Novel Oral Anticoagulants Therapy Research Articles

Comparative effectiveness of different management strategies for left atrial appendage thrombus in patients on optimal NOAC therapy

Abstract Background Left atrial appendage (LAA) thrombus is the primary cause of stroke and systemic embolism in atrial fibrillation (AF). Novel oral anticoagulants (NOACs) effectively reduce the prevalence of LAA thrombosis and stroke risk. Nonetheless, there is no clear advice for patients with a NOAC-resistant thrombus, necessitating individualized decision-making without strong support of the current guidelines. Aims To analyze patients diagnosed with an LAA thrombus despite adequate NOAC therapy and to compare the efficacy of various therapeutic strategies in achieving thrombus resolution. Methods We retrospectively analyzed patients scheduled for cardioversion or catheter ablation of AF between 2014 and 2023 who were diagnosed with LAA thrombus despite being on optimal NOAC therapy. These patients underwent follow-up transesophageal echocardiography (TEE) or cardiac CT angiography. Changes in treatment modalities were divided into four groups: transition to an alternative NOAC, switch to a vitamin K antagonist (VKA), the addition of an antiplatelet agent, or the deliberate maintenance of the current treatment. Results We analyzed the data of 90 patients comprising 103 cycles of treatment. The patients were either on rivaroxaban (41%), apixaban (32%), dabigatran (15%) or on edoxaban (12%) at the time of the initial TEE. A change to a different NOAC was observed in 37% of cases, transition to a VKA in 22%, supplementation with antiplatelet therapy in 16%, while deliberate absence of treatment modification in 25% of cases. Subsequent follow-up TEE (or CT angiography in a minority of cases) was performed at a median of 68 [43 – 94] days from the baseline evaluation. Successful thrombus resolution was achieved in 72% of cases. Evaluation of therapeutic strategies revealed that any modification of treatment was three times more effective than deliberate no change in treatment; thrombus resolution was observed in 60 (81%) vs. 17 (59%) cases (OR 3.03 [1.18 - 7.75], p = 0.021). Nevertheless, no particular strategy demonstrated superior efficacy over others. Conclusions Resolution of LAA thrombus in patients already on adequate NOAC treatment may require a revision of the prior anticoagulation strategy; however, none of the commonly employed strategies appears to exhibit distinct superiority over the rest.

Postoperative Bleeding Complications Associated With Novel Oral Anticoagulants in Mohs Micrographic Surgery.

Novel oral anticoagulants (NOACs) are commonly prescribed, recently developed anticoagulants, but limited data exist on NOAC-related bleeding complications in Mohs micrographic surgery (MMS). To assess the risk of postoperative bleeding in patients taking NOACs compared with patients taking no antithrombotic medications. A 5-year retrospective chart review of all MMS cases performed by a single surgeon was conducted. Patient and surgery characteristics, anticoagulant use, and bleeding complications were recorded. Two thousand one hundred eighty-one MMS cases in 1,545 patients were included. There were 696/2,181 cases in which patients were taking at least 1 antithrombotic medication, with 149 on NOAC monotherapy and 15 on NOAC and aspirin combination therapy. Bleeding complications occurred in 22/2,181 cases. Patients on NOAC monotherapy did not have an increased risk of bleeding complications compared with patients on no antithrombotic medications (odds ratio [OR]:1.70, 95% confidence interval [CI]: 0.36-7.97, p = .50). In contrast, patients on NOAC and aspirin combination therapy exhibited an increased bleeding risk (OR: 20.5, 95% CI: 3.99-105.7, p < .001). Novel oral anticoagulant use alone during MMS was not associated with an increased postoperative bleeding risk, supporting the safety of continuing NOAC therapy during MMS. However, NOAC and aspirin combination therapy was associated with a high postoperative bleeding risk. Nonetheless, these bleeding events did not lead to adverse long-term outcomes.

Left atrial appendage occlusion vs novel oral anticoagulation for stroke prevention in atrial fibrillation: rationale and design of the multicenter randomized occlusion-AF trial

The prevalence of atrial fibrillation (AF) is increasing globally, which is a major clinical and public health concern due to the 5-fold increased risk of stroke. Oral anticoagulation with novel oral anticoagulants (NOACs) is the current primary option for stroke prevention in patients with AF, although it increases the risk of major bleeding. Patients with prior ischemic cerebrovascular events are at particularly high risk of both recurrent ischemic events and major bleeding. Left atrial appendage occlusion (LAAO) provides an alternative option for stroke prevention in high-risk patients, however, with currently limited evidence. Thus, randomized trials comparing LAAO to NOACs are needed. The Occlusion-AF trial is designed to assess whether LAAO is non-inferior to NOAC therapy for reduction of the combined endpoint of stroke, systemic embolism, major bleeding (Bleeding Academic Research Consortium ≥ 3) and all-cause mortality in patients with AF and a recent ischemic stroke or transient ischemic attack (TIA). Investigator-initiated multicenter, multinational, randomized open-label non-inferiority trial with blinded outcome evaluation (PROBE design). Patients with documented AF, and an ischemic stroke or TIA within 6 months will be eligible for enrollment. Major exclusion criteria are modified Rankin Scale > 3 at enrollment, glomerular filtration rate < 15 ml/min, and life-expectancy less than 2 years. A total of 750 patients will be randomized 1:1 to receive either a NOAC or LAAO using the Amplatzer Amulet (Abbott, MN, USA) or Watchman FLX (Boston Scientific, MN, USA) with subsequent life-long aspirin 75 mg daily. Follow-up will be based on in-office and telephone follow-up in combination with long-term follow-up (10 years) through national hospital discharge registries in the individual Nordic countries. The primary outcome will be a composite endpoint of stroke, systemic embolism, major bleeding (BARC ≥ 3) and all-cause mortality at 2-year follow-up. The Occlusion-AF trial is designed to compare LAAO to NOAC therapy for secondary stroke prevention in AF patients with a high risk of recurrent thromboembolic events, i.e. with previous ischemic stroke or TIA, and otherwise eligible for anticoagulation. The results are expected to contribute significantly to the understanding of the effects of LAAO compared to the standard contemporary pharmacological treatment in these patients.

MP06-15 POST OPERATIVE BLEEDING AND THOMBOTIC RISK FOR PATIENTS ON NOVEL ORAL ANTICOAGULANTS (NOAC) THERAPY UNDERGOING UROLOGICAL SURGERY

You have accessJournal of UrologyStone Disease: Surgical Therapy I (MP06)1 Sep 2021MP06-15 POST OPERATIVE BLEEDING AND THOMBOTIC RISK FOR PATIENTS ON NOVEL ORAL ANTICOAGULANTS (NOAC) THERAPY UNDERGOING UROLOGICAL SURGERY Modassar Awan, Eloise Merriott, Sybghat Rahim, Ibrahim Khawaja, Sam Datta, Khalid Saja, and Zafar Maan Modassar AwanModassar Awan More articles by this author , Eloise MerriottEloise Merriott More articles by this author , Sybghat RahimSybghat Rahim More articles by this author , Ibrahim KhawajaIbrahim Khawaja More articles by this author , Sam DattaSam Datta More articles by this author , Khalid SajaKhalid Saja More articles by this author , and Zafar MaanZafar Maan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001973.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: There is a paucity of urological published data on the risks of post-operative bleeding and thrombosis for patients that discontinue NOAC treatment perioperatively. The aim of this review was to establish the incidence of post operative bleeding and thrombotic complications for patients undergoing common, predominantly endourological procedures with a moderate or high risk of post-operative bleeding. METHODS: A review was undertaken for 109 successive patients on NOAC therapy undergoing urological surgery (99 males, 10 females, median age 75.7 years with the range of 48-92 years). Data from 58 patients was reviewed retrospectively, 51 patients prospectively. In all cases NOAC therapy was stopped and re-started peri-operatively on the basis of our local guidelines (Rahim et al, EAU 2017) or individualised haematological advice given to the pre assessment clinical team.Bleeding complications were noted and categorised accordingly: requiring blood transfusion, > 30 g/L Hb drop from baseline; haematuria requiring readmission; requirement for bladder washouts or a return to theatre. Electronic discharge summaries and patient notes linked to their respective primary care practices were used to search for any thrombotic events occurring within 30 days of NOAC therapy interruption. RESULTS: Of the 109 patients; 75 (68.8%) were on Apixaban, 22 (20.2%) on Rivaroxaban, 10 (9.2%) on Dabigatran, and 2 patients (1.8%) on Edoxaban. Procedures included TURBT (30), prostate biopsies (18), TURP (9), HoLEP (12), Ureteroscopy (15), prostate biopsies (18), other (25). The NOAC was stopped on average 49.7 hours prior to surgery. The NOAC was most commonly reinitiated 72 hours after surgery (median 72 hrs, mean 110 hrs, range 24-672 hrs). There was incomplete documentation for 37 patients on the timing of NOAC restart after surgery. Bleeding complications were noted in 4 patients (3.66%). Three of the 4 patients were on Apixaban (2.75%) and one patient was on Rivaroxaban (0.92%). One patient (0.92%) was taken back to theatre for bladder washout/cystodiathermy and the other three were managed satisfactorily with catheter irrigation. One patient (0.92%) required transfusion and two patients (1.84%) had a drop in haemoglobin (>30 g/L). It was noted that the NOAC was restarted later than recommended in two of the four patients with bleeding complications, as per the surgeon’s discretion. There were no thrombotic complications within 30 days of stopping NOACs in either the prospective or retrospective groups. CONCLUSIONS: Bleeding complications, after stopping and restarting NAOCs for patients undergoing predominantly endourological procedures appear to be uncommon (<4%). The bleeding rate is in keeping with established bleeding rates for TURP in publishes series. The risk of blood transfusion or return to theatre in our reviewed series was <1%. There were no thrombotic complications in the 109 patients reviewed within one month of surgery. Source of Funding: Nothing to declare © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e95-e95 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Modassar Awan More articles by this author Eloise Merriott More articles by this author Sybghat Rahim More articles by this author Ibrahim Khawaja More articles by this author Sam Datta More articles by this author Khalid Saja More articles by this author Zafar Maan More articles by this author Expand All Advertisement Loading ...

Time to surgery and complications in hip fracture patients on novel oral anticoagulants: a systematic review.

Early surgery has been consistently demonstrated to reduce complications and mortality in hip fracture patients. There remains no general consensus, however, regarding the optimal time to surgery for hip fracture patients who are on novel oral anticoagulants (NOAC) on admission and its effect on clinical outcomes after surgery. The objective of this review was to assess the effect of preoperative NOAC therapy on time to surgery and postoperative complications in hip fracture patients. We performed a systematic review of the literature using the PubMed, Embase, and Cochrane Library electronic databases. Relevant articles were identified and included if they: (i) included patients on NOAC therapy on admission who did not undergo reversal; (ii) included a control group of patients not on any anticoagulation; (iii) included time from admission to surgery; and (iv) included one of the following outcomes: blood transfusion, venous thromboembolism (VTE), stroke, readmission, and mortality. Nine studies were included with a total of 4,419 patients. There were 414 NOAC patients and 4,005 non-anticoagulated patients. Six of the nine studies found a significant increase in time to surgery for patients on NOAC therapy. Three of the seven studies that reported rates of blood transfusion found a significantly higher incidence of transfusion in patients on NOACs. None of the studies found a significant difference in VTE and stroke. One of the two studies that reported readmissions showed a higher risk of readmission for patients on NOACs. Eight of the nine included studies found no significant difference in postoperative mortality rates between the NOAC and control groups, with the remaining study finding a higher mortality rate only in patients on NOAC therapy who underwent fixation and not those who underwent arthroplasty. These mixed findings suggest that delay to surgery may not be warranted in the urgent surgical setting of patients on NOAC therapy who sustain hip fractures.

The use of novel oral anticoagulants compared to vitamin K antagonists (warfarin) in patients with left ventricular thrombus after acute myocardial infarction.

Current guidelines recommend the use of vitamin K antagonist (VKA) for up to 3-6 months for treatment of left ventricular (LV) thrombus post-acute myocardial infarction (AMI). However, based on evidence supporting non-inferiority of novel oral anticoagulants (NOAC) compared to VKA for other indications such as deep vein thrombosis, pulmonary embolism (PE), and thromboembolic prevention in atrial fibrillation, NOACs are being increasingly used off licence for the treatment of LV thrombus post-AMI. In this study, we investigated the safety and effect of NOACs compared to VKA on LV thrombus resolution in patients presenting with AMI. This was an observational study of 2328 consecutive patients undergoing coronary angiography ± percutaneous coronary intervention (PCI) for AMI between May 2015 and December 2018, at a UK cardiac centre. Patients' details were collected from the hospital electronic database. The primary endpoint was rate of LV thrombus resolution with bleeding rates a secondary outcome. Left ventricular thrombus was diagnosed in 101 (4.3%) patients. Sixty patients (59.4%) were started on VKA and 41 patients (40.6%) on NOAC therapy (rivaroxaban: 58.5%, apixaban: 36.5%, and edoxaban: 5.0%). Both groups were well matched in terms of baseline characteristics including age, previous cardiac history (previous myocardial infarction, PCI, coronary artery bypass grafting), and cardiovascular risk factors (hypertension, diabetes, hypercholesterolaemia). Over the follow-up period (median 2.2 years), overall rates of LV thrombus resolution were 86.1%. There was greater and earlier LV thrombus resolution in the NOAC group compared to patients treated with warfarin (82% vs. 64.4%, P = 0.0018, at 1 year), which persisted after adjusting for baseline variables (odds ratio 1.8, 95% confidence interval 1.2-2.9). Major bleeding events during the follow-up period were lower in the NOAC group, compared with VKA group (0% vs. 6.7%, P = 0.030) with no difference in rates of systemic thromboembolism (5% vs. 2.4%, P = 0.388). These data suggest improved thrombus resolution in post-acute coronary syndrome (ACS) LV thrombosis in patients treated with NOACs compared to VKAs. This improvement in thrombus resolution was accompanied with a better safety profile for NOAC patients vs. VKA-treated patients. Thus, provides data to support a randomized trial to answer this question.

P1530 Dense spontaneous echo contrast and thrombus in patients on new oral anticoagulant and warfarin therapy: a retrospective audit

Abstract Background Cardioembolic stroke is a known complication of atrial fibrillation (AF), which is increasing in global prevalence. Spontaneous echo contrast (SEC) in the left atrium (LA) is a precursor for thrombus formation detected on transesophageal echocardiography (TEE). There is limited data regarding the prevalence of dense SEC and/or left atrial thrombus (LAT) detected by TEE in patients on novel oral anticoagulants (NOACs) compared with Warfarin. Purpose To determine and compare the prevalence of dense SEC and/or LAT among patients with AF/atrial flutter undergoing TEE while on continuous NOAC or Warfarin therapy. Methods Retrospective analysis of prospectively entered data for all patients who were on continuous oral anticoagulants and underwent TEE with DC cardioversion, over a 9-year period (1st January 2011 to 31st December 2018) at a public teaching hospital in NSW, Australia. SEC was classified according to emptying flow velocities, as per the European Association of Cardiovascular Imaging guidelines. Results Among the 195 patients, 94 (48%) patients were on NOAC therapy (52% Apixaban, 25% Rivaroxaban, 23% Dabigatran) while 101 (52%) patients were on Warfarin. There was no difference in age (mean ± SD: 64 ± 12 vs. 65 ± 13, p = 0.71) or proportion of males (71% vs 69%, p = 0.76) between patients on NOAC therapy compared with Warfarin. However, the NOAC therapy group had a lower prevalence of ischaemic heart disease (IHD) (18% vs. 33%, p &amp;lt; 0.05) and chronic kidney disease (CKD) (2% vs. 19%, p &amp;lt; 0.001), in addition to a lower CHA2DS2-VASc score (2.1 ± 1.7 vs 2.7 ± 1.7, p = 0.03) and higher haemoglobin levels (145.3 ± 19 vs 133.8 ± 24, p = 0.001). The overall rate of dense SEC and/or LAT detected by TEE was 9.7%. There was no significant difference in the prevalence of dense SEC and/or LAT between patients on NOACs and Warfarin (6.4% vs. 12.9%, p = 0.13). On multivariable analysis of IHD, CKD, Warfarin, NOACs and CHA2DS2-VASc score, there was no significant difference in prevalence of SEC/LAT between Warfarin and NOACs. Conclusions In this study, 6.4% of patients on continuous NOACs and 12.9% of patients on Warfarin therapy had dense SEC and/or LAT detected by TEE. Although the trend towards higher rates of dense SEC and pre-thrombus in the Warfarin group did not reach statistical significance, it still holds clinical significance as these patients cannot be cardioverted. Therefore, these data support the need to consider anticoagulant optimisation in the overall management of patients with SEC.

Abstract 17328: Novel Oral Anticoagulants in Adult Fontan Patients: A Multi-Site Experience

Introduction: Adult Fontan patients are typically prescribed antiplatelet or anticoagulant therapy to manage increased risk for thrombotic and embolic complications (TECs). There is a Class III recommendation against the use of novel oral anticoagulants (NOACs) in this population due to a paucity of data. We hypothesized that NOACs are potentially non-inferior to warfarin in adult Fontan patients. Methods: We performed a multi-site retrospective review of adult Fontan patients, evaluated at three major academic medical centers (1995-2018), prescribed NOAC, warfarin, or aspirin therapy. Results: We identified 267 adult Fontan patients: 48 on NOACs, 107 on warfarin, and 180 on aspirin (14.4% to 54.2% cross-over amongst groups). Patients were more likely to have clinically significant bleeds (“bleeds”) if on a NOAC (HR=9.3, CI=3.0-28.4) or warfarin (HR=4.1, CI=1.6-10.5) versus aspirin. Bleed hazard ratio differences between NOAC and warfarin patients were not statistically significant (HR=2.3, CI=0.9-5.9). Patients on NOACs were not more likely to suffer TECs than patients on warfarin (HR=1.7, CI=0.4-6.3) or aspirin (HR=2.8, CI=0.7-10.3). Aspirin patients were younger, healthier, and had more favorable Fontan palliation. The traditional scoring systems to predict bleeds (HAS-BLED) and TECs (CHA 2 DS 2 VASc) were not predictive in this patient population. The only risk factor we identified for bleeds was a history of/predisposition to bleeding (OR=10.2, CI=4.4-23.6). Risk factors we identified for TECs included diabetes mellitus (OR=5.0, CI=2.2-11.4), labile international normalized ratio (OR=3.7, CI=1.1-12.4), and CHF (only in the NOAC/warfarin subgroup, OR=4.4, CI=1.2-16.3). Conclusions: NOACs are a potentially noninferior alternative to warfarin for adult Fontan patients. Our findings have laid the groundwork for a randomized control trial comparing the use of NOACs to warfarin in adult Fontan patients to test noninferiority or equivalence.

Interrupted versus uninterrupted novel oral anticoagulant peri-implantation of cardiac device: A single-center randomized prospective pilot trial.

Many patients requiring cardiac implantable electronic device (CIED) implantation are on long-term oral anticoagulant therapy. While continuation of warfarin has been shown to be safe and reduce bleeding complications compared to interruption of warfarin therapy and heparin bridging, it is not known which novel oral anticoagulants (NOAC) regimen (interrupted vs uninterrupted) is better in this setting. One-hundred and one patients were randomized to receive CIED implantation with either interrupted or uninterrupted/continuous NOAC therapy before surgery. No heparin was used in either treatment arm. The primary end-point was the presence of a clinically significant pocket hematoma after CIED implantation. The secondary end-point was a composite of other major bleeding events, device-related infection, thrombotic events, and device-related admission length postdevice implantation. Both treatment groups were equally balanced for baseline variables and concomitant medications. One clinically significant pocket hematoma occurred in the uninterrupted NOAC group and none in the interrupted group (P=0.320). There was no difference in other bleeding complications. No thrombotic events were observed in either of the two groups. Despite the paucity of bleeding events, data from this pilot study suggest that uninterrupted NOAC therapy for CIED implantation appears to be as safe as NOAC interruption and does not increase bleeding complications.

Real-World Health Care Costs Based on Medication Adherence and Risk of Stroke and Bleeding in Patients Treated with Novel Anticoagulant Therapy.

With the lack of real-world evidence, the challenge for drug reimbursement policy decision makers is to understand medication adherence behavior among users of novel oral anticoagulants (NOACs) and its effect on overall cost savings. No study has examined and quantified the burden of cost in high-risk patients taking NOAC therapy. To examine the association of cost with adherence, comorbidity, and risk of stroke and bleeding in patients taking NOACs (rivaroxaban and dabigatran). A retrospective cohort study used deidentified data from a commercial managed care database affiliated with Optum Clinformatics Data Mart (January 1, 2010-December 31, 2012). Patients aged 18 years and older with ≥ 1 diagnosis of atrial fibrillation/flutter, > 1 NOAC prescription, 6-month pre-index and 12-month post-index continuous enrollment, and CHA2DS2-VASc score ≥ 1 were included. Adherence was calculated using proportion of days covered (PDC ≥ 80%) over an assessment period of 3, 6, and 12 months and compared based on level of comorbidity, stroke, and bleeding risk. The adjusted annual health care costs per patient (drug, medical, and total) were calculated using multivariable gamma regression controlling for demographic and clinical characteristics and compared across groups based on adherence over 12 months, baseline level of comorbidity, and risk of stroke and bleeding. Of 25,120 NOAC patients, 2,981 patients were included in the final cohort. Based on a PDC threshold of ≥ 80%, the adherence rate over 3, 6, and 12 months was 72%, 65%, and 54%, respectively. For all time periods, the level of adherence significantly increased (P < 0.001), with an increase in stroke risk (based on CHA2DS2VASc scores of 1, 2-3, and 4+); comorbidity (Charlson Comorbidity Index scores of 0, 1-2, and 3+); and risk of bleeding (HAS-BLED scores of 0-1, 2, and 3+). Adjusted all-cause total cost calculated for a 12-month period was significantly lower ($29,742 vs. $33,609) among adherent versus nonadherent users. Drug cost was higher ($5,595 vs. $2,233) among adherent versus nonadherent patients but was offset by lower medical costs ($23,544 vs. $30,485) costs. The overall cost significantly increased for patients with a high risk of bleeding and a high level of comorbidity. Adherence to NOAC therapy led to a reduction in overall health care cost, since higher drug costs were offset by lower medical (inpatient and outpatient) costs among adherent patients. Cost information based on adherence and risk of stroke and bleeding can help formulary decision makers to assess risk-benefit and help clinicians in developing interventions to reduce patient burden. Funding to acquire the data source was provided by the University of Rhode Island College of Pharmacy, Kingston, to support PhD dissertation work. Deshpande is currently an employee of Pharmerit International.

Novel oral anticoagulant use in adult Fontan patients: A single center experience.

Adult Fontan patients are at increased risk for thrombosis and thromboembolic complications leading to increased morbidity and mortality. Most are prescribed antiplatelet or anticoagulant therapy for thromboprophylaxis; novel oral anticoagulants (NOACs) are uncommonly used given lack of data on their use in this population and generalized concerns regarding Fontan patients' abnormal coagulation. We report the largest single-center experience with the use of NOACs for treatment and prophylaxis of thrombosis and thromboembolism in adult Fontan patients. A retrospective chart review identified 21 patients (11 female, 10 male), median age 33 years (18-50) at first initiation, who were prescribed a NOAC on 27 different occasions. The main indications for anticoagulation were arrhythmia (N = 12), thrombosis (N = 8), and persistent right to left shunts (N = 2); one patient was initially on anticoagulation for arrhythmia but restarted for thrombosis. The most common indications for initiation of a NOAC over warfarin were patient/provider preference (N = 11), labile international normalized ratio (INR) (N = 5), initiation of therapy elsewhere (N = 3), and history of poor clinical follow-up (N = 2). Over a cumulative 316 months of patient therapy, one new thrombotic event was noted. No major or nonmajor bleeding events occurred, and 10 patients experienced minor bleeding that did not require the cessation of therapy. One patient died from multiorgan system failure following an unwitnessed, out of hospital arrest. At present, 10 patients remain on NOAC therapy in the setting of ongoing arrhythmia (N = 4), history of stroke (N = 2), history of pulmonary embolism (N = 2), history of deep vein thrombosis (N = 1), and history of right ventricle thrombus (N = 1). While our study is limited by size, our results suggest that NOACs may be a non-inferior alternative to traditional anticoagulation and that further study is warranted.

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.

Perioperative management of antithrombotic therapy in patients receiving cardiovascular implantable electronic devices: a network meta-analysis.

Network meta-analysis (NMA) has advantages including being able to simultaneously compare and rank multiple treatments over traditional meta-analysis. We evaluated by a NMA the optimal antithrombotic strategy during the perioperative period of implantation of cardiovascular implantable electronic devices (CIEDs). We performed a network meta-analysis of observational studies (cohort and case-control studies). The eligible studies tested the following antithrombotic therapy during the CIED placement: aspirin, clopidogrel, warfarin, novel oral anticoagulants (NOACs), and heparin bridging. Thirty-one observational studies with 119 study arms were included (41,174 patients receiving long-term antithrombotic therapy; median age, 72.6years; 70.1% males; median follow-up, 3.6years). Aspirin (4.26 [2.88-7.22]), warfarin (3.37 [2.17-5.23]), and clopidogrel (3.30 [1.49-5.88]) reduced the risk of bleeding as compared with heparin bridging, and there was no significance difference between continued NOACs and heparin bridging (0.67 [0.21-2.18]). The comparison of commonly used protocols in the management of anticoagulant therapy revealed that continued warfarin (0.38 [0.20-0.74]), continued NOACs (0.19 [0.04-0.89]), and heparin bridging therapy (0.01 [0.05-0.21]) increased the risk of bleeding as compared that of control, and continued warfarin (3.74 [1.96-7.16]), interrupted warfarin (4.89 [2.20-10.88]), and interrupted NOACs (12.5 [1.25-100]) reduced the risk of bleeding compared with that of heparin bridging. Among various antithrombotic drugs, aspirin had the lowest bleeding risk, followed by warfarin, clopidogrel and NOACs, and heparin, with the greatest bleeding risk. NOACs therapy appears safe and effective, and interrupted NOACs may be the optimal anticoagulation protocol for use during the perioperative period of CIED implantation.

Intracranial hemorrhage during administration of a novel oral anticoagulant.

Objective: Oral anticoagulants are widely administered to patients with atrial fibrillation in order to prevent the onset of cardiogenic embolisms. However, intracranial bleeding during anticoagulant therapy often leads to fatal outcomes. Accordingly, the use of novel oral anticoagulants (NOACs), which less frequently have intracranial bleeding as a complication, is expanding. A nationwide survey of intracranial bleeding and its prognosis in Japan reported that intracranial bleeding of advanced severity was not common after NOAC administration. In this report, two cases from our institute are presented.Patients: Case 1 was an 85-year-old man with a right frontal lobe hemorrhage while under dabigatran therapy. Case 2 was an 81-year-old man who had cerebellar hemorrhage while under rivaroxaban therapy.Result: In both patients, the clinical course progressed without aggravation of bleeding or neurological abnormalities once anticoagulant therapy was discontinued.Conclusion: These observations suggest that intracranial hemorrhage during NOAC therapy is easily controlled by discontinuation of the drug. NOAC administration may therefore be appropriate despite the risk of such severe complications. Further case studies that include a subgroup analysis with respect to each NOAC or patient background will be required to establish appropriate guidelines for the prevention of cardiogenic embolisms in patients with atrial fibrillation.

The Use of Oral Anticoagulants for the Treatment of Venous Thromboembolism in Cancer Patients

Background: Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer, second to death caused by cancer itself. Guidelines from the National Comprehensive Cancer Network (NCCN) and American Society of Clinical Oncology (ASCO) support the use of low molecular weight heparin (LMWH) and vitamin K antagonists (VKA) for treatment of VTE in cancer patients. The novel oral anticoagulants (NOACs) are increasingly being used for all types of VTE, but their safety and efficacy in cancer-associated VTE has not been established. In the CLOT trial of LMWH in cancer-associated VTE, the rate of recurrent VTE was 9.0%, compared to 5.1% among the subgroup of cancer patients who received rivaroxaban in the EINSTEIN trial; bleeding rates among cancer patients in the CLOT and EINSTEIN trials were 14% and 15.2%, respectively. Due to a paucity of data, at this point neither the NCCN nor ASCO supports the use of NOACs for treatment of cancer-associated VTE.Objective: Evaluate the efficacy and safety of NOACs in cancer-associated VTE.Methods: We performed a retrospective chart review of all patients with a diagnosis of active malignancy who received a prescription for a NOAC for treatment of VTE at Yale Cancer Center between February 1, 2012, and December 31, 2014. Patients with a heritable thrombophilia or bleeding disorder were excluded. Data collected included patient demographics, body mass index (BMI), cancer type and stage, type of VTE event (deep venous thrombosis (DVT), pulmonary embolism (PE), or both), type of NOAC, compliance with NOAC therapy, appropriate NOAC dose, and potential drug-drug interactions (DDI) with NOACs. Primary outcomes were recurrent VTE, defined as the finding of new or progressive DVT or PE on imaging with or without symptoms, and clinically relevant bleeding (CRB), defined as a decrease in hemoglobin of at least 2 g/dL in a 24-hour period, a requirement for red blood cell transfusion, any critical site bleeding event, or any type of bleeding event requiring increased physician monitoring. Fisher's exact test was used to calculate p-values where appropriate.Results: 75 patients met inclusion criteria; rivaroxaban was the only NOAC used in all cases. The incidence of recurrent VTE and CRB was 7.0% (n = 5) and 25.3% (n = 19), respectively. There were two fatal events, one due to recurrent VTE and one due to major gastrointestinal bleed; in neither case was NOAC compliance, dosing, or DDIs implicated in the fatality. Over half (n = 39) of all study patients were on a concomitant medication with a known DDI with NOAC therapy; the most common such agents were ciprofloxacin, fluconazole, azithromycin and voriconazole. In only one of the 80 DDI cases was anticoagulation therapy changed. NOAC dosing was inappropriate in 20 instances, mostly due to patients not receiving the recommended loading dose prior to beginning maintenance dosing. Among the 19 occurrences of CRB, advanced stage solid tumor emerged as a statistically significant (p = 0.0151) risk factor for bleeding while on rivaroxaban.Conclusion: Treatment of cancer-associated VTE with NOAC therapy is effective, but the risk of bleeding in our cohort was higher than in other published studies. Patients with advanced stage solid tumors may be at a particularly high risk of bleeding. Prescriber practices with NOACs may require modification based on high utilization of concomitant medications with DDIs and failure to prescribe appropriate loading doses of NOACs in treatment of VTE. DisclosuresNo relevant conflicts of interest to declare.

Heart Failure and Mortality in Patients With Nonvalvular Atrial Fibrillation Started on Novel Oral Anticoagulant Therapy: A Single-Center Experience.

Heart failure (HF) is the leading cause of in-hospital morbidity and mortality in the elderly population. Coexistence of HF and atrial fibrillation (AF) increases the risk of thromboembolic events. Oral anticoagulant therapy reduces the risk of thromboembolic events in patients with AF. Novel oral anticoagulants (NOACs) have been introduced as an alternative drug for prevention from thromboembolic events in patients with nonvalvular AF. The primary aim of this study is to investigate the clinical effects of warfarin, dabigatran, and rivaroxaban in patients with nonvalvular AF. The secondary aim of this study is to reveal the predictors of all-cause mortality in patients with nonvalvular AF undergoing NOACs therapy. The study population consisted of 171 patients with nonvalvular AF. Patients were divided into 3 groups according to the usage of oral anticoagulant therapy including coumadin (51 patients), dabigatran (52 patients), and rivaroxaban (68 patients). Although CHA2DS2-VASc score was similar between groups, HAS-BLED score was significantly higher in patients using rivaroxaban. Dyspepsia and itching were more common in patients using dabigatran. Heart failure and vascular disease were more common in the nonsurviving group (10 patients) than in the surviving group (110 patients) in patients using NOACs. Among age, sex, HF, hypertension, vascular disease, and CHA2DS2-VASc, which were included in the regression model, only the presence of HF was an independent predictor of all-cause mortality in patients using NOACs. In conclusion, the mortality rate is significantly higher in patients with HF using NOACs. Moreover, HF is an independent predictor of all-cause mortality in patients using NOACs.

Abstract 14902: The Introduction of Novel Oral Anticoagulants Has Improved Overall Oral Anticoagulation Rates in Atrial Fibrillation: Insights From the NCDR PINNACLE Registry

Introduction: For patients with atrial fibrillation (AF), novel oral anticoagulants (NOACs) provide effective alternatives to warfarin. However, a better understanding is needed of how the introduction of NOAC therapy has improved use of any oral anticoagulation (OAC) for patients with AF. Methods: Within the NCDR PINNACLE registry, we identified 447,770 patients comprising 1,428,660 outpatient encounters with non-valvular AF and CHADS-VASc &gt;1 between April 1, 2008 and September 30, 2014. We examined use of any OAC, any NOAC, and of dabigatran, rivaroxaban, and apixaban individually over time. Multivariable logistic regression was performed to identify factors associated with any OAC and NOAC use at the end of the study period, including CHADS-VASc score, age, weight, CAD, PAD, dyslipidemia, stroke/TIA, heart failure, gender, hypertension, and diabetes. Results: Use of any OAC increased from 52.1 to 61.2% during the study period among patients without a documented contraindication (p for trend &lt;0.01) (Figure). Although warfarin use decreased from 52.1% to 36.8% (p for trend &lt;0.01), use of NOACs increased from 0% to 24.4% (p for trend &lt;0.01). Rivaroxaban was the most frequently prescribed NOAC at the end of the study period (12.1%), followed by dabigatran (6.6%), and apixaban (5.7%). Patient factors associated with use of OAC and NOACs are presented in the Table. Conclusions: In a large U.S. outpatient registry, introduction of NOACs into clinical practice has improved the use of any OAC for AF patients at high risk for stroke. However, more than 1 in 3 high risk patients without a documented contraindication were not treated with any OAC.

Initial Experience With Novel Oral Anticoagulants During the First 45 Days After Left Atrial Appendage Closure With the Watchman Device.

The use of oral anticoagulation or dual antiplatelet therapy (DAPT) is recommended within the first 45 days after left atrial appendage (LAA) closure using the Watchman device because of incomplete device endothelialization. This study reports for the first time the feasibility of novel oral anticoagulants (NOAC) in these patients. NOAC therapy is safe and effective after LAA closure. Interventional LAA closure was performed successfully in 45 patients. Of these, 18 patients received NOAC during the first 45 days after implantation and 27 patients received DAPT. Transesophageal echocardiography was conducted 45 days after implantation. The primary study endpoint was abnormal thrombus apposition 45 days after implantation. Secondary study endpoints were death from any cause, major adverse cardiac and cerebrovascular events (MACCE), and major bleedings. After 45 days, transesophageal echocardiography revealed no abnormal thrombus apposition. During a follow-up of 417 ± 323 days, 7 patients died. No stroke or transient ischemic attack occurred. Nonfatal myocardial infarction occurred in 1 patient. There was a nonsignificant trend for lower all-cause mortality (P = 0.159) and occurrence of MACCE (P = 0.096) in the NOAC group compared with the DAPT group. Overall, 6 patients suffered from a major bleeding (NOAC, n = 3; DAPT, n = 3). In NOAC group, major bleedings (at day 205, 688, and 736) occurred long after termination of NOAC therapy. There was no significant difference in the frequency of major bleedings in different groups. Our pilot study suggests that NOAC therapy within the first 45 days after interventional LAA closure is safe and effective.

Efficacy and safety of novel oral anticoagulants in patients with bioprosthetic valves.

Prosthetic valve replacement is performed in several hundred thousand patients worldwide annually, and many of these patients have or will ultimately develop atrial fibrillation or flutter (AF). Novel oral anticoagulants (NOACs) are not recommended in patients with AF and mechanical valves but have not been evaluated in patients with bioprosthetic valves. This study sought to evaluate the efficacy and safety of NOACs in patients with AF and bioprosthetic valves. A retrospective single-center cohort study was performed on all patients with bioprosthetic valve implantation, for whom a NOAC was prescribed for the indication of AF. Patients were evaluated for thromboembolic events including imaging confirmed ischemic stroke, clinically suspected transient ischemic attack, and major bleeding events (according to International Society on Thrombosis and Hemostasis definition). In total, 73 patients (26 female, 35.6 %) were identified. NOAC therapy began, on average, 990.0 ± 1029.1 days after bioprosthetic valve implantation for an average duration of 511.8 ± 400.8 days. Aspirin was used concomitantly in a majority of patients (72.6 %). There were no ischemic strokes identified (0.0 %) and one possible TIA (1.4 %). There were 6 (8.2 %) minor and 5 (6.9 %) major bleeding events. The use of NOAC therapy for AF in patients with bioprosthetic valves appears safe and effective in the occurrence of thromboembolic events, however, at the expense of increased bleeding. Larger studies are necessary to confirm these findings.

Novel Oral Anticoagulant Use Among Patients With Atrial Fibrillation Hospitalized With Ischemic Stroke or Transient Ischemic Attack.

Novel oral anticoagulants (NOACs) have been shown to be at least as good as warfarin for preventing stroke or transient ischemic attack in patients with atrial fibrillation, yet diffusion of these therapies and patterns of use among atrial fibrillation patients with ischemic stroke and transient ischemic attack have not been well characterized. Using data from Get With The Guidelines-Stroke, we identified a cohort of 61 655 atrial fibrillation patients with ischemic stroke or transient ischemic attack hospitalized between October 2010 and September 2012 and discharged on warfarin or NOAC (either dabigatran or rivaroxaban). Multivariable logistic regression was used to identify factors associated with NOAC versus warfarin therapy. In our study population, warfarin was prescribed to 88.9%, dabigatran to 9.6%, and rivaroxaban to 1.5%. NOAC use increased from 0.04% to a 16% to 17% plateau during the study period, although anticoagulation rates among eligible patients did not change appreciably (93.7% versus 94.1% from first quarter 2011 to second quarter 2012), suggesting a trend of switching from warfarin to NOACs rather than increased rates of anticoagulation among eligible patients. Several bleeding risk factors and CHA2DS2-VASc scores were lower among those discharged on NOAC versus warfarin therapy (47.9% versus 40.9% with CHA2DS2-VASc ≤5, P<0.001 for difference in CHA2DS2-VASc). NOACs have had modest but growing uptake over time among atrial fibrillation patients hospitalized with stroke or transient ischemic attack and are prescribed to patients with lower stroke risk compared with warfarin.