Recurrent Thromboembolism Research Articles

One year prognosis in venous thromboembolism patients treated with direct oral anticoagulants versus standard anticoagulation: Outcomes from the REMOTEV registry

In phase 3 clinical trials, direct oral anticoagulants (DOACs) as compared to standard anticoagulation (SACO) showed non-inferiority in terms of efficacy (venous thromboembolism (VTE) recurrence, all-cause death) and significantly reduced major bleeding risk. However, real-life studies remain of paramount importance when extending this observation to the general population. This study aimed to provide safety and efficacy data of DOACs use in routine patient care in a non-selected symptomatic VTE population, from the REMOTEV registry. REMOTEV is a prospective, non-interventional study of patients with acute symptomatic VTE, treated with DOACs (rivaroxaban or apixaban) or SACO (vitamin K antagonists or low molecular weight heparin alone) for at least 3 months with a follow-up of 1 year for VTE recurrence, death and bleeding complications. Patients with active cancer were excluded. From October 23rd, 2013 to December 15th, 2017, among 1159 consecutive patients included in REMOTEV, 908 were cancer-free and had completed the follow-up of 12 months or until death occurred. Among them, 905 received an anticoagulant treatment with DOAC ( n = 724, 80%) or SACO ( n = 181, 20%). The median age was 68 (51–79, 25th–75th percentiles), 88% had PE with (62%) or without (26%) deep vein thrombosis. The major bleeding, VTE recurrence and all-cause death rates were of 3.2%, 3.8%, 4.4% in the DOAC group and, respectively, of 6.6%, 5.5% and 12.1% in the SACO group. Major bleeding (HR 0.47 [95% CI, 0.24–0.94], P < 0.05), all-cause death (HR 0.36 [95% CI, 0.21–0.61], P < 0.001) and the composite of recurrent VTE, major bleeding and all-cause mortality (HR 0.52 [95% CI, 0.36–0.75], P < 0.001), but not VTE recurrence (HR 0.70 [95% CI, 0.34–1.41], P = 0.32) were significantly lower in the DOAC group compared to the SACO group ( Fig. 1 ). In REMOTEV, DOAC treatment was associated with a lower risk of major bleeding and all-cause death after 1-year follow-up.

Safety and Efficacy of Direct Oral Anticoagulant Therapy in Patients With Cancer

Background: Venous thromboembolism (VTE) is the second leading cause of death in patients with malignancy. The currently available guidelines have shown greater support for utilization of low-molecular-weight heparin (LMWH) over direct oral anticoagulants (DOACs) in cancer-associated VTE. Current data on the safety and efficacy of DOAC therapy in patients with cancer are lacking. Objective: To evaluate the safety and efficacy of the use of DOACs compared to LMWH in patients with cancer. Methods: A retrospective review of outpatient records was completed to identify patients with documented cancer diagnosis and either a DOAC or LMWH as a listed medication. Patients were excluded if they had atrial fibrillation, valvular disease, antiphospholipid antibody syndrome, current pregnancy, body mass index (BMI) >40 kg/m2 or weight >120 kg, severe renal or hepatic impairment, or were on concomitant therapy with a significant interacting medication. The primary outcome was frequency of VTE recurrence, and secondary outcomes included the frequency of major and minor bleeding and other thrombotic events. Results: One hundred fifty-six patients were included in the study population, 78 in both the DOAC and LMWH groups. Venous thromboembolism recurrence occurred in 5 (6.4%) patients in the DOAC group and 8 (10.3%) patients in the LMWH group (P = .39). There was no significant difference in major or minor bleeding or other thrombotic events between the 2 groups. Conclusion: The frequency of VTE recurrence was similar between DOACs and LMWH in patients with cancer. DOACs may be an alternative agent to LMWH for the prevention of recurrent VTE in patients with cancer.

Clinical Course of Asymptomatic Isolated Distal Deep Vein Thrombosis of the Leg: A Single-Institution Study.

Background: The natural history of asymptomatic isolated distal deep vein thrombosis (DVT) of the leg is unclear. This study aimed to describe a 3-month and 1-year clinical course after diagnosis of asymptomatic isolated distal DVT of the leg.Methods: This study included 127 patients with asymptomatic, sonographically proven isolated distal DVT who did not receive anticoagulant therapy and were retrospectively evaluated at our hospital between May 2014 and September 2016. After 3 months and 1 year, the presence or absence of venous thromboembolism recurrence and extension of DVT toward proximal veins was sonographically confirmed.Results: At 3-month and 1-year follow-ups, 125 and 109 patients were observed, respectively. All patients showed no symptoms or findings suspecting venous thromboembolism recurrence during the observation period. However, 43 patients underwent repeat ultrasonic examination, and thrombus extension was confirmed in 2 patients.Conclusions: Asymptomatic isolated distal DVT of the leg showed good prognosis, and thus uniform anticoagulation therapy was considered unnecessary. (This is a translation of Jpn J Phlebol 2018; 29(3): 309–314.)

D-dimer testing to assess the individual risk of venous thromboembolic recurrence in non-elderly patients of both genders: follow the rules!

D-dimer testing to assess the individual risk of venous thromboembolic recurrence in non-elderly patients of both genders: follow the rules!

The Role of TPA Gene Polymorphism in the Risk Of Recurrent Venous Thromboembolism in Young Patients

Introduction - Tissue plasminogen activator (TPA) is a protein involved in the breakdown of blood clots. The TPA 311 bp Ins/Del gene polymorphism influences the release of intravascular injection of TPA. However, the role of this polymorphism in pathogenesis of recurrent venous thromboembolism (VTE) remains controversial. Methods - We analyzed 208 young patients under 45 years old (101 men and 107 women, mean age – 37,4 years) with at least one confirmed episode of VTE. The patients were genotyped by PCR and subsequent gel electrophoresis for DNA polymorphism of tissue plasminogen activator gene (TPA, 311 bp Ins/Del). Intergroup differences in the distribution of genotypes were assessed by Fisher's exact method. The “odds ratios” (OR) with 95% confidence intervals (CI) and p-values were determined using the SPSS software version 17,0 (SPSS Inc, Chicago, IL, USA). Results - Recurrent VTE was diagnosed in 105 (50,5%) patients (First group). The comparison group consisted of 103 patients without disease recurrence (Second group). Recurrence of isolated deep-vein thrombosis (DVT) was diagnosed in 68,6% patients (n=72), whereas recurrent thromboembolic events were detected in 31,4% patients (n=33). The frequency of TPA Del/Del genotype was almost 2-fold decreased in patients with recurrent VTE when compared to those with single thrombotic episode (14,3% vs 28,2%, respectively; OR=0,4; 95% CI: 0,2-0,9; p=0,017). For other genotypes of this gene we haven’t found any significant difference between the compared groups (group I vs. group II): TPA Del/Ins - 53,3 % vs. 42,7 % and TPA Ins/Ins - 32,4 % vs. 29,1% (p>0,05). However, we observed significant differences in distribution of TPA genotypes between the patients with recurrence of isolated DVT and those with thromboembolic events. In particular, the frequency of TPA Del/Del genotype was 2,5 times less in the group of patients with recurrence of isolated DVT (9,7% vs. 24,2% in patients with recurrent thromboembolic events; OR=0,3; 95% CI: 0,1-1,0; p=0,049). Conclusion - The presence of TPA Del/Del genotype may have a protective effect against the risk of recurrent VTE episodes. This effect is more evident for patients with isolated DVT. Further studies are needed to confirm these findings.

Prevention of Recurrence After Thrombolysis in Acute Iliofemoral Venous Thrombosis with Rivaroxaban (Prais Study): A Prospective, Randomized, Open Label, Multicenter Trial

Introduction: Recently new oral anticoagulants (NOAC) has replaced vitamin K antagonist (VKA) for the treatment of deep vein thrombosis (DVT). But the role of NOAC after thrombolysis of acute iliofemoral DVT is not yet defined. The aim of this randomized clinical trial is to compare the safety and efficacy of rivaroxaban versus VKA after thrombolysis of acute iliofemoral DVT. Methods: Patients were recruited from 7 hospitals in Korea. After successful thrombolysis or mechanical thrombectomy of acute iliofemoral DVT, 72 patients were randomized to standard anticoagulation (enoxaparin and warfarin) or rivaroxaban. Primary efficacy outcome was recurrence of any venous thromboembolism within 6 months. Secondary safety outcome were major bleeding and clinically relevant non-major bleeding (CRNMB). Other safety variables including any adverse events, vascular events, and all-cause mortality were also analyzed. Results: Intention-to-treat analysis was done for 67 patients (35 in rivaroxaban group, and 32 in VKA group). The primary outcome of recurrent VTE occurred in 4 patients in each group (11.4% vs 12.5%; hazard ratio[HR], 0.90; 95% confidence interval [CI], 0.21 to 3.96; P=1). Major bleeding or CRNMB developed in 1 patient in the rivaroxaban group and 3 patients in the VKA group (2.9% vs 9.4%, HR, 0.28; 95% CI, 0.03 to 2.88; P=0.34). Recurrence-free survival and significant bleeding-free survival at 6 month were not different in both groups. (P=0.28 and P=0.98, respectively) Conclusion: After thrombolysis of acute iliofemoral DVT, rivaroxaban was as effective as warfarin for the prevention of DVT recurrence. Rivaroxaban group showed a tendency of lower incidence of major bleeding/CRNMB. Rivaroxaban can safely replace warfarin in patients after successful thrombolysis for acute iliofemoral DVT. (Funded by Bayer Schering Pharma; ClinicalTrials.gov number, NCT01986192.)

Rivaroxaban after Thrombolysis in Acute Iliofemoral Venous Thrombosis: A Randomized, Open-labeled, Multicenter Trial

Recently non-Vitamin K antagonist oral anticoagulants (NOAC) is replacing warfarin for the treatment of deep vein thrombosis (DVT). However, the role of NOAC after thrombolysis of acute iliofeomral DVT (IFDVT) is not yet defined. This randomized clinical trial aimed to compare the safety and efficacy of rivaroxaban versus warfarin after catheter directed thrombolysis of an IFDVT. Patients with acute DVT of both the iliac and the femoral vein (n = 72) were recruited and randomized to either standard anticoagulation (enoxaparin and warfarin, n = 35) or rivaroxaban (n = 37) after successful thrombolysis or mechanical thrombectomy. Primary efficacy outcome was a recurrence of any venous thromboembolism (VTE) within 6 months. Secondary safety outcomes included major bleeding, clinically relevant non-major bleeding (CRNMB), other adverse event, and all-cause mortality. Rate of recurrent VTE were similar in both groups (11.4% versus 12.5%; p = 0.94). Major bleeding or CRNMB was less in rivaroxaban group without significance (2.9% versus 9.4%, HR, 0.31; 95% CI, 0.03–2.96; p = 0.31). Recurrence-free survival and major bleeding-free survival at 6 months were not different in both groups. After thrombolysis of acute IFDVT, rivaroxaban was as safe and effective as warfarin in preventing DVT recurrence.

Risk of Recurrence After Withdrawal of Anticoagulation in Patients With Unprovoked Venous Thromboembolism: External Validation of the Vienna Nomogram and the Dash Prediction Score

IntroductionScales for predicting venous thromboembolism (VTE) recurrence are useful for deciding the duration of the anticoagulant treatment. Although there are several scales, the most appropriate for our setting has not been identified. For this reason, we aimed to validate the DASH prediction score and the Vienna nomogram at 12 months. MethodsThis was a retrospective study of unselected consecutive VTE patients seen between 2006 and 2014. We compared the ability of the DASH score and the Vienna nomogram to predict recurrences of VTE. The validation was performed by stratifying patients as low-risk or high-risk, according to each scale (discrimination) and comparing the observed recurrence with the expected rate (calibration). ResultsOf 353 patients evaluated, 195 were analyzed, with an average age of 53.5±19 years. There were 21 recurrences in 1 year (10.8%, 95% CI: 6.8%–16%). According to the DASH score, 42% were classified as low risk, and the rate of VTE recurrence in this group was 4.9% (95% CI: 1.3%–12%) vs. the high-risk group that was 15% (95% CI: 9%–23%) (P<.05). According to the Vienna nomogram, 30% were classified as low risk, and the rate of VTE recurrence in the low risk group vs. the high risk group was 4.2% (95% CI: 0.5%–14%) vs. 16.2% (95% CI: 9.9%–24.4%) (P<.05). ConclusionsOur study validates the DASH score and the Vienna nomogram in our population. The DASH prediction score may be the most advisable, both because of its simplicity and its ability to identify more low-risk patients than the Vienna nomogram (42% vs. 30%).

Presence of Residual Venous Thrombus at Warfarin Withdrawal: a Predictor for Recurrence after a First Episode of Symptomatic Provoked Proximal Deep Venous Thrombosis in Thai Population?

Objective: To assess the risk for venous thromboembolism (VTE) recurrence by presence of residual venous thrombus (RVT) at warfarin withdrawal following symptomatic first provoked proximal DVT.Methods: Medical records of 45 consecutive patients with symptomatic first provoked proximal DVTs who had undergone warfarin surveillance for ≥ 3 months were reviewed retrospectively. Altogether, 22 patients discontinued anticoagulation after ≥ 3 months regardless of duplex ultrasonography results of RVT diagnosed by compression ultrasonography. Another 23 patients discontinued anticoagulation after the RVT disappeared. Primary outcome was recurrent VTE.Results: Four of the 45 patients experienced recurrent VTE (8.89%), including 2 (9.00%) of 22 patients who had discontinued anticoagulant regardless of duplex ultrasonography results and 2 (8.70%) of 23 patients who discontinued anticoagulation after RVT disappearance (p = 0.963). All of the recurrent VTE were recurrent DVT.Conclusion: RVT at warfarin withdrawal was not a predictor for recurrence VTE following a first symptomatic provoked proximal DVT.

Direct Oral Anticoagulants for Prevention of Recurrent Thrombosis in Myeloproliferative Neoplasms

Background: Patients with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) are at increased risk of thrombosis. These myeloproliferative neoplasm (MPN) patients are historically treated with vitamin K antagonists (VKAs) to prevent recurrent thromboembolic events. Direct oral anticoagulants (DOACs) are novel anticoagulants that are being increasingly used in MPNs without robust evidence. We hypothesize that DOAC and VKA therapy have similar efficacy and safety in MPNs with a comparable incidence of recurrent thromboembolic and bleeding events. Methods: Using Looking Glass®, an interactive software that integrates demographic and clinical datasets for the purpose of clinical research, we identified MPN patients who were on systemic anticoagulation (AC) therapy for a documented arterial or venous thrombotic event between 1/1/2014 and 4/1/2019. Medical charts were reviewed to obtain patient demographics, MPN subtype, mutation status, date of MPN diagnosis, date and site of index thrombosis, date of AC initiation, last documented date of therapy, date and site of recurrent thrombosis, changes in therapy; date and type of major bleeding (MB) and clinically relevant non-major bleeding (CRNMB) events on AC. Primary outcome was incidence of recurrent thrombotic events while on AC. Secondary outcome was the incidence of MB and CRNMB events. Statistical analyses were performed using two-sided t-tests with α =0.05 for continuous variables, chi-square for categorical variables with samples size &gt;10 and Fisher's exact tests for categorical variables with sample size &lt;10. Results: We identified 53 patients that met the study criteria. Data on demographics, MPN subtype, mutation status, index thrombosis site, and type of AC are reported in Table 1. The majority of the patients in our cohort were females (69.8%), had a diagnosis of ET (71.7%), were JAK2V617F mutated (69.8%), and had a venous index event (75%). Median age for the entire cohort was 66.8 years (IQR 48.1-74.5) while the median age for those who had a recurrent thrombotic event on AC was 56.1 (IQR 46.4-76.1). If patients were switched from one anticoagulant to another, only the first treatment was included in the analysis. 31 (58.5%) of patients were on VKA therapy while 22 (41.5%) were on DOAC therapy. Median time of follow up was 227 and 451 days for DOACs and VKA respectively, (p = 0.01). Rates of thrombosis and bleeding were comparable within anticoagulation class. 5/22 (22.7%) and 6/31 (19.4%) of patients prescribed DOACs and VKA respectively developed recurrent thrombotic events. Median time to recurrent thrombotic event for DOACs as compared to VKA group was 568 vs 734 days (p = 0.29). 5/22 (22.7%) of those prescribed DOACs had bleeding events, 1 MB and 4 CRNMB. 11/31 (35.5%) of those prescribed VKA had bleeding events, 2 MB and 9 CRNMB. Median time to bleeding event for DOACs as compared to VKA was 56 vs 1347 days (p = 0.004). For the 53 patients on any anticoagulation, 11 (20.7%) patients had recurrent events while on AC (DOAC and VKA). In contrast, of the 14 patients who had AC therapy interrupted for any reason, 8 (57.1%) developed recurrent thrombotic events (p = 0.02). Table 2 summarizes these findings. Conclusion: We conducted a retrospective chart review study comparing the incidence of recurrent thromboembolic events on DOAC and VKA therapy. This is the largest study to date of MPN patients treated with DOACs. Based on our data, it appears that patients treated with DOACs have a comparable incidence of recurrent thrombosis and hemorrhagic events when compared to VKA therapy, although our study suggests that bleeding events may occur sooner in patients treated with DOACs. A large percentage of people with interruptions in their AC developed recurrent thrombotic events. Our data further emphasize the profound pro-thrombotic nature of MPN and therefore the need for uninterrupted anticoagulation therapy. Overall, given the comparable incidence of thrombosis and hemorrhage, DOAC therapy appears to be similar to VKA therapy in management of thrombotic complications of MPNs. The limitations of our study were as expected: a small sample size and significantly shorter median time for DOAC follow up as compared to VKA. Future, prospective large-scale studies are needed to confirm the safety and efficacy of DOAC therapy in MPNs. Disclosures Kushnir: Janssen Pharmaceuticals: Research Funding. Billett:Bayer Pharmaceuticals: Research Funding; Janssen Pharmaceuticals: Research Funding; Albert Einstein College of Medicine: Patents &amp; Royalties: Patent application pending for NETs AI software.

The Effect of Anticoagulant Choice on Venous Thromboembolism Recurrence and Bleeding in Sickle Cell Disease

Patients with sickle cell disease (SCD) experience accelerated morbidity and mortality. Venous thromboembolism (VTE), a risk factor for early mortality in SCD, occurs in 11-12% of patients with SCD by the age of 40. While indefinite anticoagulation is indicated in the SCD population, there is limited understanding of comparative efficacy and hemorrhagic risk of individual anticoagulation agents in this population. We reviewed the use of anticoagulation for treatment of VTE in patients with SCD at our institution to begin to address these questions. A retrospective chart review of all patients with SCD 18 years of age and older (currently alive or deceased) who received care at Boston Medical Center/Boston University between 2003 and 2018 was performed. VTE was defined as deep venous thrombosis (DVT) diagnosed by duplex ultrasound or pulmonary embolism (PE) diagnosed by either ventilation-perfusion scanning or computed tomography angiography. The primary efficacy outcome was the number of VTE events which occurred while the patient was receiving anticoagulation. The primary safety outcome was major bleeding as defined by the International Society on Thrombosis and Hemostasis 2005 guidelines. The medical records of 233 patients with SCD were reviewed; VTE was identified in 55 (23.6%) patients. Sixty-five percent were female. In these 55 patients, a total of 94 VTE events occurred. Fifteen (16.0%) were catheter-associated upper extremity DVTs. For the first event, initial outpatient treatment consisted of warfarin in 56%, low-molecular-weight heparin (LMWH) in 18.2%, rivaroxaban in 9.1%, apixaban in 5.5%, and fondaparinux in 3.6%. The median length of treatment was 7.3 (median: 6, IQR: 3-12) months. Recurrent VTEs occurred in 27 (49%) patients with a total of 39 recurrent events. Among the recurrent events, thirteen (33.0%) were treatment failures occurring during anticoagulation therapy (see Table 1): 7 of 37 (18.9%) on warfarin, 2 of 20 (10.0%) on LMWH, and 4 of 15 (26.7%) on rivaroxaban. Death from recurrent VTE occurred in two patients; one occurred while a patient was therapeutic on warfarin. Major bleeding occurred in two patients (3.6%); in both cases, this was intracranial hemorrhage while on warfarin. In this retrospective study, there was a high rate of VTE recurrence despite anticoagulation in patients with SCD. Treatment failure was highest with warfarin and rivaroxaban, although adherence was difficult to assess. Risk of hemorrhage and death appears higher in those prescribed warfarin. These data affirm the need for long-term anticoagulation in most patients with SCD with a VTE and support the use of direct oral anticoagulants as a first-line agent. Disclosures Sloan: Abbvie: Other: Endpoint Review Committee; Stemline: Consultancy; Merck: Other: endpoint review commitee.

D-dimer testing, with gender-specific cutoff levels, is of value to assess the individual risk of venous thromboembolic recurrence in non-elderly patients of both genders: a post hoc analysis of the DULCIS study

Male patients, especially the young, are at a higher risk of recurrent venous thromboembolism (RVTE) than females. Recent scientific reports show the use of D-dimer does not help predict RVTE risk in males. In the present report, we reviewed the data obtained in the DULCIS study (main report published in Blood 2014), focusing on D-dimer results recorded in non-elderly patients of both genders included in the study, and their relationship with RVTE events occurring during follow-up. Using specifically designed cutoff values for positive/negative interpretation, serial D-dimer measurements (performed during warfarin treatment and up to 3 months after discontinuation of anticoagulation) in 475 patients (males 57.3%) aged ≤ 65 years were obtained. D-dimer resulted positive in 46.3% and 30.5% of males and females, respectively (p = 0.001). Following management procedure, anticoagulation was stopped in 53.7% of males and 69.5% of females, who had persistently negative D-dimer results. The rate of subsequent recurrent events was 1.7% (95% CI 0.5–4.5%) and 0.4% (95% CI 0–2.5%) patient-years in males and females, respectively, with upper limits of confidence intervals always below the level of risk considered acceptable by international scientific societies for stopping anticoagulation (< 5%). In conclusion, using sensitive quantitative assays with specifically designed cutoff values and serial measurements during and after discontinuation of anticoagulation, D-dimer testing is useful to predict the risk of RVTE and is of help in deciding the duration of anticoagulation in both male and female adult patients aged up to 65 years.

PFO closure consideration for refractory hypoxia and secondary prevention of recurrent arterial thromboembolism

Acute arterial and deep venous thrombosis presenting simultaneously are uncommon medical emergencies, usually secondary to an underlying cause. We present a 64-year-old woman with concurrent bilateral pulmonary embolisms and acute thrombotic occlusion of the right brachial artery. Her work-up revealed a large patent foramen ovale (PFO), with a right to left intracardiac shunt and bilateral lower extremity deep venous thrombosis. The patient was unable to be weaned off mechanical ventilation due to her refractory hypoxia. However, after closure of the PFO the patient’s oxygenation improved. This case demonstrates the potential beneficial role of PFO closure in a hypoxic patient with a right to left intracardiac shunt. In addition, closure of the PFO may provide secondary prevention of paradoxical systemic thromboembolism.

Predictors of Not Initiating Anticoagulation After Incident Venous Thromboembolism: A Danish Nationwide Cohort Study

PurposeThe purpose of this study was to investigate potential predictors associated with not initiating anticoagulation after incident venous thromboembolism. MethodsWe linked Danish nationwide health registries to identify all patients with incident venous thromboembolism from 2003 through 2016. We defined treatment noninitiation as not claiming a prescription for an anticoagulant drug within 30 days after hospital discharge. To identify potential predictors of noninitiation, relative risks (RRs) with 95% confidence intervals (CIs) were calculated adjusting for other compliance-related factors. ResultsThe study included 38,044 patients with incident venous thromboembolism (53.2% female and median age 66.1 years). Of these, 24.1% (n = 9294) were noninitiators. Demographic and condition-related factors that predicted noninitiation included: female sex (RR 1.30; 95% CI, 1.25-1.34), age <30 vs age >65 years (RR 1.18; 95% CI, 1.13-1.33), hospitalization 0-3 days vs >3 days (RR 1.96; 95% CI, 1.87-2.07), incident deep venous thrombosis (RR 1.91; 95% CI, 1.81-2.01), and unprovoked venous thromboembolism (RR 1.13; 95% CI, 1.08-1.17). Socioeconomic factors had less influence on risk of noninitiation. Individual chronic diseases predictive of noninitiation included congestive heart failure (RR 1.27; 95% CI, 1.17-1.37), ischemic heart disease (RR 1.20; 95% CI, 1.13-1.28), and liver disease (RR 1.60; 95% CI, 1.42-1.81). ConclusionUp to one-fourth of patients diagnosed with incident venous thromboembolism did not initiate anticoagulant treatment within 30 days after hospital discharge. Identification of clinical predictors of noninitiation may enable implementation of patient-tailored strategies to improve adherence and thereby potentially prevent venous thromboembolism morbidity, mortality, and recurrence.

585 Risks of Recurrent Bleeding in Patients Hospitalized With Gastrointestinal Bleeding While on Warfarin vs Direct Oral Anticoagulants

INTRODUCTION: There is limited data on the management of anticoagulation following hospitalization for gastrointestinal bleeding (GIB) and the subsequent risks of recurrent GIB and thromboembolism in patients who are on warfarin compared to direct oral anticoagulants (DOACs). METHODS: We conducted a retrospective analysis of medical claims data from the IBM®MarketScan® Research Databases from January 1, 2008 through December 31, 2017. We collected data on adults with atrial fibrillation treated with warfarin or DOACs and subsequently hospitalized for GIB. Post discharge readmissions for recurrent GIB and thromboembolism within 180 days of initial discharge were reviewed. Univariable and multivariable cox regression were used to determine risks of recurrent GIB and thromboembolism. RESULTS: There were 2,991 patients hospitalized for GIB while on anticoagulants (warfarin, n = 1872; rivaroxaban, n = 676; dabigatran, n = 293; apixaban, n = 250). Differences between warfarin and DOAC users are reported in Table 1. Twenty-nine percent (n = 869) of warfarin users had warfarin resumed following discharge with a median time to resumption of 27 days (IQR 10-63), compared to 16% percent (n = 485) of DOAC users who had DOAC resumed (median time to resumption of 32 days (IQR 16-69). Discharge on warfarin was associated with the highest risk of recurrent GIB (HR 1.69, 95% CI 1.23-2.31) whereas discharge on dabigatran (HR 0.13, 95% CI 0.02-0.90) and apixaban (HR 0.38, 95% CI 0.14-1.01) had the lowest risk of recurrent GIB (Table 2). In a multivariable model adjusting for demographics, comorbidities, in-hospital management, source of bleeding, and post-discharge anticoagulant resumption, resumption of warfarin was associated with an increased risk of recurrent GIB (HR 1.53, 95% CI 1.07-2.18) compared to resumption of DOAC (HR 0.85, 95% CI 0.51-1.42). Variables associated with thromboembolism on multivariable regression included preceding venous thromboembolism (HR 2.42, 95% CI 1.66-3.51) and history of left ventricular assist device (HR 7.84, 95% CI 3.20-19.2). Survival analysis showed a significant association between type of anticoagulant on discharge and risk of recurrent GIB (log-rank, P = 0.001) (Figure 1). CONCLUSION: Resumption of warfarin following hospitalization for gastrointestinal bleeding was associated with an increased risk of recurrent GIB when compared to DOACs.

578 Resuming Anticoagulation Following Hospitalization for Gastrointestinal Bleeding Is Associated With Reduced Thromboembolic Events and Improved Mortality: Results From a Systematic Review and Meta-Analysis

INTRODUCTION: Systemic anticoagulants are widely prescribed for prevention and treatment of thromboembolism, but are commonly complicated by gastrointestinal bleeding (GIB). There is limited data on the management of anticoagulation after hospitalization for GIB and the subsequent risks of recurrent GIB, thromboembolism, and mortality. METHODS: We performed a systematic review and meta-analysis to determine the risk of recurrent GIB, thromboembolism and mortality after resuming anticoagulation following GIB. PubMed, Embase and Scopus were searched for randomized controlled trials and cohort studies in patients with atrial fibrillation, venous thromboembolism or valvular heart disease who received long-term warfarin or direct oral anticoagulants before experiencing GIB. Studies were included if data were available on anticoagulation management and outcomes of recurrent GIB, thromboembolism and mortality following initial hospitalization for GIB. RESULTS: A total of 5,354 studies were reviewed of which 10 were included in the meta-analysis (Figure 1). There were 2,080 patients who resumed anticoagulation and 2,296 patients who stopped their anticoagulation post index GIB (Table 1). Resumption of anticoagulation was associated with a significant increase in recurrent GIB (OR 1.646, 95% CI 1.035-2.617, P = 0.035, I2 = 55.5%) though recurrent GIB leading to death was rare (Figure 2). There was a significant decrease in thromboembolic events in patients who resumed anticoagulation compared to those who did not (OR 0.340, 95% CI 0.178-0.652, P = 0.001, I2 = 62.7%) and a significant reduction in all-cause mortality (OR 0.499, 95% CI 0.419-0.595, P = 0.000, I2 = 14.2%) (Figure 2). Optimal timing of re-initiation of anticoagulation varied, but as early as 2 weeks from index GIB or hospital discharge may be ideal. CONCLUSION: While resumption of anticoagulation following index GIB was associated with a significant increase in recurrent GIB, it was also associated with a significant decrease in thromboembolic events and all-cause mortality. Re-initiation of anticoagulation as early as 2 weeks post-GIB may be optimal.

P1026Risk factors for the occurrence of stroke after atrial fibrillation ablation

Abstract Background Risk factors for the occurrence of embolic stroke (ES) after atrial fibrillation (AF) ablation have not been fully elucidated. Our aim was to assess incidence of ES during long-term follow-up following AF ablation and to identify predicting factors associated with post-ablation ES. Methods We enrolled patients who experienced ES after AF ablation and body mass index-matched controls from AF ablation registries. Epicardial adipose tissue (EAT) was assessed using multislice computed tomography prior to ablation. Results A total of 3,464 patients who underwent AF ablation were recruited. During a mean follow-up of 47.2 months, ES occurred in 47 patients (1.36%) with a mean CHA2DS2-VAS score of 2.15 and overall incidence of ES was 0.34 per 100 patients/year. Compared with control group (n=190), ES group had more higher prior thromboembolic event and AF recurrence rates, larger LA size, lower creatinine clearance rate (CCr), and greater total and periatrial EAT volumes although no differences in AF type, CHA2DS2-VASc score, ablation extent, and anti-thrombotics use were found. On multivariate regression analysis, a prior history of thromboembolism, CCr, and periatrial EAT volume were independently associated with ES occurrence after AF ablation. Cox regression analysis Risk factor Univariate Multivariate HR (95% CI) p value HR (95% CI) p value Age 1.017 (0.984–1.051) 0.31 Prior thromboembolism 2.488 (1.134–5.460) 0.023 2.916 (1.178–7.219) 0.021 CHA2DS2-VASc score 1.139 (0.899–1.445) 0.282 CCr 0.984 (0.970–0.999) 0.038 0.982 (0.996–0.998) 0.029 LA diameter (mm) 1.070 (1.012–1.130) 0.017 1.072 (0.999–1.150) 0.054 EAT_total (ml) 1.020 (1.010–1.029) &lt;0.001 1.008 (0.993–1.023) 0.297 EAT_periatrial (ml) 1.085 (1.045–1.126) &lt;0.001 1.065 (1.005–1.128) 0.032 PVI + additional ablation 0.846 (0.460–1.557) 0.592 No anticoagulant use 0.651 (0.346–1.226) 0.184 Recurrence 2.011 (1.007–4.013) 0.048 1.240 (0.551–2.793) 0.603 CCr, creatinine clearance rate; EAT, epicardial adipose tissue; LA, left atrium; PVI, pulmonary vein isolation. K-M curve for stroke-free survival Conclusions Incidence of ES after AF ablation was lower than expected rate based on CHA2DS2-VASc score even though anticoagulants use was limited. Periatrial EAT volume, a prior thromboembolism event, and CCr were independent factors in predicting ES irrespective of AF recurrence and CHA2DS2-VASc score in patients who underwent AF ablation.

1773P - Short-term outcomes of cancer patients with pulmonary embolism according to the setting (hospital-acquired vs. outpatient) at diagnosis

BackgroundPulmonary embolism (PE) is a common condition in patients with cancer, having a wide spectrum of clinical presentation (from acute life-threatening to truly asymptomatic incidental events). The aim of this study was to assess the prognostic relevance of the variable ‘setting’ (hospital-acquired vs. outpatient) at PE diagnosis. MethodsMulticenter observational ongoing registry of consecutive patients with cancer-associated PE (2005-2018) including incidental and acute symptomatic events. The main outcome measured was the rate of overall and PE-specific 30-day mortality. Secondary outcomes were: rates of 30-day major bleeding (MB) and venous thromboembolism (VTE) recurrence. ResultsWe included a total of 617 patients (61.6% male; median age 65+11.4 years; range 19-91 years) including N=522 (85%) outpatients and N=95 (15%) inpatients at PE diagnosis. The most frequent primary tumors were: lung 32%, colorectal 14%, urologic 13%, upper GI 12%, breast 9%, gynecologic 6% and other 9%). Most of the patients (79%) had metastatic cancer and nearly half (47%) were receiving chemotherapy.The PE was incidentally found in 54% of the cases. Overall 30-day mortality occurred in 95 patients (15% of the cohort), being greater in inpatients compared to outpatients (30% vs. 13%; p<0.0001). Only 13 patients presented PE-related mortality (3% of the cohort), with no significant differences according to the setting at PE diagnosis (3.2% in inpatients vs. 1.7% in outpatients; p=0.352). Similarly, there were no differences in 30-day MB (7.4% in inpatients vs. 4.4% in outpatients; p=0.217) or VTE recurrence (4.2% in inpatients vs. 3.3% in outpatients; p=0.637) according to the setting at PE diagnosis. ConclusionsHospital-acquired PE in cancer patients was associated with a greater overall 30-day mortality compared to outpatients at PE diagnosis. This finding may be relevant for the development of PE risk-assessment models in this setting. Legal entity responsible for the studyHospital Clínic de Barcelona. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

P4671A well-defined subgroup of chronic thromboembolic pulmonary hypertension patients are positive for antiphospholipid antibodies

Abstract Introduction Recurrent thromboembolism is a major risk factor for chronic thromboembolic pulmonary hypertension (CTEPH). Antiphospholipid antibodies (aPL) are a recognized risk factor for recurrent thromboembolism, however, their contribution to the development of CTEPH is currently unknown. Purpose The aim of this study was to evaluate the prevalence of antiphospholipid autoantibodies in a large cohort of consecutive patients with CTEPH. Methods Starting May 2013 to December 2018, 297 CTEPHpatients were consecutively enrolled. Diagnosis was confirmed with standardized right heart catheterization, 2D or/and 3D pulmonary angiography in all patients.All patients were also screened for thrombophilia including lupus anticoagulant IgG/IgM anticardiolipin antibodies and IgG/IgM aβ2GPI antibodies. Clinical and demographic characteristics, laboratory profile and hemodynamic data were compared between patients with aPL positive and aPL negative laboratory profiles. Results Overall, 297 consecutive patients with CTEPH were assessed for aPLs. Of these, 23 patients (7.7%) resulted positive for laboratory tests exploring aPL. Among patients with positive aPL, profile 17 (74%) were positive for all three test exploring aPL (LA+, aCL+, aB2GPI+). When compared to CTEPH patients without aPL test positivity, those positive for aPL were significantly younger (30.0 vs 55.6 years, p&lt;0.0001), had a positive history of pulmonary embolism (95.6% vs 65.7%, p=0.003), deep venous thrombosis (78.3% vs 41.9%, p=0.0008) and were more frequently affected by other autoimmune diseases (43.5% vs 2.9%, p&lt;0.0001). Moreover, positive aPL patients showed better hemodynamics on right heart catheterization, had more proximal lesions, and had more frequently level I and II surgical classification (82.6% vs 40.5%, p=0.0002) on pulmonary angiography. Conclusions These findings suggest that young patients with pulmonary embolism should be assessed for aPLs to guide anticoagulation therapy and prevent recurrences. Additionally, younger age, more proximal lesions and less severe hemodynamic profiles make majority patients with APS good candidates for PEA surgery.

P2766Increased right ventricular burden in patients with chronic thromboembolic disease

Abstract Introduction Patients with chronic thromboembolic disease (CTED) have residual perfusion defects after pulmonary embolism (PE) but not increased pulmonary artery (PA) pressure. These patients suffer from functional limitation and have a higher risk of venous thromboembolism recurrence. Purpose In this study we wanted to explore if CTED patients had signs of increased PA pressure and right heart burden by echocardiography Methods Inclusion criteria were history of PE, age 18–75 years and PE diagnosed 6–72 months prior to inclusion. Patients with left ventricular systolic or diastolic heart failure, valvular disease, chronic pulmonary disease and chronic thromboembolic pulmonary hypertension were excluded. All patients underwent echocardiography with standard and novel methods and ventilation/perfusion (VQ)-scan. The echocardiographic examinations were blinded to the result of the VQ-scan. VQ-scan were analyzed according to the European Association of Nuclear Medicine-criteria, and deemed either positive or negative. Data are presented as mean ± SD or median ± IQR as appropriate. Independent sample t-test or Mann-Whitney U test was used for the primary statistical analysis. Multiple linear regression was used to adjust for age, BMI and systolic blood pressure. Results Table 1 VQ negative (n=58) VQ positive (n=20) p-value Adjusted Age (years) 59±8 67±6.5 0.71 Time since PE event (months) 37±19 33±17 0.42 Pulmonary artery acceleration time (ms) 145±22 119.5±26 &lt;0.001 &lt;0.001 Pulmonary artery diameter (mm) 21±3.3 25±3.6 &lt;0.01 &lt;0.01 TAPSE (mm) 25.7±3.6 24.9±4.0 0.45 RV (right ventricle) S' (cm/s) 12.7±2.3 12.8±2.7 0.78 RV isovolumic relaxation time (ms) 33±23.9 50±22 &lt;0.01 &lt;0.01 RV myocardial performance index 0.36±0.10 0.44±0.15 0.04 0.02 Tricuspid regurgitation maximum velocity (m/s) 2.3±0.3 2.7±0.4 &lt;0.001 &lt;0.001 LV (left ventricle) ejection fraction (%) 62.5±4.2 61.3±6.0 0.41 E/A 1.02±0.26 0.90±0.23 0.09 E/e' 6.8±2.0 6.5±2.2 0.75 E/A: ratio between transmitral pulsed doppler peak early (E) diastolic and atrial (A) velocity; E/e': ratio between E and peak early velocity (e') by tissue velocity. Figure 1 (error bars - mean and 95% CI) Conclusion Patients with CTED after PE have increased PA pressure and impaired RV systolic and diastolic function compared to those without residual perfusion defects. These findings indicate that CTED patients should be more thoroughly followed up.