Introduction Of Direct Oral Anticoagulants Research Articles

Primary Thromboprophylaxis for the Prevention of Venous Thromboembolism in Cancer Patients with Central Venous Catheters: A Literature Review.

Cancer is a known risk factor for venous thromboembolism (VTE). The wider adoption of immunotherapy and anti-angiogenic drugs in recent years have increased this risk further. Central venous catheters (CVCs) are widely used access devices utilized to deliver infusion therapy, mostly in ambulatory settings. The endothelial injury associated with the use of these catheters adds to the risk of VTE to already high-risk patients. The introduction of direct oral anticoagulants (DOACs), with its proven efficacy and safety in multiple clinical indications, have renewed the attention to VTE prophylaxis in cancer patients with CVC. Several clinical trials and meta-analyses had shown that both apixaban and rivaroxaban are effective in lowering the risk of VTE, without increasing the risk of bleeding. Several risk assessment models (RAM) have utilized patient-related, tumor-related, and treatment-related factors, in addition to widely available biomarkers, like Hemoglobin (Hb) level, white blood cell (WBC) and platelets counts to stratify patients into two or three VTE risk levels. In this manuscript, we review the published clinical trials and meta-analyses that attempted to study the efficacy and safety of anticoagulants, mostly the DOACs, in cancer patients with CVCs. We will also propose a practical risk-directed approach to enhance VTE prophylaxis rate.

Predictors for Adherence to Recommended Anticoagulation after Stroke Unit Discharge in Patients with Atrial Fibrillation.

Non-adherence to recommended secondary preventive anticoagulation in stroke patients with atrial fibrillation (AF) is a common phenomenon although the introduction of direct oral anticoagulants (DOACs) has simplified anticoagulation management for physicians as well as for patients. We examined the adherence of secondary preventive anticoagulation in AF patients after re-integration in their social environment 6 to 12 weeks after stroke unit and rehabilitation clinic treatment and analyzed for predictors for adherence and non-adherence. We conducted a telephone survey in consecutive patients treated between January 2013 and December 2021 at our institutional stroke unit with an acute cerebrovascular ischemic event and we analyzed discharge letters of rehabilitation clinics of those patients not anticoagulated at follow-up. All patients had known or newly diagnosed AF and in all we had recommended secondary preventive anticoagulation. Follow-up information about anticoagulant intake could be obtained in 1348 of 1685 patients (80.0%) treated within the study period. Anticoagulation rate was 91.5% with 83.6% of patients receiving DOACs and 7.9% receiving vitamin K antagonists (VKAs). Adherence to recommended anticoagulation was associated with intake of the recommended anticoagulant already at discharge (adjusted OR, 18.357; CI, 9.637 to 34.969), recommendation of a specific DOAC and dose (in contrast to "DOAC" as drug category) (adjusted OR, 2.971; CI, 1.173 to 7.255), a lower modified Rankin Scale at discharge (per point; adjusted OR, 0.813; CI, 0.663 to 0.996), younger age (per year; adjusted odds ratio [OR], 0.951; confidence interval [CI], 0.926 to 0.976), and the absence of peripheral vascular disease (adjusted OR, 0.359; CI, 0.173 to 0.746). In patients already anticoagulated at discharge adherence was 98.5%, irrespective of a patient's age, functional deficit at discharge, and peripheral vascular disease. Avoidable obstacles for non-adherence in patients not on anticoagulants at stroke unit discharge were (1) non-implementation of recommended anticoagulation by rehabilitation physicians predominantly in patients with moderate-severe or severe stroke disability (2.1%), (2) delegation of anticoagulation start from rehabilitation physicians to general practitioners/resident radiologists (1.3%), and (3) rejection of recommended anticoagulation because of patients' severe stroke disability (0.5%). Non-avoidable obstacles were contraindications to anticoagulation (2.1%) and patients' refusal (0.7%). Commencing drug administration already during stroke unit hospitalization and providing an explanation for the selection of the recommended anticoagulant in discharge letters ensures high adherence at patients' re-integration in their social environment after acute stroke treatment. If drug administration cannot be commenced before discharge, education of rehabilitation physicians by stroke physicians and the involvement of stroke physicians into the post-stroke decision process might hinder avoidable obstacles.

Cancer-associated Thrombosis in Vietnam: Literature Review and Expert Perspectives

Cancer-associated thrombosis (CAT) is a substantial burden and an emerging topic of great interest in Vietnam. The management of CAT is complex, with several challenges, including a high risk of bleeding and thrombosis, treatment burden, and low treatment motivation due to the short life expectancy of patients. Another challenge in CAT management is the low awareness among local physicians regarding CAT. The introduction of direct oral anticoagulants, which offer a better risk–benefit profile compared to conventional anticoagulation, has brought about a revolution in CAT management. To address these challenges, a group of 14 experts, including cardiologists and oncologists, convened in January 2023 to discuss and provide comprehensive information on CAT management in Vietnam, along with recommendations to optimize clinical outcomes. This review will encompass the available evidence in the medical literature and the expert opinions derived from the meeting.

Quality of Oral Anticoagulation with Vitamin K Antagonists and Direct Oral Anticoagulants in ‘real-World’ Patients: Lessons from a Five Years Audit Study

Background: Even with the introduction of direct oral anticoagulants (DOACs), anticoagulation clinics (ACs) stand with a key role in monitoring. Indeed, routine evaluation by health care professionals is recommended as it is with vitamin K antagonists (VKA) with adjustments in practices of anticoagulation management services. Quality of oral anticoagulation (QOA) is associated to better clinical outcomes in those patients with indications for such therapy. It is well established that patients receiving VKA therapy, maintenance of an international normalized ratio (INR) in the therapeutic range is essential for treatment efficacy and safety. It has been reported that ACs should aim for a time in therapeutic range (TTR) between 70-80% to optimize benefit and minimize the risk of adverse events. So far, QOA for DOACs is not fully established. Aim: Since few clinical data are available considering the new era of ACs, this study aims to describe actual trends and QOA of an AC at a large academic medical hospital. Methodology: We retrospectively analyzed 23275 appointments of 5 consecutive years (May 2018 to May 2023), corresponding to 930 patients that are regularly followed up at an outpatient AC of a central hospital under anticoagulation for at least 8 weeks. TTR (≥70%) determined by Rosendaal method was used for patients under AVK and for those individuals in DOACs, QOA was considered the presence of therapeutic plasma levels of the drugs after the European Heart Rhythm Association 2021 in, at least, one determination. Patients were divided according to target INR in 3 groups: Group 1 with target INR 2-3, including 809 patients mean age 65±18 years (mean±SD), majority (36.6%) with atrial fibrillation (AF); Group 2 with target INR 2.5-3.5, including 92 patients with mean age 70±11 years, majority (85.9%) with mechanical heart valves; Group 3 with target INR 3-4, including 29 patients with mean age 63±15 years, majority (55.5%) with antiphospholipid syndrome. Seventy patients were under DOACs (apixaban in 74.3%), with mean age of 71±17 years, majority (62.9%) with non-valvular AF, were included in Group 1 and all individuals were under direct inhibitors of factor Xa. Descriptive statistics (mean, standard deviation, minimum, maximum, chi-square), inferential statistics (t-test, A-Nova and effect sizes) tests were performed. Results: The 930 patient population, 52.2% female, mean age of 65±18 years and 87% in Group 1, showed a mortality of 17%. The mean recall interval between appointments was superior to 90 days in 94% of the population. The individuals who died in comparison with the survivors showed higher frequency of AF (54.1%) [ χ 2= 47.099; p<.001; φ=.225], were from Group 1 (93%) [ χ 2= 6.641; p=.036; φ=.085], male (59.2%) [ χ 2= 10.103; p=.001; φ=-.104] and older [76±12 vs .63±18 years (p<.001), respectively]. No differences were noticed in mortality between AVK and DOACs [ χ 2= 1.828; p=.401; φ=-.044], even DOAC patients being older than AVK patients (71±17 vs 65±17; p=.005), respectively. QOA associated with mortality being the individuals who died with higher frequency of no QOA (21.9% vs 13.9%) [ χ 2= 8.126; p=.004; φ=-.101] respectively. The individuals on AVK from Group 1 corresponding to 86% of total population showed a mean TTR of 76%, patients from Group 2 had a TTR of 72% and patients in Group 3 had TTR of 55%. From the individuals under DOACs, only 30% had at least one determination of plasma levels of the drug and all but one showed therapeutic levels. Comparatively with our previous studies related to the periods of 2006-2012 and 2012-2018, we noticed a significant decrease in patient population / appointments size (2087/ 61988) (1587/ 37931),(p <.001) with an increase of TTR in Group 1 (1927/1430 patients) (83% /72%) and Group 2 (120/125 patients) (74% / 69%) but a TTR decrease in Group 3 (40 / 32 patients) (54% / 60%) (p <.001). respectively. Mortality in the 2012- 2018 period was 18%. Conclusions and Discussion: The trends of decreasing the number of anticoagulated patients at our AC with an overall good quality of monitoring but with a low percentage of individuals under DOACs suggests that the majority of anticoagulated population is on these drugs without routine follow up in opposition to the recent recommendations. Our study underlines the importance of the quality of anticoagulation monitoring on mortality that was no different from the previous years before SARS-CoV- 2 pandemic nor between AVK and DOACs.

Abstract 17633: Age and Racial Disparities in Gastrointestinal Bleeding Incidence Among Atrial Fibrillation Patients on Direct Oral Anticoagulants: A Retrospective Cohort Study

Introduction: Atrial fibrillation (Afib), a major cause of morbidity and mortality, particularly affects the elderly. Direct oral anticoagulants (DOACs), despite being the preferred stroke risk reduction treatment in Afib patients, often result in gastrointestinal bleeding. This study aims to examine the incidence of this side effect across age and racial groups. Hypothesis: The risk of gastrointestinal bleeding while on DOACs increases with age. Racial variation in GI bleeding in Afib patients taking DOACs exists due to non-modifiable and modifiable risk factors. Methods: Utilizing the 'All of Us' national database, we conducted a retrospective cohort study of 6,961 Afib patients who started DOACs from 2018 to 2023. EHR data including ICD-9/10 codes and medication history were used to conduct the analysis. Patients who developed gastrointestinal bleeding after the introduction of DOACs within this period were identified. Incidence rates were further analyzed according to age and race. Results: Out of 6,961 Afib patients on DOACs, 791 developed gastrointestinal bleeding (21.9 cases per 1000 person-year). The incidence rate was highest among patients aged under 50 years (36.8 cases per 1000 person-year) and those over 80 years (24.0 cases per 1000 person-year). Patients aged 60-70 years had the lowest incidence rate (19.7 cases per 1000 person-year). Racial analysis revealed African-Americans had the highest incidence rates (29.3 cases per 1000 person-year), followed by Asians (21.9 cases per 1000 person-year), and Whites (19.6 cases per 1000 person-year; p<0.001). Conclusions: Our study revealed a bimodal peak in GI bleeding incidence in patients on DOACs for Afib, with heightened risk in those under 50 years and above 80 years. Racial disparities were also evident, with African-Americans at the highest risk. These findings underscore the need for further research to elucidate risk factors, particularly in younger patients and specific racial groups.

Safety of Direct Oral Anticoagulants for Gastrointestinal Hemorrhage in Patients With Nonvalvular Atrial Fibrillation: A Systematic Review and Meta-analysis of Real-world Studies.

Since the introduction of Direct Oral Anticoagulants (DOACs), "real-world" studies have investigated their safety profile on gastrointestinal hemorrhage (GIH) when used by patients with Non-Valvular Atrial Fibrillation. We performed a systematic review and meta-analysis to compile and summarize this data after Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Medline and Embase were systematically searched until April 2021. Observational studies that met predefined inclusion criteria were included and hazard ratios (HRs) with 95% CI were extracted. Subgroup analyses based on DOAC doses, history of chronic kidney disease, stroke, prior exposure to VKA (vitamin K antagonist), age, gender, geographic location of population samples, as well as Leave-One-Out and Low/Moderate Risk of Bias sensitivity analyses were performed. A random effects model was used. A total of 46 studies were included. Apixaban was associated with a reduced risk of GIH compared with Dabigatran (HR: 0.67, 95% CI, 0.56 to 0.81, I2 : 53.28%), Rivaroxaban (HR: 0.56, 95% CI, 0.44 to 0.70, I2 : 79.17%), and VKA (HR: 0.68, 95% CI, 0.60 to 0.78, I2 : 71.93%). Rivaroxaban was associated with increased GIH risk compared with Dabigatran (HR: 1.19, 95% CI, 1.02 to 1.40, I2 : 72.96%) and VKA (HR: 1.16, 95% CI, 1.05 to 1.27, I2 : 81.95%). Dabigatran was associated with similar GIH risk compared with VKA (HR: 1.11, 95% CI, 0.98 to 1.26, I2 : 87.28%). Our study shows that Apixaban was associated with a reduction in GIH risk compared with Dabigatran, Rivaroxaban and VKA, whereas Rivaroxaban was associated with an increase in GIH risk compared with both Dabigatran and VKA.

Changes in anticoagulation practice in subjects admitted with stroke associated with atrial fibrillation, following introduction of direct oral anticoagulants over 2013-2021.

The adoption of direct oral anticoagulants (DOACs) has changed practice in prevention of stroke in atrial fibrillation (AF). We used Irish data national data on stroke and anticoagulation therapy over 9 years to investigate changes in anticoagulation practice and potential consequences on stroke prevalence and thrombolysis. AF, anticoagulation, thrombolysis, and stroke data from the Irish National Audit of Stroke (INAS) 2013-2021 were reviewed. The proportion of patients with ischemic stroke (IS) and intracerebral hemorrhage (IH) with known AF admitted on anticoagulation was determined. Effects on age distribution in the population and thrombolysis practice were assessed. AF data were available on 34,630 of 35,241 individuals (98.3%) included in INAS; median age was 74 years and 56% were male. AF was found in 10,016 (28.9%, 9059 IS, 957 IH). 6313 had known AF prior to stroke (63.1%). The proportion all total IS due to AF decreased by 15.3% (31.3%-26.5%, chi-square = 24.6, p < 0.0001). The proportion of IH did not change significantly (21.6%-20.2%, chi-square = 1.8, p = 0.18). Over the 9 years, 3875 (38.6%) of the subjects with AF were recorded as receiving anticoagulants at admission. In 2013, 4.4% of AF-associated strokes were admitted on a DOAC and 21.4% on warfarin; by 2021, 44.1% were receiving a DOAC and 6.2% warfarin. There was a strong inverse correlation between the proportion of anticoagulated stroke patients and the total proportion of AF-associated strokes over time (r = -0.82, p = 0.006). In contrast, no correlation was found between increasing DOAC usage and IH (r = 0.14, p = 0.71). Increased anticoagulation usage correlated with a reduction in patients ⩾ 80 years (r = -0.83, p = 0.006) and also correlated with a relative reduction of 30.1% in subjects thrombolysed <4 h from onset (r = -0.89, p = 0.001). DOACs have led to increased use of anticoagulation, but warfarin use fell by two-thirds. There has been a reduction in the proportion of AF-associated IS without a noticeable increase in IH. Increased anticoagulation correlated with reduced numbers of strokes in those >80 years and in the proportion of patients thrombolysed.

Recommendations for the use of andexanet alfa in the management of bleeding in patients on oral factor Xa inhibitors in Switzerland: Guideline from the Working Party Hemostasis of the Swiss Society of Hematology

Anticoagulants are essential in preventing and treating thrombosis. Unfortunately, their use is accompanied by an enhanced risk of bleeding. Since the introduction of direct oral anticoagulants (DOACs), the risk of major bleeding has been reduced but not eliminated. Major bleeding events related to the use of factor Xa inhibitors can be challenging to manage. In recent years, four-factor prothrombin complex concentrates have been used in patients with severe bleeding taking oral direct factor Xa inhibitors (apixaban, edoxaban and rivaroxaban). Andexanet alfa (OndexxyaTM, AstraZeneca AG) is a specially designed recombinant version of human factor Xa that acts as a decoy receptor to reverse the effects of factor Xa inhibitors. Since 2 December 2020, andexanet alfa has been used in Switzerland for adult patients receiving apixaban or rivaroxaban when reversal of anticoagulation is required because of life-threatening or uncontrolled bleeding. However, the use of andexanet alfa remains a challenge owing to its cost, the reported thrombotic complications and the fact that its efficacy mainly relates to intracranial haemorrhage. Moreover, the use of nonspecific reversal agents together with andexanet alfa is controversial. The present recommendations on the use of andexanet alfa in the management of bleeding in patients on factor Xa inhibitors in Switzerland were developed by a group of Swiss experts from the Working Party Hemostasis of the Swiss Society of Hematology. These recommendations aim to provide support to clinicians in their decision-making in the management of patients with major bleeding receiving factor Xa inhibitors.

Heterogeneity after harmonisation: A retrospective cohort study of bleeding and stroke risk after the introduction of direct oral anticoagulants in four Western European countries.

Database heterogeneity can impact effect estimates. Harmonisation provided by common protocols and common data models (CDMs) can increase the validity of pharmacoepidemiologic research. In a case study measuring the changes in the safety and effectiveness of stroke prevention therapy after the introduction of direct oral anticoagulants (DOACs), we performed an international comparison. Using data from Stockholm, Denmark, Scotland and Norway, harmonised with a common protocol and CDM, two calendar-based cohorts were created: 2012 and 2017. Patients with a diagnosis code of atrial fibrillation 5 years preceding the 1-year cohort window were included. DOAC, vitamin K antagonist and aspirin treatment were assessed in the 6 months prior to the start of each year while strokes and bleeds were assessed during the year. A Poisson regression generated incidence rate ratios (IRRs) to compare outcomes from 2017 to 2012 adjusted for changes in individual-level baseline characteristics. In 280 359 patients in the 2012 cohort and 356 779 in the 2017 cohort, treatment with OACs increased on average from 45% to 65%, while treatment with aspirin decreased from 30% to 10%. In all countries except Scotland, there were decreases in the risk of stroke and no changes in bleeding risk, after adjustment for changes in baseline characteristics. In Scotland, major bleeding (IRR 1.09, 95% confidence interval [CI] [1.00; 1.18]) and intracranial haemorrhage (IRR 1.31, 95% CI [1.13; 1.52]) increased from 2012 to 2017. Stroke prevention therapy improved from 2012 to 2017 with a corresponding reduction in stroke risk without increasing the risk of bleeding in all countries, except Scotland. The heterogeneity that remains after methodological harmonisation can be informative of the underlying population and database.

Trends in Treatment Patterns and Outcomes of Patients With Pulmonary Embolism in Japan, 2010 to 2020: A Nationwide Inpatient Database Study.

Background The impact of major changes in the treatment practice of pulmonary embolism (PE), such as limited indications for systemic thrombolysis and the introduction of direct oral anticoagulants, is not well documented. This study aimed to describe annual trends in the treatment patterns and outcomes in patients with PE. Methods and Results Using the Japanese Diagnosis Procedure Combination inpatient database from April 2010 to March 2021, we identified hospitalized patients with PE. Patients with high-risk PE were defined as those admitted for out-of-hospital cardiac arrest or who received cardiopulmonary resuscitation, extracorporeal membrane oxygenation, vasopressors, or invasive mechanical ventilation on the day of admission. The remaining patients were defined as patients with non-high-risk PE. The patient characteristics and outcomes were reported with fiscal year trend analyses. Of 88 966 eligible patients, 8116 (9.1%) had high-risk PE, and the remaining 80 850 (90.9%) had non-high-risk PE. Between 2010 and 2020, in patients with high-risk PE, the annual proportion of extracorporeal membrane oxygenation use significantly increased from 11.0% to 21.3%, whereas that of thrombolysis use significantly decreased from 22.5% to 15.5% (P for trend <0.001 for both). In-hospital mortality significantly decreased from 51.0% to 43.7% (P for trend=0.04). In patients with non-high-risk PE, the annual proportion of direct oral anticoagulant use increased from 0.0% to 38.3%, whereas that of thrombolysis use significantly decreased from 13.7% to 3.4% (P for trend <0.001 for both). In-hospital mortality significantly decreased from 7.9% to 5.4% (P for trend <0.001). Conclusions Substantial changes in the PE practice and outcomes occurred in patients with high-risk and non-high-risk PE.

Direct Oral Anticoagulants: How Do These Drugs Work, How to Monitor, and What Is Their Role in Orthopaedic Surgery.

Postoperative venous thromboembolism is a major adverse event associated with orthopaedic surgery. With the addition of perioperative anticoagulation and antiplatelet therapy, the rates of symptomatic venous thromboembolism have dropped to 1% to 3%, and as such, practicing orthopaedic surgeons must be familiar with these medications, including aspirin, heparin, or warfarin, and the use of direct oral anticoagulants (DOACs). DOACs are increasingly being prescribed due to their predictable pharmacokinetics and increased convenience, as they do not require routine monitoring, and 1% to 2% of the general population is currently anticoagulated. Although the introduction of DOACs has yielded additional treatment options, this has also led to confusion and uncertainty regarding treatment, specialized testing, and when and what reversal agents are appropriate. This article provides a basic overview of DOAC medications, their suggested use in the perioperative setting, effects on laboratory testing, and consideration for when and how to use reversal agents in orthopaedic patients.

Trends in the Use of Oral Anticoagulants for Adults With Venous Thromboembolism in the US, 2010-2020

The introduction of direct oral anticoagulants (DOACs) has transformed the treatment of venous thromboembolism (VTE). Large health care databases offer valuable insight into how oral anticoagulants (OACs) are used in clinical practice and may aid in understanding reasons for changes in therapy. To evaluate prescribing patterns of OACs for patients with VTE and identify clinical events that precede treatment changes. This retrospective cohort study used data from a public (Medicare fee-for-service) and a commercial (IBM MarketScan) health insurance database on 298 609 patients initiating OACs within 90 days of index VTE hospitalization from January 1, 2009, to December 31, 2020. Statistical analysis was conducted from April to August 2022. Warfarin and the DOACs rivaroxaban, apixaban, dabigatran, and edoxaban. Characteristics of patients initiating different OACs, along with trends over time of patients initiating OACs, were compared. Time receiving continuous anticoagulant therapy, patterns of anticoagulant discontinuation (treatment gap of ≥30 days), and treatment switches were assessed. Clinical events in the 30 days preceding treatment modifications were identified. A total of 203 378 individuals with Medicare (mean [SD] age, 76.9 [7.6] years; 122 554 women [60.3%]) and 95 231 with commercial insurance (mean [SD] age, 57.6 [15.8] years; 47 139 women [49.5%]) were included (N = 298 609). Warfarin was the most frequent OAC prescribed (163 044 [54.6%]), followed by rivaroxaban (66 882 [22.3%]) and apixaban (65 997 [22.1%]). The proportion of patients initiating DOACs increased from 0% in 2010 to 86.8% (22 420 of 25 817) in 2019 for patients with Medicare and 92.1% (4012 of 4357) in 2020 for commercially insured patients. Patients with chronic kidney disease were more likely to initiate warfarin (35 561 [11.9%]) or apixaban (16 294 [5.5%]) than rivaroxaban (10 136 [3.4%]), and those with a history of bleeding were more likely to initiate apixaban (5424 [1.8%]) than rivaroxaban (3007 [1.0%]). Overall, patients received persistent OAC treatment for approximately 6 months (Medicare: median, 175 days [IQR, 76-327 days]; commercial insurance: median, 168 days [IQR, 83-279 days]). A total of 33 011 patients (11.1%) switched anticoagulant therapy within a year. Switching to another anticoagulant was preceded most frequently by codes for a VTE diagnostic procedure (27.2% of all switchers [8983 of 33 011]). This cohort study using data from 2 US health insurance databases suggests that most patients with VTE continued oral anticoagulant treatment for approximately 6 months. Clinical reasons for modifying anticoagulant therapy were identified in one-third of patients. Identifying reasons for treatment modification is crucial for generating valid evidence on drug safety and effectiveness.

Sex Differences in Oral Anticoagulation Therapy in Patients Hospitalized With Atrial Fibrillation: A Nationwide Cohort Study.

Background Important disparities in the treatment and outcomes of women and men with atrial fibrillation (AF) are well recognized. Whether introduction of direct oral anticoagulants has reduced disparities in treatment is uncertain. Methods and Results All patients who had an incident hospitalization from 2010 to 2019 with nonvalvular AF in Scotland were included in the present cohort study. Community drug dispensing data were used to determine prescribed oral anticoagulation therapy and comorbidity status. Logistic regression modeling was used to evaluate patient factors associated with treatment with vitamin K antagonists and direct oral anticoagulants. A total of 172 989 patients (48% women [82 833 of 172 989]) had an incident hospitalization with nonvalvular AF in Scotland between 2010 and 2019. By 2019, factor Xa inhibitors accounted for 83.6% of all oral anticoagulants prescribed, while treatment with vitamin K antagonists and direct thrombin inhibitors declined to 15.9% and 0.6%, respectively. Women were less likely to be prescribed any oral anticoagulation therapy compared with men (adjusted odds ratio [aOR], 0.68 [95% CI, 0.67-0.70]). This disparity was mainly attributed to vitamin K antagonists (aOR, 0.68 [95% CI, 0.66-0.70]), while there was less disparity in the use of factor Xa inhibitors between women and men (aOR, 0.92 [95% CI, 0.90-0.95]). Conclusions Women with nonvalvular AF were significantly less likely to be prescribed vitamin K antagonists compared with men. Most patients admitted to the hospital in Scotland with incident nonvalvular AF are now treated with factor Xa inhibitors and this is associated with fewer treatment disparities between women and men.

JAHA Go Red for Women Spotlight 2023.

JAHA Go Red for Women Spotlight 2023.

Trend of anticoagulant therapy in elderly patients with atrial fibrillation considering risks of cerebral infarction and bleeding

The introduction of direct oral anticoagulants (DOACs) has greatly changed the use of anticoagulant therapy in patients with non-valvular atrial fibrillation (Af). Therefore, this study aimed to examine changes in the proportions of oral anticoagulant prescriptions in patients with non-valvular Af aged ≥ 65 years, taking into consideration the risk of cerebral infarction and bleeding. Anticoagulant prescriptions in outpatients aged ≥ 65 years with Af were temporally analyzed using the nationwide claims database in Japan. Trends in anticoagulant prescriptions were examined according to cerebral infarction and bleeding risk. The proportion of anticoagulant prescriptions for 12,076 Af patients increased from 41% in 2011 to 56% in 2015. An increase in DOAC prescriptions was accompanied by an increase in the proportion of anticoagulant prescriptions in each group according to the CHA2DS2-VASc and HAS-BLED scores. The proportion of anticoagulant prescriptions for patients with a high risk of developing cerebral infarction and bleeding showed a marked increase. Trends in anticoagulant prescriptions in Af patient with a CHA2DS2-VASc score ≥ 2 and HAS-BLED scores ≥ 3 showed a marked increase in DOAC prescriptions. The widespread use of DOACs greatly changes the profile the prescription of anticoagulant therapy in patients with Af.

Trends in Use of Oral Anticoagulants in Older Adults With Newly Diagnosed Atrial Fibrillation, 2010-2020

Undertreatment of older adults with atrial fibrillation with anticoagulation therapy is an important practice gap. It has been posited that the availability of direct oral anticoagulants (DOACs) would improve oral anticoagulant (OAC) initiation in older adults with atrial fibrillation given their superior safety profile compared with warfarin. To systematically examine trends in OAC initiation and nonadherence in older adults with atrial fibrillation and coexisting geriatric conditions. This retrospective cohort study uses administrative claims data from Optum's Clinformatics Data Mart from January 1, 2010, to December 31, 2020. Participants included beneficiaries of Medicare Advantage plans aged 65 years and older with atrial fibrillation and elevated risk of ischemic stroke. Data analysis was performed from October 2021 to October 2022. Coexisting dementia, frailty, and anemia. The primary outcomes were OAC initiation within 12 months after the first diagnosis of atrial fibrillation per year and nonadherence with OAC per year (defined as <80% of proportion of days covered among patients newly started on OAC in each year). There were 21 603 to 51 236 patients per year (total for 2010-2020, 381 488 patients) in the OAC-eligible incident AF cohort (mean [SD] age, 77.2 [6.1] to 77.4 [6.8] years; 13 871 [51.8%] to 22 901 [49.8%] women). OAC initiation within 12 months after incident AF increased from 20.2% (5405 of 26 782 patients) in 2010 to 32.9% (7111 of 21 603 patients) in 2020. DOAC uptake increased from 1.1% (291 of 26 782 patients) to 30.9% (6678 of 21 603 patients), and warfarin initiation decreased from 19.1% (5114 of 26 782 patients) to 2.0% (436 of 21 603 patients). Older age (odds ratio [OR], 0.98; 95% CI, 0.98-0.98), dementia (OR, 0.57; 95% CI, 0.55-0.58), frailty (OR, 0.74; 95% CI, 0.72-0.76), and anemia (OR, 0.75; 95% CI, 0.74-0.77) were associated with lower odds of OAC initiation. During the study period, the median (IQR) proportion of days covered increased from 77.6% (41.0%-96.4%) to 90.2% (57.4%-98.6%), and OAC nonadherence decreased from 52.2% (2290 of 4389 patients) to 39.0% (3434 of 8798 patients). Since the introduction of DOACs, OAC initiation in older adults with has improved but remained suboptimal in 2020. Additional strategies are needed to improve stroke prophylaxis in all older adults with atrial fibrillation including those with coexisting dementia, frailty, and anemia.

Sex-differences in oral anticoagulation therapy in patients hospitalised with atrial fibrillation: a nationwide cohort study

Abstract Background Important disparities in the treatment and outcomes of women and men with atrial fibrillation are well recognized. Whether introduction of direct oral anticoagulants has reduced disparities in treatment is uncertain. Methods All patients who had an incident hospitalization from 2010 to 2019 with non-valvular atrial fibrillation in Scotland were included in this cohort study. Community drug dispensing data were used to determine prescribed oral anticoagulation therapy and comorbidity status. Logistic regression modelling was used to evaluate patient factors associated with treatment with vitamin K antagonists and direct oral anticoagulants. Results A total of 172,989 patients (48% women [82,833/172,989]) had an incident hospitalization with non-valvular atrial fibrillation in Scotland between 2010 and 2019. The proportion of patients with thromboembolic risk factors (CHA2DS2VASc score &amp;gt;0 in men and &amp;gt;1 in women) treated with oral anticoagulation therapy increased from 36.8% to 66.3% over this 10-year period. By 2019, factor Xa inhibitors accounted for 83.6% of all oral anticoagulants prescribed, while treatment with vitamin K antagonists and direct thrombin inhibitors declined to 15.9% and 0.6%, respectively. Women were less likely to be prescribed any oral anticoagulation therapy compared to men (adjusted odds ratio, aOR 0.68 [95% CI, CI 0.67–0.70]). This disparity was mainly attributed to vitamin K antagonists (aOR 0.68 [95% CI 0.66–0.70]), whilst there was less disparity in use of factor Xa inhibitors between women and men (aOR 0.92 [95% CI 0.90–0.95]). At 1 year following hospitalization with atrial fibrillation, patients not prescribed oral anticoagulation therapy were more likely to have subsequent major adverse cardiovascular events compared to those prescribed with oral anticoagulation therapy (38.8% [15,380/39,608] versus 17.0% [6,761/39,671] in women and 35.2% [12,977/36,868] versus 16.4% [7,395/45,093] in men). Conclusions Women with non-valvular atrial fibrillation were significantly less likely to be prescribed vitamin K antagonists compared to men. Most patients admitted to hospital in Scotland with incident non-valvular atrial fibrillation are now treated with factor Xa inhibitors and this is associated with less treatment disparities between women and men. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This study was supported by the British Heart Foundation through a Clinical Research Training Fellowship (FS/18/25/33454), Intermediate Clinical Research Fellowship (FS/19/17/34172), Senior Clinical Research Fellowship (FS/16/14/32023) and a Research Excellence Award (RE/18/5/34216), and a research grant to NHS Lothian from Bristol Myers Squibb Pharmaceuticals Ltd and Pfizer UK Ltd.

Trends in oral anticoagulant prescription in patients with nonvalvular atrial fibrillation in Flanders and the impact of switching patients from vitamin K antagonists to DOACS in terms of the burden caused by complications of the disease: a registry-based study

ABSTRACT Context Since the introduction of direct oral anticoagulants (DOACs) for the treatment of nonvalvular atrial fibrillation (Afib), oral anticoagulants (OACs) prescription has evolved. Aim We aim first to explore the OACs prescription behaviour in Flanders from 2002 to 2019 before exploring the impact of switching patients from vitamin K antagonists (VKAs) to DOACs in terms of the burden caused by stroke as a complication of non-valvular Afib. Methods Data were obtained from INTEGO, a Flemish, general practice-based morbidity registration network. Comprised patients had at least one visit to their GP per year between 2002 and 2019 and a follow-up of at least 1 year after the diagnosis of Afib. Public prices were retrieved from the Belgian Centre for Pharmacotherapeutic Information (BCFI) and the National Institute for Health and Disability Insurance (RIZIV/ INAMI) sites. The number of Disability-Adjusted Life Years (DALYs) was based on the Global Burden of Disease (GBD) literature. The calculation of the Number Needed to Switch (NNSw) was the basis for conducting cost-utility analyses accounting for the global benefit in terms of the cost of prevented stroke/DALY and the cost of switching Flemish ≥ 65 years patients from VKAs to DOACs in two scenarios. Results Increased DOAC use has been observed since 2012. The incremental cost effectiveness ratios (ICERs) yielded 553 to 824 €/DALY of prevented stroke. Conclusion In this registry-based study, we found a significant positive trend in OAC use in Flanders between 2002 and 2019. Switching to DOACs seems cost-effective compared to a threshold of 20000€/DALY.

A ten-year review of the impact of the transition from warfarin to direct oral anticoagulant – Has venous thromboembolism treatment become safer?

BackgroundThe introduction of direct oral anticoagulants (DOAC) has resulted in a paradigm shift in the management of venous thromboembolism (VTE). We evaluate the impact of the transition to DOAC, over the last decade, on overall VTE clinical outcomes including in first unprovoked major VTEs. MethodA retrospective analysis of all VTE admissions in non-cancer patients from January 2011 to December 2020 at Northern Health, Victoria, Australia. “Warfarin era” included events that occurred between January 2011 and December 2014 and “DOAC era” from January 2016. ResultsThere were 2687 cases involving 2508 patients (45.9 % males; median age 63 years). 98 % were symptomatic and 1261 events (47 %) were unprovoked. 1003 events occurred during the warfarin era (79 % warfarin, 6 % DOAC) and 1479 during the DOAC era (18 % warfarin, 70 % DOAC). While recurrent thrombosis during the acute phase of treatment was comparable, there were fewer recurrences during the long-term preventative phase of treatment in the DOAC era compared to warfarin era (HR 0.602, 95 % CI: 0.393–0.924, p0.020). Clinically significant bleeding events were lower in the DOAC era (HR 0.623, 95 % CI: 0.395–0.985, p = 0.043). A subanalysis of first unprovoked major VTE events (n = 602) demonstrated a significant reduction in recurrent VTE during the long-term preventative phase of treatment in the DOAC era (HR 0.296, 95 % CI: 0.097–0.901, p = 0.032) with no difference in clinically significantly bleeding rates (HR 0.529, 95 % CI 0.219–1.280, p = 0.158) between the eras. ConclusionTreatment outcomes for VTE appear to have improved over time with reduced rate of thrombotic and clinically significant bleeding complications in the DOAC era.

Evolving Knowledge on Primary and Secondary Prevention of Venous Thromboembolism in Carriers of Hereditary Thrombophilia: A Narrative Review

The association between heritability of venous thromboembolism (VTE) and thrombophilia was first reported clinically in 1956, later followed by the first description of a congenital cause of hypercoagulability-antithrombin deficiency-in 1965. Since then, our knowledge of hereditary causes of hypercoagulability, which may predispose carriers to VTE has improved greatly. Novel genetic defects responsible for severe thrombophilia have been recently identified and we have learned that a wide range of interactions between thrombophilia and other genetic and acquired risk factors are important determinants of the overall individual risk of developing VTE. Furthermore, therapeutic strategies in thrombophilic patients have benefited significantly from the introduction of direct oral anticoagulants. The present review is an overview of the current knowledge on the mechanisms underlying inherited thrombophilia, with a particular focus on the latest achievements in anticoagulation protocols and prevention strategies for thrombosis in carriers of this prothrombotic condition.