Use Of Novel Oral Anticoagulants Research Articles

Bleeding Complications After Use of Novel Oral Anticoagulants in Patients Undergoing Cardiac Surgery

The study was performed to analyze the results of open-heart surgery and bleeding complications after administration of novel oral anticoagulants (NOAC). We investigated 81 consecutive patients (median age 74 years, interquartile range [IQR]: 68 to 78) who underwent open-heart operations at our institution between July 2014 and June 2016. All patients presented for surgery while on NOAC therapy: 37 received rivaroxaban (45.7%), 35 apixaban (43.2%), and 9 dabigatran (11.1%). The calculated risk using the European System for Cardiac Operative Risk Evaluation II was 3.5% (IQR: 2.0% to 8.1%). Surgery was performed at a median 4 days (IQR: 3 to 6) after NOAC withdrawal. Reduced renal function was predictive for length of intensive care unit stay and administration of red blood cells (p < 0.0001 and p= 0.0291, respectively). The NOAC withdrawal interval significantly influenced postoperative drainage volume (p= 0.0056). Five patients needed rethoracotomy because of relevant bleeding (6.2%), 4 after apixaban (11.4%) and 1 after rivaroxaban therapy (2.7%). Apixaban showed a borderline influence on prolonged intensive care unit stay (p= 0.0736). Prolonged cardiopulmonary bypass time was predictive for thrombocyte administration (p= 0.0249). Intensive care unit stay was 2 days after NOAC withdrawal of 10 days, compared with 4.2 days without termination. Thirty-day mortality was 3.7%. A lengthy NOAC withdrawal period, particularly for patients with reduced renal function, is essential for safe open-heart surgery. We conclude that despite official recommendations, patients should whenever possible not be considered for elective cardiac surgery within 10 days of terminating NOAC treatment.

Use of Novel Oral Anticoagulants (NOACs) in Patients with Risk of Stroke in Non Valvular Atrial Fibrillation (AF)

Background: Warfarin was used for decades to prevent stroke in high risk AF patients, recent guidelines and published data is recommending use of NOACs like Rivaroxaban as an alternative to Warfarin, Its use is increasing world over because of its predictable action, less food and drug interaction and no need of monitoring for dose adjustments, considering these facts we planned to conduct a study to see the frequency of use of Rivaroxaban in our local population of AF patients with risk of stroke calculated by CHA2DS2-VASc score. Method: This cross-sectional study was done at National Institute of Cardiovascular disease (NICVD) from May 2017 to September 2017 included 137 non-valvular AF patients with high risk of stroke calculated by applying CHA2DS2-VASc score more than or equal to 2. Clinical details and information about anticoagulant medications prescribed to them was also obtained. SPSS 19 was used for the analysis, descriptive statistics such as mean ±SD, frequency and percentages were calculated. Z-test, t-test, and chi-square test were used for the assessment and comparison of data. Two sided p-value of 0.05 was considered for statistical significance. Results: Total 137 patient were included 50.4% (69) were male, 104 (75.91%) out of 137 were on Anticoagulant therapy, with 86 (62.77%) were on Warfarin and only 18 (13.14%) were taking Rivaroxaban. Conclusion: Our study showed very small percentage of non valvular AF patients with risk of stroke were prescribed Rivaroxaban. It’s important to update our treating Physicians about this novel agent which is shown to be equally effective and safe in comparison to warfarin, and easy to prescribe without monitoring to reduce stroke risk.

Dabigatran: A Novel and Rare Cause of Diffuse Alveolar Hemorrhage (DAH)

SESSION TITLE: Diffuse Lung Disease SESSION TYPE: Affiliate Case Report Slide PRESENTED ON: Sunday, October 29, 2017 at 10:45 AM - 12:00 PM INTRODUCTION: DAH is a rare, life-threatening pathology characterized by intra-alveolar hemorrhage with a spectrum of clinical presentations. This syndrome includes hemoptysis, anemia, pulmonary infiltrates and hypoxemic respiratory failure. This case is a rare presentation of DAH secondary to a Novel Oral Anticoagulant (NOAC) in the absence of systemic vasculitis. CASE PRESENTATION: An 86 year old male with past medical history of atrial fibrillation on dabigatran and congestive heart failure, was found at home, hypoxemic and bradycardic to the emergency room. The patient was also noted to be anemic, requiring 2 units of PRBC and in acute renal failure. The patient met criteria for ARDS, including a chest X-ray suggestive of bilateral diffuse pulmonary infiltrates. He was maintained on low tidal volume, high PEEP ventilator support. Bronchoscopic lavage demonstrated progressively more hemorrhagic effluent, pathognomic for DAH. Investigations for vasculitis were negative. The thrombin time was noted to be elevated and hence Idaricizumab was started and hemodialysis initiated. The patient was successfully extubated in 7 days duration. DISCUSSION: GI bleeds and intracranial hemorrhages are known complications with dabigatran, however DAH is rare with only four other cases reported in our literature review1,2. Most of these cases were prior to the advent of Idarucizumab. Dabigatran toxicity may have occurred in this patient due to the occurrence of acute renal failure. Reversal agent may have a role in treating pulmonary hemorrhage and subsequent respiratory failure secondary to the use of NOACs. Interestingly, this patient also had no prior history of vasculitides or lung disease that would predispose the patient to DAH. CONCLUSIONS: To our knowledge this is the only case where resolution of ARDS secondary to DAH by Dabigatran use was achieved with the use of Idarucizumab, hemodialysis and lung protective ventilator strategy. This highlights the importance of considering DAH as a cause of ARDS especially in the setting of anticoagulation. Increasing use of NOACs requires physicians to be aware of the adverse effects and indications for using reversal agents, when available. Reference #1: Yokoi K, Isoda K, Kimura T, Adachi T. Diffuse Alveolar Hemorrhage Associated with Dabigatran. Intern Med. 2012;51(18):2667-2668 Reference #2: Kudo, K, Tanimoto, Y, Hisamoto, A, Ichihara, E, Tanimoto, M, Kiura, K. Dabigatran etexilate-induced alveolar hemorrhage. AJRS, 1(3): 247-250, 2012. DISCLOSURE: The following authors have nothing to disclose: Shyam Shankar, Prarthna Chandar, Hatem Desoky, Ishan Malhotra, Anand Kumar Rai, Mangalore Amith Shenoy, Benhoor Shamian, Pavel Gozenput, Roman Bernstein, Pavan Irukulla, Yizhak Kupfer No Product/Research Disclosure Information

Novel Oral Anticoagulants in Direct Current Cardioversion for Atrial Fibrillation

For some patients with atrial fibrillation, direct current cardioversion (DCCV) is one strategy that can be used to establish sinus rhythm but appropriate anticoagulation is mandatory to prevent thromboembolic events. Historically, patients were anticoagulated with warfarin with bridging with unfractionated or low molecular weight heparin, however, recently novel oral anticoagulants (NOACs), apixaban, dabigatran and rivaroxaban have become more popular. Despite the increase in use, real world data on safety and efficacy is limited. We retrospectively analysed patients that underwent DCCV at Wollongong Hospital from 1 January 2014 to 30 June 2016 and compared peri-procedural anticoagulation with warfarin and the three NOACs. Patients were treated with at least 24hours of anticoagulation before and at least four weeks after the procedure unless contraindication developed. All patients underwent transoesophageal echocardiography prior to cardioversion regardless of anticoagulation type or duration. Patients with left atrial or left atrial appendage thrombus did not undergo cardioversion. We analysed the utilisation rates of NOACs and compared the incidence of post procedural ischaemic strokes and major bleeding events at eight weeks follow-up. Over the study period, 284 patients underwent DCCV; 109 (38.4%) patients were anticoagulated with warfarin and 175 (61.6%) with one of the three NOACs; 77 (27.1%) with apixaban, 60 (21.1%) with rivaroxaban and 38 (13.4%) with dabigatran. Patients treated with warfarin were on average older (71.3±9.7 vs. 65.2±12.9; p value, 0.0005) with more cardiac risk factors including documented heart failure with reduced ejection fraction (39.4% vs. 22.9%; p value, 0.0032), medically treated hypertension (76.1% vs. 48.6%; p value, 0.0001) and peripheral vascular disease (31.2% vs. 12.1%; p value, 0.0004). The NOACs were more frequently used in patients with lower CHA2DS2-VASc scores; 179 patients had a score≤3 with 52 (29.1%) patients treated with warfarin and 127 (70.9%) treated with a NOAC (p value, 0.0001). In our cohort, the use of NOACs increased over the study period from 45.6% in 2014 to 82.8% in 2016. There was a low incidence of ischaemic stroke and bleeding events in both groups, 1.8% versus 0.6% (p value, 0.5607) and 3.6% versus 1.7% (p value, 0.4343) respectively. In the NOAC group, 95 of the 174 patients were anticoagulation-naïve and anticoagulated for less than five days; in comparison to longer duration therapy there was no difference in ischaemic stroke and bleeding events. In our institution, the use of NOACs in electrical cardioversion increased significantly over the study period and in our experience, they appear to be as safe as warfarin with low rates of ischaemic stroke and major bleeding. In addition, a short duration NOAC strategy was comparable to longer duration therapy.

Risk of Intraocular Bleeding With Novel Oral Anticoagulants Compared With Warfarin

It is unclear if the risk of intraocular bleeding with novel oral anticoagulants differs compared with warfarin. To characterize the risk of intraocular bleeding with novel oral anticoagulants compared with warfarin. A systematic review and meta-analysis was undertaken in an academic medical setting. MEDLINE and ClinicalTrials.gov were searched for randomized clinical trials published up until August 2016. This search was supplemented by manual bibliography searches of identified trials and other review articles. Studies were eligible for inclusion if they were phase 3 randomized clinical trials, enrolled patients with atrial fibrillation or venous thromboembolism, compared a novel oral anticoagulant (dabigatran, rivaroxaban, apixaban, or edoxaban) with warfarin, and recorded event data on intraocular bleeding. Data on intraocular bleeding were pooled using inverse-variance, weighted, fixed-effects meta-analysis. The PRISMA guidelines were used for abstracting data and assessing quality. Independent extraction was performed by 2 investigators. Intraocular bleeding events and associated risk ratio for novel oral anticoagulants compared with warfarin. Twelve trials investigating 102 627 patients were included. Randomization to novel oral anticoagulants was associated with a 22% relative reduction in intraocular bleeding compared with warfarin (risk ratio, 0.78; 95% CI, 0.61-0.99). There was no significant heterogeneity observed (I2 = 4.8%, P = .40). Comparably lower risks of intraocular bleeding with novel oral anticoagulants were seen in subgroup analyses, with no significant difference according to the indication for anticoagulation (P for heterogeneity = .49) or the novel oral anticoagulant type (P for heterogeneity = .15). Summary estimates did not differ materially when random-effects meta-analytic techniques were used. These results suggest that novel oral anticoagulants reduce the risk of intraocular bleeding by approximately one-fifth compared with warfarin. Similar benefits were seen in both patients with atrial fibrillation and venous thromboembolism. Our data have particular relevance for patients at higher risk of spontaneous retinal and subretinal bleeding. These findings may also have important implications in the perioperative period, in which the use of novel oral anticoagulants may be superior. Future studies are required to better characterize the optimal management of patients with both ophthalmic disease and cardiovascular comorbidities requiring anticoagulation.

Mo1176 Risk of Bleeding in Patients on Uninterrupted Warfarin or Novel Oral Anticoagulants Undergoing Percutaneous Endoscopic Gastrostomy (PEG)

PEG placement is considered a high-risk procedure for bleeding. Therapeutic anticoagulation therapy with warfarin (Coumadin) or novel oral anticoagulants (NOACs) can increase the risk of bleeding during or after PEG procedure. Temporary cessation of anticoagulants or bridge therapy is suggested for high risk procedures, while balancing thromboembolic risk. Currently there is a lack of available data on risk of bleeding in patients undergoing PEG placement with uninterrupted use of warfarin or NOACs. The aim of this study is to investigate the incidence of post-PEG placement bleeding in patents with procedural uninterrupted warfarin or NOACs.

Abstract P255: Use of Novel Oral Anticoagulants Among Patients With Atrial Fibrillation Increased Even in Those With Severely Impaired Kidney Function

Novel oral anticoagulants (NOACs) are increasingly prescribed as substitutes for warfarin in patients with atrial fibrillation (AF). All of the NOACs are at least partially renally cleared, but most trials excluded patients with severe kidney dysfunction. Despite this, labels include dosing for creatinine clearance 15-30 ml/min. The objective of the study was to estimate the prevalence of NOAC use over time among people with AF, stratified by stage of chronic kidney disease (CKD). Study population included 17,280 patients with AF and at least one prescribed anticoagulant (warfarin, dabigatran, rivaroxaban, or apixaban) between 2010 and 2016 in the Geisinger Health System, a large rural health care system in Pennsylvania. Medication information was obtained from both medication orders and records. Average age of the study population was 73.6 years, 46.6% (N=8,044) were women, 98.4% (N=17,009) were Non-Hispanic White, and average estimated glomerular filtration rate (eGFR) was 70.2 ml/min/1.73 m 2 . Over the course of 2010-2016, 3.0% (N=513), 6.9% (N=1,184) and 4.6% (N=792) received at least one prescription for dabigatran, rivaroxaban, or apixaban. NOAC ever-users (N=2,392) were younger (69.1 vs. 74.3 years, P &lt;0.001) and had a higher eGFR (77.7 vs. 69.9 ml/min/1.73 m 2 ) than warfarin-only users (N=14,888). Prescription of NOACs increased from 0% to 14.7% from 2010 to 2016 ( P &lt;0.001). Prescription of NOACs increased in each category of CKD (G1-2, G3 and G4-5, all P &lt;0.001) (Figure 1). The most frequently prescribed NOAC in 2016 was rivaroxaban (8.2%) among those with eGFR&gt;60 ml/min/1.73 m 2 and apixaban (5.9% and 4.9%) among those with eGFR 30-60 ml/min/1.73 m 2 and eGFR&lt;30 ml/min/1.73 m 2 , respectively. Among the 22 patients prescribed apixaban with eGFR&lt;30 ml/min/1.73 m 2 in 2016, 22.7% (5 of 22) had eGFR&lt;15 ml/min/1.73 m 2 . In conclusion, NOAC prescriptions increased among patients with AF in all stages of CKD. Further studies to quantify the effectiveness and safety of NOACs compared to warfarin by stage of CKD are warranted.

Abstract 78: Incidence of Atrial Fibrillation Among Patients with an Embolic Stroke of Undetermined Source

Introduction: Trials are underway to evaluate the prophylactic use of novel oral anticoagulants (NOAC) in patients with embolic strokes of undetermined source (ESUS). It is uncertain whether the bleeding risks associated with prophylactic NOAC use will outweigh any stroke prevention benefit in ESUS patients who lack underlying atrial fibrillation (AF). Methods: We determined the proportion of patients in the CRYSTAL AF study who met ESUS trial criteria and had AF (≥2 minutes) detected within 3 years via an insertable cardiac monitor (ICM). Cryptogenic stroke patients ≥50 years old with a modified Rankin score ≤3 and no evidence of lacunar infarcts after an extensive stroke work up were included. Age ≥60 years and CHA 2 DS 2 VASc score ≥3 were required for patients whose index stroke occurred 3-6 months before randomization. We also compared AF detection rates between the ICM and standard monitoring arms using Kaplan-Meier estimates and computed the percentage of patients with AF detected within the initial 30 days of ICM monitoring. Results: Among the 441 patients enrolled in CRYSTAL AF, 246 (55.8%) met inclusion criteria for the ongoing ESUS trials. AF detection rates at 3 years reached 38.5% in the ICM arm vs. 2.7% in the control arm (HR 12.1 [3.7-39.3], p&lt;0.0001, Figure). In contrast, AF detection rates at 30 days were only 6.7% and 0.8% in the ICM and control arm, respectively. Conclusions: Among the subset of CRYSTAL AF patients who met the ESUS trial criteria, &gt;60% did not have AF detected via ICMs within 3 years of their index stroke event. Prophylactic NOAC use in the absence of AF may therefore increase bleeding risks without providing protection against AF-related stroke in the majority of ESUS patients. Furthermore, ICMs were superior to standard monitoring for AF detection in this ESUS population. Monitoring continuously for only the initial 30 days would have failed to identify AF in &gt;80% of patients ultimately found to have AF via an ICM.

GASTROINTESTINAL BLEEDING WITH THE USE OF NEW ORAL ANTICOAGULANTS: EPIDEMIOLOGY, RISK FACTORS, TREATMENT, AND PREVENTION

Novel oral anticoagulants (NOACs), such as the direct thrombin inhibitor dabigatran and the selective factor Xa inhibitors rivaroxaban and apixaban, are increasingly used as an effective antithrombotic drug in real clinical practice. Unfortunately, these medications can cause severe adverse events, including gastrointestinal bleeding, one of the most common events. This complication annually develops in 2–3% of patients taking NOACs. The sources of bleeding can be in both the upper or lower gastrointestinal tract (GIT). The common cause of bleeding is undiagnosed GIT neoplasms, often colorectal cancer. Clinical and cohort studies show that the greatest risk of bleeding is observed with the use of rivaroxaban. The risk factors are advanced age, concurrent administration of nonsteroidal anti-inflammatory drugs, aspirin, and other anticoagulants, gastrointestinal diseases, H. pylori infection, impaired renal and hepatic functions, and alcohol intake. Gastrointestinal bleeding is treated on general principles, by applying endoscopic and surgical techniques. Particular importance is attached to the blockade of the anticoagulant effects of NOACs. For this, the entire range of antidotes, such as idarucizumab (it has been already applied in several countries of the world), andexanet, and ciraparantag, has been recently designed and is undergoing clinical trials. Bleeding prevention involves control of risk factors, rational use of NOACs, prophylactic administration of proton pump inhibitors, timely discontinuation of anticoagulation prior to traumatic medical procedures on the gastrointestinal organs (before certain endoscopic procedures in particular).

Management strategies for atrial fibrillation.

Atrial fibrillation is the most prevalent cardiac arrhythmia, affecting 10% of those aged over 80 years. Despite multiple treatment options, it remains an independent prognostic marker of mortality due to its association with clinical sequelae, particularly cerebrovascular events. Management can be broadly divided into treatment of the arrhythmia, via rhythm or rate control, and stroke thromboprophylaxis via anticoagulation. Traditional options for pharmacotherapy include negatively chronotropic drugs such as β-blockers, and/or arrhythmia-modifying drugs such as amiodarone. More recently, catheter ablation has emerged as a suitable alternative for selected patients. Additionally, there has been extensive research to assess the role of novel oral anticoagulants as alternatives to warfarin therapy. There is mounting evidence to suggest that they provide comparable efficacy, while being associated with lower bleeding complications. While these findings are promising, recent controversies have arisen with the use of novel oral anticoagulants. Further research is warranted to fully elucidate mechanisms and establish antidotes so that treatment options can be appropriately directed.

Audit of Change in Anticoagulation Practice Prior to Direct Current Cardioversion and Incidence of Left Atrial Thrombus on Transoesophageal Echocardiogram

The use of anticoagulation with either warfarin or novel oral anticoagulants (NOAC) is routine prior to direct current cardioversion (DCCV) for atrial fibrillation or atrial flutter. Transoesophageal echocardiograms (TOE) may be performed to visually confirm and rule out LAA thrombus. We retrospectively reviewed the change in practice of anticoagulation and results of TOE prior to DCCV. 354 patients underwent DCCV from 2012 to August 2016 of which 238 had a TOE. 20 patients were lost to follow-up. The mean age was 63years (range 18-94). The mean CHADSVASC score was 2.04 (SD1.49). Warfarin usage was 75% in 2012 declining to 7% in 2016. NOAC use increased from 6% to 89% in 2016, rivaroxaban being the overwhelming choice with 73%. Of the 238 who underwent TOE, 6 had filling defects suggestive of LAA thrombus. All had ≥3 weeks of formal anticoagulation. 2 were on warfarin and had inadequate INR control. 1 patient was taking apixaban once a day. 3 were on rivaroxaban of which one TOE was re-reported as ‘suspicious’ on review. These patients were compliant and taking rivaroxaban with food. No patient had a stroke on follow-up. Our retrospective dataset shows the changing practise of clinicians, favouring NOAC over warfarin prior to DCCV. Rivaroxaban, whilst being the favoured NOAC had two confirmed LAA thrombus and one suspicious finding with no obvious cause for the failure of treatment. Whilst retrospective, this is a real-world experience and warrants further prospective evaluation.

Persistent Prothrombotic State in Atrial Fibrillation Despite Use of Novel Oral Anti-Coagulants

Background: Oral anticoagulants such as warfarin have been conventionally used for the management of atrial fibrillation (AF). Despite the effectiveness of warfarin, its use in AF patients requiring anticoagulation is suboptimal with an even greater underuse seen in elderly patients who are at higher risk of stroke. New oral anticoagulants such as rivaroxaban(R), apixaban (A), dabigitran (D) and edoxaban (E) have been approved to manage thrombotic and cardiovascular disorders including AF. The newer anticoagulants do not require continuous monitoring like warfarin and are much more convenient for patients with AF.Objective: To profile the baseline level of circulating thrombotic biomarkers plasminogen activator inhibitor (PAI-1), von Willebrand Factor (vWF), microparticle bound tissue factor (MP-TF) and prothrombin fragment 1.2 (F1.2) in patients with AF. Additionally, the effect of novel oral anticoagulants (R, A, D and E) on the levels of thrombotic biomarkers in patients with AF is assessed.Materials and Methods: Citrated blood samples were drawn from 30 patients (21 male and 9 female; mean age 59.1) prior to ablation surgery for AF at Loyola University Medical Center in Maywood, Illinois. Citrated blood was spun at 3000 rpm to obtain platelet poor plasma. Normal plasma samples from healthy controls (24 male and 24 female; mean age 33) were purchased from a commercial source (George King Biomedical, Overland Park, KS). The plasma samples were analyzed using a biochip array (Randox, London, UK) for metabolic syndrome biomarkers including PAI-1 and ELISA kits for vWF, MP-TF (Hyphen BioMed, Nueville-Sur-Oise, France) and prothrombin F1.2 (Siemens, Newark, DE).Results: Compared to the control group, circulating levels of vWF, MP-TF and PAI-1 were statistically increased in patients with AF (P<0.0001, P<0.0001, and P=0.0014, respectively). Circulating levels of prothrombin F1.2 showed no difference between the AF and the control group (P=0.2696). AF patients (n=30) were divided into two groups based on their usage (Group 1, n=17) and non-usage (Group 2, n=10) of any novel oral anticoagulant (R, A, D and E). Three patients on warfarin were excluded from this section of data analysis. A statistical increase in vWF (P=0.0018) and MP-TF (P=0.0039) remained in those taking novel oral anticoagulants compared to group 2. No difference was seen in PAI-1 (P=0.333) or F1.2 (P=0.31) between groups 1 and 2. Percent change from the normal mean was also calculated for PAI-1, vWF, MP-TF and F1.2 in group 1 (78%, 61.1%, 142%, 8.9%, respectively) and group 2 (113.6%, 16.9%, 31.7%, 41.4%, respectively) as seen in table 1.Discussion: Elevated levels of PAI-1, vWF and MP-TF seen in AF patients compared to normal provide insight into an additional risk of thrombogenesis associated with AF which is not targeted by current anticoagulant medications. Most AF patients are assessed using a stroke risk stratification scale (CHA2DS2VASc) to determine if anti-coagulants should be used to prevent stroke associated with AF. Patients in group 1 had a mean CHA2DS2VASc score of 1.15 compared to 2.18 see in group 2. This data supports studies which suggest that including levels of prothrombotic biomarkers to current risk stratification scales could be more effective in assessing the risk of stroke of patients with AF. This data also suggests that although very effective in lowering prothrombin F1.2 levels in AF, the newer anticoagulants, R,A,D and E still leave additional prothrombotic biomarkers unaffected. These unaffected biomarkers could be the potential target of future drug therapies which could lower the risk of stroke in patients with AF even more than the use of newer anticoagulants alone. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

PCV144 - Novel Oral Anticoagulants in the UK and France: Comparative Assessment of Costs of Prescriptions Dispensed in the Non-Hospital Setting

To assess and compare the expenditure on novel oral anticoagulants (NOACs) in the non-hospital setting, in England and France. Non-systematic review of publically available health authority websites and peer review journals. Prescription costs data, from 2012-2015, were obtained and analyzed for England from the Health and Social Care Information Centre Prescription Cost Analysis for England reports, and for France from the Assurance Maladie Medic’AM reports. In the UK, clinical objections raised by prescribers have limited NOAC uptake in the past; however, between 2012-2015 the costs associated to non-hospital dispensed prescriptions for the three main NOACs, rivaroxaban, apixaban and dabigatran, increased from £3,7M in 2012 to £144,2M in 2015, showing a considerable increase in expenditure, mostly due to the increase in rivaroxaban and apixaban prescription. This can be partly attributed to the issue of NICE guidance favoring the use of NOACs in non-valvular atrial fibrillation and efforts to implement NICE recommendations. Similar results have been observed in France, where costs associated to NOAC prescriptions dispensed in the non-hospital setting have increased from €56.3M in 2012 to €309,8M in 2015. In response to increasing NOAC prescription, the ANSM and Assurance Maladie consider there is a need for increased vigilance in their use. These findings highlight the considerable increase in NOAC prescriptions and costs in both England and France, and should inform future policy efforts to encourage adequate use of NOACs in order to control increasing expenditure. Between 2012 and 2015, there was a considerable increase in NOAC drug expenditures from prescriptions dispensed in the non-hospital setting, in both England and France, which suggests that policies aimed at incentivizing NOAC prescriptions have been effective, but should further factor in the increasing economic impact of these treatments.

‘The role of novel oral anticoagulants in patients undergoing cryoballoon ablation for atrial fibrillation’

AimPeri-procedural thromboembolic (TE) and hemorrhagic events are complications of major concern for patients undergoing cryoballoon (CB) ablation for atrial fibrillation (AF).While peri-procedural anticoagulation management could decrease the incidence of these complications, data on CB ablation are scarce. The role of novel oral anticoagulants (NOACs) has not been thoroughly tested in this population. MethodsIn the present study, we sought to assess acute peri-procedural complications in patients undergoing CB ablation for AF under different anticoagulation regimens; anticoagulation administration was performed according to the CHA2DS2-VASc score guidelines. To the best of our knowledge, this is the first study that compares 1) uninterrupted warfarin, 2) bridging therapy with low molecular weight heparin (LMWH), 3) aspirin and 4) NOACs in this subgroup of patients. ResultsNOACs were as effective as uninterrupted warfarin in terms of bleeding complications and TE events. Surprisingly, the aspirin group had more hemorrhagic complications than both the warfarin and NOACs groups. ConclusionIn the current study, the use of NOACs was an effective and safe approach in CB ablation.

Role of Novel Oral Anticoagulants in the Treatment of Antiphospholipid Syndrome.

Background: Antiphospholipid syndrome (APS) is an autoimmune disease characterized by thrombosis or pregnancy loss with persistent positive antibodies. Standard treatment for APS with history of thromboembolism is heparin or low-molecular-weight heparin followed by a vitamin K antagonist (VKA). Novel oral anticoagulants (NOACs) could be effective in patients with APS, but none carry indications for treatment related to APS. Clinical Evidence: Five case reports or series with rivaroxaban and dabigatran suggest thrombotic events occur most often in the higher risk population (arterial thrombosis and/or triple positive antibodies) or in patients who had recurrent VTEs on warfarin therapy. An observational cohort in 26 APS patients using dabigatran or rivaroxaban described a recurrent thrombotic event in only 1 patient after 8 months of treatment. The event-free survival rate was 87.9% at 12 months. Three controlled clinical trials are underway to evaluate the thrombotic risk of NOACs (RAPS, TRAPS, and ASTRO-APS). Discussion: There are no completed studies that evaluate the use of NOACs in APS compared to VKAs. One major disadvantage of the NOACs is the limited availability of reversal agents for patients with a major bleeding episode. An increased risk of thrombotic events is associated with arterial occlusions and triple antibody positivity APS with both warfarin and NOACs; this is currently being researched in the TRAPS study. Conclusion: Based on current available evidence, VKAs remain the standard of care in the treatment of APS. Results of ongoing trials may offer more guidance on how to appropriately use NOACs for patients with APS.

Are Some Anticoagulants More Equal Than Others? - Evaluating the Role of Novel Oral Anticoagulants in AF Ablation.

Left atrial ablation strategies are being increasingly performed as a Class 1 therapeutic indication for drug refractory paroxysmal atrial fibrillation (AF). Traditionally AF ablation has been performed with patients on uninterrupted warfarin therapy, however over the last few years, novel oral anticoagulants (NOACs) have emerged as attractive alternatives to warfarin in order to reduce stroke risk due to AF. NOACs are therefore increasingly being used instead of warfarin in the management of AF. There is also mounting evidence mainly in the form of small randomised studies and meta-analysis that have demonstrated that the use of NOACs for AF ablation is efficacious, safe and convenient. However the peri-procedural dosing protocols used in various studies especially in terms of whether NOAC use is interrupted or uninterrupted during AF ablation, have significant inter-operator and inter-institution variability. Currently there is also a lack of randomised controlled trials to validate the data obtained from meta-analyses. There is also evidence that use of NOACs may increase the requirement of unfractionated heparin during the procedure. This review article shall examine the currently available evidence-base, appraise the gaps in the current evidence and also underscore the need for larger randomised clinical trials in this rapidly developing field.

Suboptimal use of non-vitamin K antagonist oral anticoagulants: Results from the RAMSES study.

This study aimed to investigate the potential misuse of novel oral anticoagulants (NOACs) and the physicians’ adherence to current European guideline recommendations in real-world using a large dataset from Real-life Multicenter Survey Evaluating Stroke Prevention Strategies in Turkey (RAMSES Study).RAMSES study is a prospective, multicenter, nationwide registry (ClinicalTrials.gov identifier NCT02344901). In this subgroup analysis of RAMSES study, patients who were on NOACs were classified as appropriately treated (AT), undertreated (UT), and overtreated (OT) according to the European Society of Cardiology (ESC) guidelines. The independent predictors of UT and OT were determined by multivariate logistic regression.Of the 2086 eligible patients, 1247 (59.8%) received adequate treatment. However, off-label use was detected in 839 (40.2%) patients; 634 (30.4%) patients received UT and 205 (9.8%) received OT. Independent predictors of UT included >65 years of age, creatinine clearance ≥50 mL/min, urban living, existing dabigatran treatment, and HAS-BLED score of <3, whereas that of OT were creatinine clearance <50 mL/min, ongoing rivaroxaban treatment, and HAS-BLED score of ≥3.The suboptimal use of NOACs is common because of physicians’ poor compliance to the guideline recommendations in patients with nonvalvular atrial fibrillation (NVAF). Older patients who were on dabigatran treatment with good renal functions and low risk of bleeding were at risk of UT, whereas patients who were on rivaroxaban treatment with renal impairment and high risk of bleeding were at risk of OT. Therefore, a greater emphasis should be given to prescribe the recommended dose for the specified patients.

Novel oral anticoagulants in the management of coronary artery disease.

Despite advances in interventional and pharmacologic therapy, survivors of myocardial infarction remain at an increased risk of subsequent cardiovascular events. Initial pharmacological management includes both platelet inhibition and parenteral anticoagulation, whereas long-term pharmacological therapy relies on antiplatelet therapy for prevention of thrombotic complications. Biomarkers showing ongoing thrombin generation after acute coronary syndromes suggest that anticoagulants may provide additional benefit in reducing cardiovascular events. We review the pharmacokinetics of novel anticoagulants, clinical trial results, the role of monitoring, and future directions for the use of novel oral anticoagulants in the treatment of coronary artery disease. Clinical trials have shown that long-term use of oral anticoagulants decreases the risk of cardiovascular events, but they do so at a cost of an increased risk of bleeding. Future studies will need to identify optimal treatment combinations for selected patients and conditions that address both the appropriate combination of therapy and the appropriate dosage of each agent when used in combination.

Minimizing the Risk of Bleeding with NOACs in the Elderly.

Novel oral anticoagulants (NOACs) such as dabigatran, rivaroxaban, apixaban and edoxaban have gained a lot of popularity as alternatives to warfarin for anticoagulation in various clinical settings. However, there is conflicting opinion regarding the absolute benefit of NOAC use in elderly patients. Low body mass, altered body composition of fat and muscle, renal impairment and concurrent presence of multiple comorbidities predispose elderly patients to many adverse effects with NOACs that are typically not seen in younger patients. There have been reports that NOAC use, in particular dabigatran, is associated with a higher risk of gastrointestinal bleeding in the elderly. Diagnosis and management of NOAC-associated bleeding in the elderly is difficult due to the absence of commonly available drug-specific antidotes that can rapidly reverse the anticoagulant effects. Moreover, in elderly patients, a number of factors such as the presence of other comorbid medical conditions, renal insufficiency, drug interactions from polypharmacy, risk of falls and dementia need to be considered before prescribing anticoagulation therapy. Elderly patients frequently have compromised renal function, and therefore dose adjustments according to creatinine clearance for NOACs need to be made. As each NOAC comes with its own unique advantages and safety profile, an individualized case by case approach should be adopted to decide on the appropriate anticoagulation regimen for elderly patients after weighing the overall risks and benefits of therapy.

Update on Anticoagulation: What the Interventional Radiologist Needs to Know.

The novel oral anticoagulants (NOACs) represent a major advance in the treatment of patients with nonvalvular atrial fibrillation and venous thromboembolism (VTE). They have several advantages over vitamin-K antagonists such as warfarin, including more predictable pharmacokinetics and improved safety, particularly with fatal bleeding and intracranial hemorrhage. However, several issues remain surrounding the use of NOACs in certain subpopulations and with the approach to reversal. The periprocedural management of anticoagulation with these relatively new agents can also present several challenges. This article reviews the basic pharmacology, efficacy, and safety of these drugs. Several populations at higher risk for complications with use of NOACs are discussed, including those undergoing procedures. Finally, several target-specific reversal agents have either received FDA approval or likely will be approved in the near future; these agents and their roles in the approach to anticoagulation reversal will also be discussed.