Direct-acting Oral Anticoagulants Research Articles

Consensus Statement on Hemostatic Management, Anticoagulation, and Antiplatelet Therapy in Liver Transplantation.

Anticoagulation and antiplatelet therapies are increasingly used in liver transplant (LT) candidates and recipients due to cardiovascular comorbidities, portal vein thrombosis, or to manage posttransplant complications. The implementation of the new direct-acting oral anticoagulants and the recently developed antiplatelet drugs is a great challenge for transplant teams worldwide, as their activity must be monitored and their complications managed, in the absence of robust scientific evidence. In this changing and clinically heterogeneous scenario, the Spanish Society of Liver Transplantation and the Spanish Society of Thrombosis and Haemostasis aimed to achieve consensus regarding the indications, drugs, dosing, and timing of anticoagulation and antiplatelet therapies initiated from the inclusion of the patient on the waiting list to post-LT surveillance. A multidisciplinary group of experts composed by transplant hepatologists, surgeons, hematologists, transplant-specialized anesthesiologists, and intensivists performed a comprehensive review of the literature and identified 21 clinically relevant questions using the patient-intervention-comparison-outcome format. A preliminary list of recommendations was drafted and further validated using a modified Delphi approach by a panel of 24 transplant delegates, each representing a LT institution in Spain. The present consensus statement contains the key recommendations together with the core supporting scientific evidence, which will provide guidance for improved and more homogeneous clinical decision making.

Prescribing Patterns of Direct-Acting Oral Anticoagulants in Patients With Atrial Fibrillation and Chronic Kidney Disease: A Retrospective Cohort Analysis.

The association of patient and prescriber characteristics with use of warfarin versus direct-acting oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and chronic kidney disease (CKD) is not well studied. The 20% Centers for Medicare & Medicaid Services Parts A, B, and D claims data from 2010 to 2017 were used to identify patients with stage 3, 4, or 5 CKD and AF who received a DOAC (apixaban, dabigatran, rivaroxaban) or warfarin. Prescribers were categorized as cardiologists, primary care providers (PCPs), and others. Using logistic regression, we estimated odds ratios (ORs) for the association of baseline characteristics and prescriber specialty with first use of a DOAC, relative to warfarin. We identified 22,739 individuals with CKD who were newly initiated on oral anticoagulation for AF. New DOAC prescriptions increased from 490 in 2011 to 3261 in 2017, and displaced warfarin over time (1849, 2011; 945, 2017). By Q4 of 2014, cardiologists prescribed DOACs as initial treatment more frequently than warfarin, but non-cardiologists did not do so until 2015. As of 2017, apixaban was the most widely prescribed anticoagulant, comprising 56% and 50% of prescriptions by cardiologists and non-cardiologists, respectively. PCPs (OR 0.54, 0.51-0.58) and other providers (OR 0.55, 0.51-0.59) were less likely than cardiologists to prescribe DOACs. DOAC prescriptions, particularly apixaban, increased over time and gradually displaced warfarin. The total number of patients with AF and CKD receiving anticoagulation increased over time. Cardiologists increased DOAC prescriptions more rapidly than non-cardiologists.

DOACs in Mechanical and Bioprosthetic Heart Valves: A Narrative Review of Emerging Data and Future Directions.

In the recent years, there has been significant transformation in the management of valvular heart disease (VHD), as a result of new minimally invasive technologies, such as the transcatheter aortic valve implantation (TAVI). Conventionally, mechanical heart valves require anticoagulation with warfarin to prevent thrombogenic events. Lately, there has been an uptrend in the usage of direct-acting oral anticoagulants (DOACs) in both mechanical and bioprosthetic heart valves. In clinical practice, there has shown to be notable heterogeneity in the antithrombotic regimen for patients. Recommendations from clinical guidelines and emerging data on DOAC use in these settings will be critically reviewed here. Future large, randomized-controlled trials are warranted to delineate the role of DOACs in patients receiving a bioprosthetic valve/TAVI or mechanical heart valve, with and without a baseline indication for anticoagulation or antiplatelets. Until clinical trial data from well-designed studies are available, providers must remain vigilant about DOAC use in patients with VHD, especially in patients with a bioprosthetic or mechanical heart valve.

Consensus document of the Spanish Society of Digestives Diseases and the Spanish Society of Thrombosis and Haemostasis on massive nonvariceal gastrointestinal bleeding and direct-acting oral anticoagulants.

there is limited experience and understanding of massive nonvariceal gastrointestinal bleeding during therapy with direct-acting oral anticoagulants. to provide evidenced-based definitions and recommendations. a consensus document developed by the Spanish Society of Digestives Diseases and the Spanish Society of Thrombosis and Haemostasis using modified Delphi methodology. A panel was set up of 24 gastroenterologists with experience in gastrointestinal bleeding, and consensus building was assessed over three rounds. Final recommendations are based on a systematic review of the literature using the GRADE system. panelist agreement was 91.53 % for all 30 items as a group, a percentage that was improved during rounds 2 and 3 for items where clinical experience is lower. Explicit disagreement was only 1.25 %. A definition of massive nonvariceal gastrointestinal bleeding in patients on direct-acting oral anticoagulants was established, and recommendations to optimize this condition's management were developed. the approach to these critically ill patients must be multidisciplinary and protocolized, optimizing decisions for an early identification of the condition and patient stabilization according to the tenets of damage control resuscitation. Thus, consideration must be given to immediate anticoagulation reversal, preferentially with specific antidotes (idarucizumab for dabigatran and andexanet alfa for direct factor Xa inhibitors); hemostatic resuscitation, and bleeding point identification and management.

A Review of the Past, Present and Future of Cancer-associated Thrombosis Management.

Venous thromboembolism (VTE) can have a significant impact on the management, quality of life and mortality of patients with cancer. VTE occurs in 5-20% of patients with cancer, and malignancy is associated with up to 25% of all VTE. It is the second leading cause of death in ambulatory patients with cancer who are receiving chemotherapy. Increased rates of cancer-associated thrombosis are attributed to improved patient survival, increased awareness, surgery, antineoplastic treatments and the use of central venous access devices. Many factors influence cancer-associated thrombosis risk and are broadly categorized into patient-related, cancer-related and treatment-related risks. Direct-acting oral anticoagulants have shown themselves to be at least as effective in preventing recurrent VTE in patients with cancer with symptomatic and incidental VTE. This has led to a change in treatment paradigms so that direct-acting oral anticoagulants are now considered first-line agents in appropriately selected patients. In this article, we review the prior and recent landmark studies that have directed the treatment of cancer-associated thrombosis, and discuss specific factors that affect management as well as future treatment considerations.

Real-life experience of edoxaban treatment for venous thromboembolism (VTE)/pulmonary embolism (PE) in patients with isolated positive Lupus Anticoagulant (LAC) during the COVID-19 pandemic lockdown in Italy.

Direct-acting oral anticoagulants (DOACs) have established indications, according to recent guidelines for the treatment and prevention of venous thromboembolism (VTE), including pulmonary embolism (PE), with a safer profile compared to vitamin K antagonist (VKA) in terms of a lower risk for major bleeding and no need of blood coagulation tests. However, DOACs are not indicated in the treatment of patients with triple-positive antiphospholipid syndrome (APS). This limitation is often extended in clinical practice to patients with isolated positivity. The COVID-19 pandemic has sometimes made it difficult to maintain a safe VKA treatment, due to the practical difficulties of performing INR. We evaluated 39 patients with a previous unprovoked VTE/PE, who were no longer eligible for VKA treatment due to the difficulty of performing INR during the COVID-19 pandemic lockdown, in Italy. All patients had a positive LAC and refused a long-term anticoagulation with low molecular weight heparin. They were shifted to edoxaban. Any recurrence of VTE/PE occurred during the observation period (up to eight months of treatment), while only one minor bleeding event was recorded (Hazard ratio=0.06, 95% confidence interval 0.03-0.11, p=0.094). No arterial events occurred during the observation period. Hemoglobin, platelets, and creatinine were unchanged during the observation period. Edoxaban treatment may be safe and effective in preventing the recurrence of VTE/PE in patients with isolated LAC positivity, without the occurrence of arterial events.

Safety of Direct Acting Oral Anticoagulants (DOACs) in Comparison to Enoxaparin in Gastrointestinal and Genito-Urinary Cancers

Safety of Direct Acting Oral Anticoagulants (DOACs) in Comparison to Enoxaparin in Gastrointestinal and Genito-Urinary Cancers

Фармакоэкономические аспекты применения антикоагулянтов в условиях многопрофильного стационара

The article presents the dynamics of the consumption of oral anticoagulants and direct-acting anticoagulants for 2019–2021 in the Republic Clinical Hospital of the Republic of Tatarstan. Currently, anticoagulant therapy is very popular among clinicians. It is known that the economic component plays a rather important role in health care. The purpose — to analyze the costs of anticoagulant drugs in a multi-speciality hospital in 2019–2021. Material and methods. An analysis was made of the share of costs of direct-acting anticoagulants and oral anticoagulants in the total cost of medicines by years in a multi-speciality hospital using the Apteka 1C software. Results. There is a clear trend towards increased consumption of direct-acting anticoagulants and oral anticoagulants. The peak of consumption was observed in 2020 and 2021. Conclusions. The use of oral anticoagulants reduces direct costs compared to standard prophylaxis with direct anticoagulants.

Anticoagulation in patients with atrial fibrillation and liver cirrhosis.

Atrial fibrillation (AF) is an increasingly recognized comorbidity in patients with liver cirrhosis, mainly associated with nonalcoholic fatty liver disease and alcohol-associated liver disease, affecting the quality of life and prognosis. On the other hand, cirrhosis is associated with an elevated risk of both thrombosis and bleeding, making the decision about anticoagulation therapy very challenging. Direct-acting oral anticoagulants (DOACs) are approved for patients with non-valvular AF. However, there is limited clinical experience and scientific evidence about their efficacy and safety in liver cirrhosis. This review article investigates the published literature concerning the administration of DOACs and traditional antithrombotic agents, such as vitamin K antagonists and heparins, in patients with liver cirrhosis and AF.

POSA267 How Does Stakeholder Consultation Inform the Development of NICE Clinical Guidelines? The Example of Atrial Fibrillation: Diagnosis and Management

Stakeholder consultation is an integral part of the NICE clinical guideline development process. Comments received are a vital part of the robust quality-assurance and peer-review processes. The NICE guideline for Atrial Fibrillation underwent consultation (September–November 2020) giving stakeholders such as clinical and patient experts the opportunity to comment on a draft recommendation for the direct-acting oral anticoagulants (DOACs) for the management of patients with atrial fibrillation (AF).

Assessment of direct-acting oral anticoagulants for the treatment of venous thromboembolism in cancer patients in Thai Tertiary Care Hospital

Assessment of direct-acting oral anticoagulants for the treatment of venous thromboembolism in cancer patients in Thai Tertiary Care Hospital

Prescribing Patterns of Direct-Acting Oral Anticoagulants in Patients with Atrial Fibrillation and Chronic Kidney Disease: A Retrospective Cohort Analysis

Prescribing Patterns of Direct-Acting Oral Anticoagulants in Patients with Atrial Fibrillation and Chronic Kidney Disease: A Retrospective Cohort Analysis

Prevalence, contributory factors and severity of medication errors associated with direct-acting oral anticoagulants in adult patients: a systematic review and meta-analysis

PurposeThis study aimed to estimate the prevalence, contributory factors, and severity of medication errors associated with direct acting oral anticoagulants (DOACs).MethodsA systematic review and meta-analysis were undertaken by searching 11 databases including Medline, Embase, and CINHAL between January 2008 and September 2020. The pooled prevalence of errors and predictive intervals were estimated using random-effects models using Stata software. Data related to error causation were synthesised according to Reason’s accident causation model.ResultsFrom the 5205 titles screened, 32 studies were included which were mostly based in hospitals and included DOAC treatment for thromboembolism and atrial fibrillation. The proportion of study population who experienced either prescription, administration, or dispensing error ranged from 5.3 to 37.3%. The pooled percentage of patients experiencing prescribing error was 20% (95% CI 15–25%; I2 = 96%; 95% PrI 4–43%). Prescribing error constituted the majority of all error types with a pooled estimate of 78% (95%CI 73–82%; I2 = 0) of all errors. The common reported causes were active failures including wrong drug, and dose for the indication. Mistakes such as non-consideration of renal function, and error-provoking conditions such as lack of knowledge were common contributing factors. Adverse events such as potentially fatal intracranial haemorrhage or patient deaths were linked to the errors but causality assessments were often missing.ConclusionsDespite their favourable safety profile, DOAC medication errors are common. There is a need to promote multidisciplinary working, guideline-adherence, training, and education of healthcare professionals, and the use of theory-based and technology-facilitated interventions to minimise errors and maximise the benefits of DOACs usage in all settings.ProtocolA protocol developed as per PRISMA-P guideline is registered under PROSPERO ID = CRD42019122996

Comparison of the HAS-BLED versus ORBIT scores in predicting major bleeding among Asians receiving direct-acting oral anticoagulants.

This study aimed to evaluate the performance of HAS-BLED and ORBIT scores in predicting bleeding risk among Asian patients with nonvalvular atrial fibrillation (NVAF) using direct-acting oral anticoagulants (DOACs). A retrospective chart review was conducted among adult patients receiving DOACs for ≥6months during January 2013 to December 2017 in 10 tertiary care hospitals in Thailand. The area under the receiver operating curve (AUROC) method or C-statistic was used to test the diagnostic accuracy for bleeding risk classification of HAS-BLED and ORBIT scores. The predictive performances of the two scores were compared using DeLong's method. A total of 961 NVAF patients, 52.5% warfarin-naïve and 47.5% warfarin-experienced, with mean age of 74.25 ± 10.08 years, were included in the analysis. Mean HAS-BLED and ORBIT scores of the cohort were 1.98 ± 1.10 and 2.37 ± 1.71, respectively. During the mean follow-up time of 1.55 ± 1.13 years, 34 patients experienced major bleeding (2.28 events/100 patient-year). For the overall cohort, both the HAS-BLED and ORBIT scores showed similarly moderate predictive performance on bleeding with C-statistic (95% confidence interval) of 0.65 (0.57-0.74) and 0.64 (0.56-0.71), respectively. There was no statistical significance between the two scores (P = .62). Analysis based on the status of previous warfarin use was consistent with the overall cohort. Based on the calibration analysis, both HAS-BLED and ORBIT scores possessed moderate ability to identify those who experienced major bleeding from those who did not. Both HAS-BLED and ORBIT bleeding risk scores had moderate predictive performance in Asian NVAF patients receiving DOACs.

Clinician Trends in Prescribing Direct Oral Anticoagulants for US Medicare Beneficiaries

Contemporary national clinical practice guidelines recommend direct-acting oral anticoagulants (DOACs) as the first-line anticoagulant strategy over warfarin for most indications, especially among older individuals with an elevated bleeding risk. To evaluate anticoagulant prescribing and DOAC uptake by US clinicians in the Medicare population. This retrospective cohort study included all US clinicians with more than 10 Medicare oral anticoagulant prescription claims, who were included in the national Medicare Provider Utilization and Payment Data (2013-2018). Data analyses were conducted between October 2020 and October 2021. DOAC prescription in 2013. Clinicians were categorized based on 2013 prescribing as solely prescribing warfarin, DOAC, or both, and their temporal trajectories of proportionate DOAC use were examined. The analysis included 325 666 unique clinicians with more than 10 oral anticoagulant prescriptions between 2013 and 2018 (26 620 [8.2%] cardiologists, 85 563 [26.3%] internal medicine physicians, 84 369 [25.9%] family medicine physicians, and 81 161 [24.9%] advanced practice clinicians, including nurse practitioners and physician assistants). In 2013, among 91 837 prescribers, 54 501 (59.3%) prescribed only warfarin, 1918 (2.1%) prescribed only a DOAC, and 35 418 (38.6%) prescribed both. During the study period, the number of clinicians prescribing DOACs increased, but 19% continued to prescribe only warfarin in 2018. While 359 cardiologists prescribing anticoagulants (1.6%) were warfarin-only prescribers, 10 414 (20.0%) and 6296 (12.6%) of family and internal medicine physicians also prescribed only warfarin, respectively. Clinicians prescribing only warfarin in 2013 had lower proportionate DOAC use throughout the study compared with 2013 DOAC prescribers, which represents a median (IQR) of 41.9% (20.3%-61.9%) of their anticoagulant prescriptions in 2018 vs 67.0% (49.9%-82.8%) for DOAC prescribers. Despite the increase in DOAC use among Medicare beneficiaries, many clinicians in this study continued to use warfarin as their predominant or only anticoagulant instead of DOACs. There is a need to address barriers to the uptake of these medications to realize their potential benefits for patients.

Guideline-discordant dosing of direct-acting oral anticoagulants in the veterans health administration

BackgroundClear guidelines exist to guide the dosing of direct-acting oral anticoagulants (DOACs). It is not known how consistently these guidelines are followed in practice.MethodsWe studied patients from the Veterans Health Administration (VA) with non-valvular atrial fibrillation who received DOACs (dabigatran, rivaroxaban, apixaban) between 2010 and 2016. We used patient characteristics (age, creatinine, body mass) to identify which patients met guideline recommendations for low-dose therapy and which for full-dose therapy. We examined how often patient dosing was concordant with these recommendations. We examined variation in guideline-concordant dosing by site of care and over time. We examined patient-level predictors of guideline-concordant dosing using multivariable logistic models.ResultsA total of 73,672 patients who were prescribed DOACS were included. Of 5837 patients who were recommended to receive low-dose therapy, 1331 (23%) received full-dose therapy instead. Of 67,935 patients recommended to receive full-dose therapy, 4079 (6%) received low-dose therapy instead. Sites varied widely on guideline discordant dosing; on inappropriate low-dose therapy, sites varied from 0 to 15%, while on inappropriate high-dose therapy, from 0 to 41%. Guideline discordant therapy decreased by about 20% in a relative sense over time, but its absolute numbers grew as DOAC therapy became more common. The most important patient-level predictors of receiving guideline-discordant therapy were older age and creatinine function being near the cutoff value.ConclusionsA substantial portion of DOAC prescriptions in the VA system are dosed contrary to clinical guidelines. This phenomenon varies widely across sites of care and has persisted over time.

Direct acting oral anticoagulants in the treatment of left ventricular thrombus

Direct acting oral anticoagulants (DOACs) are increasingly used as off-label alternatives to vitamin K antagonists for the treatment of left ventricular (LV) thrombus. However, the efficacy and safety data is limited.

Warfarin Use Is Associated with Increased Mortality at One Year in Patients with Idiopathic Pulmonary Fibrosis.

Objectives We studied the safety and efficacy of warfarin compared to direct acting oral anticoagulant use in patients with IPF. Methods We conducted a retrospective cohort study of all patients with IPF who were prescribed warfarin or direct acting oral anticoagulants (DOACs) for cardiac or thromboembolic indications and followed at our institute for their care. Univariate tests and multivariable logistic regression analyses were used for assessing association of variables with outcomes. Results A total of 73 patients were included in the study with 28 and 45 patients in the warfarin and DOAC groups, respectively. Univariable analysis revealed a significant difference in mortality in one year between warfarin and DOAC groups (7/28 vs. 3/45, p value 0.027). Significantly more patients in the warfarin group suffered an exacerbation that required hospitalization within one year (9/28 vs. 5/45, p value 0.026). Multivariate logistic regression analysis showed that anticoagulation with warfarin was independently associated with mortality at one-year follow-up (OR: 77.4, 95% CI: 5.94–409.3, p value: 0.007). Conclusion In our study of patients with IPF requiring anticoagulants, we noted statistically significant higher mortality with warfarin anticoagulation when compared to DOAC use. Further larger prospective studies are needed to confirm these findings.

Anti-Xa Levels in Morbidly Obese Patients Using Apixaban or Rivaroxaban, Before and After Bariatric Surgery.

Despite limited evidence about the efficacy and safety of anticoagulation in patients post bariatric surgery, both vitamin K antagonists (VKA) and direct-acting oral anticoagulants (DOACs) are commonly prescribed. To evaluate plasma anti-Xa levels of DOACs in morbidly obese (MO) patients before and after a Roux-en-Y gastric bypass (RYGB) procedure. Retrospective, cross-sectional, and longitudinal study of anti-Xa activity of apixaban or rivaroxaban in MO patients (N = 41). Preoperative analysis of plasma anti-Xa levels were within the normal range in patients using apixaban (n = 29; body mass index [BMI] 44.5 ± 5.1kg/m2) as well as those using rivaroxaban (n = 12; BMI 42.6 ± 5.9kg/m2). Postoperative anti-Xa levels of apixaban were all within the therapeutic range, whereas anti-Xa levels of rivaroxaban were subtherapeutic in nine out of 14 (64%) patients. Perioperative longitudinal follow-up in patients using apixaban (n = 18) showed no significant change in anti-Xa levels after RYGB. Plasma anti-Xa levels of apixaban in MO patients remained within the therapeutic range up to a body weight of 144kg. In patients using rivaroxaban, no statistically significant relation between anti-Xa levels and bodyweight was found. After RYGB, plasma anti-Xa levels of apixaban were unaffected, whereas plasma anti-Xa levels of rivaroxaban tended to become subtherapeutic.

Association of Race and Ethnicity and Anticoagulation in Patients With Atrial Fibrillation Dually Enrolled in Veterans Health Administration and Medicare: Effects of Medicare Part D on Prescribing Disparities.

Racial and ethnic disparities in anticoagulation exist in atrial fibrillation management in Medicare and the Veterans Health Administration, but the influence of dual Veterans Health Administration and Medicare enrollment is unclear. We compared anticoagulant initiation by race and ethnicity in dually enrolled patients and assessed the role of Medicare part D enrollment on anticoagulation disparities. We identified patients with incident atrial fibrillation (2014-2018) dually enrolled in Veterans Health Administration and Medicare. We assessed any anticoagulant initiation (warfarin or direct-acting oral anticoagulants [DOACs]) within 90 days of atrial fibrillation diagnosis and DOAC use among anticoagulant initiators. We modeled anticoagulant initiation, adjusting for patient, provider, and facility factors, including main effects for race and ethnicity and Medicare part D enrollment and an interaction term for these variables. In 43 789 patients, 8.9% were Black, 3.6% Hispanic, and 87.5% White; 10.9% participated in Medicare part D. Overall, 29 680 (67.8%) patients initiated any anticoagulant, of whom 17 568 (59.2%) initiated DOACs. Lower proportions of Black (65.2%) than Hispanic (67.6%) or White (68.0%) patients initiated any anticoagulant (P=0.001) and, lower proportions of Black (56.3%) and Hispanic (55.9%) than White (59.6%) patients (P=0.001) initiated DOACs. Compared with White patients, Black patients had significantly lower initiation of any anticoagulant (adjusted odds ratio, 0.89 [95% CI, 0.82-0.97]). The adjusted odds ratios for DOAC initiation were significantly lower for Black (0.72 [95% CI, 0.65-0.81]) and Hispanic (0.84 [95% CI, 0.70-1.00]) than White patients. The interaction between race and ethnicity and Medicare part D enrollment was nonsignificant for any anticoagulant (P=0.99) and DOAC (P=0.27) therapies. In dually enrolled Veterans Health Administration and Medicare patients with atrial fibrillation, Black patients were less likely to initiate any anticoagulant, and Black and Hispanic patients were less likely to initiate DOACs. Medicare part D enrollment did not moderate the associations between race and ethnicity and anticoagulant therapies.