarkably, higher intracranial bleeding risks were observed with SSRI/SNRIs and corticosteroids.

Effectiveness and safety of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation at low risk of stroke in japan: a retrospective cohort study.

Contemporary guidelines differ in their recommendations regarding initiating non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) at low risk of stroke. This study aimed to examine the effectiveness and safety of NOACs for low-risk AF in a Japanese cohort. In this retrospective cohort study based on the JMDC Claims Database extracted between April 2011 and November 2022, we identified 13 291 patients with AF at low risk of stroke. We performed inverse probability of treatment weighting Cox regression analyses to compare the embolization and bleeding risks between the nontreatment and NOAC groups. Net clinical benefit was defined as the annual incidence of ischaemic stroke events prevented by NOACs after subtracting intracranial haemorrhage (ICH) events attributable to NOACs, multiplied by a weighting factor. The incidences of stroke and ICH in the nontreatment group were 0.47 and 0.15 per 100 person-years, respectively. The NOAC group had higher incidences of ICH (hazard ratio [HR]: 1.73, 95% confidence interval [CI]: 0.75-4.00) and stroke (HR: 1.41, 95% CI: 0.84-2.36). The net clinical benefit of NOAC treatment was -0.35% per year (95% CI: -0.99-0.29%). Non-vitamin K antagonist oral anticoagulants treatment may be associated with a slightly high risk of ICH, and it yielded a neutral clinical benefit in the present Japanese population, which provides reassurance concerning the role of ethnicity in NOAC treatment for patients with AF and suggests a need to assess comprehensive weighting of the respective risk factors.

Characteristics of Novel Anticoagulants versus Vitamin K Antagonists in the Ventricular Mural Thrombus

Background: To describe the characteristics, treatment practices, and clinical outcomes of patients with ventricular mural thrombus (VMT), with emphasis on the comparison of non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKAs). Methods: We performed a retrospective cohort study between 2010 and 2019 in Fuwai Hospital, China. Patients with VMT newly treated with either NOACs or VKAs were included. The primary outcome was the incidence rate of thrombus resolution at 3 months. Results: We included 196 patients in total—68.9% (n = 135) were treated with VKAs while 31.1% (n = 61) were on NOACs. Patients with a medical history of heart failure (HF) (odds ratio (OR) 2.10, 95% confidence interval (CI) 1.17 to 3.77, p = 0.013) and a lower left ventricular ejection fraction (OR 0.36, 95% CI 0.20 to 0.65, p = 0.001) had a higher thrombus resolution. At 3 months, a significant difference was observed in the thrombus resolution between the NOACs and VKAs group with or without adjustment (OR 2.61, 95% CI 1.39 to 4.89, p = 0.003; adjusted OR 2.93, 95% CI 1.51 to 5.66, p = 0.001). Further investigation revealed that in the majority of the subgroups, individuals receiving NOAC therapy had a superior thrombus resolution than those receiving VKA therapy. Conclusions: Patients with a medical history of HF or left ventricular ejection fraction <30% experienced greater effectiveness in thrombus resolution. Additionally, the resolution of VMT with NOAC treatment was considerably higher than that with VKA therapy at 3 months, with or without adjusting for baseline variables. Clinical Trial Registration: This study was registered at ClinicalTrials.gov as NCT 05006677 on August 4th, 2021.

Use of Direct Acting Oral Anticoagulants in Elderly Patients with Atrial Fibrillation: A Multicenter, Cross-Sectional Study in Spain.

Non-vitamin K antagonist oral anticoagulants (NOACs) have substantially improved anticoagulation. However, data on NOAC use among elderly patients are scarce. We sought to describe NOAC use among elderly AF patients in Spain. We performed a non-interventional, multicenter, multispecialty, cross-sectional study in elderly (≥75 years) AF patients treated with NOACs for stroke prevention. Patients' characteristics by NOAC treatment were compared using standardized differences (SDD). NOAC dosing was classified according to the Spanish summary of products characteristics (SmPC) into appropriate (recommended dose) and inappropriate (under and overdosed). Multivariate logistic regression analyses were used to explore factors associated with inappropriate dosing. 500 patients were included. Mean (SD) age was 81.5 (4.7) years, and 50% were women. Mean (SD) creatinine clearance was 57.4 mL/min (18.8), and 23.6% were frail. Dabigatran treatment totaled 38.4%, rivaroxaban 15.2%, apixaban 33.2%, and edoxaban 13.2%. Almost one-fourth of elderly patients treated with NOACs in Spain were inappropriately dosed (underdosing 14.4% and overdosing 9.6%). Underdosing was significantly associated with weight (OR = 1.03, 95%CI = 1.0-1.1), while higher a EHRA score decreased the risk of underdosing (OR = 0.47, 95%CI = 0.2-1.0). Overdosing was significantly associated with a history of ischemic stroke (OR = 2.95, 95%CI = 1.1-7.7). Addressing incorrect dosing among elderly AF patients is relevant to improve patient outcomes.

Gastrointestinal Bleeding on Anticoagulant Therapy: Comparison of Patients Receiving Vitamin K Antagonists and Non-Vitamin K Oral Antagonists

Objectives: Prior studies comparing Gastrointestinal (GI) bleeding in patients receiving Vitamin-K Antagonists (VKA) and Non-Vitamin K Antagonist Oral Anticoagulants (NOAC) focused on the crude rate of GI bleeding and less on severity of such events. The aim of our study was to assess characteristics of GI bleeding in patients on VKA therapy versus NOAC therapy. Methods: Retrospective data was collected from patients hospitalized with GI bleeding at Hadassah University Medical Center between January 2010 and July 2017. Retrieved data included demographics, laboratory results, clinical outcomes and details regarding the bleeding characteristics, evaluation, treatment and hospitalization. Patients were divided into two groups – those receiving VKA and those receiving NOAC. Results: 514 patients who presented with GI bleeding were included. 439 patients were on VKA treatment and 75 on NOAC treatment. Atrial fibrillation was the indication for anticoagulation in 64% of VKA patients and in 91% of NOAC patients. The mean HAS-BLED score was the same in VKA and NOAC patient groups. Major bleeding events were seen in 38.3% of VKA patients and 30.7% of NOAC patients and life-threatening bleeding was seen in 34.4% of VKA patients and 26.7% of NOAC (p<0.05). Packed red blood cell and fresh-frozen plasma transfusions were administered less in the NOAC patients as compared to the VKA patients. No statistically significant differences in length of hospitalization, re-bleeding, or mortality were seen between groups. Conclusions: GI bleeding events on NOAC therapy are less severe and use fewer hospital resources as compared to those treated with VKA.

Risk of heart failure in elderly patients with atrial fibrillation and diabetes taking different oral anticoagulants: a nationwide cohort study

BackgroundHeart failure (HF) is a critical complication in elderly patients with atrial fibrillation (AF) and diabetes mellitus (DM). Recent preclinical studies suggested that non-vitamin K antagonist oral anticoagulants (NOACs) can potentially suppress the progression of cardiac fibrosis and ischemic cardiomyopathy. Whether different oral anticoagulants influence the risk of HF in older adults with AF and DM is unknown. This study aimed to evaluate the risk of HF in elderly patients with AF and DM who were administered NOACs or warfarin.MethodsA nationwide retrospective cohort study was conducted based on claims data from the entire Taiwanese population. Target trial emulation design was applied to strengthen causal inference using observational data. Patients aged ≥ 65 years with AF and DM on NOAC or warfarin treatment between 2012 and 2019 were included and followed up until 2020. The primary outcome was newly diagnosed HF. Propensity score-based fine stratification weightings were used to balance patient characteristics between NOAC and warfarin groups. Hazard ratios (HRs) were estimated using Cox proportional hazard models.ResultsThe study included a total of 24,835 individuals (19,710 NOAC and 5,125 warfarin users). Patients taking NOACs had a significantly lower risk of HF than those taking warfarin (HR = 0.80, 95% CI 0.74–0.86, p < 0.001). Subgroup analyses for individual NOACs suggested that dabigatran (HR = 0.86, 95% CI 0.80–0.93, p < 0.001), rivaroxaban (HR = 0.80, 95% CI 0.74–0.86, p < 0.001), apixaban (HR = 0.78, 95% CI 0.68–0.90, p < 0.001), and edoxaban (HR = 0.72, 95% CI 0.60–0.86, p < 0.001) were associated with lower risks of HF than warfarin. The findings were consistent regardless of age and sex subgroups and were more prominent in those with high medication possession ratios. Several sensitivity analyses further supported the robustness of our findings.ConclusionsThis nationwide cohort study demonstrated that elderly patients with AF and DM taking NOACs had a lower risk of incident HF than those taking warfarin. Our findings suggested that NOACs may be the preferred oral anticoagulant treatment when considering the prevention of heart failure in this vulnerable population. Future research is warranted to elucidate causation and investigate the underlying mechanisms.

Early Versus Delayed Non-Vitamin K Antagonist Oral Anticoagulant Therapy After Acute Ischemic Stroke in Atrial Fibrillation (TIMING): A Registry-Based Randomized Controlled Noninferiority Study.

There are no evidence-based recommendations on the optimal time point to initiate non-vitamin K antagonist oral anticoagulants (NOACs) after acute ischemic stroke in patients with atrial fibrillation. We aimed to investigate the efficacy and safety of early versus delayed initiation of NOAC in these patients. TIMING (Timing of Oral Anticoagulant Therapy in Acute Ischemic Stroke With Atrial Fibrillation) was a registry-based, randomized, noninferiority, open-label, blinded end-point study at 34 stroke units using the Swedish Stroke Register for enrollment and follow-up. Within 72 hours from stroke onset, patients were randomized to early (≤4 days) or delayed (5-10 days) NOAC initiation, with choice of NOAC at the investigators' discretion. The primary outcome was the composite of recurrent ischemic stroke, symptomatic intracerebral hemorrhage, or all-cause mortality at 90 days. The prespecified noninferiority margin was 3%. Secondary outcomes included the individual components of the primary outcome. Between April 2, 2017, and December 30, 2020, 888 patients were randomized to either early (n=450) or delayed (n=438) initiation of NOAC. No patient was lost to 90-day follow-up. Mean age was 78.3 years (SD, 9.9 years); 46.2% were women; 49.1% had previously known atrial fibrillation; and 17.5% prior stroke. The primary outcome occurred in 31 patients (6.89%) assigned to early initiation and in 38 patients (8.68%) assigned to delayed NOAC initiation (absolute risk difference, -1.79% [95% CI, -5.31% to 1.74%]; Pnoninferiority=0.004). Ischemic stroke rates were 3.11% and 4.57% (risk difference, -1.46% [95% CI, -3.98% to 1.07%]) and all-cause mortality rates were 4.67% and 5.71% (risk difference, -1.04% [95% CI, -3.96% to 1.88%]) in the early and delayed groups, respectively. No patient in either group experienced symptomatic intracerebral hemorrhage. Early initiation was noninferior to delayed start of NOAC after acute ischemic stroke in patients with atrial fibrillation. Numerically lower rates of ischemic stroke and death and the absence of symptomatic intracerebral hemorrhages implied that the early start of NOAC was safe and should be considered for acute secondary stroke prevention in patients eligible for NOAC treatment. URL: http://www. gov; Unique identifier: NCT02961348.

Non-vitamin K antagonist oral anticoagulants (NOACs) attenuate valvular calcification in patients with severe aortic stenosis

Abstract Background In vitro studies has demonstrated that non-vitamin K antagonist oral anticoagulants (NOACs) down-regulated the expression of proteins responsible for valve calcification and inflammation in valve interstitial cells (VICs) cultures. Aims Our goal was to evaluate whether long-term anticoagulation with NOACs, including dabigatran (thrombin inhibitor), rivaroxaban and apixaban (FXa inhibitors) can impair the valvular calcification and inflammation in patients with severe AS. Methods We enrolled 38 patients with severe AS aged 70±5.9 years (mean gradient - PGmean: 50mmHg, max gradient - PGmax: 80mmHg), including 18 individuals with AS and concomitant atrial fibrillation taking NOACs for at least 3 years (51±10 months) (AS-NOACs group). Stenotic aortic valves were obtained during valve replacement surgery. Valvular calcification was estimated ex vivo using micro-computed tomography (micro-CT). Total volume of each calcification (bone volume - BV), the distribution of clods sizes of calcification parts (trabecular thickness -Tbth) and the volume of the hardest / most calcified part (hard CT) of each valve were assessed. Valvular expression of bone morphogenetic protein 2 (BMP-2) and NFκB was evaluated by immunostaining. The fluorescence intensity (FI) was computed as the ratio (%) of positively and negatively stained areas. Results AS patients did not differ from AS-NOACs participants with regard to demographic or risk factors. Micro-CT analysis showed 65.5% lower BV in AS-NOACs valves compared to patients not taking NOACs (87±47 mm3 vs. 252±146 mm3, p=0.0017). Of note, in AS-NOACs patients Tbth showed strong association with transvalvular pressure gradients (PGmean: r=0.76, p=0.033; PGmax: r=0.77, p=0.01), as clinical measures of the AS severity. The duration of anticoagulation was associated with the lower Tbth (from 0.35 mm for 60 months to 0.51 mm for 36 months, p&amp;lt;0.01), which suggests that long NOACs treatment changed the pattern of valvular calcification, leading to formation of calcium deposits with reduced volume. Moreover, in AS-NOACs patients BV correlated with hard CT (r=−0.69, p=0.027), suggesting that the lesions increase their volume but do not ossify. Valvular expression of BMP-2 and NFκB was 44% and 33% decreased in AS-NOACs patients, compared to those without such treatment and the expression of both proteins was positively associated (r=0.34, p=0.001). Moreover, in AS-NOACs patients the expression of BMP-2 and NFκB was observed mainly in the fibrosa layer of the leaflets, but not in the deeper layers of tissue, as in AS patients without NOACs treatment. Conclusions NOACs can inhibit the increase of valvular calcium volume and its ossification via suppressed NFkB expression. Our study may suggest that long-term anticoagulation with NOACs could slow down the rate of AS progression, at least in patients with an indication for anticoagulant therapy. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Polish National Science Centre

Adherence and persistence to oral anticoagulants in patients with atrial fibrillation: A Belgian nationwide cohort study.

BackgroundSince non-vitamin K antagonist oral anticoagulants (NOACs) do not require coagulation monitoring, concerns of lower adherence and persistence to NOACs than vitamin K antagonists (VKAs) have been raised. Moreover, little is known on the frequency of permanent cessation and switching between anticoagulants in patients with atrial fibrillation (AF). Therefore, persistence, reinitiation, switching and adherence to oral anticoagulants (OACs) were investigated.Materials and methodsAF patients with a first OAC prescription claim between 2013 and 2019 were identified in Belgian nationwide data. Persistence, reinitiation and switching were estimated using Kaplan-Meier analyses. Adherence was investigated using the proportion of days covered (PDC). Predictors for non-adherence and non-persistence were identified by multivariable logistic regression.ResultsAmong 277,782 AF patients, 69.6% NOAC and 37.2% VKA users were persistent after 1 year, whereas 44.3% and 18.9% after 5 years, respectively. After one year, 67.1% rivaroxaban, 68.1% dabigatran, 69.8% apixaban, and 76.9% edoxaban users were persistent. Among subjects having discontinued NOAC or VKA treatment, 75.4% and 46.1% reinitiated any OAC within 5 years, respectively. VKAs were more frequently switched to NOACs than vice versa (17.6% versus 2.5% after 1 year). After 1 year, a high PDC (≥ 90%) was observed in 87.8% apixaban, 88.6% dabigatran, 91.3% rivaroxaban, and 94.7% edoxaban users (90.2% NOAC users). Adherence and persistence were higher in older, female subjects, while lower in subjects with dementia or hyperpolypharmacy.ConclusionAdherence and persistence to NOACs were high. However, 10% of subjects were non-adherent after 1 year and one-fourth did not reinitiate anticoagulation within 5 years after NOAC discontinuation.

Oral anticoagulants in patients with atrial fibrillation at low stroke risk: a multicentre observational study.

AimsThere is currently no consensus on whether atrial fibrillation (AF) patients at low risk for stroke (one non-sex-related CHA2DS2-VASc point) should be treated with an oral anticoagulant.Methods and resultsWe conducted a multi-country cohort study in Sweden, Denmark, Norway, and Scotland. In total, 59 076 patients diagnosed with AF at low stroke risk were included. We assessed the rates of stroke or major bleeding during treatment with a non-vitamin K antagonist oral anticoagulant (NOAC), a vitamin K antagonist (VKA), or no treatment, using inverse probability of treatment weighted (IPTW) Cox regression. In untreated patients, the rate for ischaemic stroke was 0.70 per 100 person-years and the rate for a bleed was also 0.70 per 100 person-years. Comparing NOAC with no treatment, the stroke rate was lower [hazard ratio (HR) 0.72; 95% confidence interval (CI) 0.56–0.94], and the rate for intracranial haemorrhage (ICH) was not increased (HR 0.84; 95% CI 0.54–1.30). Comparing VKA with no treatment, the rate for stroke tended to be lower (HR 0.81; 95% CI 0.59–1.09), and the rate for ICH tended to be higher during VKA treatment (HR 1.37; 95% CI 0.88–2.14). Comparing NOAC with VKA treatment, the rate for stroke was similar (HR 0.92; 95% CI 0.70–1.22), but the rate for ICH was lower during NOAC treatment (HR 0.63; 95% CI 0.42–0.94).ConclusionThese observational data suggest that NOAC treatment may be associated with a positive net clinical benefit compared with no treatment or VKA treatment in patients at low stroke risk, a question that can be tested through a randomized controlled trial.

Time at home among nonvalvular atrial fibrillation patients treated with non-vitamin K antagonist oral anticoagulants versus warfarin

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. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bristol-Myers Squibb Company and Pfizer Inc.

Time at home among nonvalvular atrial fibrillation patients treated with non-vitamin K antagonist oral anticoagulants: an ARISTOPHANES analysis

Abstract Background Patient-centered outcomes, such as home time, are becoming increasingly important quality-of-life measures. There are limited data on the impact of oral anticoagulants (OACs) on home time among patients with non-valvular atrial fibrillation. Purpose This analysis, based on the previously published ARISTOPHANES study, used five US insurance claims databases (CMS Medicare and four commercial databases) to compare home time among NVAF patients who were prescribed non-vitamin K antagonist OACs (NOACs). Methods Adult NVAF patients who were newly prescribed apixaban, dabigatran, or rivaroxaban (01JAN2013–30SEP2015) were selected. Time at home was calculated as the number of days from the index date (NOAC prescription) without any of the following: an inpatient, skilled nursing facility (SNF) or nursing facility, hospice, or inpatient rehabilitation facility admission. Time at home and without external AF-related care was defined as days from index date without any events from the home time endpoint or any days with a claim for bleeding, stroke/systemic embolism (S/SE), AF, or an INR test. Time at home and without external AF-related care were measured during the 180 days of follow-up; patients were required to have been alive and have 180 days of follow-up post index. In each database, three 1:1 NOAC-NOAC propensity-score-matched (PSM) cohorts were created before combining the databases. For each NOAC-NOAC matched cohort, Poisson regression was conducted to compare time at home and time at home without external AF-related care. Results After PSM, 37,314 apixaban-dabigatran, 107,236 apixaban-rivaroxaban, and 37,693 rivaroxaban-dabigatran patient pairs were created of which 37–44% had 180 days of follow-up available. Across the NOAC cohorts, approximately 21–25% of patients had an admission to a hospital, SNF, nursing facility, rehabilitation center, or hospice during the 180-day follow-up. The time at home was generally consistent between the NOAC cohorts (177 days); however, apixaban patients had 0.5 more days at home compared to rivaroxaban patients. Across all NOAC cohorts, 7–8% had a claim for a S/SE, 11–15% had a claim for bleeding, and 15–22% had an INR test, while 87–89% of all patients had an AF-claim during the 180-day follow-up. Patients prescribed apixaban had 1 more day at home without external AF-related care compared to dabigatran, and 1.5 more days at home without external AF-related care compared to rivaroxaban. Dabigatran had &amp;lt;1 more day at home without external AF-related care compared to rivaroxaban. Conclusion Among NVAF patients treated with NOACs, there were small differences in the time at home and time at home without external AF-related care during the first 6 months of NOAC treatment. As NVAF is a chronic condition, it is important to understand the impact of NOAC treatment on these patient-centered outcomes. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bristol-Myers Squibb Company and Pfizer Inc.

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

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 &amp;gt;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. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bristol-Myers Squibb Company and Pfizer, Inc.

Oral anticoagulation patterns and prognosis in octogenarian patients with atrial fibrillation.

The relationship between oral anticoagulants (OACs) and prognosis in elderly patients with atrial fibrillation (AF)has not been adequately explored. In this retrospective cohort study, we identified subjects aged over 80 from a database of 1140 AF patients discharged from the cardiology ward of a single tertiary center between 2015 and 2018. We examined the OAC treatment of octogenarian patients at discharge [VKA (vitamin K antagonist), NOAC (non-vitamin K antagonist oral anticoagulant), no OAC treatment]. We analyzed follow-up data of patients on OAC at discharge. The primary endpoint was all-cause death. The secondary endpoint was the incidence of stroke and major bleeding. The association of NOAC versus VKA treatment with these endpoints was assessed with multivariable Cox regression, using the VKA group as reference. A total of 330 octogenarian patients with AF were included with a mean (± SD) age of 83.9 ± 3.5years. At discharge, 53.3% received a NOAC, 30% a VKA, and 16.7% no OAC. Patients on OAC were followed-up over a median of 2.6-years . The adjusted risk of all-cause death was not different in the NOAC group, compared with the VKA group (hazard ratio [HR], 0.72; 95% confidence intervals [CI] 0.50-1.03; P = 0.07). The risk of stroke or major bleeding was not different either (all P > 0.05). In conclusion,in this cohort of post-discharge octogenarian patients with AF, the risk for all-cause death was similar in NOAC versus VKA users, after adjustment for baseline covariates. No differences in stroke and major bleeding events among these treatment groups were revealed.

Pharmacotherapy of atrial fibrillation in COVID-19 patients.

The coronavirus pandemic disease 2019 (COVID-19) has changed the face of contemporary medicine. However, each and every medical practitioner must be aware of potential early and late complications of COVID-19, its impact on chronic diseases - especially ones as common as atrial fibrillation (AF) - and the possible interactions between patients' chronic medications and pharmacotherapy of COVID-19. Patients with AF due to comorbidities and, often, elderly age are assumed to be at a higher risk of a severe course of COVID-19. This expert consensus summarizes the current knowledge regarding the pharmacotherapy of AF patients in the setting of the COVID-19 pandemic. In general, anticoagulation principles in quarantined or asymptomatic individuals remain unchanged. Nevertheless, it is advisable to switch from vitamin K antagonists to non-vitamin K antagonist oral anticoagulants (NOACs) whenever possible due to their consistent benefits and safety with fixed dosing and no monitoring. Additionally, in AF patients hospitalized due to mild or moderate COVID-19 pneumonia, we recommend continuing NOAC treatment or to switching to low-molecular-weight heparin (LMWH). On the other hand, in severely ill patients hospitalized in intensive care units, intravenous or subcutaneous dosing is preferable to oral, which is why the treatment of choice is either LMWH or unfractionated heparin. Finally, particularly in critical scenarios, the treatment strategy in COVID-19 patients with AF should be individualized based on possible interactions between anticoagulants, antiarrhythmics, antivirals, and antibiotics. In this consensus, we also discuss how to safely perform COVID-19 vaccination in anticoagulated AF patients.

Natural History of Isolated Below-Knee Vein Thrombosis in Patients with Spinal Cord Injury.

In the general population, serial imaging is recommended over anticoagulant therapy for below-knee deep vein thrombosis (BKDVT). However, no clinical trial in Asian patients with spinal cord injury and BKDVT has been performed. Therefore, we evaluated the natural course of BKDVT in patients with acute spinal cord injury. We retrospectively analyzed inpatients with spinal cord injury with BKDVT between 2016 and 2020. All patients underwent inpatient rehabilitation treatment and duplex ultrasonographic examination of both the lower extremities at follow-up. After screening 172 patients with acute spinal cord injury for deep vein thrombosis using duplex ultrasound, 27 patients with below-the-knee deep vein thrombosis were included in this study. The mean lower-extremity motor score (median, interquartile range) was 66.0, 54.0–74.5. Sixteen patients received a non-vitamin K antagonist oral anticoagulant (NOAC) for anticoagulation. None of the patients had proximal propagation according to the follow-up duplex ultrasonography. BKDVT disappearance was not significantly different between the NOAC treatment and non-treatment groups. Asian patients with spinal cord injury have a low incidence of venous thromboembolism and favorable natural history of BKDVT. We recommend serial imaging over anticoagulant therapy for BKDVT in these patients.

Persistence and adherence to non-vitamin K antagonist oral anticoagulant treatment in patients with atrial fibrillation across five Western European countries

AimsTo assess persistence and adherence to non-vitamin K antagonist oral anticoagulant (NOAC) treatment in patients with atrial fibrillation (AF) in five Western European healthcare settings.Methods and resultsWe conducted a multi-country observational cohort study, including 559 445 AF patients initiating NOAC therapy from Stockholm (Sweden), Denmark, Scotland, Norway, and Germany between 2011 and 2018. Patients were followed from their first prescription until they switched to a vitamin K antagonist, emigrated, died, or the end of follow-up. We measured persistence and adherence over time and defined adequate adherence as medication possession rate ≥90% among persistent patients only.ResultsOverall, persistence declined to 82% after 1 year and to 63% after 5 years. When including restarters of NOAC treatment, 85% of the patients were treated with NOACs after 5 years. The proportion of patients with adequate adherence remained above 80% throughout follow-up. Persistence and adherence were similar between countries and was higher in patients starting treatment in later years. Both first year persistence and adherence were lower with dabigatran (persistence: 77%, adherence: 65%) compared with apixaban (86% and 75%) and rivaroxaban (83% and 75%) and were statistically lower after adjusting for patient characteristics. Adherence and persistence with dabigatran remained lower throughout follow-up.ConclusionPersistence and adherence were high among NOAC users in five Western European healthcare settings and increased in later years. Dabigatran use was associated with slightly lower persistence and adherence compared with apixaban and rivaroxaban.

Appropriate intraprocedural initial heparin dosing in patients undergoing catheter ablation for atrial fibrillation receiving uninterrupted non-vitamin-K antagonist oral anticoagulant treatment

BackgroundTo clarify the appropriate initial dosage of heparin during radiofrequency catheter ablation (RFCA) in patients with atrial fibrillation (AF) receiving uninterrupted nonvitamin K antagonist oral anticoagulant (NOAC) treatment.MethodsA total of 187 consecutive AF patients who underwent their first RFCA in our center were included. In the warfarin group (WG), an initial heparin dose of 100 U/kg was administered (control group: n = 38). The patients who were on NOACs were randomly divided into 3 NOAC groups (NG: n = 149), NG110, NG120, and NG130, and were administered initial heparin doses of 110 U/kg, 120 U/kg, and 130 U/kg, respectively. During RFCA, the activated clotting time (ACT) was measured every 15 min, and the target ACT was maintained at 250–350 s by intermittent heparin infusion. The baseline ACT and ACTs at each 15-min interval, the average percentage of measurements at the target ACT, and the incidence of periprocedural bleeding and thromboembolic complications were recorded and analyzed.ResultsThere was no significant difference in sex, age, weight, or baseline ACT among the four groups. The 15 min-ACT, 30 min-ACT, and 45 min-ACT were significantly longer in the WG than in NG110 and NG120. However, no significant difference in 60 min-ACT or 75 min-ACT was detected. The average percentages of measurements at the target ACT in NG120 (82.2 ± 23.6%) and NG130 (84.8 ± 23.7%) were remarkably higher than those in the WG (63.4 ± 36.2%, p = 0.007, 0.003, respectively). These differences were independent of the type of NOAC. The proportion of ACTs in 300–350 s in NG130 was higher than in WG (32.4 ± 31.8 vs. 34.7 ± 30.6, p = 0.735). Severe periprocedural thromboembolic and bleeding complications were not observed.ConclusionsFor patients with AF receiving uninterrupted NOAC treatment who underwent RFCA, an initial heparin dosage of 120 U/kg or 130 U/kg can provide an adequate intraprocedural anticoagulant effect, and 130 U/kg allowed ACT to reach the target earlier.Trial registration: Registration number: ChiCTR1800016491, First Registration Date: 04/06/2018 (Chinese Clinical Trial Registry http://www.chictr.org.cn/index.aspx).

Risk Factors for Intracerebral Hemorrhage in Patients With Atrial Fibrillation on Non-Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention.

[Figure: see text].