Therapeutic Oral Anticoagulation Research Articles

Abstract 18414: Risk of Stroke After Atrial Fibrillation Ablation in Patients Without Pre-Ablation Left Atrial Appendage Evaluation

Introduction: Currently, transesophageal echocardiography (TEE), intracardiac echocardiography (ICE), or CT angiography (CTA) are often though not always performed to assess the left atrial appendage (LAA) prior to ablation to reduce the risk of stroke. We seek to evaluate in a large, real-world registry if rates of stroke are similar in patients who do not have this evaluation and are on at least three weeks of anticoagulation prior to ablation. Methods: The REAL-AF registry is a multicenter prospective registry that is enrolling patients undergoing AF ablation at high-volume centers. Data from a total of 2704 patients (mean age 66 ± 11 years, 42% female) receiving index ablation for paroxysmal and persistent AF were obtained and included in the analysis. The patients who suffered strokes within 12 months of ablation were analyzed. Results: A total of 1522 (56%) patients received TEE, 1143 (42%) received ICE, 153 (6%) received both TEE and ICE, 95 (4%) received CTA, and 97 (4%) did not received any evaluation for LAA clots pre-ablation. CHA 2 DS 2 VASc was significantly higher in the not screened group compared to the screened group ((3.18 [2.84 - 3.51]) vs 2.65 [2.59 - 2.71], p < 0.01). Three patients (0.1%) suffered strokes after ablation, two who had been screened by ICE, and one who had not been screened. No patients who were screened by TEE or CTA suffered strokes. All three patients with strokes were on therapeutic oral anticoagulation prior to ablation. The two patients screened with ICE had a CHA2DS2VASC of 2 and 7, while the patient without screening had a score of 6. Patients who were not screened had a statistically significant higher likelihood of having a stroke compared to those who received LAA screening with TEE, ICE, or CTA (OR = 13.2 [1.2 - 147], p = 0.04). Conclusion: While absolute rates of stroke after AF ablation are low, in our cohort occurring in only 0.1% of patients, there was a statistically significantly higher odds of developing stroke in patients who did not have their LAA screened prior to ablation.

Abstract 17496: Exploring the Benefits: Role of Repeat Transesophageal Echocardiography (TEE) in Patients Anticoagulated for Four Weeks

Background: A left atrial appendage (LAA) thrombus is a well-known complication of atrial fibrillation (AF). Vitamin K antagonists (VKAs) have been well studied been considered the gold standard for thromboembolic prophylaxis. We present a case of LAA thrombus despite compliance with VKAs. Clinical presentation: A 70-year-old female with atrial fibrillation and diabetes presented with left-sided weakness and left facial droop, CT head showed right middle cerebral artery infarct. Vitals were unremarkable. Electrocardiogram showed AF with a rapid ventricular response. She was on warfarin with the most recent international normalized ratio level of 2.3. Transthoracic echocardiography revealed an ejection fraction of 55%, severe left ventricular hypertrophy, and severely dilated left atrium (LA) with LA diameter of 5.3 cm (>= 4.7 cm in women indicates severe dilatation). Transesophageal echocardiography (TEE) with bubble study demonstrated a large thrombus in the LAA with evidence of patent foramen ovale. The pulse wave Doppler (PWD) of the LAA on TEE also showed an LAA velocity of <20 cm/sec, which indicated that there was the highest probability that the thrombus was forming within LAA. Hypercoagulability work-up for thrombosis while on Coumadin such as anti-B2 glycoprotein, anticardiolipin, and factor V Leiden mutation were negative. The patient was started on enoxaparin with appropriate follow-up upon discharge. Discussion: The prevalence of LAA thrombus in patients with AF receiving a minimum of 3 weeks of anticoagulation, was approximately 3%. The presence of a LAA thrombus is a known contraindication to cardioversion and catheter ablation in patients with AF as it can result in cardioembolic stroke. However, current guidelines for cardioversion do not recommend pre-procedural TEE in patients undergoing cardioversion for AF if they have been on therapeutic oral anticoagulation for at least 3 weeks while TEE use remains variable before catheter ablation.

After ICH, starting long-term therapeutic oral anticoagulation in patients with AF reduces MACE at 1 to 3 y.

Cochrane A, Chen C, Stephen J, et al. Antithrombotic treatment after stroke due to intracerebral haemorrhage. Cochrane Database Syst Rev. 2023;1:CD012144. 36700520.

Antithrombotic treatment after stroke due to intracerebral haemorrhage.

Antithrombotic treatment after stroke due to intracerebral haemorrhage.

Yield of Echocardiography in Ischemic Stroke and Patients With Transient Ischemic Attack With Established Indications for Long-Term Direct Oral Anticoagulant Therapy: A Cross-Sectional Diagnostic Cohort Study.

BackgroundWe aimed to determine the diagnostic yield of transthoracic (TTE) and transesophageal echocardiography (TEE) in patients with ischemic stroke and transient ischemic attack with established indications for direct oral anticoagulants before the index event.Methods and ResultsThis was a retrospective cohort study of consecutive patients with preceding established indications for long‐term therapeutic direct oral anticoagulants presenting to a single comprehensive stroke center with ischemic stroke or transient ischemic attack. Choice of echocardiography modality was based on expert recommendations. The primary outcome was a composite of prespecified management‐relevant high‐risk findings adjudicated by an expert panel, based on TTE and TEE reports according to evidence‐based recommendations. Explorative analyses were performed to identify biomarkers associated with the primary outcome. Of 424 patients included (median [interquartile range] age, 78 [70–84] years; 175 [41%] women; National Institutes of Health Stroke Scale, 4 [1–12]; 67% atrial fibrillation), 292 (69%) underwent echocardiography, while 132 (31%) did not. Modality was TTE in 191 (45%) and TEE in 101 (24%). Median time from index event to echocardiography was 2 (1–3) days. TTE identified 26 of 191 (14%) patients with 35 management‐relevant pathologies. TEE identified 16 of 101(16%) patients with 20 management‐relevant pathologies. Most management‐relevant findings represented indicated coronary artery disease and valvular pathologies. In a further 3 of 191 (2%) patients with TTE and 4 of 101 (4%) patients with TEE, other relevant findings were identified. Variables associated with management‐relevant high‐risk pathologies included more severe stroke, diabetes, and laboratory biomarkers (NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide], C‐reactive protein, d‐dimer, and troponin levels).ConclusionsIn patients with established indications for long‐term direct oral anticoagulant therapy and stroke who received echocardiography, both TTE and TEE identified a relevant and similar proportion of management‐relevant high‐risk pathologies and predictive biomarkers could help to guide diagnostic workup in such patients.

Glycoprotein IIb/IIIa receptor targeted PET/CT imaging: a novel diagnostic tool for detecting bioprosthetic valve thrombosis

Abstract Background/Introduction Bioprosthetic valve thrombosis (BPVT) is an important clinical entity eventually following both bioprosthetic surgical and transcatheter aortic valve replacement. Although dynamic contrast-enhanced 4D-MDCT has improved the diagnosis of BPVT, more sensitive and pathology-specific non-invasive imaging tools are lacking. Recently, the glycoprotein IIb/IIIa receptor targeted, elarofiban-derived PET/CT imaging radiotracer [18F]GP1 has been successfully used for visualization of acute venous and arterial thrombi. Purpose We hypothesized that [18F]GP1 PET/CT imaging is suitable to detect BPVT. Methods In this proof-of-concept study, patients after bioprosthetic aortic valve replacement with symptomatic, severe hemodynamic valve dysfunction and confirmed hypoattenuated leaflet thickening (HALT) in dynamic 4D-MDCT were offered to participate in compassionate use examinations to undergo PET/CT imaging with the investigational [18F]GP1 PET tracer at baseline and after a 12-week course of therapeutic oral anticoagulation. Results This case series reports on three patients after aortic valve replacement. Two patients with symptomatic, obstructive BPVT as confirmed by echocardiography and 4D-MDCT fulfilled specified criteria and underwent [18F]GP1 PET/CT imaging. [18F]GP1 PET/CT clearly distinguished between blood pool activity and thrombotic foci. Clot-to-blood ratios at baseline were 8.2 and 4.5, respectively. A 12-week trial of therapeutic oral anticoagulation was associated with a regression of mean transprosthetic pressure gradient and reversal of HALT. Follow-up 4D-MDCT corroborated thrombus resolution in both patients. Correspondingly, [18F]GP1 PET/CT imaging demonstrated decreased tracer uptake in both patients. Clot-to-blood ratio at follow-up visit decreased to 1.2 and 2.9, respectively. While absent tracer uptake was seen in patient #1, residual tracer uptake was observed in patient #2 suggestive of ongoing platelet aggregation. One asymptomatic SAVR patient was examined with [18F]GP1 PET/CT for a different compassionate use and no thrombotic foci were detected on the leaflets. Conclusions [18F]GP1 PET/CT is a novel imaging technique in patients with obstructive BPVT. In a head-to-head comparison we show that [18F]GP1 PET/CT may have incremental diagnostic value over dynamic contrast-enhanced 4D-MDCT alone by detection of sites of ongoing platelet aggregation at the molecular level. [18F]GP1 PET/CT may serve as a novel, highly sensitive tool to overcome some limitations of current diagnostic imaging modalities for detecting BPVT and may prove useful for the monitoring and guidance of therapeutic interventions. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Life Molecular Imaging provided material for [18F]GP1 radiolabeling free of charge as part of an ongoing research collaboration.

Prevalence of Left Atrial Thrombus in Anticoagulated Patients With Atrial Fibrillation

BackgroundThe prevalence of left atrial (LA) thrombus in patients with atrial fibrillation (AF) or atrial flutter (AFL) on guideline-directed anticoagulation is not well known, yet this may inform transesophageal echocardiogram (TEE) use before cardioversion or catheter ablation. ObjectivesThe purpose of this study was to quantify LA thrombus prevalence among patients with AF/AFL on guideline-directed anticoagulation and to identify high-risk subgroups. MethodsEMBASE, MEDLINE, and CENTRAL were systematically searched from inception to July 2020 for studies reporting on LA thrombus prevalence among patients with AF/AFL undergoing TEE following at least 3 weeks of continuous therapeutic oral anticoagulation with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). Meta-analysis was performed using random effects models. ResultsThirty-five studies describing 14,653 patients were identified. The mean-weighted LA thrombus prevalence was 2.73% (95% confidence interval [CI]: 1.95% to 3.80%). LA thrombus prevalence was similar for VKA- and DOAC-treated patients (2.80%; 95% CI: 1.86% to 4.21% vs. 3.12%; 95% CI: 1.92% to 5.03%; p = 0.674). Patients with nonparoxysmal AF/AFL had a 4-fold higher LA thrombus prevalence compared with paroxysmal patients (4.81%; 95% CI: 3.35% to 6.86% vs. 1.03%; 95% CI: 0.52% to 2.03%; p < 0.001). LA thrombus prevalence was higher among patients undergoing cardioversion versus ablation (5.55%; 95% CI: 3.15% to 9.58% vs. 1.65%; 95% CI: 1.07% to 2.53%; p < 0.001). Patients with CHA2DS2-VASc scores ≥3 had a higher LA thrombus prevalence compared with patients with scores ≤2 (6.31%; 95% CI: 3.72% to 10.49% vs. 1.06%; 95% CI: 0.45% to 2.49%; p < 0.001). ConclusionsLA thrombus prevalence is high in subgroups of anticoagulated patients with AF/AFL, who may benefit from routine pre-procedural TEE use before cardioversion or catheter ablation.

Heavy menstrual bleeding in women on oral anticoagulants

BackgroundAlthough heavy menstrual bleeding (HMB) is a known complication of anticoagulant therapy, rates of HMB in users of the direct oral anticoagulants (OACs) apixaban and rivaroxaban are largely unknown. MethodsWe performed a retrospective cohort study of menstruating women prescribed rivaroxaban, apixaban and warfarin over a six-year period (2012–2018). The primary outcome was HMB requiring medical or surgical intervention. We used descriptive statistics and logistic regression to evaluate associations between OAC type, age, history of HMB, and the primary outcome. ResultsWe identified 195 women of reproductive-age with a new therapeutic OAC prescription (62 on rivaroxaban, 54 on apixaban, 79 on warfarin). A minority (26/195, 13.3%) had a documented history of HMB, including 9 rivaroxaban users, 7 apixaban users and 10 warfarin users but most women (117/195, 60%) had no menstrual history documented. One third of subjects (64/195) required treatment for HMB within 6 months of starting OAC therapy. After controlling for a history of HMB, rivaroxaban users were 1.4 times more likely to require treatment as compared to users of other OACs. DiscussionWe found an association between rates of HMB necessitating medical or surgical intervention and rivaroxaban use. We also found that the majority of women did not have a documented menstrual history, suggesting that many providers do not inquire about menstrual bleeding when starting OAC therapy. Menstruating women, particularly those with a history of HMB, may be at increased risk for HMB necessitating medical treatment depending on the type of OAC used.

High Fluctuation Between Anticoagulants, Frequent Off-Label Dosing, and No Difference Concerning Outcomes: Results of a Real-Life Cohort Study

BackgroundRecently published studies indicated a high proportion of patients taking direct oral anticoagulants (DOACs) are off-label under- or overdosed. The present study aimed at investigating whether off-label dosages are corrected over time and whether off-label doses are associated with differences in bleeding rates, ischemic stroke, or venous thromboembolism. MethodsIn this retrospective cohort study, patients presenting to our emergency department between January 1 and December 31, 2018, with therapeutic oral anticoagulation were included (ie, vitamin-K antagonists [VKAs], rivaroxaban, apixaban, edoxaban, and dabigatran) and follow-up for a maximum of 2 years until December 31, 2019, was made. Detailed chart reviews were performed for each case concerning characteristics, indication, bleeding complications, or changes in the used substance or dosage. ResultsWe reviewed 2588 consultations of 1228 patients receiving therapeutic oral anticoagulation. During the maximum follow-up period of 2 years vitamin K antagonists and rivaroxaban lost the largest proportions in favor of apixaban. The overall distribution of dosage correctness remained almost unimproved (correct dosing in 62.5%, underdosing in 23.6%, coverdosing in 13.9%).The corresponding outcomes did not differ with respect to bleeding events, ischemic stroke, or venous thromboembolism among various anticoagulants as well as between correct and off-label doses. ConclusionsA rising proportion of existing oral anticoagulation regimes was changed to apixaban, while the proportion of off-label dosages of all oral anticoagulants remained stable. No difference in bleeding rates, de novo strokes, or thromboembolisms was found between anticoagulants as well as between correct and off-label doses.

Technology-Based Interventions in Oral Anticoagulation Management: Meta-Analysis of Randomized Controlled Trials

BackgroundAn increasing number of patients have received prophylactic or therapeutic oral anticoagulants (OACs) for thromboembolic complications of diseases. The use of OACs is associated with both clinical benefits and risks. Considering the challenges imposed by this class of drugs, as well as the enormous progress made in portable device technology, it is possible that technology-based interventions may improve clinical benefits for patients and optimize anticoagulation management.ObjectiveThis study was designed to comprehensively evaluate the role of technology-based interventions in the management of OACs.MethodsWe searched 6 databases—PubMed, EMBASE, Cochrane, Cumulative Index to Nursing and Allied Health Literature, Scopus, and PsycINFO—to retrieve relevant studies published as of November 1, 2019, to evaluate the effect of technology-based interventions on oral anticoagulation management. RevMan (version 5.3; Cochrane) software was used to evaluate and analyze clinical outcomes. The methodological quality of studies was assessed by the Cochrane risk of bias tool.ResultsA total of 15 randomized controlled trials (RCTs) were selected for analysis. They reported data for 2218 patients (1110 patients in the intervention groups and 1108 patients in the control groups). A meta-analysis was performed on the effectiveness and safety data reported in the RCTs. Technology-based interventions significantly improved the effectiveness of oral anticoagulation management (mean difference [MD]=6.07; 95% CI 0.84-11.30; I2=72%; P=.02). The safety of oral anticoagulation management was also improved, but the results were not statistically significant. Bleeding events were reduced (major bleeding events MD=1.02; 95% CI 0.78-1.32; I2=0%; P=.90; minor bleeding events MD=1.06, 95% CI 0.77-1.44; I2=41%; P=.73) and thromboembolism events were reduced (MD=0.71; 95% CI 0.49-1.01; I2=0%; P=.06). In general, patients were more satisfied with technology-based interventions, which could also improve their knowledge of anticoagulation management, improve their quality of life, and reduce mortality and hospitalization events.ConclusionsUsing technology to manage OACs can improve the effectiveness and safety of oral anticoagulation management, result in higher patient satisfaction, and allow greater understanding of anticoagulation.

Stroke and left atrial thrombi after cryoballoon ablation of atrial fibrillation: incidence and predictors. Results from a long-term follow-up.

Stroke after catheter ablation (CA) of atrial fibrillation (AF) is a potential complication with long term consequences. Aim of this study was to determine incidence and potential predictors of stroke and left atrial appendage (LAA) thrombi after AF ablation with cryo-energy. Two hundred nine consecutive patients with symptomatic drug refractory AF (65% male; 61 ± 11 yo, 69% paroxysmal AF, mean CHA2DS2-VASc score 2 ± 1.4) were enrolled between October 2012 until December 2015. Long term follow-up was performed with outpatient clinic visits at 6-month intervals. Incidence of stroke after CA was 1.4% (3/209 pts) at long term follow-up. Two out of 3 pts experienced stroke during the first 3month after CA and one after 36months. At long term follow-up LAA thrombi were found in two patients (1%) that were on therapeutic oral anticoagulation. Recurrence of AF was found in 4 out of 5 pts with stroke or LAA thrombi. Patients with stroke or LAA thrombi did not differed from those without in term of age, gender, CV risk factors, LA size and AF type. They differed only for EHRA score (2.4 vs 1.3, p = 0.01) before CA. At multivariate analysis after correction for age, gender, LA size, LVEF and AF type, only EHRA score (β 1.92, 95% C.I. 1.3-35 p = 0.02), was an independent predictor of stroke/LAA thrombi. Incidence of stroke after cryoablation is low, with a relative higher prevalence during the first 3months after CA. Prospective, multicenter long-term registries are needed for a better stroke risk stratification.

Hypo-attenuated leaflet thickening in surgically-implanted mitral bioprosthesis

BackgroundHypo-attenuated leaflet thickening (HALT) in bioprosthetic aortic valve has been studied, but its equivalent in bioprosthetic mitral valve (bMV) remains uncharacterized. We sought to identify the prevalence, hemodynamic characteristics, and significance of anticoagulation therapy in bMV HALT.MethodsA single-center cross-sectional study of 53 consecutive patients who underwent mitral valve replacement (MVR) with bMV between 2007 and 2017 was conducted. Cardiac-gated contrasted CT scans were obtained. Anticoagulant and antiplatelet therapy use were ascertained at the time of hospital discharge and CT scanning. Patient characteristics, postoperative stroke, and hemodynamic profile by echocardiogram were obtained to descriptively characterize the prevalence and characteristics associated with bMV HALT.ResultsThree patients (5.7%) were found to have a HALT on bMV. The mean time from index MVR to CT scan was 3.4 ± 0.8 years in HALT cohort and 3.4 ± 2.7 years in non-HALT cohort. Fifty patients (94.3%) were discharged on warfarin, and 37 patients (69.8%) were on warfarin at the time of CT scans. One patient with HALT was on therapeutic warfarin at the time of the CT scan that identified HALT. All three patients were asymptomatic at the time of CT scan. In patients with HALT, mean transmitral pressure gradient were 8, 5, and 2.7 mmHg, all with trivial or mild mitral regurgitation.ConclusionsIn this study, the prevalence of HALT was low at 5.7%, all presenting without symptoms. One patient presented with HALT while on therapeutic oral anticoagulation, which may suggest thrombotic etiology may not adequately explain HALT.

Apixaban Versus Dalteparin for Thromboprophylaxis in Patients with Acute Spinal Cord Injury: A Pilot Study

Background: Patients with acute spinal cord injury (SCI) have a high risk of venous thromboembolism despite thromboprophylaxis. Low molecular weight heparin (LMWH), the current standard of care, is inconvenient for long term thromboprophylaxis, costly, and partially effective. Direct oral anticoagulants (DOACs) have been shown to be at least as effective and as safe as LMWH in other thromboprophylaxis settings but there is no randomized evaluation of DOACs in this population. Aim: By conducting a feasibility randomized trial, we aimed to determine the likely recruitment rate of eligible patients into an RCT in which patients with acute SCI were randomized to a prophylactic dose of LMWH or apixaban. Methods: A pilot study was performed at Hamilton General Hospital (HGH). Adult patients with an acute traumatic SCI presenting to the hospital within 1 week of SCI and at least 36 h after the injury were included. Exclusion criteria were the need for therapeutic oral anticoagulation prior to enrolment; active bleeding, intracranial or peri-spinal hematoma, or a bleeding disorder; pregnancy or breastfeeding; severe renal failure (creatinine clearance ≤30 ml/min); severe cirrhosis (Child-Pugh class C); severe thrombocytopenia (platelets &lt;50), unsuitability as determined by the attending physician; geographic inaccessibility; failure to obtain written consent; previous hypersensitivity to study drugs; or expected short hospital admission (≤7 days) due to a minor injury. Eligible patients were randomized to apixaban 2.5 mg twice daily or dalteparin 5000 units once daily for 90 days or until fully mobilized, whatever came first. The primary feasibility outcome was recruitment rate per year. We expected a recruitment rate of 20 patients per year based on an estimated admission rate in a retrospective study at HGH. The primary efficacy outcome was a composite of symptomatic, objectively verified, venous thromboembolism (upper or lower limb deep vein thrombosis (DVT) and/or pulmonary embolism (PE)) or sudden death where PE cannot be excluded. This outcome did not include a catheter-associated DVT. The primary safety end-point was major bleeding. Results: A total of 26 eligible patients were screened and 8 patients were enrolled per year resulting in a recruitment yield of 30.8% (95% confidence interval: 16-50%). The reasons for exclusion included: presence of an epidural hemorrhage (n=8), failure to obtain consent (n=2), not suitable for the study (n=2), &gt;1 week from SCI (n=2), indication for therapeutic anticoagulation (n=2), active bleeding (n=1), and minor injury with an expected short hospital admission (n=1). Four patients were randomized to each drug. Median age was 61 (range 51 to 70) and 7 (87.5%) were males. There were no symptomatic VTE or sudden deaths. One patient randomized to apixaban had major bleeding. There were no serious adverse events. Conclusions: Our pilot study is the first randomized trial to examine the role of a DOAC compared with LMWH for thromboprophylaxis in this high-risk group. The primary feasibility outcome was not met, and therefore a multicenter RCT is unlikely to be feasible. The efficacy and safety of DOACs on this indication should be evaluated in registry- or health care database studies. Disclosures Eikelboom: Heart and Stroke Foundation: Research Funding; Sanofi Aventis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Glaxo Smith Kline: Honoraria, Research Funding; Eli Lilly: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria, Research Funding; Bayer: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding.

Oral Anticoagulation in Patients in the Emergency Department: High Rates of Off-Label Doses, No Difference in Bleeding Rates

BackgroundEmpirically, a significant proportion of patients using direct oral anticoagulation (DOAC) take off-label reduced doses. We aimed to investigate the prevalence, indications, dosages, and bleeding complications of oral anticoagulants on admission to the emergency department. MethodsIn this retrospective analysis, patients presenting to our emergency department between January 1 and December 31, 2018, with therapeutic oral anticoagulation were included (ie, vitamin-K antagonists, rivaroxaban, apixaban, edoxaban, and dabigatran). A detailed chart review was performed for each case concerning characteristics, indication, and bleeding complications. ResultsA total of 19,662 consecutive cases in the emergency department were reported: 1721 (9%) had therapeutic oral anticoagulation. Vitamin-K antagonists (41%), rivaroxaban (36%), and apixaban (19%) were the most common. Stroke prophylaxis in patients with atrial fibrillation (63.2%) and venous thromboembolism (24.1%) were the most common indications. In 27 cases (1.6%), no indication could be identified; further, 32% of patients were classified to have either off-label doses of DOACs or an international normalized ratio (INR) out of range (in vitamin-K antagonists), whereas 20% were classified as off-label underdosed and 12% as overdosed. No difference in the likelihood of bleeding on admission could be found between the respective drugs. Only concomitant use of aspirin was significantly associated with presence and higher severity of bleeding. ConclusionsVitamin-K antagonists are still the most widely used drug followed by rivaroxaban. A significant proportion of patients are being prescribed off label-doses. While no difference was found for the respective anticoagulants with respect to bleeding, concomitant aspirin use was a significant predictor for bleeding in our collective.

Oral anticoagulation and left atrial thrombi resolution in nonrheumatic atrial fibrillation or flutter: A systematic review and meta-analysis.

Oral anticoagulation (OAC) is prescribed for left atrial thrombi (LAT) in nonrheumatic atrial fibrillation (AF) and/or atrial flutter (AFL). The study objective was to review the existing evidence regarding LAT resolution in nonrheumatic AF and/or AFL with OAC agents. Data sources included PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) between January 1, 1991 and February 10, 2017. English-language studies that assessed LAT resolution with OAC agents in subjects with nonrheumatic AF and/or AFL, by serial transesophageal echocardiography, and with follow-up times ≥ 3weeks and<1 year, were selected. Study quality was assessed using recommendations adapted from the Agency for Healthcare Research and Quality. Pooled LAT resolution rates were evaluated for vitamin K antagonist (VKA) studies and low risk of bias warfarin studies. The pooled LAT resolution rate of 619 subjects from 16 VKA studies was 63.7% (95% confidence interval [CI], 53.3%-72.9%). The pooled LAT resolution rate of 94 subjects from four studies that specified warfarin use, exclusion of prior long-term therapeutic OAC, and target international normalized ratio (INR) ≥ 2.0 and/or average achieved INR ≥ 2.0 was 79.3% (95% CI, 69.8%-86.4%). Two studies in direct-acting oral anticoagulants (DOACs) reported LAT resolution rates of 89.5% (17 of 19) for dabigatran and 41.5% (22 of 53) for rivaroxaban. Warfarin is the most studied initial OAC agent for treating LAT in nonrheumatic AF and/or AFL with a resolution rate of nearly 80%. Further studies in DOACs are warranted.

Oral anticoagulation and platelet inhibition after atrial appendage occlusion

In Europe left atrial appendage occluders (LAAO) are most frequently used in patients with contraindications for oral anticoagulation (OAC); therefore, the classical therapeutic OAC scheme from the PROTECT-AF trial (vitaminK antagonist plus acetylsalicylic acid) is usually changed to dual anti-platelet therapy (DAPT) after implantation of aWatchman® or Amulet® LAAO (St. Jude Medical/Abbott, Eschborn, Germany). For many years, patients with an LAAO received DAPT for 1-6months. The current standard comprises DAPT for 3months, followed by permanent acetylsalicylic acid monotherapy if the transesophageal echocardiogram excludes athrombus at the site of the LAAO. In patients with high risk of bleeding, anti-platelet therapy can be stopped at 3months after an individual risk-benefit calculation. There are no randomized studies on the risk of bleeding and stroke/embolism in patients with an LAA occluder under DAPT versus OAC. Experience from the EWOLUTION registry shows that NOACs may be used as an alternative with low bleeding and thrombus risks. In patients with a suboptimal implantation result, thrombus on the LAAO or specific risk factors, variations of the standard scheme have to be applied and if necessary lifelong DAPT or NOAC therapy has to be used. Thrombi on the LAAO occur in approximately 4-6% of patients and are associated with avery low short-term stroke risk.

Impact of pre-admission oral anticoagulation on ischaemic stroke volume, lesion pattern, and frequency of intracranial arterial occlusion in patients with atrial fibrillation.

Therapeutic oral anticoagulation on hospital admission reduces morbidity and mortality after acute ischaemic stroke in patients with atrial fibrillation (AF). The underlying mechanism is not fully understood. In order to assess the impact of INR-level on admission on stroke volume, lesion pattern and the frequency of intracranial arterial occlusion, we analysed serial MRI measurements in AF patients suffering acute ischaemic stroke. This subgroup analysis of the prospective '1000Plus' study included patients with acute ischaemic stroke and known AF or a first episode of AF in hospital. All patients underwent serial brain magnetic resonance imaging. Stroke patients were categorized as follows: Group1, phenprocoumon intake, international normalized ratio (INR) ≥1.7 on admission, no thrombolysis; Group2, INR < 1.7 on admission, thrombolysis; and Group3, INR < 1.7, no thrombolysis. In 98 AF patients {77 ± 9 years, 60% male; median National Institute of Health Stroke Scale [NIHSS] score on admission 5 (interquartile range [IQR] 2-8)} with known AF before admission, territorial infarction was less often found in Group 1 (n = 20) compared with Group 2 + 3 (20% vs. 47%, P = 0.022). Arterial occlusion rate on admission differed among groups (30%, 75%, and 35%, respectively, P = 0.004) but not between Group 1 vs. Group 2 + 3 (30% vs. 45%, P = 0.31). Median FLAIR volume on Days 5-7 was lower in Group1 compared with Group 2 (n = 20) [3.2 cm3 (IQR 1.1-11.3) vs. 18.6 cm3 (IQR 8.2-49.4); P = 0.009] but not compared with Group 2 + 3 [7.8 cm3 (IQR 1.6-25.9); P = 0.23]. An INR ≥ 1.7 on admission was not associated with smaller stroke volume in multivariable regression analysis. Adding 57 patients with a first AF episode during the in-hospital stay, similar results were observed in 155 AF patients. In this AF cohort, an INR ≥ 1.7 at stroke onset affects lesion pattern but does not affect significantly lower stroke volume and the frequency of arterial occlusion on admission.

Risk of Stroke and Recurrence After AF Ablation in Patients With an Initial Event-Free Period of 12 Months.

Because of the unclear prognostic effects of ablation of atrial fibrillation (AF), oral anticoagulation (OAC) is often continued after ablation even in asymptomatic patients. We sought to determine the frequency of stroke and AF recurrence in patients on and off therapeutic OAC 1 year after a successful AF ablation. Patients that underwent AF ablation and were free of AF 12 months after ablation were selected from our AF database. During follow-up (FU), patients were screened for recurrence of AF, changes in OAC or antiarrhythmic medication, and the occurrence of stroke or transient ischemic attack (TIA). A total of 398 patients (median age 60.7 years [50.8, 66.8], 25% female) were investigated. The median duration of FU was 529 (373, 111,3.5) days. OAC was discontinued in 276 patients (69.3%). During FU, 4 patients (1%) suffered from stroke and 55 patients (13.8%) experienced a recurrence of AF. Persistent AF was significantly associated with a greater chance of AF recurrence (49.1% vs. 26.8%; P = 0.001). Neither CHADS2 nor CHA2DS2-VASc-Score nor recurrence of AF were significantly different in patients with or without stroke. There was a trend toward a higher percentage of coronary artery disease among patients that experienced stroke (50% vs. 10%; P = 0.057). The overall risk of stroke and AF recurrence is low in patients with a recurrence free interval of at least 12 months after AF ablation. Of note, recurrence of AF was not associated with a higher risk of stroke in our study population.

Incidence and Risk Factors for Venous Thromboembolism in Patients with Spinal Cord Injury: A Retrospective Study

Introduction: The true incidence of venous thromboembolism (VTE) in patients with acute spinal cord injury (SCI) is unclear. The management of thromboprophylaxis varies among clinicians and is challenging due to the balance against bleeding. There is limited data on the risk factors associated with VTE in patients with an acute SCI.Methods: We performed a retrospective chart review of consecutive adult patients with acute traumatic or non-traumatic SCI presenting within 1 week of injury from 2009 to 2015. We excluded patients who were already on therapeutic oral anticoagulation, those who had a short hospital admission (<7 days), and patients who had early transfer to a different hospital location (<30 days from the initial admission). The primary outcome was incidence of symptomatic, objectively verified deep vein thrombosis (DVT) and/or pulmonary embolism (PE) within 90 days. Secondary outcomes were major bleeding, all-cause mortality, and fatal PE. Step-wise cox modeling analyses were used to identify risk factors for VTE.Results: A total of 211 eligible patients were initially screened and 60 patients were excluded: 34 patients had short hospital admissions, 17 were transferred to a different hospital location (median time of 11 days, range 5 to 29 days), 3 had another reason for admission, and 6 patients were already on therapeutic anticoagulation. The remaining 151 patients with acute SCI were analyzed. Median age was 51 (range 17 to 91 years) and 106 (70%) were males. Patients were followed for a median of 90 days (range 1 to 90 days) and the median length of hospital stay was 79 days (range 1 to 90 days). Hundred and eleven patients (73.5%) had paraplegia or tetraplegia, 10 patients (6.6%) had no neurological impairment, and the degree of impairment was unspecified in 30 patients (19.9%). A total of 112 patients (74.2%) had a traumatic SCI with a fracture, 34 (22.5%) had a traumatic SCI without a fracture, and 5 (3.3%) had a non-traumatic SCI. Ninety four patients (62.2%) had a SCI alone versus 57 (37.8%) who had other sites of injury in addition to a SCI. The median duration of thromboprophylaxis was 65 days (range 2 to 90 days). Majority of the patients (59.6%) received low-dose low-molecular-weight heparin (LMWH) either alone (85 of 151, 56.3%) or sequentially with warfarin (5 of 151, 3.6%) with international normalized ratio range of 2 to 3 compared to 48 patients (31.8%) who received increased intensity LMWH either alone (9 of 151, 6%) or sequentially with low-dose LMWH (39 of 151, 25.8%). Thirteen patients (8.6%) had no thromboprophylaxis. Of the 151 patients included in the analysis, 17 patients (11%) had symptomatic VTE (9 PEs, 6 lower extremity DVT, 1 upper extremity DVT, and 1 with both a DVT and PE). The median time of VTE occurrence was 18 days (range 2 to 65 days) (Figure 1). There was no statistical difference in rate of VTE between the standard prophylactic LMWH group compared to those who received increased intensity LMWH (13.3% versus 8.3%, respectively; odds ratio [OR] 0.59, 95% confidence interval [CI], 0.13-2.1, p = 0.58). Six patients (4%) had major bleeding and none had a fatal PE. The median time of major bleeding occurrence was 17 days (range 8 to 40 days). The all-cause mortality rate was 13.9%. The median time of all-cause death was 6 days (range 1 to 61 days). In the univariate analyses, male sex (OR 14.95; 95% CI, 1.05-49.1, p = 0.003) and having other sites of injuries along with SCI (OR 2.6; 95% CI. 0.8- 8.7, p = 0.049) were significantly associated with the risk of VTE. In stepwise Cox modeling, independent contributors to risk for VTE were other sites of injuries (hazard ratio [HR] 6.07), age (HR 1.05 per year) and to some extent the presence of leg paresis/para- or tetraplegia (HR 2.7), whereas hypertension appeared to reduce the risk (HR 0.18). The gender variable could not be included due to zero events for females.Conclusions: Symptomatic VTE is still today a frequent complication in patients with acute SCI and can occur early after injury. Male sex, age and presence of other sites of injuries along with SCI were independent risk factors for symptomatic VTE. Future randomized trials assessing the role of direct oral anticoagulants versus the current standard of care using low-dose LMWH among these higher risk patients are needed. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Effect of anticoagulation on cardioembolic stroke severity, outcomes and response to intravenous thrombolysis.

Our objective was to evaluate the effect of anticoagulation on cardioembolic stroke (CS) severity, outcomes, and response to intravenous thrombolysis (IVT). Observational study of CS patients admitted to a Stroke Center (2010-2013). The sample was classified into three groups based on pre-stroke oral anticoagulants (OAC) treatment (all acenocumarol) and the international normalized ratio (INR) on admission: (1) non-anticoagulated or anticoagulated patients with INR <1.5, (2) anticoagulated with INR 1.5-1.9 and (3) anticoagulated with INR ≥2. We compared demographic data, vascular risk factors, symptomatic intracranial hemorrhage, severity on admission (NIHSS) and 3 month outcomes (mRS). Overall 475 patients were included, 47.2% male, mean age 75.5 (SD 10.7) years old, 31.8% were on OAC. 76% belonged to the INR <1.5 group, 13.3% to the INR 1.5-1.9 and 10.5% to the INR >2. 35%of patients received IVT. Multivariate analyses showed that an INR ≥2 on admission was a factor associated with a higher probability of mild stroke (NIHSS <10) (OR 2.026, 95% CI 1.006-4.082). Previous OAC in general (OR 2.109, 95% CI 1.173-3.789) as well as INR 1.5-1.9 (OR 3.676, 95% CI 1.510-8.946) were associated with favorable outcomes (mRS ≤2). OAC was not related to stroke outcomes in the subgroup of IVT patients. Therapeutic OAC levels are associated with lesser CS severity, and prior OAC treatment with favorable outcomes. In this study, OAC are not related with response to IVT.