Use Of DOACs Research Articles

Predictors of inappropriate dosing of direct oral anticoagulants in nonagenarian patients with atrial fibrillation

Abstract Background Direct oral anticoagulants (DOACs) are presented as a good option for older patients owing to their safety profile. However, the dosing can become challenging especially in this population. Objective Our aim is to evaluate the predictors of inappropriate dosing of DOACs. Methods The authors analyzed the use of DOACs in 726 patients aged ≥90 years with a diagnosis of atrial fibrillation (AF) from a retrospective multicenter registry from 3 health areas in Spain. We studied the dosing, differentiating between appropriate dose, underdosing or overdosing. To evaluate the best predictive model, the Akaike information criterion (AIC) was used. Results Follow-up was 27.7±18.3 months. Mean age was 93.0±5.2 years, and 60.1% of patients were female. 339 patients received rivaroxaban (47.3%), 237 apixaban (33.1%), 105 dabigatran (14.7%) and 35 edoxaban (4.9%). An important proportion of patients received a suboptimal dose (41.5%, n=297): 35.3% underdosed and 6.1% overdosed. The rate of suboptimal dosing was higher for apixaban and lower for dabigatran (Figure 1A). In our registry we found as a predictors of inappropriate dosing: kidney function (Chronic Kidney Disease Epidemiology Collaboration), odds Ratio (OR) 1.04; 95% CI: 1.03–1.05, P<0.001; weight measured in kilograms, OR 1.04; 95% CI: 1.01–1.07, P=0.012; and high blood pressure (HBP), OR 1.61; 95% CI: 1.02–2.53, P=0.041 (Figure 1B). Other variables such as HASBLED, CHADSVASc, anemia, prior bleeding, or concomitant use of antiplatelet therapy, were not significantly associated. Conclusions We want to highlight that the use of an inappropriate dose of DOAC in older patients is common, about 40% in our study. Apixaban was the most frequently underdosed DOAC. HBP, weight, and kidney function were associated with an inappropriate dosing prescription. Therefore, it is important to carefully evaluate the characteristics of the patient to prescribe the appropriate dose that guarantees a correct action. Funding Acknowledgement Type of funding sources: None. Dosing of DOACsPredictors of inappropriate dosing

Direct Oral Anticoagulants in Patients with Obesity and Atrial Fibrillation: Position Paper of Italian National Association of Hospital Cardiologists (ANMCO).

The use of the direct oral anticoagulants dabigatran, rivaroxaban, apixaban and edoxaban (DOACs) offers some major advantages over warfarin and other vitamin K antagonists (VKAs). One advantage is the possibility to use a fixed dose in normal-weight patients, overweight patients and patients with obesity. However, the “one size fits all” strategy raised a concern regarding the possibility to undertreat patients with a high body mass index. No randomized controlled trials (RCTs) have ever compared VKAs and DOACs in this population. We analyzed data from the literature on DOAC pharmacokinetics and pharmacodynamics, results from the four pivotal phase III trials on non-valvular atrial fibrillation, retrospective observational studies and metanalyses. While we are aware of the limitation imposed by the absence of specific RCTs, we propose the position of the Italian Association of Hospital Cardiologists (ANMCO) on the use of DOACs in patients with obesity based on the existing evidence.

Pharmacokinetics of Direct Oral Anticoagulants in Patients With Atrial Fibrillation and Extreme Obesity

PurposeDirect oral anticoagulants (DOACs) are recommended in preference to vitamin K antagonists (VKAs) for stroke prevention in patients with atrial fibrillation (AF) eligible for oral anticoagulation therapy; however, data and clinical experiences supporting the use of DOACs in patients with a body mass index ≥40 kg/m2 or weight >120 kg remain limited. The aim of this study was to evaluate the pharmacokinetic properties of DOACs in patients with AF and extreme obesity. MethodsWe enrolled all consecutive patients with AF and extreme obesity undergoing treatment with DOACs followed up at Monaldi Hospital, Naples, Italy. To determine peak plasma and trough levels of DOACs, plasma samples were collected at 2nd, 4th, 6th, and 12th hours from the last dose intake in patients receiving apixaban and dabigatran and at the 2nd, 4th, 6th, and 24th hours in those receiving edoxaban and rivaroxaban. The DOACs’ peak and trough plasma levels obtained from our study population were compared with those sourced from pharmacokinetic studies among patients without obesity, defined as a normal reference range in the literature. If at least 1 peak or trough plasma level was found ​​below or above the normal reference ranges, the patients were classified as having out-of-range DOAC plasma levels. Study population was then divided into in-range and out-of-range groups. Baseline characteristics, including DOAC treatment, were compared between the 2 groups. Univariate and multivariate logistic regression analysis were performed to identify baseline variables associated with DOACs’ plasma concentration out of the expected range. FindingsA total of 58 patients (mean [SD] age, 70.93 [8.73] years; 40% female) with extreme obesity (mean [SD] body mass index. 44.43 [3.54] kg/m2) and AF while undergoing DOAC treatment were included in the present study. In 9 patients (15.5 %), the DOAC plasma concentrations were out of the expected ranges (out-of-range group);, indicating a greater likelihood of edoxaban 30 mg treatment (33% vs 2%; P < 0.01) and inappropriate DOAC underdosing (56% vs 4%; P < 0.005) compared with the in-range group. According to the multivariate logistic analysis (P = 0.0011), the inappropriate DOAC underdosing (hazard ratio = 29.37; P = 0.0002) was an independent predictor of DOAC plasma levels out of the expected ranges. ImplicationsPatients with extreme obesity and AF who were receiving DOAC therapy had DOAC plasma concentrations in the expected range. The inappropriate DOAC underdosing seems to be the only independent clinical factor associated with a plasma concentration of the drug out of the expected range.

Impact of a pharmacist‐to‐dose direct oral anticoagulant protocol on medication errors at an academic medical center

AbstractBackgroundDirect oral anticoagulants (DOACs) are considered high‐risk medications and pose a serious threat to patients if mismanaged. Furthermore, medication error rates involving DOACs in the acute care setting range from 25% to 40%. To reduce medication error rates at our institution, we implemented a pharmacist‐driven DOAC protocol that permitted pharmacists to independently order and monitor DOACs pursuant to a consult order.ObjectiveTo determine the impact of a pharmacist‐to‐dose DOAC protocol on medication errors at an academic medical center.MethodsThis was a retrospective, single‐center cohort study using a pre‐post design to evaluate the impact of a pharmacist‐to‐dose DOAC protocol on rates of medication errors. Patient data were evaluated during a 6‐month period before and after the implementation of the protocol. Patients were excluded if they were receiving a DOAC for an indication other than venous thromboembolism and/or atrial fibrillation.ResultsA total of 502 patients (pre‐phase = 256; post‐phase = 246) admitted to the hospital and receiving a DOAC were included in the study. A total of 41 patients in the pre‐phase received a medication error involving a DOAC compared with 22 patients in the post‐phase (16% vs 8.9%; relative risk reduction 44%; P = .017). Rates of near misses were numerically higher in the post‐phase group (7.4% vs 11.8%; P = .1), and rates of discharge DOAC errors were numerically lower (8.5% vs 4.9%; P = .1). The most common error was underdosing (N = 31).ConclusionIn this study, the implementation of a pharmacist‐to‐dose DOAC protocol was associated with a 44% reduction in DOAC‐related medication errors. These findings underscore the impact of a protocolized approach to DOAC management, as well as the role of pharmacists in overseeing inpatient DOAC use and reducing medication errors.

The effect of chronic DOAC treatment on clinical outcomes of hospitalized patients with COVID-19.

BackgroundRecent findings indicate that thrombosis is one of the underlying pathophysiology and complication of COVID‐19 infection. Therefore, the prognosis of the disease may be more favourable in people who were under oral anticoagulant treatment before the COVID‐19 diagnosis. This study aims to evaluate the effects of chronic DOAC use on ICU admission and mortality in hospitalized patients due to COVID‐19 infection.MethodBetween 1 September and 30 November 2020, 2760 patients hospitalized in our hospital due to COVID‐19 were screened. A total of 1710 patients who met the inclusion criteria were included in the study. The patients were divided into two groups as those who use DOAC due to any cardiovascular disease before the COVID‐19 infection and those who do not.ResultsSeventy‐nine patients were enrolled in the DOAC group and 1631 patients in the non‐DOAC group. Median age of all study patient was 62 (52‐71 IQR) and 860 (50.5%) of them were female. The need for intensive care, in‐hospital stay, and mechanical ventilation were observed at higher rates in the DOAC group. Mortality was observed in 23 patients (29%) in the DOAC group, and it was statistically higher in the DOAC group (P = .002). In the multivariable analysis, age (OR: 1.047, CI: 1.02‐1.06, P < .001), male gender (OR: 1.8, CI: 1.3‐2.7, P = .02), lymphocyte count (OR: 0.45, CI: 0.30‐0.69, P < .001), procalcitonin (OR: 1.12, CI: 1.02‐1.23, P = .015), SaO2 (OR: 0.8, CI: 0.77‐0.82, P < .001) and creatinine (OR: 2.59, CI: 1.3‐5.1, P = .006) were found to be associated with in‐hospital mortality. DOAC treatment was not found to be associated with lower in‐hospital mortality in multivariable analysis (OR:1.17, CI: 0.20‐6.60, P = .850).ConclusionOur study showed that the use of DOAC prior to hospitalization had no protective effect on in‐hospital mortality and intensive care need in hospitalized COVID‐19 patients.

Dose specific effectiveness and safety of DOACs in patients with non-valvular atrial fibrillation: A Canadian retrospective cohort study

BackgroundDirect oral anticoagulants (DOACs) have been proven to be effective and safe for prevention of ischemic stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). However, suboptimal adherence, variable dosing and use in patient populations that otherwise would have been excluded from clinical trials may impact the efficacy and safety profile of DOACs in a routine care setting. We compared stroke, bleeding, and mortality rates on and off therapy for standard and low-dose DOACs (apixaban, rivaroxaban, dabigatran) versus warfarin in a Canadian cohort. We also assessed persistence of DOACs compared to warfarin. MethodsWe conducted six 1-1 propensity-score matched retrospective cohort analyses using Quebec health administrative databases (2011–2017). NVAF patients (≥18 years) covered by the public medication insurance plan entered the cohort on the first OAC dispensation date. We excluded those with OAC use in the previous year or stroke or bleeding diagnoses in the previous two years. Follow-up ended at death, March 2017 or end of medication coverage by the public plan. Time-dependent Cox regression was applied. ResultsWe evaluated 10,893 patients initiated on apixaban (7206 standard, 3687 low-dose), 10,190 on rivaroxaban (7396 standard, 2794 low-dose), 5884 on dabigatran (2756 standard, 3128 low-dose), and propensity score-matched warfarin users. Across standard-dose DOACs, compared to warfarin, stroke risks were similar; bleeding risks were lower with apixaban (hazard ratio 0.63; 95% confidence interval 0.52–0.77) and dabigatran (0.47; 0.35–0.64) but not rivaroxaban (0.93; 0.79–1.10); death risks were lower with all DOACs. For low-dose DOACs, rivaroxaban demonstrated higher stroke (1.79; 1.21–2.64) and bleeding risks (1.37; 1.09–1.73); other agents had stroke risks similar to warfarin and bleeding risks lower than warfarin; only low-dose dabigatran had lower death risk (0.59; 0.52–0.68). Treatment discontinuation was lower with DOACs versus warfarin with the exception of low-dose rivaroxaban. The risks of stroke were 2–4 folds higher during time off any OAC versus time on warfarin. The risks of death were higher, while the risks of bleeding were generally lower during times off any OAC. ConclusionsStandard-dose DOACs had similar stroke, better persistence and mortality profiles than warfarin. Only standard dose apixaban and dabigatran had better bleeding profiles than warfarin. Low-dose rivaroxaban had worse persistence, stroke and bleeding profiles than warfarin, while low-dose apixaban and dabigatran had similar stroke and better bleeding profiles. Real-world use of DOACs may explain some of the differences observed in Canadian routine care versus the phase III clinical trials.

The prevention and treatment of bleeding associated with direct oral anticoagulants

Direct оral Anticoagulants (DOACs) include direct thrombin inhibitor (dabigatran) and factor X inhibitors (rivaroxaban, apixaban, edoxaban, betrixaban). The) are widely used worldwide for the prevention and treatment of venous thrombosis. The popularity of DOACs is explained by convenient and predictable pharmacodynamics, the lack of need for regular monitoring of the therapeutic effect, as well as more predictable food-drug interaction and bioavailability. However, like any other anticoagulants, DOACs are characterized by an increased risk of bleeding, especially gastrointestinal one. The correct approach to the prescription of DOACs and prevention of bleeding during treatment including the intake of anticoagulants can significantly reduce the probability of life-threatening complications. In the case of bleeding, the use of specific and nonspecific DOACs antidotes is indicated. Significant bleeding requires the attending physician to know a clear course of action in accordance with published algorithms to save the patient’s life.

Abstract 16088: Mortality Trend Among Patients With Atrial Fibrillation on Long Term Anticoagulation Who Developed Intracranial Hemorrhage: Insights From the National Inpatient Database From 2006 to 2014

Introduction: Intracranial hemorrhage (ICH), is a potential complication of anticoagulation use in atrial fibrillation (AF). During the last decade, guidelines have evolved from recommending vitamin K antagonists to a preference for DOACs in the case of non-valvular AF after FDA approval in 2010. Data have reported that DOACs have a lower rate of ICH and an overall better clinical profile when compared to VKA. Aim: We sought to describe the rate of ICH and its associated mortality h with the increment in the use of DOACs over the period of 2006 to 2014 in the US population with AF. Methods: We queried the NIS database 2006-2014. AF patients, patients using long term anticoagulation, and intracranial hemorrhage admissions were selected using the appropriate ICD-9 codes. Time trend was analyzed using Chi-square. In-hospital mortality was evaluated by binomial logistic regression. Results: We found a 30740346 weighted population with AF between 2006 and 2014. 16.8 % were long term users of anticoagulants. Of them, 1.1% (n: 56400) were admitted due to ICH. Long term anticoagulation use in AF went from 13.3% in 2006 to 17.3% in 2010 (p&lt;0.001). Among AF patients, 30.7% of patients had in-hospital death when admitted for ICH using long term anticoagulation. Long term anticoagulation was associated with increased in-hospital death in ICH patients aOR 1.31 (95% CI 1.24 - 1.39) when compared to those not using long term anticoagulation. Patients with AF and long term use of anticoagulants showed an increased frequency of in-hospital mortality from 32.7% in 2006 to 34.2% in 2007 and a decrease to 30.9% up to 2010. The decrease in mortality rate was more notorious from 2010 to 2014 going to 25.8% (p&lt; 0.001). Conclusions: The rate of ICH diagnosis among anticoagulated atrial fibrillation patients has remained stable after the introduction of DOACs. Rates of inpatient death have decreased from 2006 to 2014 having the most notorious inflection point in 2010 after the progressive introduction of DOACs .

Abstract 15824: Safety and Efficacy of Periprocedural Direct Oral Anticoagulant versus Aspirin Use for Reduction of the Risk of Cerebrovascular Events in Patients Undergoing Ventricular Tachycardia Radiofrequency Catheter Ablation (STROKE-VT)

Background: The STROKE-VT is an ongoing, multicenter, randomized controlled trial that studies the differences in cerebrovascular events between DOAC vs ASA use post procedurally in ischemic and non-ischemic cardiomyopathy patients undergoing left ventricular tachycardia radiofrequency ablation (VT RFA). Methods: 52 Eligible patients scheduled for VT RFA were randomized 1:1 post procedurally to a DOAC (n=26; Dabigatran-11/Rivaroxaban-12 &amp; Apixaban-3) or ASA (n=26, 81mg) for 30 days. VT ablation was performed under moderate sedation or general anesthesia either through retrograde aortic (n=28) or transseptal (n=24) approach. All patients were given IV heparin for ACT&gt;300msec. Study drug was administered 3 hours after hemostasis. A brain MRI was done within 6-12 hours post VTRFA and at 30 days. NIH stroke scale was used to assess for neurological changes before, after and at 30 day follow up. Results: 52 patients (M:F- 4.2:1) with 55% ICM were enrolled. DOAC group was slightly older (65±8 vs 60±6 yrs, p=0.04)), had longer procedural (186±76 vs 150±51, p&lt;0.001) and RF time (45 ± 23 vs 24±23, p=0.01) and greater use of transseptal approach (58 vs 42%, p=0.03) compared to the ASA group. One patient in the ASA group had a TIA in the immediate postop period. 31% (16/52) had acute asymptomatic cerebral embolizations (ACE) (25% vs 5% with Retrograde aortic approach). DOAC group had a significantly lower incidence of ACE at 1 month f/u MRI (8 vs 38%, p&lt;0.001). On multivariate analysis predictors of acute post VTRFA ACE were retrograde aortic approach, prolonged procedure and RFA time, while delayed ACE was ASA therapy. Two patients died of progressive heart failure with one in each group. 1 patient had a TIA during f/u in the ASA group. Conclusions: DOAC decrease the incidence of delayed ACE after VTRFA. However, retrograde aortic approach and prolonged procedural and RFA time can increase the risk of acute ACE.

Direct Oral Anticoagulants for Myeloproliferative Neoplasms (MPN-DOACs): Results from an International Study on 442 Patients

Direct Oral Anticoagulants for Myeloproliferative Neoplasms (MPN-DOACs): Results from an International Study on 442 Patients

Stroke, systemic embolism and bleeding rate in non-valvular atrial fibrillation patients without anticoagulation on the real world data in Japan

Abstract Background Anticoagulant therapy is recommended in patients with non-valvular atrial fibrillation (NVAF) for those with CHADS2 ≥2. However, there have been significant number of subjects with CHADS2 ≥2 who receive no anticoagulation. Most of reported real world data have been collected mainly before wide spread use of DOAC. This study evaluated the clinical outcome of no anticoagulant drug therapy in NVAF. Methods This study is a non-interventional, observational, retrospective cohort study of NVAF patients in Mie-LIP Database, which is a regional clinical database joining 1 university hospital and 8 general hospitals in Mie prefecture in Japan. Patient enrolment was conducted from 1st Jan. 2016 to 31st Dec. 2018. The primary outcome events are ischemic stroke, systemic embolism, and bleeding events (bleeding to need a blood transfusion, intracranial bleeding, intraocular bleeding, and gastrointestinal bleeding). Results 7001 patients were included in the current analysis, 2550 patients, 36.4% were treated without any anticoagulant drug therapy. Table 1 shows patients with no anticoagulant drug therapy, mean age was 75.4 years and 42.2% of patients were female. The most frequent comorbidities included hypertension (50.0%), diabetes mellitus (28.2%), heart failure (14.0%), ischemic stroke (12.7%), vascular disease (14.4%) respectively. The annual incidence of ischemic stroke, systemic embolism per 100 person-years is 3.7, and that in each CHADS2 group is 0: 1.4, 1: 1.4, 2: 3.2, 3–6: 8, respectively in Figure 1. The annual incidence of bleeding events is 1.5, and that in each CHADS2 group is 0: 0.7, 1: 1.0, 2: 1.2, 3–6: 2.9, respectively. Conclusions Approximately one-thirds of subjects have not received any anticoagulation in the modern DOAC in daily clinical practice in Japan. The rate of ischemic stroke and systemic embolism increased by CHADS2. Stroke or SEE rate was very low in subjects with CHADS2 ≤1, supporting no indication of anticoagulation in current guidelines. Regarding subjects with CHADS2&amp;gt;2, considering the higher risk of stroke, use of anticoagulant drug therapy is recommended. Funding Acknowledgement Type of funding source: None

Use of direct oral anticoagulants is associated with better long-term outcomes in patients with atrial fibrillation and heart failure as compared with vitamin K antagonists

Abstract Background Direct oral anticoagulants (DOACs) have been shown to be safe and effective in patients with atrial fibrillation (AF) as compared with warfarin, a vitamin K antagonist. However, the safety and efficacy of DOACs in patients with AF and heart failure (HF) have been unclear. Purpose The purpose of this study was to determine whether DOACs can improve long-term outcomes in patients with AF and HF as compared with warfarin. Methods We analyzed the JROADHF registry, which was a multicenter registry of patients hospitalized for the worsening HF in Japan. Baseline data were collected during the episode of index hospitalization from April 2013 to March 2014. Follow-up data were collected up to 4.5 years after the index hospitalization. Patients with AF and creatinine clearance ≥15 ml/min/1.73m2 were included. Valvular heart disease, congenital heart disease, and constrictive pericarditis were excluded. Eligible patients were divided into two groups according to the use of warfarin or DOACs. The primary outcome was defined as all-cause death. The secondary outcomes were defined as cardiovascular death, composite of all-cause death or cardiovascular hospitalization, and composite of stroke death or stroke related hospitalization. A one to one propensity case-matched analysis was used. Complete case analysis and multiple imputation analysis were also conducted as sensitivity analyses. Results Out of the 14,847 patients in this registry, 2,175 had AF, creatinine clearance ≥15 ml/min/1.73m2 and discharged alive. Propensity score matching yielded 475 pairs. In matching cohort, mean age was 76.5 years and 513 (54.0%) was male. Mean left ventricular ejection fraction was 48.6±16.4%. During a mean follow-up of 3.2 years, patients with DOACs had a lower incidence rate of all-cause death than those with warfarin (75.2 vs. 99.9 death per 1000 patient-years; rate ratio (RR) 0.75; 95% confidence interval [CI] 0.59–0.96; P=0.022). The incidence of cardiovascular death tended to be lower in DOAC group (30.9 vs. 43.1; incidence rate ratio 0.72; 95% CI 0.49–1.04; P=0.081). There were no significant differences in the incidence of composite of all cause death or cardiovascular hospitalization (252.3 vs. 269.4; RR 0.94; 95% CI 0.79–1.11; P=0.45) or composite of stroke death or stroke related hospitalization (13.1 vs. 16.7; RR 0.79; 95% CI 0.39–1.59; P=0.50). Cox regression model showed that DOAC was associated with lower mortality than warfarin (hazard ratio (HR) 0.75; 95% CI 0.59–0.96; P=0.023). Complete case analysis (HR 0.78; 95% CI 0.63–0.98; P=0.035) and multiple imputation analysis (HR 0.78; 95% CI 0.68–0.84; P&amp;lt;0.001) also showed the same results. A restricted cubic spline analysis demonstrated that the effectiveness of DOACs over warfarin waned with age, and DOACs were effective in patients younger than 80 years old. Conclusion Use of DOACs was associated with better long-term outcome in patients with HF as compared with warfarin. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Japan Agency for Medical Research and Development

Direct Oral Anticoagulant Use in Chronic Kidney Disease and Dialysis Patients With Venous Thromboembolism: A Systematic Review of Thrombosis and Bleeding Outcomes.

To evaluate how treatment with DOACs for VTE affects thrombosis and bleeding outcomes compared to warfarin in CKD and dialysis patients. A literature search was conducted for studies evaluating VTE and bleeding outcomes with DOAC use in CKD and dialysis patients. Searches conducted through EMBASE, MEDLINE/PubMed, Scopus, and Cochrane Central Register of Controlled Trials, from inception to September 22, 2020. Randomized controlled trials, cohort studies, and case series with ≥10 patients included. From 7286 studies, nine studies met inclusion criteria. There was no significant difference between DOACs (dabigatran, rivaroxaban, apixaban) and warfarin for reducing recurrent VTE and bleeding events in moderate CKD patients. The risk of overall major bleeding increased when the degree of kidney impairment increased. There was no significant difference between apixaban and warfarin for VTE outcomes in dialysis patients. There continues to be a controversial debate whether it may be more beneficial to use DOACs versus warfarin in CKD/dialysis patients with venous thromboembolism (VTE). The risk vs benefit of using DOACs in the CKD/ESKD population should continue to be evaluated for each individual patient. Apixaban may be used cautiously as an alternative in acute VTE treatment in severe CKD patients. Insufficient evidence is available to suggest the use of dabigatran and rivaroxaban in this patient population. The benefit of using DOACs in this population for VTE treatment should be weighed against the potential bleeding risk in patients with CKD.

Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation and cancer a meta-analysis

BackgroundDirect oral anticoagulants (DOACs) are recommended as first-line anticoagulants in patients with atrial fibrillation (AF). However, in patients with cancer and AF the efficacy and safety of DOACs are not well established.ObjectiveWe performed a meta-analysis comparing available data regarding the efficacy and safety of DOACs vs vitamin K antagonists (VKAs) in cancer patients with non-valvular AF.MethodsAn online search of Pubmed and EMBASE libraries (from inception to May, 1 2020) was performed, in addition to manual screening. Nine studies were considered eligible for the meta-analysis involving 46,424 DOACs users and 182,797 VKA users.ResultsThe use of DOACs was associated with reduced risks of systemic embolism or any stroke (RR 0.65; 95% CI 0.52–0.81; p 0.001), ischemic stroke (RR 0.84; 95% CI 0.74–0.95; p 0.007) and hemorrhagic stroke (RR 0.61; 95% CI 0.52–0.71; p 0.00001) as compared to VKA group. DOAC use was associated with significantly reduced risks of major bleeding (RR 0.68; 95% CI 0.50–0.92; p 0.01) and intracranial or gastrointestinal bleeding (RR 0.64; 95% CI 0.47–0.88; p 0.006). Compared to VKA, DOACs provided a non-statistically significant risk reduction of the outcomes major bleeding or non-major clinically relevant bleeding (RR 0.94; 95% CI 0.78–1.13; p 0.50) and any bleeding (RR 0.91; 95% CI 0.78–1.06; p 0.24).ConclusionsIn comparison to VKA, DOACs were associated with a significant reduction of the rates of thromboembolic events and major bleeding complications in patients with AF and cancer. Further studies are needed to confirm our results.

USE OF DIRECT ACTING ORAL ANTICOAGULANTS FOR PULMONARY EMBOLISM AND DVT IN PATIENTS WITH CIRRHOSIS

SESSION TITLE: Pulmonary Vascular Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Direct acting oral anticoagulants are increasingly used in the treatment of venous thromboembolism including deep venous thrombosis and pulmonary embolism, however their use in patients with cirrhosis is unclear Patients with cirrhosis were excluded from the clinical trials conducted for DOACs and DOACs are currently not approved for use in Child Class C cirrhosis, and data on these patients remains very scarce METHODS: In this retrospective cohort study, we compared the clinical outcomes of cirrhotics treated with DOACs and Warfarin for DVT or PE at our institute. RESULTS: A total of 225 patients with cirrhosis on anticoagulation for DVT or PE were included for analysis, of which 113 were female (50.2%). Of these patients, 176 patients and 55 patients were diagnosed with DVT and PE at the time of anticoagulant initiation respectively (6 patients had both). 73 patients (32.4%) were prescribed warfarin while 152 patients received DOACs (67.6%). Eliquis was the most frequent DOAC (84 patients), followed by Xarelto (68 patients). 66 patients (29.3%) had advanced (Child C) cirrhosis; 26 patients in warfarin and 40 in DOAC group respectively. 37 patients (16.4%) experienced a significant bleeding event during follow up. There was no difference in the rate of bleeding in the two groups; 25 patients in DOAC group and 12 patients in warfarin group (16.4% in both separate groups). Univariate analysis revealed that type of anticoagulant (p = 0.999), indication (p = 0.66), gender (p = ), concurrent antiplatelets (p = 0.89), presence of varices (p = 0.62), platelet level (p = 0.36) were not associated with bleeding events while presence of advanced (Child C cirrhosis) was associated with bleeds at follow up (p = 0.015). Multivariable logistic regression model was fitted incorporating age, time on anticoagulant, antiplatelet therapy, child C cirrhosis, and type of anticoagulant as covariates and bleeds at follow up as dependent variable. Only Child C cirrhosis was found to be independently linked to increased risk of bleed (OR: 2.46, 95% CI 1.18 – 5.12). Prescription of DOAC compared to warfarin was not linked to bleeding (OR 1.16, 95% CI 0.53 – 2.52). A total of 5 patients experienced failure of anticoagulation (recurrent thromboembolism while anticoagulated); 2 in DOAC group and 3 patients in warfarin group. CONCLUSIONS: No difference in bleeding rates was found between DOAC and Warfarin groups in patients with cirrhosis anticoagulated for DVT and PE, including patients with Child Class C cirrhosis. Patients with Child C cirrhosis are more likely to bleed compared to those with Child Class and A and B cirrhosis. CLINICAL IMPLICATIONS: DOAC use is unstudied in Child C cirrhosis and is currently not approved. Our study adds vital new data elucidating safety and efficacy of DOAC use in patients with cirrhosis for these indications. DISCLOSURES: No relevant relationships by Sana Ali, source=Web Response No relevant relationships by Yousaf Hadi, source=Web Response No relevant relationships by Ali Khan, source=Web Response no disclosure on file for Justin Kupec; No relevant relationships by Dhairya Lakhani, source=Web Response No relevant relationships by Syeda Fatima Naqvi, source=Web Response No relevant relationships by FNU Rida Ul Jannat, source=Web Response

S1230 Non-Vitamin K Oral Anticoagulants (NOACs) vs Low Molecular Weight Heparin (LMWH) for the Treatment of Venous Thromboembolism in the Setting of Gastrointestinal and Pancreato-Biliary Malignancies—A Meta-Analysis

INTRODUCTION: The safety and efficacy of NOAC use compared with low molecular weight heparin (LMWH) use, the current standard of care for the treatment of gastrointestinal and pancreatobiliary cancer associated venous thromboembnolism (GI-CAVTE), has not been well studied. METHODS: A systematic review of Medline and Embase was conducted from inception to April 2020 to identify studies reporting the use of NOACs and LMWH for the treatment of GI-CAVTE. A meta-analysis of proportions as well as a comparative meta-analysis was performed to assess safety and efficacy. GI bleeding events were recorded and reported descriptively. RESULTS: Three observational studies enrolling 561 patients (213 on NOACs; 348 on LMWH) were found, 154 of whom were females. Pancreatobiliary malignancies were the most common in the NOAC group (N = 79), followed by gastric cancer (N = 41) and colorectal cancer (N = 21). In contrast, gastric cancer was the most common malignancy in the LMWH arm (N = 149), followed by pancreatobiliary malignancy(N = 135), and colorectal cancer (N = 11). The risk of bias as assessed by the ROBINS-I tool was moderate in 1 and serious in 2 studies. The OBR was 29% (23–35) with NOAC use, of which 28% (16–40%) were major bleeds and 81% (70-91%) were CRNMB. In contrast, the OBR with LMWH use was 20% (16–24%), of which 38% (26–49%) were major bleeds and 67% (56–78%) were CRNMB. Fatal bleeding events occurred in 7% (0–15%) of patients on NOACs and 9% (1–16%) of patients on LMWH. The risk of OBR was higher with NOAC use (RR 1.61; 1.19-2.19; I2 = 37.4%), as was the risk of CRNMB (RR 1.86; 1.27-2.72; I2 = 0%). However, no difference in major bleeding and fatal bleeding risk was found with NOAC versus LMWH use. Table 1 summarizes the reported gastrointestinal bleeding events across studies. The rVTE rate was 4% (1–6%) with NOAC use and 2% (1–4%) with LMWH use. There was no difference in the risk of rVTE, rDVT, rPE, or fatal VTE with NOAC versus LMWH use. CONCLUSION: NOACs may pose a greater risk of bleeding, particularly CRNMB, in patients with GI-CAVTE. We did not identify any signal of superior efficacy in term of rVTE, rDVT, or rPE risk with NOAC use compared with LMWH. The risk of bleeding from luminal malignancies while on NOACs remains to be studied further before any conclusions can be made. on Due to lack of randomized trials and a high number of observational studies, our findings are hypothesis generating at best, and further studies are needed to validate our findings.Table 1.: Reported Gastrointestinal Bleeding with DOAC and LMWH Use. CRNMB = Clinically relevant non-major bleeding; GI = gastrointestinalFigure 1.: Meta-Analysis of Proportions - Safety and Efficacy Endpoints - NOACs vs LMWH.Figure 2.: Comparative Meta-Analysis of Safety and Efficacy - NOAC vs LMWH.

The Effectiveness and Safety of Direct Oral Anticoagulants Following Lower Limb Fracture Surgery: A Systematic Review and Meta-analysis.

Venous thromboembolism (VTE) is a well-established complication after many orthopaedic injuries, such as hip and lower limb fractures. The use of direct oral anticoagulants (DOACs, previously termed novel oral anticoagulants) is well-established as thromboprophylaxis after major elective orthopaedic surgery, but not in the nonelective setting. The aim of this study was to investigate the effectiveness and safety of DOACs after nonelective lower limb fracture surgery. A systematic literature search of the MEDLINE, EMBASE, CINAHL, and CENTRAL databases was conducted. No limitation was placed on publication date, with only manuscripts printed in English were eligible. Included studies were either randomized controlled trials or prospective and retrospective comparative studies. Included studies compared DOACs to conventional methods of thromboprophylaxis in the postoperative period after surgical management of lower limb fractures. Outcomes included VTE, bleeding, wound complications, mortality, and adverse events. Eight studies met inclusion criteria, of which 7 compared direct factor Xa inhibitors (XaIs) with conventional VTE prophylaxis and one study compared a direct thrombin inhibitor with conventional VTE prophylaxis. Revman 5.3 (Nordic Cochrane Centre, Denmark) was used to complete the meta-analysis and generate forest plots. XaIs were shown to have lower rates of deep vein thrombosis (Odds ratio 0.59; 95% confidence interval, 0.46-0.76; P < 0.0001) and less pharmacologically attributable adverse events (Odds ratio 0.62; 95% confidence interval, 0.46-0.82; P = 0.0007). There was difference between DOACs and conventional VTE prophylaxis regarding mortality, PE, symptomatic deep vein thrombosis, or bleeding events. The results generally support the use of DOACs for VTE prophylaxis after nonelective lower limb fracture surgery, such after hip fracture. The results more strongly support the use of XaIs; however, more evidence is needed to fully assess DOACs' role in clinical practice. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Preliminary findings regarding the use of direct oral anticoagulants in cerebral venous thrombosis

BackgroundDirect oral anticoagulants (DOACs) have entered the treatment paradigms of various conditions based upon large randomized controlled trials. However, use of DOACs for thrombosis at unusual sites, such as cerebral venous thrombosis (CVT), is less clear as the ability to conduct large randomized controlled trials is limited by its rarity. Furthermore, its use in the setting of malignancy or in the elderly remains an area of ongoing research. ObjectiveOur aim was to assess the outcomes in CVT patients treated with DOACs compared to warfarin. We also sought to elucidate whether its use was safe in the setting of malignancy or in the elderly. MethodsRetrospectively assess the differences in clinical outcomes in patients hospitalized with CVT in the Lifespan Health System. ResultsBetween 1 July 2004 and 1 March 2020, 46 adult patients with CVT fulfilled inclusion criteria. No significant differences in outcomes were observed between the DOAC (N = 8) and vitamin K antagonist (VKA) (N = 38) cohorts. The use of DOACs did not result in an increased rate of acute complications, recurrent venous thromboembolism (VTE) and/or CVT, World Health Organization (WHO) grade 3 or 4 bleeding rates, or differences in clinical improvement per the modified Rankin scale. Furthermore, in patients with underlying metastatic cancer (N = 2) or in patients > 80 (N = 1) who received a DOAC, there was no increase in adverse events or significant differences in outcome when compared to warfarin. ConclusionPatients who received a DOAC in the treatment of CVT demonstrated no differences in outcomes when compared to warfarin.

Seasonal Variations in the Incidence of Ischemic Stroke, Extracranial and Intracranial Hemorrhage in Atrial Fibrillation Patients.

Ischemic stroke (IS) and major bleeding, which are serious adverse events in patients with atrial fibrillation (AF), could have seasonal variations, but there are few reports. In the Shinken Database 2004-2016 (n=22,018), 3,581 AF patients (average age, 63.5 years; 2,656 men, 74.2%; 1,388 persistent AF, 38.8%) were identified. Median CHADS2and HAS-BLED scores were both 1 point. Oral anticoagulants were prescribed for 2,082 (58.1%) patients (warfarin, 1,214; direct oral anticoagulants [DOACs], 868). Incidence and observation period (maximum 3 years) of IS, extracranial hemorrhage (ECH), and intracranial hemorrhage (ICH) were counted separately for the northern hemisphere seasons. During the mean follow-up period of 2.4 years, there were totals of 90 IS, 73 ECH, and 33 ICH cases. The respective incidence rates per 1,000 patient-years in spring, summer, autumn, and winter were 8.5, 8.8, 7.5, and 16.8 for IS, 7.2, 9.7, 3.8, and 13.1 for ECH, and 2.7, 1.9, 3.8, and 7.0 for ICH. The number of patients with DOACs relatively increased among those with ECH in summer. Significant seasonal variations were observed for IS, ECH, and ICH events in AF patients, and were consistently the highest in winter. A small peak of ECH was observed in summer, which seemed, in part, to be related to increased DOAC use.

Comparing stroke prevention therapy of direct oral anticoagulants and vitamin K antagonists in patients with atrial fibrillation: a nationwide retrospective observational study

BackgroundDirect oral anticoagulants (DOACs) are not only increasingly being used for the initial stroke prevention therapy but progressively also substitute vitamin K antagonist (VKA) treatment in patients with non-valvular atrial fibrillation (AF). DOACs have been compared regarding therapeutic efficacy and adverse outcomes to warfarin in several pivotal studies and showed non-inferiority in terms of stroke prevention and superiority in terms of bleeding complications. However, comprehensive comparative studies are lacking for phenprocoumon, a VKA prescribed frequently outside the USA and the UK and accounting for 99% of all VKA prescriptions in Germany. Patients treated with phenprocoumon seem to meet more often international normalized ratio values in the therapeutic range, which may have implications concerning their efficacy and safety. This study aims at comparing the risk of stroke and bleeding in phenprocoumon- and DOAC-treated patients with AF in an adequately powered observational study population.MethodsRetrospective analysis of stroke and bleeding incidence of 837,430 patients (1.27 million patient years) treated with DOAC or phenprocoumon for stroke prevention in German ambulatory care between 2010 and 2017. Relative risks of stroke and bleeding were estimated by calculating cox regression-derived hazard ratios (HR) and 95% confidence intervals (CI) of propensity score-matched cohorts.ResultsPatients treated with DOAC had an overall higher risk for stroke (HR 1.32; CI 1.29–1.35) and a lower risk for bleeding (0.89; 0.88–0.90) compared to phenprocoumon. When analyzed separately, the risk for stroke was higher for dabigatran (1.93; 1.82–2.03), apixaban (1.52; 1.46–1.58), and rivaroxaban (1.13; 1.10–1.17) but not for edoxaban (0.88; 0.74–1.05). The risk for bleeding was lower for dabigatran (0.85; 0.83–0.88), apixaban (0.71; 0.70–0.73), and edoxaban (0.74; 0.68–0.81) but not for rivaroxaban (1.03; 1.01–1.04).ConclusionsThis study provides a comprehensive view of the stroke and bleeding risks associated with phenprocoumon and DOAC use in Germany. Phenprocoumon may be preferable to DOAC treatment for the prevention of strokes in AF in a real-world population cared for in ambulatory care.