Direct Oral Anticoagulants Prescription Research Articles

Predictors of adherence to direct oral anticoagulants after cardiovascular or bleeding events in Medicare Advantage Plan enrollees with atrial fibrillation.

Direct oral anticoagulants (DOACs) are recommended for patients with atrial fibrillation (AF) given their improved safety profile. Suboptimal adherence to DOACs remains a significant concern among individuals with AF. However, the extent of adherence to DOACs following a cardiovascular or bleeding event has not been fully evaluated. To evaluate the pattern of adherence trajectories of DOACs after a cardiovascular or bleeding event and to investigate the sociodemographic and clinical predictors associated with each adherence trajectory by using claims-based data. This retrospective study was conducted among patients with AF prescribed with DOACs (dabigatran/apixaban/rivaroxaban) between July 2016 and December 2017 and who were continuously enrolled in the Texas-based Medicare Advantage Plan. Patients who experienced a cardiovascular or bleeding event while using the DOACs were further included in the analysis. The sample was limited to patients who experienced a clinical event such as a cardiovascular or bleeding event while using the DOACs. The clinical events considered in this study were cardiovascular (stroke, congestive heart failure, myocardial infarction, systemic embolism) and bleeding events. To assess adherence patterns, each patient with a DOAC prescription was followed up for a year after experiencing a clinical event. The monthly adherence to DOACs after these events was evaluated using the proportion of days covered (PDC). A group-based trajectory model incorporated the monthly PDC to classify groups of patients based on their distinct patterns of adherence. Predictors associated with each trajectory were assessed using a multinomial logistic regression model, with the adherent trajectory serving as the reference group in the outcome variable. Among the 694 patients with AF who experienced clinical events after the initiation of DOACs, 3 distinct adherence trajectories were identified: intermediate nonadherent (30.50%), adherent (37.7%), and low adherent (31.8%); the mean PDC was 0.47 for the intermediate nonadherent trajectory, 0.93 for the adherent trajectory, and 0.01 for low adherent trajectory. The low-income subsidy was significantly associated with lower adherence trajectories (odds ratio [OR] = 4.81; 95% CI = 3.07-7.51) and with intermediate nonadherent trajectories (OR = 1.57; 95% CI = 1.06-2.34). Also, nonsteroidal anti-inflammatory drug use was significantly associated with lower adherence trajectories (OR = 5.10; 95% CI = 1.95-13.36) and intermediate nonadherent trajectories (OR = 3.17; 95% CI = 1.26-7.93). Other predictors significantly associated with both nonadherent trajectories are type of DOACs (OR = 0.53; 95% CI = 0.35-0.79), presence of coronary artery disease (OR = 1.89; 95% CI = 1.01-3.55), and having 2 or more clinical events (OR = 1.65; 95% CI = 1.09-2.50). Predictors identified provide valuable insights into the suboptimal adherence of DOACs among Medicare Advantage Plan enrollees with AF, which can guide the development of targeted interventions to enhance adherence in this high-risk patient population.

Inappropriate Underdosing of Direct Oral Anticoagulants in Atrial Fibrillation Patients: Results from the START2-AF Registry.

Background: Direct oral anticoagulants (DOACs) are recommended for stroke prevention in non-valvular atrial fibrillation (NVAF) patients. We aimed to describe the prevalence of inappropriate DOACs dose prescription in the START2-AF Registry, the outcomes according to the appropriateness of the dosage, and the factors associated with inappropriate dose prescription. Methods: Patients' demographics and clinical data were prospectively collected as electronic files in an anonymous form on the website of the START2-Registry; DOACs dosage was determined to be appropriate when prescribed according to the European Heart Rhythm Association Guidelines. Results: We included 5943 NVAF patients on DOACs; 2572 (46.3%) were female patients. The standard dose (SD) was prescribed to 56.9% of patients and the low dose (LD) was prescribed to 43.1% of patients; 38.9% of all NVAF patients received an inappropriate LD DOAC and 0.3% received inappropriate SD. Patients treated with LD DOAC had a significantly higher rate of all bleedings (RR 1.5; 95% CI 1.2-2.0), major bleedings (RR 1.8; 95% CI 1.3-1.7), and mortality (RR 2.8; 95% CI 1.9-4.1) with respect to patients treated with SD DOAC. No difference was found among patients treated with appropriate and inappropriate LD regarding bleeding, thrombotic, and mortality rates. Age, body weight <60 kg, and renal failure were significantly associated with inappropriate LD DOAC prescription. Conclusions: Inappropriate LD DOACs in NVAF patients is not associated with a reduction in bleeding risk, nor with an increased thrombotic risk. Instead, it is associated with higher mortality rate, suggesting that, in clinical practice, underdosing is preferred for patients at particularly high risk for adverse events.

Appropriateness of direct oral anticoagulant prescribing in older subjects with atrial fibrillation discharged from acute medical wards.

Knowledge on the prescriptive practice of direct oral anticoagulants (DOACs) in older subjects with atrial fibrillation (AF) hospitalized in acute medical wards is limited. This study aimed to evaluate the prevalence and appropriateness of DOAC prescriptions in hospitalized older subjects with AF, discharged from acute medical wards. We analysed a cohort of 609 subjects with AF, aged ≥65 years (mean age 85 years) enrolled from 39 geriatric and nephrology wards in Italy. DOAC prescriptive appropriateness was evaluated according to the summary of product characteristics (smPC), 2019 Beers and STOPP criteria, and drug-drug interactions (DDIs). At hospital discharge, 33% of patients with AF were prescribed with DOAC, 26% with vitamin-K antagonist, while 41% did not receive any anticoagulant. Among subjects on DOAC therapy, 31% presented a violation of the smPC criteria (mainly underdosage-17%), while 48% and 18% presented a Beers/STOPP inappropriate prescription, or a DDI, respectively. Older age, lower body mass index (BMI), cancer and higher estimated glomerular filtration rate (eGFR) were independently associated with DOAC underdosage or missed prescription (age: adjusted odds ratio [aOR] 1.06, 95% confidence interval [95% CI] 1.00-1.12 for underdosage; eGFR: aOR 1.04, 95% CI 1.02-1.07 for underdosage; BMI: aOR 0.95, 95% CI 0.91-0.99 for missed prescription; cancer: aOR 1.93, 95% CI 1.19-3.13 for missed prescription). This study showed a suboptimal DOAC prescriptive practice in older in-patients, with frequent missed prescription and DOAC underdosage. Contrary to current recommendations, physicians appear overly concerned by bleeding risk in real-life older and frailer subjects. Strategies should be developed to promote appropriate DOAC prescription in the hospital setting.

Potential of Direct Oral Anticoagulant in Bleeding After Gastric Endoscopic Submucosal Dissection: A Systematic Review and Meta-Analysis.

An increasing number of patients are undergoing gastric endoscopic submucosal dissection (ESD) with active prescriptions of direct oral anticoagulants (DOACs). Only a few reports have described the effects of DOAC intake on postoperative bleeding. We aimed to investigate the bleeding risk associated with DOACs after gastric ESD. Clinical studies published up to April 2022 showing bleeding rates after gastric ESD in patients taking DOACs were identified using electronic searches. The primary outcome was the rate of bleeding after gastric ESD in patients receiving DOACs compared to those not receiving antithrombotic therapy. In this meta-analysis, odds ratios (ORs) were calculated and pooled using a random effects model. The secondary outcome was the difference in the bleeding rate between patients treated with DOACs and those treated with warfarin and antiplatelet drugs. Seven studies were included in this meta-analysis. The pooled analysis showed that DOACs had a higher bleeding rate than non-thrombotic therapy (17.0% vs. 3.4%; OR 5.72; 95% confidence interval [CI], 4.33-7.54; I2 = 0%). The bleeding risk associated with DOAC administration was similar to that associated with warfarin (17.0% vs. 20.0%; OR 0.83; 95% CI 0.59-1.18; I2 = 0%), whereas it was higher than that associated with antiplatelet administration (16.9% vs. 11.0%; OR 1.63; 95% CI 1.14-2.34; I2 = 8%). This meta-analysis reveals that the bleeding risk of DOACs is higher than that of non-antithrombotics and antiplatelets, whereas it is comparable to that of warfarin. Gastric ESD in patients on anticoagulants requires careful postoperative management.

Real-world Data on Treatment Patterns and Bleeding in Cancer-associated Thrombosis: Data from the TROLL Registry.

Background International guidelines are increasingly recommending direct oral anticoagulants (DOACs) as the first-line treatment for cancer-associated thrombosis (CAT). However, data regarding treatment patterns and adherence to guidelines in patients with CAT are scarce. Objectives This study aimed to explore anticoagulant treatment patterns in patients with CAT and to calculate the incidence rates of bleeding events. Methods Patients ≥18 years with active cancer and a first-time venous thromboembolism between 2005 and 2020 were identified through the Venous T hrombosis R egistry in Østf OL d Hospita L . Outcome measures were patterns of anticoagulant treatment during the study period and bleeding events. We calculated overall incidence rates per 100 person-years and 6- and 12-month cumulative incidence of major and clinically relevant nonmajor bleeding (CRNMB) during anticoagulant treatment. Results Median age of 842 CAT patients at the time of thrombosis was 69 years (interquartile range 61-77), and 443 (52.6%) were men. In total, 526 patients (62.5%) had pulmonary embolism and 255 (30.3%) had deep vein thrombosis. Low molecular weight heparin (LMWH) was prescribed to 713 (85.8%) patients, whereas 64 (7.7%) received DOACs and 54 (6.5%) received vitamin K antagonists as the initial anticoagulant treatment. Prescription of DOACs as initial treatment increased from 3.0% in 2013/2014 to 18.0% in 2019/2020. The incidence rate of major bleeding was 6.9 (95% confidence interval [CI] 5.2-9.2) and 10.1 (95% CI 8.0-12.9) in CRNMB. Conclusion Most patients were treated with LMWH. However, a gradual shift in treatment toward DOACs was observed. Overall, bleeding complications were rare and comparable to those reported in randomized trials.

Pharmacist-led interventions in optimising the use of oral anticoagulants in patients with atrial fibrillation in general practice in England: a retrospective observational study.

Oral anticoagulation (OAC) is the mainstay of treatment for the prevention of strokes in patients with atrial fibrillation (AF). Direct oral anticoagulants (DOACs) account for increasing OAC in patients with AF. However, prescribing DOACs for patients with established AF poses various challenges and general practice pharmacists may have an important role in supporting their management. To investigate the effectiveness of pharmacist-led interventions in general practice in optimising the use of OAC therapies in AF. A retrospective observational study in general practices in Bradford. The data were collected retrospectively from 1 November 2018-31 December 2019 using electronic health record data. The data were analysed: 1) to identify patients with AF not on OAC; 2) to describe inappropriate DOAC prescriptions; and 3) to calculate HAS-BLED scores. Overall, 76.3% (n = 470) of patients with AF received OAC therapy, and of these, 63.4% received DOACs. Pharmacist-led interventions increased DOAC prescribing by 6.0% (P = 0.03). Inappropriate DOAC use was identified in 24.5% of patients with AF, with underdosed and overdosed identified in 9.7% and 14.8%, respectively. Post-intervention, inappropriate prescribing was reduced to 1.7%. The mean HAS-BLED score decreased from 3.00 to 2.22 (P<0.01). Successful transition from vitamin K antagonist (VKA) therapy to DOACs was achieved in 25.7% of patients. Pharmacist-led interventions have successfully improved the use of OAC therapies in patients with AF, and effectively managed the bleeding risks and transition from VKA to DOAC therapy, in line with guidelines.

Extended Full Dose Versus Low Dose Direct Oral Anticoagulants in Cancer and Overweight Patients

Background: Reduced or low-dose direct oral anticoagulants (DOACs) have been studied in randomized control trials for the extended prevention of venous thromboembolism (VTE) after 6 months of treatment at full, therapeutic doses. The real-world effectiveness as well as utilization of this approach in clinical practice compared to continuing at therapeutic doses is unclear. Aims: Examine the effectiveness, safety and utilization of reduced-dose DOACs in cancer patients and overweight patients. Methods: Consecutive patients with VTE were identified using the Mayo Clinic VTE Registry from March 1st, 2013 to December 31st, 2021. Patients were followed prospectively for outcomes of VTE recurrence, death, major bleeding and clinically relevant non major bleeding (CRNMB) either in person or by survey. Patients with recurrent VTE or bleeding during the first 3 months were excluded from further analysis. After completion of anticoagulation treatment for 3 months with either rivaroxaban or apixaban, patients continuing anticoagulation were evaluated in a nested case-control study. Results: A total of 404 patients (283 (70%) on apixaban and 121 (30%) on rivaroxaban) were identified in the low dose DOAC and 3060 in the full dose anticoagulation group. Overall, the mean age was 60.7 years (SD 14.4), mean weight was 89.9 kg (SD 23.8) and 55.1% were males. Within the full cohort, patients with active cancer were less likely to be prescribed low dose DOACs (HR 0.56; 95%CI 0.42-0.73; p&amp;lt;0.001). However, low dose DOAC prescription was more likely in patients with pulmonary embolism alone (HR 1.48; 95%CI 1.21-1.80; p&amp;lt;0.001) or in combination with DVT (HR 1.54; 95%CI 1.25,1.90; p&amp;lt;0.001). Patients transitioned to low dose DOACs had similar age, sex and weight compared to the full dose anticoagulation group, however, fewer patients with weight ≥120 kg had reduced dosing (HR 0.68; 95%CI 0.46,0.99; p=0.046). The mean time to start of a low dose DOAC was 5.1 months overall, 5.4 months in cancer patients, and 3.6-4.9 months in non-cancer patients (Table 1). Non-cancer patients had significantly lower transition numbers in those ≥120kg (HR 0.62; 95%CI 0.40,0.97; p=0.038). In non-cancer patients In comparing weight, ≥120kg to &amp;lt;120kg, in the low dose group, only death was statistically different with higher risk in those ≥120kg (HR 6.44; 95%CI1.27,32.81; p=0.025). Cancer patients transitioned to low dose DOACs around 5 months on average with a median of 3.3 months. Apixaban continued to be the dominant DOAC used (78%) in the low dose group. The cancers with the most patients on low dose DOACs include lymphoma, prostate, melanoma, ovarian, and breast. There was no significant difference in VTE recurrence or death in the cancer group on different DOAC doses. Conclusion: Our results show that anticoagulant prescribers are not always waiting until 6 months to transition to low doses and low doses are being utilized in cancer patients despite lack of cancer-specific studies during the analyzed time period. Although the sample size limits the precision of this analysis, we did not find statistically significant increases in VTE recurrence with low dose DOACs in either cancer patients or with elevated body weight. We did find CRNMB but not MB was observed more frequently in weights above 120kg, possibly from unadjusted confounding in this unadjusted analysis.

Improving frequency and appropriateness of direct oral anticoagulant (DOAC) prescribing for af through integrated pharmacy-led care

Abstract Background Anticoagulants for stroke-risk reduction in atrial fibrillation (AF) are underutilised and international literature shows 10-25% of patients on a direct oral anticoagulant (DOAC) for AF are prescribed an inappropriate dose, increasing the risk of stroke and bleeding. NHS England targets are for 90% high-risk AF patients to be prescribed anticoagulation by 2029. Purpose A new pharmacy-led integrated care model was developed to improve the frequency and quality of prescribing and monitoring of DOACs for AF in line with national guidance. This abstract describes the results when this model of care was rolled out across a large UK city. Methods The integrated model of care was designed to provide a multi-pronged approach and empower primary care pharmacy teams to prescribe and manage DOACs for AF. The model includes an education and training programme, a weekly specialist-run virtual clinical discussion service, a 48-hour turn around advice and guidance service and a clinical tool that identifies and makes recommendations for patients on an unlicensed dose of a DOAC. Results 16,594 patients are included on the city’s AF register. From April-November 2022, an additional 1,339 (8%) patients were anticoagulated. An increase from 76.3% to 84.3% of patients on the AF register. Dosing as per manufacturers Summary of Product Characteristics (SmPC) improved for all DOACs. In April 2022 an incorrect dose was prescribed for 10%, 15% and 12% of patients respectively on apixaban, edoxaban and rivaroxaban. In November 2022 incorrect dosing reduced across the board to 7%, 8% and 7% of patients respectively. 914 patients prescribed an inappropriate dose had their dose adjusted to meet SmPC recommendations based on relevant characteristics (renal function, age, weight, serum creatinine, interacting medicines). Monitoring according to local guidelines also increased. Experience of staff was overwhelmingly positive and demonstrated growth in knowledge, skills, and activity amongst primary care pharmacy teams. Rapid access to specialist support allowed patients to be managed close to home. Conclusions This integrated care model improves frequency and appropriateness of DOAC prescribing for patients with AF. The model results in incorrect dosing lower than any described in international literature. The service model is sustainable and scalable, grows cross-sector clinical leadership and develops relationships between primary and secondary care. The next steps are to roll this model out across a large region.

Abstract 16693: Trends in the Use of Oral Anticoagulation for Nonvalvular Atrial Fibrillation Vary by Specialty: Real World Results From a Large Integrated Health Care System 2011-2022

Introduction: Direct Oral anticoagulants (DOACs) have demonstrated superiority or non inferiority to vitamin K antagonists (VKAs) for stroke/embolic prevention in patients with nonvalvular atrial fibrillation (NVAF). However, clinical inertia may delay widespread adoption of newer therapies in medicine. Hypothesis: We evaluated whether uptake of DOACs into clinical medicine varied by physician specialty. Methods: We performed a retrospective review of patients with NVAF within the Geisinger Health System from 2011-2022. Longitudinal yearly trends for new/initial prescriptions (Rx) of DOAC vs VKA by cardiology or primary care (PCP) specialties Results: We identified patients with NVAF initiated on an oral anticoagulant from the years 2011 through 2023. Figures 1 and 2 demonstrate a statistically significant linear yearly increase in new Rx for DOACs for both cardiology and PCP specialties.By 2022, DOACs currently account for 96% of all new oral anticoagulant Rx by cardiologists and 90% of Rx by PCP. New Rx for DOAC by PCP lagged cardiology at all time points. Cardiology initial Rx &gt;50% DOAC by 2015 while PCP did not achieve this mark until 2018. Conclusions: In this real-world setting, we observed a significant increase in DOAC use as the initial prescription for patients with NVAF by both cardiology and primary care specialties.Significant difference in the adoption of DOAC was noted between cardiology and primary care specialties.Primary care use of DOAC as first Rx for NVAF increased over time but lagged cardiology by 2-3 years.

Abstract 16063: African American's Are Prescribed Direct Oral Anticoagulants at Lower Rate Than White Patient's in an Inpatient Cohort With Diagnosis of Atrial Fibrillation

Introduction: Previous studies have demonstrated racial disparities in the treatment of atrial fibrillation (AF). Potential explanations for disparities in care include cost and insurance coverage issues. This has not been examined in relation to anticoagulation (AC) therapy for thromboembolic prophylaxis of AF in a more contemporary practice using an inpatient cohort. Hypothesis: For hospitalized patients with AF, is there disparity in the rate of prescription of direct oral anticoagulant (DOAC) therapy at discharge for Black compared to White patients? Methods: A single-center retrospective query of all patients hospitalized at a University Hospital with a primary or secondary diagnosis of “AF” in 2022 and a prescription for AC at time of discharge was performed using EPIC. Baseline characteristics and AC prescription were compared between Black and White patients using the χ2 test for categorical variables and t test for continuous variables. Results: There were 275 patients that met the inclusion criteria. Demographics were 38.2% female, 66.5% White, and 14.9% Black (Table). DOAC was prescribed at discharge for 66.1% of White and in 55.0% of Black patients (p=0.01). The distribution of type of AC prescribed at discharge is shown (Figure). Conclusions: There is an ongoing racial disparity in the rate of DOAC prescription in hospitalized patients with AF, despite similar insurance status. Further investigation into underlying reasons for these differences and ways to eliminate disparities is warranted.

Inappropriate dosing of direct oral anticoagulants: findings from a clinical vignette study and physician survey

ABSTRACT Objective Direct oral anticoagulants (DOACs) are first-line therapy for stroke prevention for 1.4 million atrial fibrillation (AF) patients in the UK. However, the rates of DOAC dosing below evidence-based recommendations are estimated between 9% and 22%. This study explores specific patient and physician factors associated with prescribing inappropriate DOAC underdoses. Methods DOAC-prescribing physicians within the UK completed both a clinical vignette survey, which contained 12 hypothetical patient profiles designed to replicate DOAC prescribing scenarios, and a physician survey to capture sociodemographic, clinical experience, and prescriber-related beliefs and motivations related to DOAC prescribing. Eight patient factors based on a literature search and an expert consultation process were varied within the vignettes. Associations between the prescribers’ dosing choices and patient factors were explored via multilevel logistic regression. The analysis is focused on the most frequently selected DOACs, apixaban and rivaroxaban, both of which have different dosing guidelines. Results In all, 336 prescribers (69% male; 233/336) completed the survey, mostly general physicians (GPs) (45%) or cardiology specialists (36%) with a mean of 17.9 years’ experience. Most prescribers (73%; 244/336) inappropriately underdosed at least once; rates between GPs and specialists were nearly identical. Patient factors most strongly associated with apixaban inappropriate underdosing included a history of major bleeding and falls. For rivaroxaban, these were major bleeding and severe frailty. Only 32% (106/335) of prescribers reported DOAC dosing guidelines as the sole influence on their prescribing behaviour. Among prescribers who did not inappropriately underdose, greater prescribing confidence was aligned to increased perception of inappropriate underdose risk. Conclusions Overall, patient factors such as major bleeding and severe frailty were found to be associated with inappropriate underdosing of apixaban and rivaroxaban. Furthermore, prescribers who were more confident in DOAC prescribing, and were more worried about the risk of stroke, were significantly less likely to inappropriately underdose. These findings suggest that all prescribers, regardless of speciality, may benefit from education and training to raise awareness of the risks associated with inappropriate DOAC underdosing.

Apixaban and rivaroxaban's physiologically-based pharmacokinetic model validation in hospitalized patients: A first step for larger use of a priori modeling approach at bed side.

When used in real-world conditions, substantial interindividual variations in direct oral anticoagulant (DOAC) plasma concentrations are observed for a given dose, leading to a risk of over- or under-exposure and clinically significant adverse events. Physiologically-based pharmacokinetic (PBPK) models could help physicians to tailor DOAC prescriptions in vulnerable patient populations, such as those in the hospital setting. The present study aims to validate prospectively PBPK models for rivaroxaban and apixaban in a large cohort of elderly, polymorbid, and hospitalized patients. In using a model of geriatric population integrating appropriate physiological parameters into models first optimized with healthy volunteer data, observed plasma concentration collected in hospitalized patients on apixaban (n = 100) and rivaroxaban (n = 100) were adequately predicted (ratio predicted/observed area under the concentration curve for a dosing interval [AUCtau ] = 0.97 [0.96-0.99] geometric mean, 90% confidence interval, ratio predicted/observed AUCtau = 1.03 [1.02-1.05]) for apixaban and rivaroxaban, respectively. Validation of the present PBPK models for rivaroxaban and apixaban in in-patients represent an additional step toward the feasibility of bedside use.

Direct Oral Anticoagulant Use Early After Cardiac Surgery: A Retrospective Cohort Study

BackgroundThere is limited literature guiding the prescribing of direct oral anticoagulants (DOACs) early after cardiac surgery as this population has been excluded from landmark randomized controlled trials. This study aims to determine the rate of in-hospital DOAC use compared with warfarin early after cardiac surgery, evaluate factors associated with DOAC use, determine difference in postoperative length of stay, and characterize bleeding events. MethodsA retrospective cohort study was conducted in adult patients with indications for anticoagulation and receiving either a DOAC or warfarin after cardiac surgery during their index hospitalization. Patients were excluded if they had any contraindications to DOAC use. The primary outcome was the proportion of patients discharged on a DOAC compared with warfarin. ResultsOf included 210 patients, 30% received DOACs and 70% received warfarin on discharge. The most common DOAC used was apixaban (74.6%), and median postoperative day of initiation was 5 days. Patients receiving DOACs were older (70.8 vs 68.0 years), had less valvular heart disease (38.1% vs 63.9%), were more likely to be on DOACs preoperatively (50.8% vs 31.3%), and were more likely to have undergone coronary artery bypass graft alone (54.0% vs 24.5%) compared with those on warfarin. Postoperative length of stay (7 vs 9 days; P = 0.59) and in-hospital bleeding (1.6% vs 2.0%; P = 1.00) did not differ between DOAC and warfarin groups. ConclusionsAt a quaternary referral centre for cardiac surgery, DOACs were used in approximately one-third of patients with an indication for anticoagulation early after cardiac surgery.

Management of Patients Treated with Direct Oral Anticoagulants in Clinical Practice and Challenging Scenarios.

It is well established that direct oral anticoagulants (DOACs) are the cornerstone of anticoagulant strategy in atrial fibrillation (AF) and venous thromboembolism (VTE) and should be preferred over vitamin K antagonists (VKAs) since they are superior or non-inferior to VKAs in reducing thromboembolic risk and are associated with a lower risk of intracranial hemorrhage (IH). In addition, many factors, such as fewer pharmacokinetic interactions and less need for monitoring, contribute to the favor of this therapeutic strategy. Although DOACs represent a more suitable option, several issues should be considered in clinical practice, including drug-drug interactions (DDIs), switching to other antithrombotic therapies, preprocedural and postprocedural periods, and the use in patients with chronic renal and liver failure and in those with cancer. Furthermore, adherence to DOACs appears to remain suboptimal. This narrative review aims to provide a practical guide for DOAC prescription and address challenging scenarios.

Effect of previous INR control during VKA therapy on subsequent DOAC adherence and persistence, in patients switched from VKA to DOAC.

Introduction Current guideline suggests a switch from vitamin K antagonist (VKA) to direct oral anticoagulant (DOAC) in patients with low time in therapeutic range (TTR<70%). Poor INR control may be the result of poor compliance, and might therefore be associated with subsequent DOAC intake. Therefore, this study evaluates the effect of previous TTR and other measures of INR control on DOAC non-adherence and non-persistence, in patients who switched from VKA to DOAC. Methods 437 patients who switched from VKA to DOAC between 2012 and 2019 were included using data from Certe Thrombosis Service, IADB.nl pharmacy community database University Groningen and Statistics Netherlands. DOAC prescriptions were used to determine non-adherence and non-persistence. INR control (i.e. TTR, time under therapeutic range (TUR) and INR variability) was assessed during the last 180 days of VKA use. Multivariable regression models were applied to determine the association between INR control and DOAC non-persistence / non-adherence. Results On VKA, 67.7% of the patients had a TTR below 70%. DOAC non-persistence was 39.8% (95% CI 33.4-45.5%) during a median follow-up of 34.4 months [IQR 19.1-49.2]. Approximately 80% of persistent patients were DOAC-adherent. Low TTR was not associated with DOAC non-persistence (HR 1.14, 95% CI 0.69-1.87) and DOAC non-adherence (OR 1.38, 95% CI 0.67-2.84), nor were TUR and INR variability. Conclusion Previous INR control during VKA therapy is not associated with subsequent DOAC non-adherence and non-persistence. This study suggests that INR control on VKA cannot, and therefore should not be used for predicting DOAC adherence or persistence.

Serial changes in the trends of direct oral anticoagulant use and incidence of thromboembolisms and major bleeding events in very old patients with non-valvular atrial fibrillation.

Direct oral anticoagulants (DOACs) have become the first-line antithrombotic therapy in patients with non-valvular atrial fibrillation (NVAF). During this period, the incidence of thromboembolisms and major bleeding events has decreased. However, no studies have shown a correlation between them, and even fewer data are available on older patients. Therefore, we evaluated the serial changes in oral anticoagulant (OAC) use and the correlation between DOAC use and the incidence of adverse events among very old patients with NVAF. We conducted a historical cohort study in 1320 consecutive patients with NVAF aged ≥80 years who received medical treatment for AF from March 2011 to February 2021. We analysed the temporal trends regarding patients using OACs, including the DOAC prescription rate and incidence of adverse events. Over the last decade, the number of patients using OACs has increased from 228 to approximately 600 person-years. The DOAC prescription rate has significantly increased (4-90%, P < 0.001). The age of the patients and proportion of patients with a HASBLED score ≥3 significantly increased (84 ± 4 to 86 ± 4 years, 16-25%, P < 0.001, respectively). The composite incidence of thromboembolisms and major bleeding events significantly decreased (7.02-3.30 events/100 person-years, P < 0.001). The incidence of thromboembolisms and major bleeding events might be inversely correlated with the increase in the DOAC prescription rate in patients with NVAF aged ≥80 years.

Pre-hospital use of direct oral anticoagulants agents is associated with a lower risk of major bleeding events in critically ill patients: A single academic center experience

BackgroundThe last decade has witnessed significant advancements in direct oral anticoagulants (DOACs), transforming the landscape of anticoagulation therapy. With the uptrend in DOACs use, critical care physicians are encountering more patients with pre-hospital DOACs prescription. Safety and real world outcomes-related data on DOACs use in critically ill patients are scarce. ObjectiveWe assess the risk of major bleeding (MB) events and patient-centered outcomes with pre-hospital use of direct oral anticoagulant agents (DOACs) compared to warfarin therapy. MethodsObservational study in a single large academic center from January 1st, 2012, through May 4th, 2018. We included adult critically ill patients with warfarin or one of the DOACs, as active medications at the time of hospital admission. The primary outcome was major bleeding (MB), based on the ISTH criteria Results99,481 patients were screened; 558 and 3037 patients were included in the final analysis for the DOAC and warfarin groups, respectively. Multivariable analysis showed that the pre-hospital use of DOACs was associated with lower odds for major bleeding events, GI bleeding, need for endoscopic intervention, hemorrhagic shock, any blood transfusion; but higher odds of intracranial bleeding, as compared to warfarin use. There was no difference in hospital length of stay or ICU-free days. ConclusionsPre-hospital use of DOACs among critically ill patients is associated with lower major bleeding events, GI bleeding, need for endoscopic intervention, and blood transfusion but a higher risk for intracranial bleeding.

Prescription of DOACs in Patients with Atrial Fibrillation at Different Stages of Renal Insufficiency.

Atrial fibrillation (AF) and renal insufficiency often coexist and are increasingly prevalent with advancing age. Both the risk of thromboembolic events and bleeding propensity are higher in patients with AF and impaired renal function versus those with good renal health. Direct oral anticoagulants (DOACs) are being increasingly preferred over vitamin K antagonists (VKAs) in the treatment of patients with AF and impaired renal function as VKAs may accelerate progression of chronic kidney disease. DOACs, however, are eliminated by the kidneys to varying degrees, and their dosages must be adapted in accordance with renal function. Since creatinine clearance (CrCl) monitoring is recommended in patients with AF receiving DOAC therapy, CrCl must be routinely monitored in patients at the start and during the course of anticoagulation to avoid deviation from Summary of Product Characteristics dosage specifications. This review article provides an overview of current knowledge on the selection and dose of DOACs including apixaban, dabigatran, edoxaban and rivaroxaban in AF patients at different stages of renal insufficiency, with a special focus on elderly patients with comorbidities and receiving multiple medications. The groups discussed in this review include patients with varying levels of CrCl including hyperfiltration or CrCl > 90ml/min, CrCl < 90-50ml/min, CrCl < 50-30ml/min, CrCl < 30-15ml/min and end-stage renal disease or on dialysis.

Clinical Outcomes of Direct Oral Anticoagulants vs Warfarin for Extended Treatment of Venous Thromboembolism

Extending the duration of oral anticoagulation for venous thromboembolism (VTE) beyond the initial 3 to 6 months of treatment is often recommended, but it is not clear whether clinical outcomes differ when using direct oral anticoagulants (DOACs) or warfarin. To compare rates of recurrent VTE, hospitalizations for hemorrhage, and all-cause death among adults prescribed DOACs or warfarin whose anticoagulant treatment was extended beyond 6 months after acute VTE. This cohort study was conducted in 2 integrated health care delivery systems in California with adults aged 18 years or older who received a diagnosis of incident VTE between 2010 and 2018 and completed at least 6 months of oral anticoagulant treatment with DOACs or warfarin. Patients were followed from the end of the initial 6-month treatment period until discontinuation of anticoagulation, occurrence of an outcome event, health plan disenrollment, or end of the study follow-up period (December 31, 2019). Data were obtained from the Kaiser Permanente Virtual Data Warehouse and electronic health records. Data analysis was conducted from March 2022 to January 2023. Dispensed prescriptions of DOACs or warfarin after a 6-month initial treatment for VTE. The primary outcomes were rates per 100 person-years of recurrent VTE, hospitalizations for hemorrhage, and all-cause death. Comparison of DOAC and warfarin outcomes were performed using multivariable Cox proportional hazards regression. A total of 18 495 patients (5477 [29.6%] aged ≥75 years; 8973 women [48.5%]) with VTE who were treated with at least 6 months of anticoagulation were identified, of whom 2134 (11.5%) were receiving DOAC therapy and 16 361 (88.5%) were receiving warfarin therapy. Unadjusted event rates were lower for patients receiving DOAC therapy than warfarin therapy for recurrent VTE (event rate per 100 person-years, 2.92 [95% CI, 2.29-3.54] vs 4.14 [95% CI, 3.90-4.38]), hospitalizations for hemorrhage (event rate per 100 person-years, 1.02 [95% CI, 0.66-1.39] vs 1.81 [95% CI, 1.66-1.97]), and all-cause death (event rate per 100 person-years, 3.79 [95% CI, 3.09-4.49] vs 5.40 [95% CI, 5.13-5.66]). After multivariable adjustment, DOAC treatment was associated with a lower risk of recurrent VTE (adjusted hazard ratio [aHR], 0.66; 95% CI, 0.52-0.82). For patients prescribed DOAC treatment, the risks of hospitalization for hemorrhage (aHR, 0.79; 95% CI, 0.54-1.17) and all-cause death (aHR, 0.96; 95% CI, 0.78-1.19) were not significantly different than those for patients prescribed warfarin treatment. In this cohort study of patients with VTE who continued warfarin or DOAC anticoagulation beyond 6 months, DOAC treatment was associated with a lower risk of recurrent VTE, supporting the use of DOACs for the extended treatment of VTE in terms of clinical outcomes.

Direct Oral Anticoagulants Affect Activated Clotting Time During and Bleeding Events After Percutaneous Coronary Intervention

Inappropriately high activated clotting time (ACT) during percutaneous coronary intervention (PCI) is associated with an increased risk of bleeding events. However, whether the prescription of direct oral anticoagulants (DOACs) affects ACT kinetics during heparin use and adverse clinical events in patients who underwent PCI remains unclear. We aimed to evaluate the relations between ACT changes during and adverse clinical events after PCI in patients who were prescribed DOAC. This observational study included 246 patients who underwent PCI at the 2 cardiovascular centers who were not receiving warfarin and whose ACT was recorded immediately before and 30minutes after injection of unfractionated heparin. Patients were divided into 2 groups according to DOAC prescription at the time of the index PCI: DOAC users (n=31) and nonusers (n=215). Any bleeding and systemic thromboembolic events were investigated until 30days after PCI. The average age of this population was 70.5years, and 66.3% were male. Average ACT was significantly higher in DOAC users than nonusers both before and 30minutes after unfractionated heparin induction (157.2±30.1 vs 131.8±25.1seconds, p<0.001; 371.1±122.2 vs 308.3±82.2seconds, p<0.001; respectively). The incidence of systemic thromboembolism after PCI was low and comparable between the 2 groups (0% vs 3.7%, p=0.60). However, the rate of any bleeding event was significantly higher in DOAC users than in nonusers (16.1% vs 4.7%, p=0.028). Patients receiving DOAC have higher ACT during PCI and higher incidence of bleeding events than those not receiving DOAC.