Oral Anticoagulant Group Research Articles

PCV31 - ANTICOAGULANTS IN OLDER PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION AFTER INTRACRANIAL HEMORRHAGE

Patients with non-valvular atrial fibrillation (NVAF) who survive an intracranial hemorrhage (ICH) have an increased risk of ischemic stroke and systemic emboli (IS/SE). We investigated whether starting oral anticoagulants (OAC) among older NVAF patients after an ICH was associated with a lower risk of IS/SE and mortality, but offset by an increase in major bleeding. Cohort study assembled from administrative data from the Quebec RAMQ and Med-Echo databases. We identified older adults (> 65 years) with NVAF from 1995 to 2015 who were discharged in the community. All patients with incident ICH were included. Patients were categorized as no or OAC exposure. Outcomes included IS/SE, all-cause mortality, recurrent ICH and other major bleeding after a quarantine period of 6 weeks. Crude event rates were calculated at 1-year of follow-up, and Cox proportional Hazard models and a time-dependent binary exposure were used to calculate adjusted HRs (AHR). Cohort of 681 NVAF patients with ICH aged 83 years on average. The rate (per 100 person-years) for IS/SE, death, ICH and major bleeding were 3.3, 40.6, 11.4 and 2.7 for the no OAC group; and 2.6, 16.3, 5.2 and 5.2 for OAC group, respectively. The AHR for IS/SE and death was 0.23 (0.14-0.39) (95% confidence interval), 0.40 (0.18-0.89) for recurrent ICH and 2.26 (0.96-5.36) for major bleeding comparing OAC exposure to non-exposed. Initiating OAC after ICH in older individuals with NVAF is associated with a reduction of IS/SE and mortality as well as recurrent ICH supporting it’s use after ICH.

Assessment of Outcomes of Treatment With Oral Anticoagulants in Patients With Atrial Fibrillation and Multiple Chronic Conditions

Comparative effectiveness and safety of oral anticoagulants in patients with atrial fibrillation (AF) and multiple chronic conditions (MCC) are unknown. To determine whether there are differences in efficacy and safety of dabigatran, rivaroxaban, and warfarin regarding stroke prevention and bleeding rates, respectively, in elderly patients with AF with MCC. This retrospective comparative effectiveness analysis included data from the population-based Medicare beneficiaries database, evaluating patients with new AF diagnosed from January 1, 2010, to December 31, 2013, who initiated an oral anticoagulant within 90 days of diagnosis. Patients with CHA2DS2-VASc scores of 1 to 3, 4 to 5, and 6 or higher; HAS-BLED scores of 0 to 1, 2, and 3 or higher; and Gagne comorbidity scores of 0 to 2, 3 to 4, and 5 or higher were categorized as having low, moderate, or high morbidity, respectively. Within morbidity categories, patients receiving dabigatran, rivaroxaban, or warfarin were matched using a 3-way propensity matching, and the relative hazards of stroke, major hemorrhage (MH), and death were evaluated. Data analysis included follow-up from the date of initial anticoagulant use through December 31, 2013. Rivaroxaban (20 mg once daily), dabigatran (150 mg twice daily), or warfarin therapy. Ischemic stroke, MH, and death. The study cohort included 21 979 patients using dabigatran (mean [SD] age, 75.8 [6.4] years; 51.1% female), 23 177 using rivaroxaban (mean [SD] age, 75.8 [6.4] years; 49.9% female), and 101 715 using warfarin (mean [SD] age, 78.5 [7.2] years; 57.3% female). In the propensity-matched cohorts, there were no differences in stroke rates between the 3 oral anticoagulant groups. Dabigatran users had lower hazard of MH compared with warfarin users among patients with low MCC (hazard ratio [HR], 0.62; 95% CI, 0.47-0.83; P < .001; for MCC defined as low CHA2DS2-VASc score), and similar risk in patients with moderate to high MCC. While there was no difference in MH between rivaroxaban and warfarin users, rivaroxaban users had significantly higher MH risk compared with dabigatran users in the medium and high comorbidity groups (HR, 1.24; 95% CI, 1.04-1.48; P = .02 and HR, 1.28; 95% CI, 1.05-1.56; P = .01, respectively). Dabigatran and rivaroxaban users had lower rates of death compared with warfarin users (HR ranged from 0.52-0.84), across comorbidity levels. Oral anticoagulants are similarly effective in stroke prevention among patients with AF with MCC. However, dabigatran and rivaroxaban use may be associated with lower rates of mortality in patients with MCC.

Feasibility and safety of percutaneous epicardial access for mapping and ablation for ventricular arrhythmias in patients on oral anticoagulants

This study aimed to assess the risk of procedure-related complications of percutaneous epicardial access (EpiAcc) for radiofrequency catheter ablation (RFA) of ventricular arrhythmias (VAs) in patients chronically treated oral anticoagulants (OACs) with warfarin compared to those not on OACs. We analyzed 205 patients (53 ± 16years, 155 males) undergoing percutaneous EpiAcc as part of an RFA for VAs, and compared the outcome between patients chronically on OACs with warfarin (OAC group) and those without (non-OAC group). Forty-seven patients (23%) were chronically treated on OACs before their procedure. EpiAcc in patients on OAC (OAC group) was not associated with an increased risk of cardiac tamponade (11% vs. 6%, p = 0.238) compared to non-OAC group, but a higher risk of need for blood transfusion (17% vs. 6%; p = 0.013). With respect to the OAC group, the international normalized ratio (INR) on the day of the RFA was ≥ 2.0 in 9 patients (19%) and < 2.0 in the remaining 38 patients (81%). The rate of all complication and blood transfusion were similar between them (11% vs. 21%; p = 0.496, 11% vs. 18%; p = 0.600). Percutaneous EpiAcc in patients on chronic OAC with warfarin did not significantly increase the risk of cardiac tamponade, but was associated with a higher risk of need for blood transfusion. EpiACC in patients with an INR > 2.0 is reasonable in experienced hands when clinical indications are strong.

82 The Impact of Stroke Prophylaxis on Clinical Outcomes After US Emergency Department Diagnosis and Discharge for Atrial Fibrillation

There is evidence that oral anticoagulation (OAC) reduces stroke and mortality risk in patients with atrial fibrillation (AF); however, the clinical outcomes after a US emergency department (ED) evaluation for AF are unknown. This analysis seeks to determine the impact of early prescribing and long-term compliance of OAC on the rate of ischemic stroke and mortality after an ED evaluation for AF. In this retrospective, Medicare, fee-for-service cohort of beneficiaries age ≥65, discharged from the ED from 2011-2012 with a new diagnosis of AF and no OAC prescription filled in the 90 days prior were included. Patients were stratified by filling of an OAC prescription (by any provider) within 10 days of ED diagnosis (early) versus not, and were considered compliant (≥80% medication possession ratio, MPR) versus non-compliant (<80% MPR) during their entire observed follow-up (time until the end of the study or time until their first event). Ischemic strokes were identified via ICD-9 codes from inpatient claims data and censored to the available data. Patients who had an adverse event before filling their early OAC prescription were excluded from the analysis. Descriptive statistics and Kaplan Meier curves with time to ischemic stroke were generated to compare patients with and without an early OAC. Of 9,139 with a new AF diagnosis, 24.1% were prescribed an early OAC. Patients with an early OAC were more likely to be younger (mean age early OAC 76.5 versus no early OAC 77.5 years), less likely to be female (58.1% versus 64.1%), and have a lower co-morbidity burden (mean Charlson score 2.7 versus 3.1) (all p<0.001). Among patients with early OACs, compliant patients (n=1380) were older (77 versus 75.1 years), female (61.6% versus 52.1%), and higher stroke-risk with CHA2DS2-VASc (3.1 versus 2.7) (all p<0.001). During the study period, there were 133 (1.9%) ischemic stroke events in the group not treated with an early OAC as compared to 14 (1.0%) in the early OAC compliant and 14 (1.7%) in the early OAC non-compliant group (Figure). In the no early OAC group, there were 665 deaths (9.6%), compared to 50 (3.6%) in early OAC compliant versus 33 (4.0%) in early OAC non-compliant. In patients with a new diagnosis of AF, an early OAC in compliant patients may make a long-term impact on clinical outcomes and warrants further investigation in methods to improve early OAC prescribing.

Efficacy and safety of novel oral anticoagulants versus vitamin K antagonists in the treatment of venous thromboembolism

&lt;p&gt;The aim of this meta-analysis was to systematically evaluate the efficacy and safety of novel oral anticoagulants and vitamin K antagonists in the treatment of venous thromboembolism. A total of 6 studies met the inclusion criteria and a total of 19,350 patients with venous thromboembolism were included. Among them, rivaroxaban (3 RCTs, n=90/3,449/4,832); dabigatran (2 RCTs, n=200/2,539); edoxaban (1 RCT, n=8,240). The results of meta-analysis showed that the total bleeding rate after treatment with the vitamin K antagonist group was higher than with the new oral anticoagulant group (OR=0.82, 95% confidence interval 0.75-0.90, p&amp;lt;0.0001), and the difference was highly statistically significant. Overall, new oral anticoagulants are compara-ble to vitamin K antagonists, but new oral anticoagulants can reduce the occurrence of bleeding events and the safety was superior to vitamin K antagonists.&lt;/p&gt;

Direct oral anticoagulants do not worsen traumatic brain injury after low-level falls in the elderly

BackgroundFalls are now the leading cause of trauma and represent the most common type of trauma in the elderly. The use of anticoagulants is increasing in older patients, but there are little data on outcomes after traumatic brain injury while anticoagulated with direct oral anticoagulants compared with warfarin. We hypothesized that anticoagulated patients would have a greater mortality and complications than nonanticoagulated patients, and patients on direct oral anticoagulants would have more fatal outcomes after low-level falls because of lack of reversal agents. MethodsPatients 65 years or older admitted to level 1–3 trauma centers with 24-hour neurosurgical care were identified through the administrative database of 19 Trinity Health hospitals. Patients with International Classification of Diseases, Ninth Revision, codes consistent with low-level fall and traumatic brain injury from May 2013 through October 2015 were included. Preadmission warfarin or direct oral anticoagulant use was extracted from admission reconciliation of medications in the database. ResultsA total of 700 patients met inclusion criteria with 177 on anticoagulants before admission. Anticoagulated patients had more cardiac (P < .001), pulmonary (P < .001), and clotting (P < .02) comorbidities. Warfarin patients had the greatest neurosurgical intervention rate at 18% compared with direct oral anticoagulants (2.8%, P < .02) or nonanticoagulation (11%, P < .02). No difference was identified in overall mortality and mortality after neurosurgical intervention between the nonanticoagulated, warfarin, or direct oral anticoagulant groups. Warfarin patients received more plasma (P < .001) and red cell transfusions (P = .035) with greater intensive care unit stays (P < .001) compared with direct oral anticoagulant or nonanticoagulated patients. With logistic regression, only advancing age (P < .05) and a lesser Glasgow Coma Scale score (P < .01) were associated with greater mortality. ConclusionOlder direct oral anticoagulant patients with traumatic brain injury after low-level fall did not have increased morbidity or mortality compared with those treated with warfarin or who were not treated with anticoagulants. Concerns over the use of direct oral anticoagulant agents in this population may be overstated and deserve more scrutiny.

Selection of Oral Anticoagulants in Ischemic Stroke Patients with Nonvalvular Atrial Fibrillation

BackgroundAnticoagulant therapy is indicated for management of ischemic stroke patients with nonvalvular atrial fibrillation. We retrospectively investigated how oral anticoagulants were selected for ischemic stroke patients with nonvalvular atrial fibrillation. MethodsThis study included 297 stroke patients with nonvalvular atrial fibrillation admitted to our hospital between September 2014 and December 2017, and who were subsequently transferred to other institutions or discharged home. Baseline clinical characteristics were compared between patients prescribed warfarin and those prescribed direct-acting oral anticoagulants. ResultsIn total, 280 of 297 (94.3%) patients received oral anticoagulant therapy, including 36 with warfarin, while 244 received direct oral anticoagulants. Age, percentage of heart failure, CHADS2 score before stroke onset, percentage of treatment with warfarin on admission, percentage of feeding tube at hospital discharge, and modified Rankin Scale at hospital discharge were significantly higher in the warfarin group versus the direct oral anticoagulants group, while creatinine clearance was significantly higher in the direct oral anticoagulant group. By multiple logistic regression, taking warfarin at admission and higher modified Rankin Scale at hospital discharge were associated with warfarin selection, while higher creatinine clearance was associated with direct oral anticoagulant selection (warfarin: odds ratio [OR] 7.10 [95% confidence interval {CI} 2.83-17.81]; modified Rankin Scale at hospital discharge: [OR] 1.47 [95% {CI} 1.06-2.04]; creatinine clearance: [OR] .97 [95% {CI} .95-.99]). ConclusionsSelection of oral anticoagulants in acute ischemic stroke patients with nonvalvular atrial fibrillation was influenced by warfarin use at admission, clinical severity at hospital discharge, and renal function.

Abstract P021: Oral Anticoagulant Use and Risk of Incident Dementia in Persons With Atrial Fibrillation

Background: Current guidelines recommend oral anticoagulation for the prevention of stroke in most patients with atrial fibrillation (AF). Direct oral anticoagulants (DOACs) are associated with lower risk of ischemic stroke and intracranial bleeding than warfarin and, therefore, may reduce risk of dementia among patients with AF. Hypothesis: AF patients initiating DOACs for stroke prevention will have lower risk of dementia than patients initiating warfarin. Methods: We used data from two US healthcare claim databases, MarketScan (2007-2015) and Optum Clinformatics (2009-2015). Using validated algorithms, we identified patients with AF who initiated oral anticoagulation. Dementia was defined as having an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code of 290.xx, 294.xx, or 331.0. Comorbidities and use of other medications were defined based on inpatient, outpatient, and pharmacy claims. We performed a series of head-to-head comparisons of different oral anticoagulants (warfarin, dabigatran, rivaroxaban, and apixaban) in propensity score-matched cohorts. In each database, multivariable-adjusted Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident dementia for each comparison of propensity score-matched cohorts, adjusting for age, sex, comorbidities, use of other medications, and markers of socioeconomic status (in the Optum database only). We meta-analyzed database-specific results using a random-effects model. Results: The analysis included 307,099 AF patients from the MarketScan database and 161,346 from the Optum database, of which 6,572 and 4,391 respectively had a diagnosis of incident dementia. Mean follow up ranged between 0.7 to 2.3 years and incident of diagnosed dementia between 7 to 14 cases per 1000 person-years across different oral anticoagulant initiator groups. Patients initiating DOACs had a lower risk of incident dementia than those initiating warfarin (dabigatran: HR 0.85, 95%CI 0.71, 1.01; rivaroxaban: HR 0.85, 95%CI 0.76, 0.94; apixaban: HR 0.80, 95%CI 0.65, 0.97). There were no differences in risk of incident dementia comparing DOAC user groups (dabigatran vs. rivaroxaban: HR 1.02, 95%CI 0.79, 1.32; dabigatran vs. apixaban: HR 0.92, 95%CI 0.63, 1.36; apixaban vs. rivaroxaban: HR 1.01, 95%CI 0.86, 1.19). Conclusions: Patients with AF initiating DOACs experienced lower rates of incident dementia than warfarin users. No obvious benefit was observed for any particular DOAC in relation to dementia rates.

Real-world antithrombotic therapies and clinical outcomes after second-generation drug-eluting stent implantation in patients with atrial fibrillation: a multi-center cohort study.

Previous reports have focused on cardiovascular and bleeding events in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). However, antithrombotic treatment strategies and clinical outcomes after second-generation drug-eluting stents (DES) implantation in AF patients remain to be determined. We enrolled 244 consecutive AF patients treated with second-generation DES. The study population was derived from multi-center AF registry (including 8 centers in Japan) from 2010 to 2012. Prescription of antithrombotic agents and clinical outcomes were retrospectively examined. Ninety-two patients (37.7%) were prescribed dual antiplatelet therapy (DAPT) at discharge and 152 patients (62.3%) were given DAPT plus oral anticoagulation (OAC) with warfarin. The median follow-up period was 730days. Kaplan-Meier analysis showed that major adverse cardiac and cerebrovascular events (MACCE) were not significantly different (2-year event rate, 17.6 vs. 13.5%, p = 0.37), but bleeding events were significantly higher in the DAPT plus OAC group than in the DAPT group (2-year event rate, 6.1 vs. 17.9%, p = 0.033). In a sub-analysis of DAPT plus OAC patients, adequate time in the therapeutic range (TTR) group (TTR ≥ 65%) was not significantly different from the suboptimal OAC group (TTR < 65%) for bleeding events, but it had a lower incidence of MACCE, resulting in better net clinical outcomes (composite of MACCE and major bleeding, 2-year event rate, 9.2 vs. 27.8%, p = 0.008). DAPT plus OAC remains more common in AF patients undergoing PCI with second-generation DES. Under adequate TTR, DAPT plus OAC showed better net clinical outcomes by reducing MACCE without increasing bleeding.

Bezpečnější antikoagulační léčba - použití idarucizumabu (Praxbind®): série kazuistik ze studie RE-VERSE AD a klinické praxe

RE-VERSE AD, a prospective multicentric cohort study, examined the effect of idarucizumab on 2 cohorts of patients anticoagulated with dabigatran - in cohort A in patients with uncontrollable or life threatening bleeding, in cohort B in patients who undergo acute surgery. Within the study patients were intravenously administered 5 g antidote divided into 2 doses per 2.5 g within 15 min to eliminate the anticoagulation effect of dabigatran. A series of case studies is presented to describe the use of idarucizumab within the RE-VERSE AD study and in clinical practice in the period of 2015-2016 at the University Hospital Hradec Králové. The included examples illustrate the benefit of dabigatran as the only drug so far from the group of direct oral anticoagulants which has an antidote.Key words: antidote - bleeding - dabigatran - direct oral anticoagulants - DOAC - high risk of bleeding - idarucizumab - intervention.

Taking Warfarin with Heparin Replacement and Direct Oral Anticoagulant Is a Risk Factor for Bleeding after Endoscopic Submucosal Dissection for Early Gastric Cancer

Background: Although bleeding after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) remains problematic, especially in patients taking anticoagulants, there are differing views on the ideal and optimal management for these patients. This study investigated the risk of bleeding after ESD in patients taking anticoagulants. Methods: We enrolled 61 consecutive patients taking anticoagulants (anticoagulant group) and 968 patients taking no antithrombotic agents (non-antithrombotic group) treated with ESD for EGC between December 2010 and October 2016. We analyzed the risk factors for bleeding after ESD in relation to the various clinical factors. Results: Incidences of bleeding after ESD were significantly higher (14%; 11/76) in the anticoagulant group compared to the non-antithrombotic group (3%; 40/1,167). Moreover, bleeding after ESD was significantly more common in patients in the warfarin monotherapy group (14%; 5/37) and in the direct oral anticoagulant (DOAC) monotherapy group (22%; 4/18), compared to the non-antithrombotic group. Multivariate analysis revealed that dialysis, the use of anticoagulants, and an operation time ≥75 min were independent risk factors for bleeding after ESD. Conclusions: Our data suggest that patients who take warfarin and receive heparin bridging, and those who take DOAC medication, are prone to bleeding after ESD for EGC.

Single-center, retrospective evaluation of safety and efficacy of direct oral anticoagulants versus low-molecular-weight heparin and vitamin K antagonist in patients with cancer.

The safety and efficacy of direct oral anticoagulants in cancer patients is currently unclear. Low-molecular-weight heparin remains the standard of care for cancer patients with venous thromboembolism, with warfarin, a vitamin K antagonist, as an alternative. Clear recommendations do not exist for patients with both active cancer and non-valvular atrial fibrillation. The objectives of this study were to report safety and efficacy outcomes of direct oral anticoagulants, low-molecular-weight heparin, and vitamin K antagonist in cancer patients with venous thromboembolism or non-valvular atrial fibrillation. Retrospective chart review of adult cancer patients from 2012 to 2015 who received an antineoplastic agent and an anticoagulant. A total of 258 patients were reviewed: 80 patients in direct oral anticoagulant group, 95 patients in low-molecular-weight heparin group, and 83 patients in vitamin K antagonist group. Sixty-seven percent of patients were on an anticoagulant for acute or chronic venous thromboembolism. Major bleeding events were similar across the groups (15% direct oral anticoagulant vs 17% low-molecular-weight heparin vs 18% vitamin K antagonist). The most common type of major bleeding event was gastrointestinal bleeding. A total of five fatal bleeding events occurred. Venous thromboembolism recurrence rates were higher in both direct oral anticoagulant (18%) and low-molecular-weight heparin (12%) groups while lower in vitamin K antagonist group (10%) compared to previous studies. Cancer patients receiving direct oral anticoagulants, low-molecular-weight heparin, or vitamin K antagonist had similar rates of major bleeding events, with gastrointestinal bleeding being the most common event. Venous thromboembolism recurrence rates were higher in direct oral anticoagulant and low-molecular-weight heparin groups than prior studies. Randomized trials are warranted to establish clear safety and efficacy in this population.

Electrical isolation of the left atrial appendage by Maze-like catheter substrate modification: A reproducible strategy for pulmonary vein isolation nonresponders?

The ablation strategy for atrial fibrillation (AF) despite pulmonary vein isolation (PVI) is controversial. Left atrial appendage isolation (LAAI) may contribute to improve outcome. We describe an ablation approach ("Maze-like"-LAAI) that (1) modifies the underlying LA substrate by linear ablation (2) eliminates the LAA as a putative AF trigger site and (3) incorporates an unambiguous procedural endpoint. The role of LAA closure (LAAC) after LAAI was investigated. Patients with atrial tachyarrhythmias nonresponsive to PVI underwent a LAAI ablation procedure. LAAI was achieved by combining (a) an anterior line, (b) a LA roof line and (c) a mitral isthmus line. Patients continued oral anticoagulation (OAC) therapy or underwent LAAC ≥6 weeks after LAAI. Maze-like LAAI was attempted in our center in 107 of 3,611 AF ablation procedures (2.9%) and achieved in 88 of 107 patients (82%). In 8 of 107 (7%) patients cardiac tamponade occurred, all managed conservatively. During follow-up sinus rhythm was established in 65% at 1 year. After LAAI, 45 patients remained on OAC and 40 underwent LAAC. In both groups 1 patient experienced a bleeding complication. Thromboembolism exclusively occurred in the OAC group in 3 (7%) patients. LAA isolation by Maze-like substrate modification may be considered a viable option for PVI non-responders. It offers a reproducible approach with an unambiguous procedural endpoint and leads to a favorable clinical outcome. However, extensive LA ablation increased the risk of tamponade. Consecutive LAA occlusion may offer a nonpharmacologic strategy to overcome the high thromboembolic risk associated with absent mechanical LAA contraction.

Managing patients taking edoxaban in dentistry.

BackgroundAnticoagulation therapy is used in several conditions to prevent or treat thromboembolism. A new group of oral anticoagulants with clear advantages over classic dicoumarin oral anticoagulants (warfarin and acenocoumarol) has been developed in recent years. The Food and Drug Administration has approved edoxaban, dabigatran, rivaroxaban and apixaban. Their advantages include: predictable pharmacokinetics, drug interactions and limited food, rapid onset of action and short half-life. However, they lack a specific reversal agent.Material and MethodsThis paper examines the available evidence regarding rivaroxaban and sets out proposals for clinical guidance of dental practitioners treating these patients in primary dental care. A literature search was conducted through July 2016 for publications in PubMed and Cochrane Library using the keywords “edoxaban”, “dabigatran”, “rivaroxaban”, “apixaban”, “new oral anticoagulants”, “novel oral anticoagulants”, “bleeding” and “dental treatment” with the “and” boolean operator in the last 10 years.ResultsThe number of patients taking edoxaban is increasing. There is no need for regular coagulation monitoring of patients on edoxaban therapy. For patients requiring minor oral surgery procedures, interruption of edoxaban is not generally necessary. Management of patients on anticoagulation therapy requires that dentists can accurately assess the patient prior to dental treatments.ConclusionsTheir increased use means that oral care clinicians should have a sound understanding of the mechanism of action, pharmacology, reversal strategies and management of bleeding in patients taking edoxaban. There is a need for further clinical studies in order to establish more evidence-based guidelines for dental patients requiring edoxaban. Key words:Edoxaban, dabigatran, rivaroxaban, apixaban, novel oral anticoagulants, bleeding.

Dental management of patients taking novel oral anticoagulants (NOAs): Dabigatran.

BackgroundA new group of oral anticoagulants (dabigatran, rivaroxaban, apixaban and edoxaban) with clear advantages over classic dicoumarin oral anticoagulants (warfarin and acenocoumarol) has been developed in recent years. Patients being treated with oral anticoagulants are at higher risk for bleeding when undergoing dental treatments.Material and MethodsA literature search was conducted through April 2016 for publications in the ISI Web of Knowledge, PubMed and Cochrane Library using the keywords “dabigatran”, “rivaroxaban”, “apixaban”, “edoxaban”, “new oral anticoagulants”, “novel oral anticoagulants”, “bleeding” and “dental treatment”.ResultsThere is no need for regular coagulation monitoring of patients on dabigatran therapy. Whether or not to temporarily discontinue dabigatran must be assessed according to the bleeding risk involved in the dental procedure to be performed.ConclusionsThe number of patients under treatment with new oral anticoagulants will increase in the coming years. It is essential to know about the pharmacokinetics and pharmacodynamics of new oral anticoagulants and about their interactions with other drugs. It is necessary to develop clinical guidelines for the perioperative and postoperative management of these new oral anticoagulants in oral surgical procedures, and to carefully evaluate the bleeding risk of dental treatment, as well as the thrombotic risk of suppressing the new oral anticoagulant. Key words:Dabigatran, rivaroxaban, apixaban, edoxaban, novel oral anticoagulants, bleeding.

MANAGEMENT AND OUTCOMES IN ACUTE CORONARY SYNDROME WITH ATRIAL FIBRILLATION IN “NON-INVASIVE” CLINIC

Aim. To evaluate the management and outcomes in acute coronary syndrome patients (ACS) comorbid with atrial fibrillation (AF) during in-patient period and in 12 months from ACS onset. Material and methods. Into multicenter prospective registry (CCH № 29 of Moscow), beginning December 2013, during 12 months, all consecutive patients included, with ACS, and AF on baseline ECG. Follow-up was continued during hospitalization and in 12 months from ACS (phone call). Results. Totally, 234 patients included. Mean age 72,0±11,6 y.o., 65+73,5%, females — 68,8%, anamnesis of myocardial infarction (MI) — 35,9%, diabetes — 23,9%, known AF before ACS — 65,0%, non-ST-elevation ACS — 97,9%, Killip >I — 7,3%, ST depression on baseline ECG — 89,9%, high troponin level — 59,0%, GRACE risk of fatal outcome >140 points. — 75,2%, median CHA2 DS2 -Vasc — 5 pts. At discharge from hospital, 44% patients received double antiplatelet treatment (DAT), 38% — aspirin with oral anticoagulant (OAC), 33% — warfarin, 23% — new OAC (NOAC). During hospitalization (median 14 days) 7 patients died (3,0%). In 12 months the outcomes were followed in 210 patients (89,8%). By 12 months from ACS onset, 18,1% patients died, and in 12 months but after discharge — 15,3%. New MI after discharge had 1,5%, stroke — 2,5%, and bleeding — 3,5% patients. The part of fatal outcomes in 12 months did not differ in DAT or aspirin with OAC groups (12,1% vs 12,8%; p=0,88). The “remained” prescription rate (i.e. adherence) in 12 months after ACS was maximum for aspirin, OAC and NOAC (71%, 58%, 63%, resp.) and minimum for DAT and aspirin with OAC (20% and 27%, resp.). The independent predictors of death after discharge from hospital up to 12 months from ACS onset were the baseline hemoglobin 140 pts. (OR 6,88; 95% CI 1,44-32,80; р=0,015) and non-prescription of aspirin in discharge (OR 3,21; 95% CI 1,20-8,61; р=0,02). Conclusion. The results of observational study of ACS and AF patients, admitted to Moscow city “non-invasive” clinic, showed high rate of fatal outcomes in 12 months after ACS (18,1%), low adherence to the prescribed treatment after discharge. Also, in the group studied, there were predictors of fatal outcomes in 12 months after ACS.

Venous thromboembolism treatment outcomes in cancer patients and effect of third-party payers on anticoagulant choice.

The purpose of this study is to compare the rates of recurrent VTE among cancer patients treated with parenteral agents to the oral anticoagulants. This single-center study was a retrospective chart review of cancer patients with recurrent VTE between January 1, 2009 and December 31, 2014. The primary outcome of the study is the rate of recurrent VTE in patients who received a parenteral anticoagulant (enoxaparin, dalteparin, fondaparinux) versus those who received oral anticoagulants (warfarin and rivaroxaban). Other outcomes investigated include risk factors associated with recurrent VTE events and influence of third-party payer on anticoagulant selection. Four hundred fifty-seven patients met inclusion criteria (178 in the oral anticoagulant group and 279 in the parenteral anticoagulant group). Patients with Medicare were more likely to have received an oral anticoagulant (P=0.003) and patients with private insurance were more likely to have received a parenteral anticoagulant (P=0.004). There were 23 recurrent VTE events, 12 events (6.7%) in the oral anticoagulant group and 11 events (3.94%) in the parenteral group (P=0.182). The only significant risk factor noted to increase risk of recurrent VTE was the presence of an IVC filter (adjusted OR 4.38, 95% CI 1.67-11.53, P=0.003). While there is no statistical difference in VTE events between groups, the oral anticoagulant group numerically had a higher rate. Important associations were found to have an influence on anticoagulant selection and risk of recurrent VTE. These factors must be incorporated into decision making when treating cancer patients with VTE.

Abstract 17220: Treatment Persistence and Discontinuation With Rivaroxaban, Dabigatran and Warfarin for Stroke Prevention in Patients With Non-valvular Atrial Fibrillation

Introduction: Continuous use of oral anticoagulant (OAC) therapy is essential for reducing the risk of stroke in patients with non-valvular atrial fibrillation. To date, no single study has compared persistence and discontinuation rates between rivaroxaban, dabigatran and warfarin users. Hypothesis: To compare persistence and discontinuation rates between rivaroxaban, dabigatran and warfarin users with non-valvular atrial fibrillation. Methods: A retrospective cohort analysis of the United States MarketScan claims databases was performed. This included adult patients newly initiated on rivaroxaban, dabigatran or warfarin between 1 November 2011 and 31 December 2013 with a baseline CHA2DS2-VASc score ≥2, ≥2 atrial fibrillation diagnosis codes (427.31) and ≥6 months of continuous medical and pharmacy benefits prior to OAC initiation (index date). Propensity score matching was performed in a two-step process to match patients on rivaroxaban with dabigatran 1:1 and with warfarin 1:1. Patients were followed until the earliest of in-hospital death, end of continuous enrolment or end of study period. Persistence was defined as absence of refill gap of &gt;60 days. Discontinuation was defined as no additional refill for &gt;90 days and through end of follow-up. Cox proportional hazards models were estimated to examine hazard ratios (HRs) of OAC non-persistence and discontinuation. Results: A total of 32,634 patients were included (N=10,878/OAC group). At 3 months’ follow-up, treatment persistence was 79.2%, 69.6% and 70.9% for rivaroxaban, dabigatran and warfarin users, respectively, dropping to 70.2%, 57.8% and 58.8% after 6 months, 60.1%, 44.7% and 42.0% after 1 year and 50.4%, 30.6% and 26.5% after 2 years. On regression, rivaroxaban use was associated with a decreased hazard of non-persistence compared with dabigatran (HR=0.64; 95% confidence interval [CI] 0.62-0.67) and warfarin (HR=0.62; 95% CI 0.59-0.64), and a decreased rate of discontinuation versus dabigatran (HR=0.61; 95% CI 0.58-0.64) and warfarin (HR=0.65; 95% CI 0.62-0.68). Conclusions: This matched patient analysis indicated significantly higher persistence and lower discontinuation rates with rivaroxaban compared with dabigatran and warfarin.

Endovascular Treatment for Acute Ischemic Stroke in the Setting of Anticoagulation.

Oral anticoagulation (OAC) plays a major role in atrial fibrillation stroke prevention but represents a contraindication to intravenous tissue-type plasminogen activator. Intra-arterial therapy remains a potential reperfusion strategy in these patients; however, supporting data are scarce. Retrospective analysis of prospectively collected consecutive intra-arterial therapies from October 2010 to March 2015 comparing OAC (vitamin-K antagonists and novel oral anticoagulants) versus normal hemostasis versus intravenous tissue-type plasminogen activator patients. Primary safety end point is parenchymal hematoma. Secondary safety end point is 90-day mortality. Efficacy end points are successful reperfusion (modified Thrombolysis in Cerebral Infarction, 2b-3) and good outcome (90-day modified Rankin Scale score of 0-2). Logistic regression for predictors of parenchymal hematoma was performed. A total of 604 patients were qualified for the study. Baseline and outcomes variables were overall similar for vitamin-K antagonists (n=29) and novel oral anticoagulants (n=17) patients. When compared with normal hemostasis (n=265) and intravenous tissue-type plasminogen activator (n=297), OAC (n=46) patients were older and had more comorbidities. There were no statistically significant differences in the rates of parenchymal hematoma (8% versus 5%; P=0.42), 90-day modified Rankin Scale score of 0 to 2 (30% versus 40%; P=0.26), and 90-day mortality (32% versus 26%; P=0.46) among OAC and normal hemostasis patients. Similarly, there were no significant differences between OAC and intravenous tissue-type plasminogen activator patients in terms of parenchymal hematoma (8% versus 4%; P=0.16), 90-day modified Rankin Scale score of 0 to 2 (30% versus 43%; P=0.13), and 90-day mortality (32% versus 22%; P=0.18). The use of OAC was not associated with the occurrence of parenchymal hematoma on multivariate logistic regression analysis. Intra-arterial therapy seems to be safe in patients taking OACs; however, our study showed a nonsignificant increase in hemorrhage and mortality with a nonsignificant decrease in good outcomes in comparison with non-OAC patients. Although these nominal differences may have been related to older age and more comorbidities in the OAC group, larger studies are needed to confirm our findings given our limited sample size.

An Observational Study of the Factor Xa Inhibitors Rivaroxaban and Apixaban as Reported to Eight Poison Centers

Rivaroxaban and apixaban are part of a new group of oral anticoagulants targeting factor Xa and approved by the Food and Drug Administration in 2011 and 2012. These oral anticoagulants are administered at fixed daily doses, without the need for laboratory-guided adjustments. There are limited data available on supratherapeutic doses or overdose of the oral Xa inhibitors. This study characterizes the clinical effect in patients exposed to rivaroxaban and apixaban. A retrospective study collected data from 8 regional poison centers covering 9 states. Cases were initially identified by a search of the poison centers' databases for case mentions involving a human exposure to Xarelto, rivaroxaban, Eliquis, or apixaban. Inclusion criteria included single-substance exposure. Exclusion criteria were animal exposure, polysubstance exposure, or information call. Data for the study were collected by individual chart review, including case narratives, and compiled into a single data set. There were 223 patients: 124 (56%) were female patients, mean age was 60 years, and 20 were children younger than 12 years (9%). One hundred ninety-eight patients ingested rivaroxaban (89%) and 25 ingested apixaban (11%). Dose was reported in 182 rivaroxaban patients, with a mean dose of 64.5 mg (range 15 to 1,200 mg), and in 21 apixaban patients, with a mean dose of 9.6 mg (range 2.5 to 20 mg). For rivaroxaban, prothrombin time was measured in 49 patients (25%) and elevated in 7; partial thromboplastin time, measured in 49 (25%) and elevated in 5; and international normalized ratio, measured in 61 (31%) and elevated in 13. For apixaban, prothrombin time was measured in 6 patients (24%) and elevated in none; partial thromboplastin time, measure in 6 (24%) and elevated in none; and international normalized ratio, measured in 5 patients (20%) and elevated in none. Bleeding was reported in15 patients (7%): 11 rivaroxaban and 4 apixaban. The site of bleeding was gastrointestinal (8), oral (2), nose (1), bruising (1), urine (1), and subdural (1). The subdural bleeding occurred after fall and head injury. All cases with bleeding involved long-term ingestions. Coagulation test results were normal in most patients with bleeding: prothrombin time 5 of 6 (83%), partial thromboplastin time 5 of 6 (83%), and international normalized ratio 5 of 9 (55%). Blood products were used in 7 rivaroxaban patients (1 suicide) and 3 apixaban patients. No bleeding or altered coagulation test results occurred in children, which all involved a one-time ingestion. All 12 suicide attempts involvedrivaroxaban: altered coagulation test results occurred for 5 patients (42%), no bleeding occurred in any suicide attempt patient, 1 patient was treated with fresh frozen plasma (international normalized ratio 12.47), and dose by patient history didnot predict risk of altered coagulation or bleeding. Two rivaroxaban patients experienced elevation of hepatic transaminase levels greater than 1,000 U/L. Bleeding after Xa inhibitor ingestion as a single agent is uncommon. Prothrombin time, partial thromboplastin time, or international normalized ratio may be elevated in a minority of cases but appears unreliable to measure risk of bleeding. Massive acute ingestion in suicide attempt may result in significant anticoagulation. Single exploratory ingestion by children was not associated with toxicity.