Discontinuation Of Anticoagulation Research Articles

Factors influencing left ventricular thrombus resolution and its significance on clinical outcomes.

A left ventricular thrombus (LVT) is not uncommon in patients with impaired LV systolic function. However, the treatment strategy for LVT has not yet been fully established. We aimed to identify the factors influencing LVT resolution and the significance of LVT resolution on clinical outcomes. We retrospectively investigated patients diagnosed with LVT with left ventricular ejection fraction (LVEF)<50% on transthoracic echocardiography from January 2010 to July 2021 in a single tertiary centre. LVT resolution was monitored through serial follow-up transthoracic echocardiography. The primary clinical outcome was a composite of all-cause death, stroke, transient ischaemic attack, and arterial thromboembolic events. LVT recurrence was also evaluated in patients with LVT resolution. There were 212 patients diagnosed with LVT (mean age, 60.5±14.0years; male, 82.5%). The mean LVEF was 33.1±10.9%, and 71.7% of patients were diagnosed with ischaemic cardiomyopathy. Most patients were treated with vitamin K antagonists (86.7%), and 28 patients (13.2%) were treated with direct oral anticoagulants or low molecular weight heparin. LVT resolution was observed in 179 patients (84.4%). LVEF improvement failure within 6months was a significant factor hindering LVT resolution (hazard ratio, HR: 0.52, 95% confidence interval, CI: 0.31-0.85, P=0.010). During a median 4.0years of follow-up (interquartile range, IQR: 1.9 to 7.3years), 32 patients (15.1%) experienced primary outcomes (18 all-cause deaths, 15 strokes, and 3 arterial thromboembolisms) and 20 patients (11.2%) experienced LVT recurrence after LVT resolution. LVT resolution was independently associated with a lower risk for primary outcomes (HR: 0.45, 95% CI: 0.21-0.98, P=0.045). In the patients with resolved LVT, discontinuation or duration of anticoagulation after resolution were not significant predictors for LVT recurrence, but LVEF improvement failure at LVT resolution was associated with a significantly higher risk of LVT recurrence (HR: 3.10, 95% CI: 1.23-7.78, P=0.016). This study suggests that LVT resolution is an important predictor for favourable clinical outcomes. LVEF improvement failure interfered with LVT resolution and appeared to be a crucial factor for LVT recurrence. After LVT resolution, continuation of anticoagulation did not seem to impact LVT recurrence and the prognosis.

Trends in the Use of Oral Anticoagulants for Adults With Venous Thromboembolism in the US, 2010-2020

The introduction of direct oral anticoagulants (DOACs) has transformed the treatment of venous thromboembolism (VTE). Large health care databases offer valuable insight into how oral anticoagulants (OACs) are used in clinical practice and may aid in understanding reasons for changes in therapy. To evaluate prescribing patterns of OACs for patients with VTE and identify clinical events that precede treatment changes. This retrospective cohort study used data from a public (Medicare fee-for-service) and a commercial (IBM MarketScan) health insurance database on 298 609 patients initiating OACs within 90 days of index VTE hospitalization from January 1, 2009, to December 31, 2020. Statistical analysis was conducted from April to August 2022. Warfarin and the DOACs rivaroxaban, apixaban, dabigatran, and edoxaban. Characteristics of patients initiating different OACs, along with trends over time of patients initiating OACs, were compared. Time receiving continuous anticoagulant therapy, patterns of anticoagulant discontinuation (treatment gap of ≥30 days), and treatment switches were assessed. Clinical events in the 30 days preceding treatment modifications were identified. A total of 203 378 individuals with Medicare (mean [SD] age, 76.9 [7.6] years; 122 554 women [60.3%]) and 95 231 with commercial insurance (mean [SD] age, 57.6 [15.8] years; 47 139 women [49.5%]) were included (N = 298 609). Warfarin was the most frequent OAC prescribed (163 044 [54.6%]), followed by rivaroxaban (66 882 [22.3%]) and apixaban (65 997 [22.1%]). The proportion of patients initiating DOACs increased from 0% in 2010 to 86.8% (22 420 of 25 817) in 2019 for patients with Medicare and 92.1% (4012 of 4357) in 2020 for commercially insured patients. Patients with chronic kidney disease were more likely to initiate warfarin (35 561 [11.9%]) or apixaban (16 294 [5.5%]) than rivaroxaban (10 136 [3.4%]), and those with a history of bleeding were more likely to initiate apixaban (5424 [1.8%]) than rivaroxaban (3007 [1.0%]). Overall, patients received persistent OAC treatment for approximately 6 months (Medicare: median, 175 days [IQR, 76-327 days]; commercial insurance: median, 168 days [IQR, 83-279 days]). A total of 33 011 patients (11.1%) switched anticoagulant therapy within a year. Switching to another anticoagulant was preceded most frequently by codes for a VTE diagnostic procedure (27.2% of all switchers [8983 of 33 011]). This cohort study using data from 2 US health insurance databases suggests that most patients with VTE continued oral anticoagulant treatment for approximately 6 months. Clinical reasons for modifying anticoagulant therapy were identified in one-third of patients. Identifying reasons for treatment modification is crucial for generating valid evidence on drug safety and effectiveness.

Fetal pulmonary valvuloplasty for pulmonary atresia with intact ventricular septum: a single-center clinical experience.

Fetal pulmonary valvuloplasty for pulmonary atresia with intact ventricular septum: a single-center clinical experience.

Repeat pulmonary thromboendarterectomy outcomes: A 15-year single-center retrospective review

ObjectiveChronic thromboembolic pulmonary hypertension is potentially curable via pulmonary thromboendarterectomy. A minority of patients experience recurrence of their symptoms and are eligible for repeat pulmonary thromboendarterectomy. However, little data exist regarding risk factors and outcomes for this patient population. MethodsWe performed a retrospective review of the University of California San Diego chronic thromboembolic pulmonary hypertension quality improvement database, including all patients who underwent pulmonary thromboendarterectomy from December 2005 to December 2020. Of the 2019 cases performed during this period, 46 were repeat pulmonary thromboendarterectomy procedures. Demographics, preoperative and postoperative hemodynamics, and surgical complications were compared between the repeat pulmonary thromboendarterectomy group and 1008 first pulmonary thromboendarterectomy group. ResultsRepeat pulmonary thromboendarterectomy recipients were more likely to be younger, to have an identified hypercoagulable state, and to have higher preoperative right atrial pressure. Etiologies of recurrent disease include incomplete initial endarterectomy, discontinuation of anticoagulation (noncompliance or for medical reasons), and anticoagulation treatment failure. Patients who received repeat pulmonary thromboendarterectomy had significant hemodynamic improvement, but less pronounced compared with patients who received first pulmonary thromboendarterectomy. Repeat pulmonary thromboendarterectomy was associated with an increased risk of postoperative bleeding, reperfusion lung injury, residual pulmonary hypertension, and increased ventilator, intensive care unit, and hospital days. However, hospital mortality was similar between the groups (2.2% vs 1.9%). ConclusionsThis is the largest reported series of repeat pulmonary thromboendarterectomy surgery. Despite an increase in postoperative complications, this study demonstrates that repeat pulmonary thromboendarterectomy surgery can result in significant hemodynamic improvement with acceptable surgical mortality in an experienced center.

Perioperative Considerations in Management of the Severely Bleeding Coagulopathic Patient.

Inherited and acquired coagulopathy are frequently associated with major bleeding in severe trauma, cardiac surgery with cardiopulmonary bypass, and postpartum hemorrhage. Perioperative management is multifactorial and includes preoperative optimization and discontinuation of anticoagulants and antiplatelet therapy in elective procedures. Prophylactic or therapeutic use of antifibrinolytic agents is strongly recommended in guidelines and has been shown to reduce bleeding and need for allogeneic blood administration. In the context of bleeding induced by anticoagulants and/or antiplatelet therapy, reversal strategies should be considered when available. Targeted goal-directed therapy using viscoelastic point-of-care monitoring is increasingly used to guide the administration of coagulation factors and allogenic blood products. In addition, damage control surgery, which includes tamponade of large wound areas, leaving surgical fields open, and other temporary maneuvers, should be considered when bleeding is refractory to hemostatic measures.

C-reactive protein and D-dimer in cerebral vein thrombosis: Relation to clinical and imaging characteristics as well as outcomes in a French cohort study

IntroductionCerebral venous sinus thrombosis (CVST) is a rare disease with highly variable clinical presentation and outcomes. Clinical studies suggest a role of inflammation and coagulation in CVST outcomes. The aim of this study was to investigate the association of inflammation and hypercoagulability biomarkers with CVST clinical manifestations and prognosis. MethodsThis prospective multicenter study was conducted from July 2011 to September 2016. Consecutive patients referred to 21 French stroke units and who had a diagnosis of symptomatic CVST were included. High-sensitivity C-reactive protein (hs-CRP), neutrophil-to-lymphocyte ratio (NLR), D-dimer, and thrombin generation using calibrated automated thrombogram system were measured at different time points until 1 month after anticoagulant therapy discontinuation. ResultsTwo hundred thirty-one patients were included. Eight patients died, of whom 5 during hospitalization. The day 0 hs-CRP levels, NLR, and D-dimer were higher in patients with initial consciousness disturbance than in those without (hs-CRP: 10.2 mg/L [3.6-25.5] vs 23.7 mg/L [4.8-60.0], respectively; NLR: 3.51 [2.15-5.88] vs 4.78 [3.10-9.59], respectively; D-dimer: 950 μg/L [520-2075] vs 1220 μg/L [950-2445], respectively). Patients with ischemic parenchymal lesions (n = 31) had a higher endogenous thrombin potential5pM than those with hemorrhagic parenchymal lesions (n = 31): 2025 nM min (1646-2441) vs 1629 nM min (1371-2090), respectively (P = .0082). Using unadjusted logistic regression with values >75th percentile, day 0 hs-CRP levels of >29.7 mg/L (odds ratio, 10.76 [1.55-140.4]; P = .037) and day 5 D-dimer levels of >1060 mg/L (odds ratio, 14.63 [2.28-179.9]; P = .010) were associated with death occurrence. ConclusionTwo widely available biomarkers measured upon admission, especially hs-CRP, could help predict bad prognosis in CVST in addition to patient characteristics. These results need to be validated in other cohorts.

Direct Oral Anticoagulants Versus Vitamin K Antagonists for the Treatment of Left Ventricular Thrombi—Insights from a Swiss Multicenter Registry

Current guidelines recommend vitamin K antagonists (VKAs) for the treatment of a left ventricular thrombus (LVT). However, direct oral anticoagulants (DOACs) show superior safety and efficacy compared with VKAs in most thromboembolic disorders. Nevertheless, DOACs remain poorly investigated for the treatment of LVT. To describe the thrombus resolution rate and clinical efficacy of DOACs versus VKAs in patients with LVT, we analyzed consecutive patients with confirmed LVT from a multicenter echocardiography database. Echocardiograms and clinical end points were evaluated independently. The thrombus resolution rate and clinical outcomes were compared according to the underlying anticoagulation regimen. In total, 101 patients were included (17.8% women, mean age 63.3 ± 13.2 years), 50.5% had recently experienced a myocardial infarction. The mean left ventricular ejection fraction was 36.6 ± 12.2%. DOACs versus VKAs were used in 48 and 53 patients, respectively. The median follow-up was 26.6 (interquartile range 11.8;41.2) months. Among patients receiving VKAs compared with DOACs, the thrombus resolved more rapidly within the first month in those taking VKAs (p=0.049). No differences were seen between the 2 groups with respect to major bleedings, strokes, and other thromboembolic events. In each group, LVT recurred in 3 of the subjects (a total of 6) after discontinuation of anticoagulation. In conclusion, DOACs appear to be a safe and effective alternative to VKAs for the treatment of LVTs, but the rate of thrombus dissolution within 1 month after initiation of anticoagulation appears to be higher with VKAs. A sufficiently powered randomized trial is required to definitively define the role of DOACs in the treatment of LVT.

Safety and effectiveness of anticoagulation with non-vitamin K antagonist oral anticoagulants and warfarin in patients on tuberculosis treatment

Anti-tuberculosis treatment can cause significant drug-drug interaction and interfere with effective anticoagulation. However, there is a lack of evidence and conflicting data on the optimal oral anticoagulation in patients treated for tuberculosis. We investigated the safety and effectiveness of anticoagulation with non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in patients on anti-tuberculosis treatment. Patients on concomitant oral anticoagulation and anti-tuberculosis treatment including rifampin were identified from the Korean nationwide healthcare database. Subjects were censored at discontinuation of either anticoagulation or rifampin. The outcomes of interest were major bleeding, death, and ischemic stroke. A total 2090 patients (1153 on warfarin, 937 on NOAC) were included. NOAC users, compared to warfarin users, were older, had a lower prevalence of hypertension, heart failure, ischemic stroke, and aspirin use and a higher prevalence of cancer, with no significant differences in CHA2DS2-VASc or HAS-BLED scores. There were 18 major bleeding events, 106 deaths, and 50 stroke events during a mean follow-up of 2.9 months. After multivariable adjustment, the use of NOAC was associated with a lower risk of incident ischemic stroke (HR 0.51, 95% CI 0.27–0.94), while there was no significant difference in risk for major bleeding or death compared with warfarin. These results suggest that NOACs have better effectiveness for stroke prevention and similar safety compared with warfarin in patients on concomitant anti-tuberculosis treatment. This is the first study assessing the safety and effectiveness of NOACs compared to warfarin in this clinical scenario.

Residual pulmonary vascular obstruction and recurrence after acute pulmonary embolism: a systematic review and meta-analysis of individual participant data

We aimed to assess the relationship between residual pulmonary vascular obstruction (RPVO) on planar lung scan after completion of at least 3 months of anticoagulant therapy for acute pulmonary embolism (PE) and the risk of recurrent venous thromboembolism (VTE) or death due to PE one year after treatment discontinuation. The systematic review was registered with the International Prospective Registry of Systematic Reviews (PROSPERO: CRD42017081080). The primary outcome measure was to generate a pooled estimate of the rate of recurrent VTE at one year in patient with RPVO diagnosed on planar lung scan after discontinuation of at least 3 months of anticoagulant treatment for an acute PE. Individual data were obtained for 809 patients. RPVO (ie, obstruction >0%) was found in 407 patients (50.3%) after a median of 6.6 months of anticoagulant therapy for a first acute PE. Recurrent VTE or death due to PE occurred in 114 patients (14.1%), for an annual risk of 6.4% (95% confidence interval, 4.7%-8.6%). Out of the 114 recurrent events, 63 occurred within one year after discontinuation of anticoagulant therapy corresponding to a risk of 8.1% (6.4%-9.8%) at 1 year. The risk of recurrent VTE at one year was 5.8% (4.4-7.2) in participants with RPVO <5%, vs 11.7% (9.5-13.8) in participants with RPVO ≥5%. RPVO is a significant predictor of the risk of recurrent venous thromboembolism. However, the risk of recurrent events remains too high in patients without residual perfusion defect for it to be used as a stand-alone test to decide on anticoagulation discontinuation.

Safety of discontinuation of anticoagulants after venous thromboembolism: whether D-dimer level should be taken into account?

Due to the continued risk of recurrence after a first episode of proximal deep vein thrombosis (DVT) of the lower extremities and/ or pulmonary embolism (PE) occurring without major transient risk factors, long-term use of anticoagulants is indicated in many cases. One attractive way to individualize the duration of treatment in these cases appears to be the assessment of blood D-dimer concentration. However, according to the prospective studies PROLONG, PROLONG II and REVERSE II, even persistent normalization of blood D-dimer concentration does not guarantee the absence of relapse. The available evidence also does not allow a differentiated approach to the assessment of the role of D-dimer for cases where proximal DVT and/or PE occurs in patients without identifiable risk factors or with minor risk factors. An attempt to clarify some of these uncertainties was made in the prospective APIDULCIS study, which included 732 patients who first had proximal DVT and/or PE, with symptoms occurring in the absence of obvious provoking factors (75.6% of cases) or associated with minor (weak) and transient risk factors (24.4%). The prerequisites included a normal blood D-dimer concentration. Patients were discontinued anticoagulants and blood D-dimer concentration measurements were repeated after 15, 30, and 60 days. If it remained low, the anticoagulant was not resumed (39.1% of cases), and when it first increased, apixaban was administered in a dose of 2.5 mg twice daily. The APIDULCIS study confirmed that anticoagulants cannot be discontinued after 1 year of use after the first unprovoked episode of proximal DVT and/or PE, even with persistent normal blood D-dimer concentration; it was shown that recurrence rate after the first episode of proximal DVT and/or PE, provoked by a minor transient risk factor, is high enough even after at least 1 year of anticoagulant treatment and at stable normal blood D-dimer concentration after their cancellation; comfirmed the effectiveness and safety of a reduced dose of apixaban (2.5 mg 2 times a day) during prolonged treatment of the first episode of proximal DVT and/or PE.

Pharmacomechanical thrombectomy for total-subtotal deep vein thrombosis

To improve treatment outcomes in patients with late stages of total-subtotal deep vein thrombosis using pharmacomechanical thrombectomy. We compared treatment outcomes in 2 homogeneous groups of patients with deep vein thrombosis and severe acute venous insufficiency. Standard anticoagulation (apixaban) was performed in the first group (n=20), endovascular treatment was applied in the second group (n=20). Regional catheter thrombolysis was performed at the first stage, and percutaneous mechanical thrombectomy was performed at the second stage. Incidence of hemorrhagic syndrome was assessed. The results were evaluated after one year considering patency of deep veins and severity of venous outflow disorders. Hemorrhagic complications occurred in 15% and 25% of patients, respectively. This required discontinuation of anticoagulation throughout the treatment and subsequent appointment of minimum doses of apixaban. Complete restoration of vein patency was observed in 20% and 55%, partial recanalization - 45% and 25%, minimal recovery - in 35% and 20% of patients, respectively. In the first group, venous outflow disorders were absent in 20% of patients, mild disorders were registered in 45%, moderate - 20%, severe - 15% of patients. In the second group, these values were 55%, 25%, 20% and 0% of patients, respectively. Pharmacomechanical thromboectomy can improve treatment outcomes.

Interventional treatment of haemorrhoids in anticoagulated patients

Anticoagulants are currently widely used for cardiological reasons, stroke prevention and in other vascular diseases. Colorectal surgeons face patients suffering from haemorrhoids who are put on anticoagulant therapy in their everyday practice. Anticoagulation strategy for patients undergoing interventional treatment of haemorrhoids has not been discussed in detail in the literature so far. Standard management of grade 1-3 haemorrhoids includes rubber band ligation (RBL), sclerotherapy (SCL) and infrared coagulation (IRC) after unsuccessful conservative treatment. The rates of postprocedural bleeding range from 0.9-2.8% after rubber band ligation, 0-2.7% after sclerotherapy and 5% after infrared coagulation. Surgical procedures including dearterialization, haemorrhoidectomy and stapled haemorrhoidopexy are indicated in more advanced degrees as the third line of treatment and are complicated by postoperative bleeding in 1.4-5.9% and 2-7.9% patients, respectively. Haemorrhoidectomy is the best option in grade 4 haemorrhoids and is associated with 6.2-8.4% risk of bleeding. However, closed haemorrhoidectomy, Ligasure technique and/or anal tamponade can reduce this risk. Surgical guidelines recommend continuing acetylsalicylic acid in low bleeding risk procedures, including haemorrhoidal surgery. However, postoperative bleeding after rubber band ligation was more common in the aspirin group. On the other hand, haemorrhage incidence after sclerotherapy did not differ significantly between the group on anticoagulation compared with the group without anticoagulation. Haemorrhoidectomy should be postponed for 6 months in patients receiving dual antiplatelet therapy. According to the guidelines, vitamin K antagonists should be discontinued 5 days before haemorrhoidal surgery. Minimal bleeding risk procedures do not require discontinuation of anticoagulation,but this option seems to be hazardous for patients undertaking rubber band ligation. Sclerotherapy, on the other hand, could not require warfarin discontinuation if the international normalized ratio (INR) is within therapeutic range. Novel oral anticoagulants (NOACs) should be discontinued 1 day before low bleeding risk operations, including haemorrhoidectomy and resumed 1 day after the procedure. In conclusion, all anticoagulants should be ceased prior to operation except for aspirin. There are not clear recommendations on the perioperative protocols for continuation or discontinuation of blood thinners in patients undergoing minimally invasive procedures.

Management of venous thromboembolism in far-advanced cancer: current practice

ObjectivesVenous thromboembolism (VTE) is common in advanced cancer. Guidelines suggest that indefinite anticoagulation be considered for patients with ongoing active cancer. There are no data on the management of cancer-associated...

Ten year real world experience with ultrafiltration for the management of acute decompensated heart failure

BackgroundRandomized controlled trials (RCT) of ultrafiltration (UF) have demonstrated conflicting results regarding its efficacy and safety. ObjectiveWe reviewed 10 years of data for adjustable UF during heart failure hospitalizations in a real world cohort. MethodsWe performed a retrospective, single center analysis of 335 consecutive patients treated with adjustable rate UF using the CHF Solutions Aquadex Flex Flo System from 2009 to 2019. ResultsCompared to previous RCTs investigating UF, our cohort was older, with worse renal impairment and more antecedent HF hospitalizations in the year preceding therapy. Mean fluid removal with UF was 14.6 l. Mean weight loss with UF was 15.6 lbs (range 0.2–57 lbs) and was sustained at 1–2 week follow-up. Mean creatinine change upon stopping UF, at discharge and follow-up (mean 30 days) was +0.11 mg/dl, +0.07 mg/dl and +0.11 mg/dl, respectively. HF rehospitalizations at 30 days, 90 days and 1 year were 12.4 %, 14.9 % and 27.3 % respectively. On average patients had 1.74 fewer hospitalizations for HF in the year following UF when compared to 12 months preceding UF. Major bleeding defined as requiring discontinuation of anticoagulation occurred in 3.6 % of patients. ConclusionsCompared with previous UF trials, our study demonstrates that UF compares favorably for HF rehospitalizations, renal function response, and weight/volume loss. Importantly, our real world experience allowed for the adjustment of UF rate during therapy and we believe this is a major contributor to our favorable outcomes. In clinical practice, UF can be a safe and effective strategy for decongestion.

Seizures, deep vein thrombosis, and pulmonary emboli in a severe case of May–Thurner syndrome: a case report

BackgroundMay–Thurner syndrome is a vascular disorder caused by the right common iliac artery compressing the left common iliac vein against the lumbar spine, causing distal venous stasis and potentially leading to fibrous change in the venous wall structure. Although May–Thurner syndrome is most commonly discovered in females upon investigation of new-onset deep vein thrombosis, we present the case of an otherwise healthy 29-year-old male with severe May–Thurner syndrome who presented with seizures, bilateral deep vein thrombosis, and diffuse pulmonary emboli. Seizures constituted the earliest presenting symptoms for the patient. Although it is difficult to prove that the patient’s seizures were related to the May–Thurner syndrome, this possible association renders this case extraordinary.Case presentationThis report describes the case of a 29-year-old previously healthy white male with a severe case of left-sided May–Thurner syndrome that required extensive medical and interventional treatment. The patient experienced two seizures, one month apart, both of which occurred while residing at high altitude. The patient had no prior history of seizures, and epilepsy was ruled out. Three weeks after the second seizure, he presented to the emergency room with hemoptysis, dyspnea, and severe leg pain. Sites of thrombus were confirmed in both legs and diffusely in the lungs. Etiological work-up after treatment with intravenous tissue plasminogen activator revealed May–Thurner syndrome. Hematology workup including genetic testing showed no evidence of coagulopathy. Bilateral common iliac venous stents were placed to attempt definitive treatment. Despite stenting, the patient had another thrombotic event with associated sequelae after discontinuation of anticoagulation. The patient has not had another seizure since the stents were placed. Despite the negative testing, the patient remains on lifelong chemoprophylaxis in the event of an undiscovered hypercoagulopathy.ConclusionsThe care team theorizes that the seizures resulted from hypoxia due to May–Thurner syndrome-induced hemostasis and associated thrombotic events, the high-altitude location of his residence at the time he experienced the seizures, and shallow breathing during sleep. For patients with lower limb venous thrombosis, May–Thurner syndrome should be considered in the differential diagnosis. Endovascular treatment followed by extended prophylactic anticoagulation therapy until the patient is determined to be no longer at risk for thrombosis is recommended. Post-venoplasty thrombosis is a common complication of endovascular treatment of May–Thurner syndrome and should be carefully monitored.

Abstract 15031: Anticoagulation Status and Risk of Stroke Following Leak-Closure Procedure for Residual Leak After Occlusion of the Left Atrial Appendage in Patients With Atrial Fibrillation

Introduction: Studies have shown a correlation between leaks following left atrial appendage occlusion procedure and thromboembolic (TE) events. Hypothesis: We investigated the benefits of leak-closure in terms of safe discontinuation of oral anticoagulation (OAC) and minimization of the stroke-risk. Methods: Consecutive patients undergoing leak-closure procedure at our institution were included in the analysis. Procedures included closure with endovascular coils or Amplatzer plug or by using radiofrequency ablation (RFA). Persistence of the leak was verified by multiplane transesophageal echocardiogram (TEE) using color Doppler. Follow-up TEE were performed 60 ± 15 days post-procedure to evaluate LAA closure and patients were kept on OAC until then. After confirmation of closure, they were transitioned to ASA 81 mg/day. All patients were monitored quarterly for thromboembolic (TE) events. Results: A total of 139 post-Watchman patients undergoing leak-closure were included in the analysis (RFA: 10, Amplatzer plug: 5, coil-closure: 124). Pre-coil closure TE events were reported in 7 (5%) subjects. Moderate (3-4 mm) and severe (≥5 mm) leak were detected in 118 (85%) and 21 (15%) patients respectively. After the leak-closure procedure, complete sealing of the leak was confirmed at the follow-up TEE in 138 (99.2%) patients. Figure 1 shows significant reduction in TE events following the leak-closure procedure (p=0.031). During the 2-year follow-up period, six deaths were reported due to unrelated causes. Of the remaining 133 subjects, two patients were on DAPT because of history of coronary artery disease, two with prior stroke were on half-dose OAC and the remaining 129 (95.8%) were on ASA 81 mg/day. No TE events were reported in patients that transitioned to ASA. Conclusions: In this series, successful percutaneous leak-closure not only minimized the risk of stroke but also enabled the majority of patients to discontinue OAC without any TE events.

Performance Status and Long-Term Outcomes in Cancer-Associated Pulmonary Embolism: Insights From the Hokusai-VTE Cancer Study

BackgroundPerformance status (PS) is a reliable prognostic tool for overall survival in patients with cancer-associated pulmonary embolism (PE). However, its association with venous thromboembolism (VTE) recurrence and bleeding remains unclear. ObjectivesThe aim of this study was to investigate whether PS at the time of PE diagnosis and its course during follow-up are linked to VTE-related outcomes. MethodsIn this post hoc analysis of the Hokusai-VTE Cancer study, multivariable survival analysis was used to examine the association of PS with anticoagulation discontinuation and the composite primary outcome of VTE recurrence or major bleeding in patients with cancer-associated PE. PS was assessed using the Eastern Cooperative Oncology Group (ECOG) scale at baseline and at predefined study follow-up visits. ResultsOverall, 652 patients with cancer-associated PE were included. During 12-month follow-up, PS worsened in 317 of 642 patients (49.4%) with complete ECOG data at the end of follow-up. Those with worse ECOG values over follow-up were more likely to discontinue anticoagulation for any reason apart from death (adjusted HR: 1.59; 95% CI: 1.31-1.93). The composite primary outcome occurred in 57 of 500 patients with baseline ECOG status 0 or 1 and in 32 of 152 patients with ECOG status 2 (cumulative incidence at 12 months 10.7% [95% CI: 8.2%-13.9%] vs 14.4% [95% CI: 9.7%-21.3%]). Worse ECOG values during follow-up were associated with greater risk for the composite outcome (adjusted HR: 2.13; 95% CI: 1.24-3.67). ConclusionsECOG PS is a valuable indicator for predicting VTE-related outcomes and may inform decision making regarding anticoagulation during follow-up in patients with cancer-associated PE.

Benefits and harms of oral anticoagulants for atrial fibrillation in nursing home residents with advanced dementia.

Approximately 20% of older persons with dementia have atrial fibrillation (AF). Nearly all have stroke risks that exceed the guideline-recommended threshold for anticoagulation. Although individuals with dementia develop profound impairments and die from the disease, little evidence exists to guide anticoagulant discontinuation, and almost one-third of nursing home residents with advanced dementia and AF remain anticoagulated in the last 6 months of life. We aimed to quantify the benefits and harms of anticoagulation in this population. Using Minimum Data Set and Medicare claims, we conducted a retrospective cohort study with 14,877 long-stay nursing home residents aged ≥66 between 2013 and 2018 who had advanced dementia and AF. We excluded individuals with venous thromboembolism and valvular heart disease. We measured anticoagulant exposure quarterly, using Medicare Part D claims. The primary outcome was all-cause mortality; secondary outcomes were ischemic stroke and serious bleeding. We performed survival analyses with multivariable adjustment and inverse probability of treatment (IPT) weighting. In the study sample, 72.0% were female, 82.7% were aged ≥80 years, and 13.5% were nonwhite. Mean CHA2 DS2 VASC score was 6.19 ± 1.58. In multivariable survival analysis, anticoagulation was associated with decreased risk of death (HR 0.71, 95% CI 0.67-0.75) and increased bleeding risk (HR 1.15, 95% CI 1.02-1.29); the association with stroke risk was not significant (HR 1.08, 95% CI 0.80-1.46). Results were similar in models with IPT weighting. While >50% of patients in both groups died within a year, median weighted survival was 76 days longer for anticoagulated individuals. Persons with advanced dementia and AF derive clinically modest life prolongation from anticoagulation, at the cost of elevated risk of bleeding. The relevance of this benefit is unclear in a group with high dementia-related mortality and for whom the primary goal is often comfort.

Oral Anticoagulant Discontinuation and Its Predictors in Patients with Atrial Fibrillation.

Background: Oral anticoagulants (OACs) are important in reducing the risk of ischaemic stroke in people with atrial fibrillation (AF). Although patients need to take their OAC continuously, it has been suggested that discontinuation is common in clinical practice, and this could predispose patients to thrombotic complications. Aims: To investigate the rate of OAC discontinuation and its predictors in patients with AF, using national data from Australian general practices. Methods: We analysed data obtained from NPS MedicineWise’s MedicineInsight dataset. We included patients with a recorded diagnosis of AF who newly started an OAC between 1 January 2013 and 31 December 2017. Patients were considered persistent if an OAC was prescribed continuously without discontinuing more than 60 days gap in therapy. The follow-up period was 12 months post-initiation. Multivariable models were used for the analysis of predictors. Results: Of 16,075 patients included in the cohort, 47.3% were females, and the mean age was 74.6 (SD 10.2) years. The overall OAC discontinuation rate was 13.2% (confidence interval (CI) 12.6–13.7%) by 12 months post-initiation. The discontinuation rates for warfarin, apixaban, dabigatran and rivaroxaban were 18.3% (95% CI 17.2–19.5%), 10.1% (95% CI 9.2–11.0%), 10.9% (95% CI 9.4–12.5%) and 12.2% (95% CI 11.4–13.2%), respectively. Warfarin had a significantly higher risk of discontinuation compared to direct-acting OACs. Factors that are known to increase the risk of stroke (older age, diabetes, and hypertension) were associated with better persistence. Conclusions: A relatively high proportion of patients with AF continued OAC therapy by 12 months post-initiation. Positively, patients with the highest risk of stroke and lowest risk of bleeds seemed to have better persistence.

Patterns of anticoagulant prescribing and renal function changes in patients with atrial fibrillation

Abstract Background The prevalence of atrial fibrillation (AF) is nearly three times higher in patients with chronic kidney disease (CKD) than the general population. These patients have an increased risk of stroke and systemic thromboembolism (SSE) as well as bleeding. The role for direct oral anticoagulants (DOACs) in those with advanced CKD and AF remains controversial. Studies show that patients on DOACs for AF with advanced CKD have similar risk of SSE and bleeding compared to those on warfarin, but these failed to account for changes in renal function over time. Purpose We sought to evaluate the pattern of oral anticoagulant prescribing, class switching, discontinuation and renal function trajectory in patients with AF in the last decade, coinciding with the development of DOACs. Methods Using linked administrative databases, we assessed patients 66 years of age and older with a new diagnosis of non-valvular AF between April 1, 2012 and March 31, 2020 who were started on oral anticoagulation within 90 days of diagnosis. Participants required a baseline serum creatinine (Cr) measurement in the year preceding AF diagnosis. Cr values were used to calculate the estimated glomerular filtration rate (eGFR) using the CKD Epidemiology Collaboration equation. Kidney function was tracked at baseline and longitudinally among patients prescribed DOACs versus warfarin using the Laboratories Information System. Anticoagulant class switching was tracked and discontinuation was defined if a new prescription for anticoagulation was not filled after 90 days of their last prescription ending. Results A total of 57,574 participants were included in the study; 48,662 were started on DOACs and 8,912 were started on warfarin. In April 2012, 83.8% of patients were prescribed warfarin; however, the proportion of first prescriptions significantly evolved over time to DOACs (Figure 1). Of those started on DOACs, 13,383 (27.5%) discontinued therapy, 34,918 (71.8%) remained on therapy and 361 (0.7%) switched to warfarin. The rate of discontinuation among those started on warfarin was higher with 4,144 (46.5%) stopping, 3,172 (35.6%) continuing therapy and 1,596 (17.9%) switching to DOACs. Most patients (75.6%) who switched to DOACs from warfarin remained on DOACs until the occurrence of dialysis, renal transplantation, death, or the last follow-up date (March 31, 2020). At baseline, the mean eGFR in the warfarin group was 56.2 compared with 66.3 mL/min/1.73 m2 in the DOAC group (p&amp;lt;0.01). Over the course of study, more than half of the subjects in both groups had a 20% or more decline in eGFR (Figure 2). Conclusion Given the degree of renal function decline and frequency of anticoagulant class switching in our cohort, existing observational studies comparing DOACs to warfarin in patients with AF and CKD may be limited. In order to better compare DOACs to warfarin in this population, time-varying covariates like renal function should be included in modelling. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): CIHR Foundation Grant