Clinical comprehensive evaluation of direct oral anticoagulants for patients with atrial fibrillation in China.

BACKGROUND: Direct oral anticoagulants (DOACs) are increasingly recommended over warfarin in stroke prevention for patients with non-valvular atrial fibrillation (AF). However, there is an important evidence gap in choosing the most appropriate DOAC for Chinese patients in clinical practice. METHODS: A multi-criteria decision analysis (MCDA) was adopted to build a scoring framework. Attributes and criteria were identified and determined by a scoping literature review, two rounds of Delphi surveys, and a consensus meeting. Weights of each attribute and criterion in the framework were determined using analytic hierarchy process (AHP). Evidence was collected based on the domestic or at least Asian data. Scoring methods for each criterion were developed depended on their characteristics and determined with an expert consensus meeting. Comprehensive scores of each DOAC were calculated based on the utility scores of each criterion and their corresponding weights. RESULTS: A total of 5 attributes, including safety, efficacy, costs/cost-effectiveness, suitability, and accessibility, were determined, and 16 criteria were under the 5 attributes. The safety and efficacy were ranked as the top two important attributes with the weights of 38.8% and 35.9%, respectively, while the suitability received the lowest weight of 7.9%. The comprehensive score for edoxaban was the highest (72.3), followed by dabigatran (49.7), rivaroxaban (37.9), and apixaban (35.8). CONCLUSIONS: This study provided a scoring framework developed for comprehensive evaluation of DOACs in China. The ranking of DOACs could help to support the decision-making in clinical practice. The framework could provide a reference for comprehensive evaluation of other drugs.

Trends in utilization, reimbursement, and price for DOACs and warfarin in the US Medicaid population from 2000 to 2020.

The use of direct oral anticoagulants (DOACs) is widely increasing in the United States (US). Warfarin has been the conventional anticoagulant used in the past few decades, but it has been gradually replaced by DOACs. The objective of the study was to analyze trends in utilization, reimbursement, and price for those anticoagulants in the US Medicaid population. Retrospective data analysis was conducted using the National Summary Files for the Medicaid State Drug Utilization Data. Study drugs included dabigatran, rivaroxaban, apixaban, edoxaban and warfarin. The study assessed secular trends of utilization, reimbursement, and per-prescription price. The data was collected from the first quarter of 2000 through to the second quarter of 2020 restricted for outpatient prescriptions only. During the 21-year study period, a substantial rise in total expenditures on warfarin and DOACs was observed from $144 million in 2000 to $694 million in 2020. Moreover, the utilization of DOACs has increased significantly since the first approval of Xarelto in 2010 from 1079 in 2011 to 1.5 million in 2019. The per-prescription price of DOACs increased from an average of $200 in 2011 to $407 in 2020. Conversely, the total number of prescriptions of Warfarin and branded Coumadin decreased from 2.4 million to 1.4 million and from 3.9 million to less than a million, respectively. The present study demonstrated a change in the trends of US expenditure and utilization for warfarin and DOACs with DOACs representing the majority of market share of both spending per prescription and reimbursement.

Effectiveness and safety of direct oral anticoagulants versus warfarin in patients with atrial fibrillation and advanced kidney disease.

BACKGROUND: The effectiveness and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and advanced kidney disease (AKD) has not been fully established. OBJECTIVES: To determine the effectiveness and safety related to pooled or specific DOACs to that with warfarin in patients with AF and AKD. METHODS: Patients with AF and AKD (estimated glomerular filtration rate < 30 mL/min) who received DOAC or warfarin from July 2011 to December 2020 were retrospectively identified in a medical center in Taiwan. Primary outcomes were hospitalized for stroke/systemic embolism and major bleeding. Secondary outcomes included any ischemia and any bleeding. RESULTS: A total of 1,011 patients were recruited, of whom 809 (80.0%) were in the DOACs group (15.3% dabigatran, 25.4% rivaroxaban, 25.2% apixaban, and 14.1% edoxaban), and 202 (20.0%) in the warfarin group. DOACs had considerably lower risks of stroke/systemic embolism (adjusted hazard ratio [aHR] 0.29; 95% CI, 0.09-0.97) and any ischemia (aHR, 0.42; 95% CI, 0.22-0.79), but had comparable risks of major bleeding (aHR, 0.99; 95% CI, 0.34-2.92) and any bleeding (aHR, 0.74; 95% CI, 0.50-1.09) than warfarin. Apixaban was linked to considerably lower risks of any ischemia (aHR, 0.13; 95% CI, 0.04-0.48) and any bleeding (aHR, 0.53; 95% CI, 0.28-0.99) than warfarin. CONCLUSION: Among patients with AF and AKD, DOACs were linked to a lower risk of ischemic events, and apixaban was linked to a lower risk of any ischemia and any bleeding than warfarin.

Apixaban Dosing Patterns Versus Warfarin in Patients With Nonvalvular Atrial Fibrillation Receiving Dialysis: A Retrospective Cohort Study.

BACKGROUND & OBJECTIVES: Comparison of clinical outcomes across anticoagulation regimens using different apixaban dosing or warfarin is not well-defined in patients with nonvalvular atrial fibrillation (AF) who are receiving dialysis. This study compared these outcomes in a US national cohort of patients with kidney failure receiving maintenance dialysis. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Patients receiving dialysis represented in the US Renal Data System database 2013-2018 who had AF and were treated with apixaban or warfarin. EXPOSURE: First prescribed treatment with apixaban dosed according to the label, apixaban dosed below the label, or warfarin. OUTCOME: Ischemic stroke/systemic embolism, major bleeding, and all-cause mortality. ANALYTICAL APPROACH: Cox proportional hazards models with inverse probability of treatment weighting. Analyses simulating an intention-to-treat (ITT) approach as well as those incorporating censoring at drug switch or discontinuation (CAS) were also implemented. Inverse probability of censoring weighting was used to account for possible informative censoring. RESULTS: Among 17,156 individuals, there was no difference in risk of stroke/systemic embolism among the label-concordant apixaban, below-label apixaban, and warfarin treatment groups. Both label-concordant (HR, 0.67 [95% CI, 0.55-0.81]) and below-label (HR, 0.68 [95% CI, 0.55-0.84]) apixaban dosing were associated with a lower risk of major bleeding compared with warfarin in ITT analyses. Compared with label-concordant apixaban, below-label apixaban was not associated with a lower bleeding risk (HR, 1.02 [95% CI, 0.78-1.34]). In the ITT analysis of mortality, label-concordant apixaban dosing was associated with a lower risk versus warfarin (HR, 0.85 [95% CI, 0.78-0.92]) while there was no significant difference in mortality between below-label dosing of apixaban and warfarin (HR, 0.97 [95% CI, 0.89-1.05]). Overall, results were similar for the CAS analyses. LIMITATIONS: Study limited to US Medicare beneficiaries; reliance on administrative claims to ascertain outcomes of AF, stroke, and bleeding; likely residual confounding. CONCLUSIONS: Among patients with nonvalvular AF undergoing dialysis, warfarin is associated with an increased risk of bleeding compared with apixaban. The risk of bleeding with below-label apixaban was not detectably less than with label-concordant dosing. Label-concordant apixaban dosing is associated with a mortality benefit compared to warfarin. Label-concordant dosing, rather than reduced-label dosing, may offer the most favorable benefit-risk trade-off for dialysis patients with nonvalvular AF.

Complexity and clinical significance of drug-drug interactions (DDIs) in oncology: challenging issues in the care of patients regarding cancer-associated thrombosis (CAT).

Cancer patients have an increased risk of developing venous thromboembolic events. Anticoagulation management includes prophylactic or therapeutic doses of low molecular weight heparins (LMWHs) or direct oral anticoagulants (DOACs). However, the management of thrombosis in patients with cancer is complex due to various individual and disease-related factors, including drug-drug interactions (DDIs). Furthermore, DDIs may impact both, cancer and venous thrombosis, treatment effectiveness and safety; their relevance is highlighted by the advances in cancer therapeutics. Given that these new oncology drugs are extensively used, more attention should be given to monitoring potential DDIs to minimize risks. Recognition of DDIs is of utmost importance in an era of rapid developments in cancer treatments and introduction of novel treatments and protocols. When managing cancer-associated thrombosis (CAT), the concomitant use of a DOAC and a moderate or strong modulator (inhibitor or inducer) of CYP3A4 or a P-glycoprotein (P-gp) is most likely to be associated with significant DDIs. Therefore, LMWHs remain the first-line option for the long-term management of CAT under these circumstances and physicians must consider utilizing LMWHs as first line. This review describes the risk of DDIs and their potential impact and outcomes in patients with cancer associated thrombosis (CAT) receiving anticoagulation.

CKD Progression in Medicare Beneficiaries With Nonvalvular Atrial Fibrillation Treated With Apixaban Versus Warfarin.

RATIONALE & OBJECTIVE: Comparing kidney disease progression among patients treated with direct oral anticoagulants (DOACs) versus warfarin has not been well studied. We hypothesized that apixaban would be associated with lower risks of progression of chronic kidney disease (CKD) and progression to incident kidney failure than warfarin in patients with atrial fibrillation (AF). STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Medicare recipients with stage 3, 4, or 5 CKD and incident AF who received a new prescription for apixaban or warfarin from 2013 through 2017. EXPOSURE: Apixaban or warfarin. OUTCOMES: Progression to incident kidney failure or, separately, to a more advanced stage of CKD. ANALYTICAL APPROACH: Marginal structural cause-specific proportional hazards models with inverse probability weighting to estimate marginal hazard ratios (HRs) for each outcome. HRs compared apixaban to warfarin in intention-to-treat and censored-at-drug-switch analyses. RESULTS: 12,816 individuals met inclusion criteria (50.3% received apixaban; 49.7% received warfarin). After weighting, the mean age of the cohort was 80 ± 7 years, 51% were women, and 88% were White. Approximately 84% had stage 3, 15% had stage 4, and 1% had stage 5 CKD. In the intention-to-treat analysis, apixaban, relative to warfarin, was associated with an HR of developing incident kidney failure of 0.98 (95% confidence interval [CI], 0.79-1.22) and of CKD stage progression of 0.90 (95% CI, 0.82-0.99). Corresponding HRs for censored-at-drug-switch analyses were 0.81 (95% CI, 0.56-1.17) and 0.81 (95% CI, 0.70-0.92). Results were similar for a series of subgroup and sensitivity analyses. LIMITATIONS: CKD was defined based on diagnosis codes from claims; findings may not be generalizable to non-Medicare CKD populations. CONCLUSIONS: Apixaban, compared with warfarin, was associated with lower risk of CKD stage progression, but not with incident kidney failure.

Can direct oral anticoagulants be used in kidney transplant recipients?

BACKGROUND: Kidney transplant recipients(KTRs) are at an increased risk of venous thromboembolism (VTE) and atrial fibrillation(AF). Direct oral anticoagulants (DOACs) have shown important advantages over vitamin K antagonists; however, in KTRs, concerns regarding interactions and use in severe kidney disease may limit their use. This evaluation describes a large UK kidney transplant center's experience of DOACs in KTRs with CrCl > 15 mL/min. METHODS: Electronic records were reviewed for all adult KTRs at Manchester University Foundation Trust Hospitals taking DOACs between January 2018 and October 2020 with VTE or AF. The primary outcome was trough and peak DOAC levels within the expected reference ranges and secondary outcomes included bleeding and thrombotic events. RESULTS: In 31 KTRs taking DOACS, eight patients had a CrCl < 30 mL/min. Overall, 94% (62/66) of DOAC levels were within the recommended ranges. There were no thrombotic events and four bleeding events (two major and two clinically relevant non-major bleeds). The overall bleeding rate was 6.9 per 100 patient-years at risk. CONCLUSIONS: There was no evidence of a significant interaction of apixaban or rivaroxaban with CNIs based on expected DOAC and CNI levels. Their use was found to be safe and effective with no VTE events and bleeding episodes similar to published trial data.

Calibrated automated thrombogram II: removing barriers for thrombin generation measurements.

BACKGROUND: Thrombin generation (TG) assessed by Calibrated Automated Thrombogram (CAT-I) reflects the overall capacity of plasma to generate thrombin, thus evaluating the balance between the anti- and procoagulant processes. However, with this method the calibrator curve is usually not measured until completion which has a severe impact on the calculation of the TG parameters, especially under conditions where almost all substrate is consumed. In addition, direct thrombin inhibitor (DTI) cannot be present in the calibration sample due to inhibition of the calibrator. We have developed a modified TG assay (CAT-II) and performed head-to-head comparison with the CAT-I method using the same fluorometer. Furthermore, we have compared our CAT-II method to a new automated TG instrument (ST®-Genesia) using the same calibration method. METHODS: TG was assessed with CAT-I and CAT-II using the same fulorometer and with ST®-Genesia in control plasma and plasma containing different anticoagulants (dabigatran, rivaroxaban, apixaban) and plasmas to which common interfering substances, bilirubin, hemoglobin and lipids were added. In CAT-I, calibration was against the same plasma containing calibrator in the presence of fluorogenic substrate (Z-GGR-AMC). In contrast, CAT-II method and ST®-Genesia used a standard concentration of thrombin in buffer and 7-amino-4-methylcoumarin (AMC) in a separate plasma sample for calibration. RESULTS: TG obtained from CAT-I using anticoagulant-free plasmas was lower compared with TG from CAT-II but both methods demonstrated an intra-assay variation less than 5% on all measured parameters. When comparing the two different calibration methods in the presence of different anticoagulants, a high correlation was seen in the presence of rivaroxaban and apixaban (R2 > 0.97), but not with dabigatran, a direct thrombin inhibitor. CAT-II method showed dose-dependent inhibition of TG in the presence of dabigatran, while CAT-I was not able to detect it. Both methods were able to correct for the interfering substances. CONCLUSIONS: Our results showed high similarity between the results of CAT-I and CAT-II method when it is applied in control plasmas and plasmas not inhibited with a direct thrombin inhibitor. Furthermore, both the CAT-II method and ST-Genesia using the same calibration method were able to detect the effect of all oral anticoagulants. Taken together, applying a new calibration method is a significant improvement for monitoring patients on direct thrombin inhibitors while not introducing any bias to results obtained on other types of samples.

Four-Factor Prothrombin Complex Concentrate for the Reversal of Direct Oral Anticoagulants.

BACKGROUND: The prevalence of direct oral anticoagulants (DOACs) has increased with continued evidence of their efficacy and ease of use. However, the rise in their utilization also surfaced a concern regarding their reversal in patients actively bleeding and/or those requiring invasive procedures. Up until 2018, there were several reversal options available including 4-factor prothrombin complex concentrate (4-factor PCC), activated charcoal, desmopressin, and tranexamic acid. Then, in 2018, andexanet alpha, a recombinant factor Xa, was approved for the reversal of apixaban and rivaroxaban in patients with life-threatening or uncontrolled bleeding. Nonetheless, because 4-factor PCC is more easily attainable and cost-effective, it continues to be the more favorable option for many health-care professionals. METHODS: This retrospective chart review was conducted at NYU Winthrop Hospital in patients who received 4-factor PCC for the reversal of DOACs from January 2018 to July 2018. Patient charts were reviewed and relevant data was collected (admitting diagnosis, dose of 4-factor PCC utilized, etc). RESULTS: Fifty-three patients were evaluated with 85% experiencing a positive response and complete recovery following the administration of 4-factor PCC; 8 (15%) patients died after receiving 4-factor PCC, none as a result of its administration; 3 patients died secondary to other underlying comorbidities, 4 patients died due to an intracranial hemorrhage, and 1 died due to hematoma of the tongue. CONCLUSION: Based on the results thus far, the use of 4-factor PCC may be a good treatment option in patients requiring DOAC reversal.

Risk of Cardiovascular Events and Mortality Among Elderly Patients With Reduced GFR Receiving Direct Oral Anticoagulants.

RATIONALE & OBJECTIVE: Evidence for the efficacy of direct oral anticoagulants (DOACs) to prevent cardiovascular (CV) events and mortality in older individuals with a low estimated glomerular filtration rate (eGFR) is lacking. We sought to characterize the association of oral anticoagulant use with CV morbidity in elderly patients with or without reductions in eGFRs, comparing DOACs with vitamin K antagonists (VKAs). STUDY DESIGN: Population-based retrospective cohort study. SETTINGS & PARTICIPANTS: All individuals 66 years or older with an initial prescription for oral anticoagulants dispensed in Ontario, Canada, from 2009 to 2016. EXPOSURE: DOACs (apixaban, dabigatran, and rivaroxaban) compared with VKAs by eGFR group (≥60, 30-59, and<30mL/min/1.73m2). OUTCOMES: The primary outcome was a composite of a CV event (myocardial infarction, revascularization, or ischemic stroke) or mortality. Secondary outcomes were CV events alone, mortality, and hemorrhage requiring hospitalization. ANALYTICAL APPROACH: High-dimensional propensity score matching of DOAC to VKA users and Cox proportional hazards regression. RESULTS: 27,552 new DOAC users were matched to 27,552 new VKA users (median age, 78 years; 49% women). There was significantly lower risk for CV events or mortality among DOAC users compared with VKA users (event rates of 79.78 vs 99.77 per 1,000 person-years, respectively; HR, 0.82 [95% CI, 0.75-0.90]) and lower risk for hemorrhage (event rates of 10.35 vs 16.77 per 1,000 person-years, respectively; HR, 0.73 [95% CI, 0.58-0.91]). There was an interaction between eGFR and the association of anticoagulant class with the primary composite outcome (P<0.02): HRs of 1.01 [95% CI, 0.92-1.12], 0.83 [95% CI, 0.75-0.93], and 0.75 [95% CI, 0.51-1.10] for eGFRs of≥60, 30 to 59, and<30mL/min/1.73m2. No interaction was detected for the outcome of hemorrhage. LIMITATIONS: Retrospective observational study design limits causal inference; dosages of DOACs and international normalized ratio values were not available; low event rates in some subgroups limited statistical power. CONCLUSIONS: DOACs compared with VKAs were associated with lower risk for the composite of CV events or mortality, an association for which the strength was most apparent among those with reduced eGFRs. The therapeutic implications of these findings await further study.

DOAC-Remove abolishes the effect of direct oral anticoagulants on activated protein C resistance testing in real-life venous thromboembolism patients.

Background Direct oral anticoagulants (DOACs) may cause false results of activated protein C resistance (APC-R) ratio. DOAC-Remove, a new reagent based on activated carbon, has been designed to eliminate the interference of DOACs on coagulation assays. The aim of the study was to investigate whether the use of DOAC-Remove enables to determine APC-R in patients treated with DOACs. Methods We assessed 74 venous thromboembolism (VTE) patients, including 25 on rivaroxaban, 25 on apixaban and 24 taking dabigatran. APC-R was determined using the Russell Viper Venom Time (RVVT)-based clotting test. APC-R and DOAC concentrations were tested at baseline and following DOAC-Remove. Thrombophilia, including factor V Leiden (FVL) mutation was tested. Results FVL mutation was found in 20 (27%) patients. The APC-R ratio at baseline was measurable in 43 patients (58.1%), including 20 (80%) on rivaroxaban, 19 (76%) on apixaban and four (16.7%) on dabigatran. In patients with measurable APC-R at baseline, the ratio >2.9 was found in 23 patients (53.5%). In 16 (37.2%) subjects APC-R ratio <1.8 suggested FVL mutation which was genetically confirmed. Four (9.3%) FVL carriers on dabigatran showed negative/equivocal APC-R results. In 11 (14.9%) patients taking rivaroxaban or apixaban, in whom blood was collected 2-5 h since the last dose, we observed unmeasurable APC-R. DOAC-Remove almost completely eliminated all plasma DOACs. After addition of DOAC-Remove all APC-R ratios were measurable. In four FVL carriers on dabigatran with false negative APC-R, DOAC-Remove resulted in APC-R ratios <1.8. Conclusions DOAC-Remove effectively reduces DOACs concentration in plasma, which enables FVL testing using APC-R.

The management of patients with acute ischemic stroke while on direct oral anticoagulants (DOACs): data from an Italian cohort and a proposed algorithm.

Approximately 1-2% of patients with non-valvular atrial fibrillation have an acute ischemic stroke (AIS) while on direct oral anticoagulant (DOAC) treatment every year. However, current evidence on stroke subtypes, pathophysiology and factors leading to the failure of DOAC preventive therapy in a "real world" setting is still scanty. This study aimed at investigating whether there is any relationship between DOAC plasma levels and the stroke occurrence, on the basis of the phenotypic classification and pathophysiology of the stroke, in a cohort of DOAC-treated patients admitted to our hospital for AIS over 1-year period. A total of 28 patients had DOAC plasma levels determined in emergency and were included in the study, nine patients receiving dabigatran, 11 rivaroxaban and 8 apixaban. The DOAC levels were low in 8/28 patients (28.6% of the sample), intermediate in 4 (14.3%) and high in 16 (57.1%). The most prevalent stroke subtype was the small vessel disease, according to the A-S-C-O phenotypic classification, in 53.6% of our sample. The most common clinical presentation was "minor stroke" in 71.4% of the cases. There was a significantly higher proportion of patients with high DOAC levels in the small vessel group, compared to the cardioembolic group without other phenotypes. The question arises as to the most suitable clinical management of AIS in these patients on DOACs. In the current absence of clear evidence, taking into account the DOAC levels (low/intermediate/high) and the underlying stroke pathophysiology, we present a flowchart of our proposed clinical management of ischemic stroke in patients while on DOAC.

The use of 4F-PCC to correct direct oral anticoagulant-induced coagulopathy: An observational analysis.

BACKGROUND: With the approval of four-factor prothrombin complex concentrate (4F-PCC, Kcentra) for the reversal of vitamin K antagonist-associated bleeding in the United States, it has become a relatively common practice for 4F-PCC to be used in an "off-label" fashion to correct coagulopathy caused by direct oral anticoagulants (DOACs). However, the efficacy and safety of 4F-PCC have not been well studied in this scenario. MATERIALS AND METHODS: We performed a retrospective observational study on the off-label use of 4F-PCC for reversing bleeding associated with DOACs in a level 1 trauma centre between November 2014 and February 2017. International normalised ratio (INR) and Hgb prior to and post 4F-PCC infusion, clinical outcome and thromboembolic events within 24 hours and 45 days of 4F-PCC administration were collected. RESULTS: We identified 24 patients on DOACs who received 4F-PCC for severe haemorrhage and emergent surgeries. Most patients showed improved haemorrhage as demonstrated by stabilised intracranial haemorrhage sizes and/or by steady Hgb levels. No thromboembolic event was identified within 24 hours of 4F-PCC administration. However, 16.7% patients (4/24) experienced thromboembolic events 2 to 45 days after receiving 4F-PCC. CONCLUSION: Our data showed that 4F-PCC was relatively efficient in correcting DOAC-induced coagulopathy. We did notice that 16.7% of patients experienced some form of thromboembolic events in the days-to-weeks after 4F-PCC administration, although the imputability of 4F-PCC in these processes (vs their underlying disease) is difficult to determine. Additional prospective studies would be warranted to further evaluate the safety of 4F-PCC for this off-label indication.

Use of Direct Oral Anticoagulants in Patients with Sickle Cell Disease and Venous Thromboembolism: A Prospective Cohort Study of 12 Patients.

Patients with sickle cell disease have an increased risk of venous thromboembolism (VTE) and with a mortality 2-fold higher. The anticoagulation of VTE in a young population is an important question. Indeed, hemorrhagic complications of anticoagulation may occur more frequently than in the general population. The use of a direct oral anticoagulant (DOAC) is not recommended for VTE in patients with sickle cell disease because those patients were not included in the clinical studies. We aimed to study the safety of using DOACs in a prospective cohort of patients with sickle cell disease and VTE. We prospectively followed the cohort of all sickle cell disease patients undergoing recent DOAC treatment for VTE at a sickle cell disease reference center. Twelve patients received rivaroxaban for VTE (eight women and four men). The median age was 27 years (20-45). The sickle cell disease variants included homozygous Hb SS (HBB: c.20A>T) in eight patients, Hb S-ß+-thalassemia (Hb S-ß+-thal) in two, Hb S-ß0-thal in one and Hb S-Hb C (HBB: c.19G>A) in one. The cumulative duration of follow-up was 3134 days under rivaroxaban treatment. There were two thrombotic events, including a patient with a double positivity of antiphospholipid antibodies. No major bleeding was observed, and 6/12 patients presented minor bleeding (epistaxis: n = 4; anal fissure bleeding: n = 1; menorrhagia n = 4). Of these, 3/6 required their treatment to be switched to apixaban, which stopped the bleeding. Direct oral anticoagulants may be an alternative treatment for VTE in patients with sickle cell disease, except for an associated antiphospholipid syndrome.

Management of Direct Oral Anticoagulants in Patients with Atrial Fibrillation Undergoing Cardioversion.

Atrial fibrillation the most common cardiac arrhythmia. Its incidence rises steadily with each decade, becoming a real "epidemic phenomenon". Cardioversion is defined as a rhythm control strategy which, if successful, restores normal sinus rhythm. This, whether obtained with synchronized shock or with drugs, involves a periprocedural risk of stroke and systemic embolism which is reduced by adequate anticoagulant therapy in the weeks before or by the exclusion of left atrial thrombi. Direct oral anticoagulants are safe, manageable, and provide rapid onset of oral anticoagulation; they are an important alternative to heparin/warfarin from all points of view, with a considerable reduction in bleedings and increase in the safety and quality of life of patients.

Direct oral anticoagulants in oncology in clinical praxis.

Relation between oncological diseases and venous thrombo-embolism (VTE) is well known for almost 2 centuries. In 1823 Bouillaud assumed by three patients with tumor and recent deep vein thrombosis (DVT), that peripheral edema of lower limbs emerges as a result of „obturation“ of veins by „fibrinous coagulum“ (caillot fibrineux), which was induced by oncological disease. French physician Armand Trousseau wrote about this relation in his book „Phlegmasia alba dolens” again in the year 1865. Many studies were developed in times of Bouillaud a Trousseau, which just confirmed existence of relation between tumor and VTE. Oncological disease presents a significant risk factor of formation of VTE. Recent references favorising the use of light molecular weight heparin (LMWH) in long-term anticoagulation therapy of patients with cancer. Recently we have just few clinical data about efficiency and safety of direct oral anticoagulants (DOACs) in oncological patients, however many meta-analysis of clinical studies has shown benefit of therapy with DOACs towards conventional therapy. Key words: direct oral anticoagulants (DOACs) - oncology - venous thromboembolism.

New predictive model for acute gastrointestinal bleeding in patients taking oral anticoagulants: A cohort study.

BACKGROUND AND AIM: The study developed a predictive model of long-term gastrointestinal (GI) bleeding risk in patients receiving oral anticoagulants and compared it with the HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratios, Elderly, Drugs/alcohol concomitantly) score. METHODS: The study periodically followed a cohort of 508 patients taking oral anticoagulants (66 direct oral anticoagulants users and 442 warfarin users). Absence of GI bleeding at an initial examination and any subsequent GI bleeding were confirmed endoscopically. The bleeding model was developed by multivariate survival analysis and evaluated by Harrell's c-index. RESULTS: During a median follow-up of 31.4 months, 42 GI bleeds (8.3%) occurred: 42.8% in the upper GI tract, 50.0% in the lower GI tract, and 7.1% in the middle GI tract. The cumulative 5 and 10-year probability of GI bleeding was 12.6% and 18.5%, respectively. Patients who bled had a significantly higher cumulative incidence of all-cause mortality (hazard ratio 2.9, P < 0.001). Multivariate analysis revealed that absence of proton pump inhibitor therapy, chronic kidney disease, chronic obstructive pulmonary disease, history of peptic ulcer disease, and liver cirrhosis predicted GI bleeding. The c-statistic for the new predictive model using these five factors was 0.65 (P < 0.001), higher than the HAS-BLED score of 0.57 (P = 0.145). CONCLUSIONS: Gastrointestinal bleeding increased the risk of subsequent mortality during follow-up of anticoagulated patients, highlighting the importance of prevention. The study developed a new scoring model for acute GI bleeding risk based on five factors (no-proton pump inhibitor use, chronic kidney disease, chronic obstructive pulmonary disease, history of peptic ulcer disease, and liver cirrhosis), which was superior to the HAS-BLED score.

Hospital length of stay in patients initiated on direct oral anticoagulants versus warfarin for venous thromboembolism: a real-world single-center study.

This study was conducted to describe the real-world hospital length of stay in patients treated with all of the U.S. Food and Drug Administration approved direct oral anticoagulants (DOACs) versus warfarin for new-onset venous thromboembolism (VTE) at a large, tertiary, academic medical center. A retrospective cohort analysis of all adult patients diagnosed with acute onset VTE was conducted. Of the 441 patients included, 261 (57%) patients received DOACs versus 180 (41%) patients received warfarin. In the DOAC group, a total of 92 (35%) patients received rivaroxaban, followed by 83 (32%) patients received apixaban, 50 (19%) patients received dabigatran, and 36 (14%) patients received edoxaban. Patients initiated on DOACs had a statistically significant shorter hospital length of stay compared to patients initiated on warfarin (median 3 days, [IQR 0-5] vs. 8 days [IQR 5-11], P < 0.05). Despite the shorter hospital length of stay in patients receiving DOACs, the overall reported differences between the DOACs group and the warfarin group in terms of recurrent VTE, major bleeding, intracranial bleeding, and gastrointestinal bleeding at 3 and 6 months were deemed to be statistically insignificant.

Evaluation of anticoagulation selection for acute venous thromboembolism.

Treatment of venous thromboembolism (VTE) has been confined to parenteral agents and oral vitamin K antagonists for decades; however, with the approval of the direct oral anticoagulants (DOACs), clinicians now have more options. This study aims to evaluate the real world prescribing practices of all oral anticoagulants for VTE at a single center. A retrospective cohort analysis of all adult patients diagnosed with acute onset VTE was conducted. Of the 105 patients included in the analysis, 45 (43 %) patients received warfarin and 60 (57 %) patients received a DOAC. Rivaroxaban and apixaban were the most common DOACs initiated. There were significantly more patients in the warfarin group with an eCrCl of <60 ml/min compared to patients who received a DOAC (77.8 % vs. 15 %; P < 0.05). There were significantly less patients in the warfarin group with serum aminotranferase concentrations three times the upper limit of normal compared to those who received a DOAC (15.6 % vs. 55 %; P < 0.05). Patients who received a DOAC had less days on parenteral anticoagulation compared to patients who received warfarin (median 2.5 days [IQR 0-4] vs. 6 days [IQR 5-7], p < 0.05). Patients who received a DOAC had a shorter hospital length of stay compared to patients who received warfarin (median 3 days [IQR 2-4] vs. 8 days [IQR 6-10], p < 0.05). This analysis showed that DOACs are being prescribed more than warfarin for treatment of new onset VTE. Renal and liver function may influence the agent prescribed. Utilization of DOACs may decrease the hospital length of stay.