Era Of Direct Oral Anticoagulants Research Articles

Trends in prior antithrombotic medication and risk of in-hospital mortality after spontaneous intracerebral hemorrhage: the J-ICH registry

Spontaneous intracerebral hemorrhage (SICH) remains a devastating form of stroke. Prior use of antiplatelets or warfarin before SICH is associated with poor outcomes, but the effects of direct oral anticoagulants (DOACs) remain unclear. This study aimed to clarify trends in prior antithrombotic use and to assess the associations between prior use of antithrombotics and in-hospital mortality using a multicenter prospective registry in Japan. In total, 1085 patients were analyzed. Prior antithrombotic medication included antiplatelets in 14.2%, oral anticoagulants in 8.1%, and both in 1.8%. Prior warfarin use was significantly associated with in-hospital mortality (odds ratio [OR] 5.50, 95% confidence interval [CI] 1.30–23.26, P < 0.05) compared to no prior antithrombotic use. No such association was evident between prior DOAC use and no prior antithrombotic use (OR 1.34, 95% CI 0.44–4.05, P = 0.606). Concomitant use of antiplatelets and warfarin further increased the in-hospital mortality rate (37.5%) compared to warfarin alone (17.2%), but no such association was found for antiplatelets plus DOACs (8.3%) compared to DOACs alone (11.9%). Prior use of warfarin remains an independent risk factor for in-hospital mortality after SICH in the era of DOACs. Further strategies are warranted to reduce SICH among patients receiving oral anticoagulants and to prevent serious outcomes.

Statins use and recurrent venous thromboembolism in the direct oral anticoagulant era: insight from the COMMAND VTE Registry-2.

Statins were reported to have a potential effect of primary prevention of venous thromboembolism (VTE), although that of secondary prevention remains uncertain. To investigate the association between statins use and recurrent VTE in the current era. The COMMAND VTE Registry-2 is a multicenter registry enrolling 5,197 consecutive VTE patients among 31 centers in Japan between January 2015 and August 2020. We divided the entire cohort into 2 groups according to statins use at the time of discharge; the statins (N = 865) and no statins groups (N = 4332). The statins group was older (72.9 vs. 66.7 years, P < 0.001), and less often had active cancer (22.0% vs. 30.4%, P < 0.001). The cumulative incidence of discontinuation of anticoagulation was significantly lower in the statins group (60.3% vs. 52.6%, Log-rank P < 0.001). The cumulative 5-year incidence of recurrent VTE was significantly lower in the statins group (6.8% vs. 10.1%, Log-rank P = 0.01). Even after adjusting for the confounders, the lower risk of the statins group relative to the no statins group remained significant for recurrent VTE (HR 0.65, 95% CI 0.45-0.91, P = 0.01). The cumulative 5-year incidence of major bleeding was significantly lower in the statins group (12.2% vs. 14.1%, Log-rank P = 0.04), although, after adjusting for the confounders, the risk of the statins group relative to the no statins group turned to be insignificant (HR 0.77, 95% CI 0.59-1.00, P = 0.054). In this large real-world VTE registry, statins use was significantly associated with a lower risk for the recurrent VTE in the current era.

Practical Suggestions for an Optimal Management of Vitamin K Antagonists: Italian Federation of Centers for the Diagnosis of Thrombotic Disorders and the Surveillance of the Antithrombotic Therapies (FCSA) Position Paper

AbstractIn the era of direct oral anticoagulants, vitamin K antagonists retain a clinically relevant role in thrombotic disorders. In Italy, approximately 20% of the patients on anticoagulant therapies receives a VKA, in most cases warfarin. The optimal management of this drug is challenging and cannot disregard its intricate and unpredictable pharmacokinetic properties and patient's thrombotic and bleeding risk. Several clinical issues encountered during warfarin treatment are still unanswered and are tentatively addressed by physicians. In this regard, the Italian Federation of Centers for the diagnosis of thrombotic disorders and the Surveillance of the Antithrombotic therapies (FCSA) provides some experience-based good clinical practice's suggestions on the following topics: (1) how to start the anticoagulant treatment with warfarin and warfarin induction regimen; (2) how to manage a subtherapeutic INR value; (3) how to manage a supratherapeutic INR value in asymptomatic patients; and (4) how to manage the association of warfarin with interfering drugs.

Coronary events in elderly patients with non-valvular atrial fibrillation: a prespecified sub-analysis of the ANAFIE registry

Real-world data on coronary events (CE) in elderly patients with atrial fibrillation (AF) are lacking in the direct oral anticoagulant era. This prespecified sub-analysis of the ANAFIE Registry, a prospective observational study in > 30,000 Japanese patients aged ≥ 75 years with non-valvular AF (NVAF), investigated CE incidence and risk factors. The incidence and risk factors for new-onset CE (a composite of myocardial infarction [MI] and cardiac intervention for coronary heart diseases other than MI), MI, and cardiac intervention for coronary heart diseases other than MI during the 2-year follow-up were assessed. Bleeding events in CE patients were also examined. Among 32,275 patients, the incidence rate per 100 patient-years was 0.48 (95% confidence interval (CI): 0.42–0.53) for CE during the 2-year follow-up, 0.20 (0.16–0.23) for MI, and 0.29 (0.25–0.33) for cardiac intervention for coronary heart diseases other than MI; that of stroke/systemic embolism was 1.62 (1.52–1.73). Patients with CE (n = 287) likely had lower creatinine clearance (CrCL) and higher CHADS2 and HAS-BLED scores than patients without CE (n = 31,988). Significant risk factors associated with new-onset CE were male sex, systolic blood pressure of ≥ 130 mmHg, diabetes mellitus (glycated hemoglobin ≥ 6.0%), CE history, antiplatelet agent use, and CrCL < 50 mL/min. Major bleeding incidence was significantly higher in patients with new-onset CE vs without CE (odds ratio [95% CI], 3.35 [2.06–5.43]). In elderly patients with NVAF, CE incidence was lower than stroke/systemic embolism incidence. New-onset CE (vs no CE) was associated with a higher incidence of major bleeding.Trial registration: UMIN000024006.Graphical

Clinical features and long-term outcomes of venous thromboembolism in the warfarin era versus in the direct oral anticoagulant era

Abstract Background/Introduction After the introduction of direct oral anticoagulant (DOAC) for venous thromboembolism (VTE), DOAC for VTE have prevailed all over the world, which could change the daily clinical practice and clinical outcomes. However, there have been still limited data on the issue in the real world. Purpose We aimed to investigate demographics, practice patterns and long-term clinical outcomes in patients with VTE comparing a large observational study in the warfarin era and that in the DOAC era. Methods The COMMAND VTE Registry-1 (enrolled 3,027 VTE patients among 29 center between January 2010 and August 2014 in the warfarin era) and Registry-2 (enrolled 5,197 VTE patients among 31 centers between January 2015 and August 2020 in the DOAC era) are the series of a multicenter observational study in Japan enrolling consecutive patients with acute symptomatic VTE. Results Patients characteristics were comparable in most of aspects between the groups, whereas prevalence of active cancer was higher in the Registry-2 (Registry-1: 23% vs. Registry-2: 29%, P&amp;lt;0.001). As for oral anticoagulation therapy, 88% (2,676/3,027) of patients were treated with warfarin in the Registry-1 and 79% (4,128/5,197) of patients were treated with DOAC in the Registry-2. The proportion of patients admitted to the hospital was lower in the Registry-2 (80% vs. 69%, P&amp;lt;0.001). The discontinuation rate of anticoagulation therapy was significantly higher in the Registry-2 (42.8% vs. 52.5% at 3-year, Log rank P&amp;lt;0.001). The cumulative 5-year incidence of recurrent VTE was lower in the Registry-2 (10.5% vs. 9.5%, Log rank P=0.02), which remained significant even after adjusting the confounders (adjusted hazard ratio [HR]: 0.78 (0.65-0.93), P=0.006). There was no significant difference in the cumulative incidence of major bleeding between the groups (12.1% vs. 13.7%, Log-rank P=0.26), which remained insignificant even after adjusting the confounders (adjusted HR: 1.03 (0.89-1.20), P=0.67). After stratifying a total cohort into sub-groups according to the risk classification of recurrent VTE in the current guidelines (major transient risk factors, minor transient risk factors, unprovoked, non-malignant persistent risk factors, and active cancer), the risks of recurrent VTE and major bleeding were significantly lower in the Registry-2 among active cancer group (recurrent VTE: 17.7% vs 10.1% at 5-year, Log rank P&amp;lt;0.001, major bleeding: 26.6% vs 20.4% at 5-year, Log rank P=0.04), while those were not significantly different between the groups among other sub-groups. Conclusion In the current series of large real-world VTE registries, there seemed to be a significant risk reduction of recurrent VTE in the DOAC era compared with in the warfarin era, while there was no sign of increased risk of major bleeding in the DOAC era.

Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism in the era of direct oral anticoagulants: from the COMMAND VTE Registry-2

Abstract Background/Introduction Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening complication after acute pulmonary embolism (PE), and the global need for the diagnosis and prediction of CTEPH is increasing. However, the incidence has not been fully evaluated in the era of direct oral anticoagulants (DOACs). Purpose To clarify the incidence and risk factors for CTEPH after acute PE in the DOAC era. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic venous thromboembolism (VTE) patients among 31 centers in Japan between January 2015 and August 2020. The primary outcome was the incidence of CTEPH in patients with acute PE. The secondary outcome was the adjusted hazard ratio for the prediction of CTEPH development. Results Of the 5197 VTE patients enrolled in the COMMAND VTE Registry-2, 2787 patients had acute PE. After a median 747-day follow-up of 2787 acute PE patients, 48 CTEPH were identified (cumulative incidence 2.4%). The incidence of CTEPH did not significantly differ between the treatments of DOACs (2.3%) and vitamin K antagonists (3.7%). Multivariable Cox regression analysis showed that female sex (adjusted hazard ratio 2.20 [95% CI 1.11 to 4.36], p=.024), right heart load on echocardiography and/or CT (adjusted hazard ratio 12.77 [95% CI 4.51 to 36.19], p&amp;lt;.0001), longer days from onset to diagnosis (each 1 day, adjusted hazard ratio 1.03 [95% CI 1.00 to 1.07], p=.044), lower D-dimer level (each 1 μg/mL, adjusted hazard ratio 0.96, [95% CI 0.93 to 0.99], p=.021) and unprovoked PE (adjusted hazard ratio 2.85, [95% CI 1.32 to 6.17], p=.008) were associated with the development of CTEPH. Conclusions The cumulative incidence of CTEPH after acute PE in the DOAC era was 2.4%. Stratification of the risk of developing CTEPH may be useful for follow-up of acute PE.Cumulative incidence of CTEPH

Clinical features and long-term outcomes of cancer-associated venous thromboembolism: transition from the warfarin era to the direct oral anticoagulant era

Abstract Background/Introduction After the introduction of direct oral anticoagulant (DOAC) for venous thromboembolism (VTE), DOAC for VTE have prevailed all over the world. The usefulness of DOAC for cancer-associated VTE has also been recently reported and may change the daily clinical practice and clinical outcomes. However, there have been still limited data on the issue in the real world. Purpose We aimed to investigate the clinical characteristics, anticoagulation strategies, and long-term clinical outcomes of patients with cancer-associated VTE comparing a large observational study in the warfarin era and that in the DOAC era. Methods The COMMAND VTE Registry-1 (enrolled 3,027 VTE patients among 29 center between January 2010 and August 2014 in the warfarin era) and Registry-2 (enrolled 5,197 VTE patients among 31 centers between January 2015 and August 2020 in the DOAC era) are the series of a multicenter observational study in Japan enrolling consecutive patients with acute symptomatic VTE. In the present study, we evaluated patients with cancer-associated VTE of 695 cases from Registry-1 and 1507 cases from Registry-2. Results As for oral anticoagulation therapy, 83% (2,576/695) of patients were treated with warfarin in the Registry-1 and 80% (1,199/5,197) of patients were treated with DOAC in the Registry-2. Patients in the Registry-2 were slightly older (67±12 vs. 68±13 years, P=0.005), had a slightly higher body weight (55±12 vs. 57±13 kg, P=0.03), and more frequently had pulmonary embolism (44% vs. 49%, P=0.004). Patients in the Registry-2 were less frequently admitted to the hospital among those with out-of-hospital-onset VTE (83% vs. 66%, P&amp;lt;0.001), and median length of hospitalization was shorter in patients in the Registry-2 (16 [IQR: 11-26] vs. 14.5 [IQR: 9-24] days, P=0.01). AS for cancer types, lung cancer, colorectal cancer and stomach cancer were significantly higher in patients in the Registry-1 (18% vs. 15%, P=0.04; 14% vs. 10%, P=0.008; 9% vs. 6%, P=0.007). There was no significant difference in the discontinuation rate of anticoagulation therapy between the 2 groups (56.7% vs. 62.7% at 3-year, Log rank P=0.10). The cumulative 5-year incidence of recurrent VTE, major bleeding and all cause-death were significantly lower in patients in the Registry-2 (17.7% vs. 10.1%, P&amp;lt;0.001; 26.6% vs. 20.4%, P=0.045; 73.1% vs. 64.8%, P=0.003), while there were no significant differences in the cumulative 5-year incidences of intracranial bleeding (5.7% vs. 3.2%, P=0.056) nor major gastrointestinal bleeding between the 2 groups (13.9% vs. 10.1%, P=0.30) (Figure). Conclusion The introduction of DOAC for cancer-associated VTE could have a potential benefit of reducing the risk of recurrent VTE and major bleeding, although gastrointestinal bleeding might be still a major concerns even in the DOAC era.FigureFigure

Abstract 14256: Examining the Efficacy of Inferior Vena Cava Filters in the Direct Oral Anticoagulant Era

Introduction: No previous reports have adequately demonstrated whether inferior vena cava filters prevent pulmonary embolism, and reports of disadvantages, such as worsening venous thrombosis, have led to a decrease in the frequency of their use. However, in actual clinical practice, patients often encounter situations in which they expect to benefit from inferior vena cava filters; hence, exploratory studies examining their efficacy continue. Hypothesis &amp; Methods: We analyzed data from the COMMAND VTE Registry-2, a multi center, retrospective, observational study of symptomatic venous thrombosis in the DOAC era, for cases using inferior vena cava filters. Results: A total of 5197 cases of venous thrombosis were enrolled, among whom 483 (9%) had inferior vena cava filters implanted. The inferior vena cava filter was implanted long-term and removed in 6% and 3% of cases, respectively. Inferior vena cava filters tended to be implanted in patients with active cancer patients, with more patients with terminal cancer, on anticancer therapy, and with distant metastases having long-term filter implantation (P = 0.001). After inferior vena cava filter implantation, the inferior vena cava filter implantation group showed a significantly lower incidence of pulmonary embolism within 30 days after the onset of initial venous thrombosis (P = 0.011). However, Kaplan-Meier analysis during a median follow-up of 854 days showed that long-term implantation of inferior vena cava filters significantly increased incidence of deep vein thrombosis (P = 0.001), whereas multivariate analysis found that long-term implantation of inferior vena cava filters was an independent risk factor for deep vein thrombosis (HR: 2.096, 95% CI: 1.254-3.508, P = 0.005). Conclusions: Inferior vena cava filters may be effective in preventing pulmonary emboli in the short term; however, even in the DOAC era, long-term filter implantations were associated with an increased incidence of deep vein thrombosis.

Interpreting coagulation mixing study results in the era of direct oral anticoagulants.

Interpretation of coagulation mixing studies is complicated by interference arising from direct oral anticoagulants (DOACs), which are increasingly prescribed. In this retrospective study, we reviewed 1035 consecutive coagulation mixing studies performed from 2017 to 2021. Three hundred and ninety-nine cases with normal prothrombin time (PT) and activated partial thromboplastin time (aPTT) were excluded. aPTT mixing studies were performed at time 0 and after 60 min of incubation. We confirmed the presence of interfering factors with additional laboratory testing, medication records, and medical history. Mixing corrected most prolonged PT samples (93%), but 32 cases showed incomplete correction. Of these 32 cases, 18 were confounded by DOAC use, and 3 by factor V (FV) inhibitor. We observed an unusual pattern of prolongation of aPTT after incubation, which was previously considered a characteristic of specific factor inhibitors, most commonly FVIII inhibitor. However, we found that lupus anticoagulant (28%) and DOAC (25%) contributed to this pattern similarly as specific factor inhibitors (28%). Coagulation laboratories should be aware of interference arising from DOACs and other factors in PT/aPTT mixing studies, especially in some unusual correction patterns.

Low bleeding acceptance is associated with increased death risk in patients with atrial fibrillation on oral anticoagulation.

Bleeding is the most feared complication of anticoagulation. We sought to investigate whether the bleeding risk acceptance has a prognostic value during long-term follow-up in the era of direct oral anticoagulants (DOACs) among patients with atrial fibrillation (AF). We studied 167 consecutive AF outpatients [aged 68.8 SD 10.6 years; 141 (84.4%) on DOACs]. The bleeding acceptance was assessed based on the Bleeding Ratio defined as the declared maximum number of major bleedings that a patient would be willing to accept to prevent one major stroke. We recorded cerebrovascular ischemic events, major or clinically relevant non-major bleeds (CRNMB), and mortality. A median Bleeding Ratio was 4 (IQR 2-5). During follow-up of 946 patient-years, cerebrovascular ischemic events and/or death were observed in 28 patients (3.3%/ year) and major bleeding or CRNMB in 33 (4.6%/ year). The Bleeding Ratio was lower in patients who experienced cerebrovascular events or death (p = 0.004), but not bleeding. Patients with the Bleeding Ratio 0-3 were more often non-persistent to the OAC therapy, and more likely to have cerebrovascular event or die than those with higher bleeding acceptance (odds ratio 2.55; 0.95% CI 1.08-6.02) which was driven by the impact on mortality. The multiple Cox proportional hazards model showed that lower Bleeding Ratio, higher CHA2DS2-VASc score, and older age predicted cerebrovascular events or death during follow-up. AF patients who are willing to accept fewer serious bleedings to avoid major stroke during anticoagulation are more likely to experience death and/or cerebrovascular ischemic events, but not bleeding, what might be related to non-persistence.

Anticoagulation strategies and long-term recurrence in patients with venous thromboembolism in the era of direct oral anticoagulants

BackgroundThere has been limited data on anticoagulation strategies and long-term recurrence in patients with venous thromboembolism (VTE) in the era of direct oral anticoagulant (DOAC). MethodsThe COMMAND VTE Registry-2 is a multicenter retrospective cohort study enrolling 5197 consecutive patients with acute symptomatic VTE between January 2015 and August 2020 among 31 centers in Japan. In this primary report, the entire cohort was divided into 5 groups; major transient risk factors (N = 475, 9.1%), minor transient risk factors (N = 788, 15%), unprovoked (N = 1913, 37%), non-malignant persistent risk factors (N = 514, 9.9%), and active cancer (N = 1507, 29%) groups. ResultsDOACs were administered in 79% of patients who received oral anticoagulants. Discontinuation of anticoagulant at 1 year was most frequent in the major transient risk factors group (57.2%, 46.3%, 29.1%, 32.0%, and 45.6%). The cumulative 5-year incidence of recurrent VTE was lowest in the major transient risk factors group (2.6%, 6.4%, 11.0%, 12.1%, and 10.1%, P < 0.001). The cumulative 5-year incidence of major bleeding was highest in the active cancer group (9.8%, 11.4%, 11.0%, 15.5%, and 20.4%, P < 0.001). After discontinuation of anticoagulation therapy, the cumulative 5-year incidence of recurrent VTE was highest in the unprovoked group (3.3%, 11.0%, 24.9%, 17.5%, and 11.8%, P < 0.001). ConclusionsIn this large real-world VTE registry, anticoagulation strategies and long-term recurrence widely differed depending on the baseline characteristics. Detailed risk stratifications of recurrent VTE could be useful for decision-making of anticoagulation strategies, whereas the bleeding-risk assessment might be especially important in the era of DOAC. Clinical Trial RegistrationURL: http://www.umin.ac.jp/ctr/index.htm Unique identifier: UMIN000044816.

Inappropriate Combined Antiplatelet and Anticoagulant Therapy in Older Patients with Atrial Fibrillation: Trend over Time (2009-18).

Antiplatelet therapy, when prescribed in combination with anticoagulant therapy to older patients with atrial fibrillation and no recent cardiovascular event, is inappropriate and a reversible risk factor of major bleeding. We aimed to assess the trend over time of the prevalence of inappropriate combined antiplatelet and anticoagulant therapy and to determine its associated factors during the direct oral anticoagulant era. This was a study of consecutive older patients (age ≥75 years) with atrial fibrillation, receiving anticoagulant therapy upon admission, and undergoing a comprehensive geriatric assessment during their first admission in a Belgian teaching hospital between 2009 and 2018. Antiplatelet therapy was considered inappropriate in the absence of a recent cardiovascular event. We studied the prevalence of inappropriate combined antiplatelet and anticoagulant therapy by 2-year periods and assessed its associated factors since the year 2013. Inappropriate combined antiplatelet and anticoagulant therapy was identified in 21% of the 654 patients (median age 84 years, 51% women), with a prevalence decreasing (p ≤ 0.01) from 25% (2009-10) to 14.8% (2017-18). Among the 469 patients recruited during the direct oral anticoagulant era, inappropriate combined antiplatelet and anticoagulant therapy (19%) was associated in a multivariable analysis with a history of stroke/transient ischemic attack (odds ratio 2.13, p = 0.007), anticoagulation with low-molecular-weight heparin (odds ratio 3.44, p = 0.015), and a history of vascular disease (odds ratio 5.68, p < 0.001). While inappropriate combined antiplatelet and anticoagulant therapy has declined over the last decade, there is still room for improvement. Antiplatelet deprescribing should be considered in all patients with inappropriate combined antiplatelet and anticoagulant therapy, including those with vascular disease and no recent cardiovascular event.

Abstract 141: Contemporary Trends In Oral Anticoagulation Utilization After Acute Ischemic Stroke With Atrial Fibrillation: The Treatment Disparities In Stroke And Atrial Fibrillation Study

Background: Acute ischemic stroke (AIS) is a devastating consequence of atrial fibrillation (AF), which is preventable with oral anticoagulants (OACs). The goal of this study was to evaluate contemporary trends and disparities in OAC use at hospital discharge in patients with AIS and AF in the era of direct oral anticoagulants (DOACs). Methods: Data on 34,715 cases admitted to hospital for AIS with AF were obtained from the Florida Stroke Registry, 2017-2021. Baseline sociodemographics, medical history, stroke and hospital characteristics and anticoagulant status were compared by OAC use at discharge. Multivariable logistic regression was used to identify predictors of OAC non-use after AIS with AF after adjusting for confounders. Temporal trends in the frequency of OAC use at hospital discharge was assessed from 2010-2021. Results: From 2017-2021, a total of 21,011 (61%) patients with AIS and AF were discharged on OAC (median age 77 years; 49% female; 74% white, 13% black, 13% Hispanic). The rate of DOAC use increased from 43% to 59%, and the rate of warfarin use declined from 13% to 6% from 2017-2021. The overall use of OAC at hospital discharge increased by 9% from 2017-2021, and by 13% from 2010-2021. After adjustment, stroke hospital designation was the strongest predictor of OAC non-use with 4-fold higher odds of OAC non-use at discharge from an Acute Stroke Ready Hospital compared with a Comprehensive Stroke Center (P=0.012). Increasing age, male sex, renal insufficiency, lower CHA2DS2-VASc, NIHSS ≥5, mRS 3-5, ambulation status, and discharge destination were significant predictors of OAC non-use after AIS with AF. Conclusion: OAC use increased by 13% over the last decade in patients with AIS and AF in Florida. Previously identified race/ethnic disparities did not persist in 2017-2021; however, sex, stroke hospital designation, stroke severity, medical comorbidities, functional disability, and ambulation status had a significant impact on OAC use after AIS with AF.

Comparison of Maintenance Dose Predictions by Warfarin Dosing Algorithms Based on Chinese and Western Patients.

Warfarin has a long record of safe and effective clinical use, and it remains one of the most commonly prescribed drugs for the prevention and treatment of thromboembolic conditions even in the era of direct oral anticoagulants. To address its large interindividual variability and narrow therapeutic window, the Clinical Pharmacogenetics Implementation Consortium has recommended using pharmacogenetic dosing algorithms, such as the ones developed by the International Warfarin Pharmacogenetics Consortium (IWPC) and by Gage et al, to dose warfarin when genotype information is available. In China, dosing algorithms based on local patient populations have been developed and evaluated for predictive accuracy of warfarin maintenance doses. In this study, percentage deviations of doses predicted by 15 Chinese dosing algorithms from that by IWPC and Gage algorithms were systematically evaluated to understand the differences between Chinese and Western algorithms. In general, dose predictions by Chinese dosing algorithms tended to be lower than those predicted by IWPC or Gage algorithms for the most prevalent VKORC1 and CYP2C9 genotypes in the Chinese population. The extent of negative prediction deviation appeared to be largest in the younger age group with smaller body weight. Our findings are consistent with previous reports that Asians have a higher sensitivity to warfarin and require lower doses than Western populations.

Establishment and Utilization of an Advanced Practice Provider-Led Clinic for Newly Diagnosed Venous Thromboembolism

BACKGROUND: Evidence supports treating most patients with venous thromboembolism (VTE) as outpatients. There is hesitancy among some healthcare providers to manage patients with these high-risk acute conditions, on high-risk medications, without close and reliable follow-up. In the era of direct oral anticoagulants (DOACs), the financial complications associated with appropriate anticoagulation further complicate management. The benign hematology group at the University of North Carolina (UNC) at Chapel Hill developed an Advanced Practice Provider (APP)-led clinic to address this area of need, aiming to improve efficacy and safety in the outpatient setting for patients with acute VTE. METHODS: An APP-led acute VTE clinic, "Walk-In DVT Clinic", located within Benign Hematology was established with one appointment reserved each weekday. Patients with newly diagnosed VTE can be referred by any UNC-affiliated provider. A triage system with direct pager and phone line ("1-DVT") is available during business hours. For patients referred after-hours through the Emergency Department (ED), direct scheduling is available 24 hours/day. Patients are seen by the APP (physician assistant or nurse practitioner) with hematologist oversight. Pharmacist support is available for questions about drug interactions, medication access, and other needs. Patient education and counseling on diagnosis and anticoagulation is provided. Patients are evaluated for risk factors which contributed to the VTE, and follow-up for longer-term discussion of anticoagulation plans is scheduled. Following appointment, patients have access to nurse and provider assistance for bleeding complications, anticoagulation management for surgical/procedural planning, medication access, or other complications. Here we present demographics and referral data for patients seen in the first two years. RESULTS: Since initiation, a total of 234 patients have been seen, of which data was available for 229. Specifically, 84 in the first year (8/24/20 through 7/31/21) and 150 in the second year (8/1/21 through 7/31/22). Of these, 72% were ED referrals, and 12.7% required financial assistance of some kind. In the second year, 59.3% of referrals were ED, and 10% required medication assistance of some kind. Patient demographics are listed in the table below. In the second year, significant changes in medical plan (examples: dose errors, misdiagnosis) were identified in 19 cases (12.67%). The median time to appointment in the first year was 4 days and in the second year was 5 days (including weekend days). DISCUSSION: The "Walk-In DVT” clinic grew quickly in its first year and continued to grow in the second year, nearly doubling in utilization. In the first year, time-to-visit median was 4 days, and the program's aim was to decrease this. However, with increased utilization, this metric increased to 5 days. As a consequence, a second APP has been hired to improve access. The types of providers referring to the clinic diversified, with more referrals from surgical and medicine specialties and a lower overall percentage of ED follow-ups. This finding supports progress in one goal of the clinic, to have providers who diagnose a VTE refer directly to the DVT Walk-In Clinic rather than send them to the ED. Expanding the network of outpatient providers using the clinic is a future goal. The demographics of patients showed an increase in use by African American and Hispanic patients. Importantly, the increase in Hispanic patients has highlighted the need for better patient education materials translated to Spanish, prompting efforts to produce and translate new materials. In summary, since its inception, the APP-led "DVT Walk-In Clinic” has grown in utilization, diversity of referrals, and diversity of patients served, with new focus on patient education tools and expanding access. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Real-life contemporary vitamin K antagonist is still associated with very low time in therapeutic range despite strict international normalized ratio monitoring: Results of big data analysis.

This study aimed to determine the results of INR monitoring in patients on vitamin K antagonists (VKAs) and the time in therapeutic range (TTR) in 'real-world' settings. Retrospective analysis of 836,857 INR measurements performed in adults from February 2010 to August 2015 in two districts in the French Brittany region. Of the 836,857 INR measurements, 94.9% were ordered by general practitioners and 2.0% by cardiologists. The number of tests increased by 10-year age categories up to the age-group of 80-90years. The number of INR measurements increased from 169,636 in 2011 to 176,184 in 2012, but then decreased slightly to 162,597 in 2013 and 164,427 in 2014. Mean coefficient of variation of INR was 19.0%, and mean TTR was 29.0%. TTR was higher in women than in men (31% vs. 18%), in older than in younger patients (19.1% at 40years and 38.6% at 100years) and in patients with arrhythmias than in those with deep vein thrombosis/pulmonary embolism (44.4% versus 19.4%) (p<10-5 for each comparison). Median interval between INR measurements was 14days [7-28]; it was prolonged in men vs women, rural vs urban regions, older vs younger patients and when requested by GPs vs cardiologists. The interval was shorter for patients with INR outside the therapeutic range versus patients with INR within the therapeutic range (9days [5-21] vs. 18days [10-29], p<10-10 ). VKAs are still frequently prescribed in this era of direct oral anticoagulants. The low TTR cannot be explained by inadequate INR monitoring.

Isolated Distal Deep Vein Thrombosis in the Direct Oral Anticoagulant (DOAC) Era – Should Our Management Change?

Objectives: There remains no consensus management for isolated distal deep vein thrombosis (IDDVT), with current data inconclusive and dating back to the warfarin era. In the current direct oral anticoagulant (DOAC) era, optimal management of IDDVT needs to be re-assessed. Methods: A retrospective evaluation of patients treated with therapeutic anticoagulation for IDDVT in the DOAC era (2013-2016) was compared with historically published data from the warfarin era (2011-2012). Results: 247 patients were evaluated, 103 from the DOAC era and 122 from the warfarin era. There were less provoked events in the DOAC cohort (45.6% vs 66.7%, p=

Inherited Thrombophilia in the Era of Direct Oral Anticoagulants.

Severe inherited thrombophilia includes rare deficiencies of natural anticoagulants (antithrombin and proteins C and S) and homozygous or combined factor V Leiden and FII G20210A variants. They are associated with a high thrombosis risk and can impact the duration of anticoagulation therapy for patients with a venous thromboembolism (VTE) event. Therefore, it is important to diagnose thrombophilia and to use adapted anticoagulant therapy. The widespread use of direct anticoagulants (DOACs) for VTE has raised new issues concerning inherited thrombophilia. Concerning inherited thrombophilia diagnosis, DOACs are directed toward either FIIa or FXa and can therefore interfere with coagulation assays. This paper reports DOAC interference in several thrombophilia tests, including the assessment of antithrombin, protein S, and protein C activities. Antithrombin activity and clot-based assays used for proteins C and S can be overestimated, with a risk of missing a deficiency. The use of a device to remove DOACs should be considered to minimize the risk of false-negative results. The place of DOACs in the treatment of VTE in thrombophilia patients is also discussed. Available data are encouraging, but given the variability in thrombosis risk within natural anticoagulant deficiencies, evidence in patients with well-characterized thrombophilia would be useful.

The impact of advanced age on anticoagulant therapy for acute venous thromboembolism

Introduction Management of venous thromboembolic events (VTE) has been completely changed after the introduction of direct oral anticoagulants (DOAC). VTE is common in the geriatric population, but the management of DOACs remains complex because of the lack of specific data in this polymedicated fragile population. An exhaustive search of anticoagulants in the indication of VTE was performed on PubMed, including data from clinical trials, observational studies, real-world data, drug-drug interaction studies, as well as various guidelines from scientific societies. Areas covered The present review aims to summarize our current knowledge on the era of DOACs in the management of VTE in the elderly. This involves learning the pharmacokinetics/pharmacodynamics of drugs specific to geriatrics, the problem of drug-drug interactions, and the main randomized clinical trials validating the use of DOACs. Expert opinion DOACs have become an essential part of the management of VTE in the elderly, both for their efficacy and safety. However, we are faced with a list of unmet needs, such as the relevance of DOACs in the very elderly, cancer patients, and those with renal impairment. Clinicians and pharmacists must remain cautious about comedications, as well as about the patient’s comorbidities.

Osteonecrosis of the Femoral Head in Patients with Hypercoagulability-From Pathophysiology to Therapeutic Implications.

Osteonecrosis of the femoral head (ONFH) is a debilitating disease with major social and economic impacts. It frequently affects relatively young adults and has a predilection for rapid progression to femoral head collapse and end-stage hip arthritis. If not diagnosed and treated properly in the early stages, ONFH has devastating consequences and leads to mandatory total hip arthroplasty. The pathophysiology of non-traumatic ONFH is very complex and not fully understood. While multiple risk factors have been associated with secondary ONFH, there are still many cases in which a clear etiology cannot be established. Recognition of the prothrombotic state as part of the etiopathogeny of primary ONFH provides an opportunity for early medical intervention, with implications for both prophylaxis and therapy aimed at slowing or stopping the progression of the disease. Hereditary thrombophilia and hypofibrinolysis are associated with thrombotic occlusion of bone vessels. Anticoagulant treatment can change the natural course of the disease and improve patients’ quality of life. The present work focused on highlighting the association between hereditary thrombophilia/hypofibrinolysis states and ONFH, emphasizing the importance of identifying this condition. We have also provided strong arguments to support the efficiency and safety of anticoagulant treatment in the early stages of the disease, encouraging etiological diagnosis and prompt therapeutic intervention. In the era of direct oral anticoagulants, new therapeutic options have become available, enabling better long-term compliance.