Incidence Of Hemorrhagic Events Research Articles

Optimal antiplatelet therapy after revascularization of left subclavian artery during TEVAR

BackgroundThoracic endovascular aortic repair (TEVAR) is a minimally invasive technique used to treat type B aortic dissections. Left subclavian artery (LSA) reconstruction is required when treating patients with involvement of LSA. The best antiplatelet therapy after LSA reconstruction is presently uncertain.MethodsThis study retrospectively analyzed 245 type B aortic dissection patients who underwent left subclavian artery revascularization during TEVAR. Out of 245 patients, 159 (64.9%) were in the single antiplatelet therapy (SAPT) group, receiving only aspirin, and 86 (35.1%) were in the dual antiplatelet therapy (DAPT) group, receiving aspirin combined with clopidogrel. During the 6-month follow-up, primary endpoints included hemorrhagic events (general bleeding and hemorrhagic strokes), while secondary endpoints comprised ischemic events (left upper limb ischemia, ischemic stroke, and thrombotic events), as well as death and leakage events. Both univariate and multivariate Cox regression analyses were performed on hemorrhagic and ischemic events, with the Kaplan-Meier method used to generate the survival curve.ResultsDuring the six-month follow-up, the incidence of hemorrhagic events in the DAPT group was higher (8.2% vs. 30.2%, P < 0.001). No significant differences were observed in ischemic events, death, or leakage events among the different antiplatelet treatment schemes. Multivariate Cox regression analysis showed that DAPT (HR: 2.22, 95% CI: 1.07–4.60, P = 0.032) and previous chronic conditions (HR:3.88, 95% CI: 1.24–12.14, P = 0.020) significantly affected the occurrence of hemorrhagic events. Chronic conditions in this study encompassed depression, vitiligo, and cholecystolithiasis. Carotid subclavian bypass (CSB) group (HR:0.29, 95% CI: 0.12–0.68, P = 0.004) and single-branched stent graft (SBSG) group (HR:0.26, 95% CI: 0.13–0.50, P < 0.001) had a lower rate of ischemic events than fenestration TEVAR (F-TEVAR). Survival analysis over 6 months revealed a lower risk of bleeding associated with SAPT during hemorrhagic events (P = 0.043).ConclusionsIn type B aortic dissection patients undergoing LSA blood flow reconstruction after synchronous TEVAR, the bleeding risk significantly decreases with the SAPT regimen, and there is no apparent ischemic compensation within 6 months. Patients with previous chronic conditions have a higher risk of bleeding. The CSB group and SBSG group have less ischemic risk compared to F-TEVAR group.

Relation between duration of dual antiplatelet therapy and risk of ischemic stroke after stent-assisted treatment of cerebral aneurysm (DAPTS ACE-registry)

BackgroundThe optimal duration of dual antiplatelet therapy (DAPT) in patients with cerebral aneurysm who undergo stent-assisted coil embolization (SACE) has not been established. We aimed to clarify the association between...

Vascular compactness of unruptured brain arteriovenous malformation predicts risk of hemorrhage after stereotactic radiosurgery

The aim of the study was to investigate whether morphology (i.e. compact/diffuse) of brain arteriovenous malformations (bAVMs) correlates with the incidence of hemorrhagic events in patients receiving Stereotactic Radiosurgery (SRS) for unruptured bAVMs. This retrospective study included 262 adult patients with unruptured bAVMs who underwent upfront SRS. Hemorrhagic events were defined as evidence of blood on CT or MRI. The morphology of bAVMs was evaluated using automated segmentation which calculated the proportion of vessel, brain tissue, and cerebrospinal fluid in bAVMs on T2-weighted MRI. Compactness index, defined as the ratio of vessel to brain tissue, categorized bAVMs into compact and diffuse types based on the optimal cutoff. Cox proportional hazard model was used to identify the independent factors for post-SRS hemorrhage. The median clinical follow-ups was 62.1 months. Post-SRS hemorrhage occurred in 13 (5.0%) patients and one of them had two bleeds, resulting in an annual bleeding rate of 0.8%. Multivariable analysis revealed bAVM morphology (compact versus diffuse), bAVM volume, and prescribed margin dose were significant predictors. The post-SRS hemorrhage rate increased with larger bAVM volume only among the diffuse nidi (1.7 versus 14.9 versus 30.6 hemorrhage per 1000 person-years in bAVM volume < 20 cm3 versus 20–40 cm3 versus > 40 cm3; p = 0.022). The significantly higher post-SRS hemorrhage rate of Spetzler-Martin grade IV–V compared with grade I–III bAVMs (20.0 versus 3.3 hemorrhages per 1000 person-years; p = 0.001) mainly originated from the diffuse bAVMs rather than the compact subgroup (30.9 versus 4.8 hemorrhages per 1000 person-years; p = 0.035). Compact and smaller bAVMs, with higher prescribed margin dose harbor lower risks of post-SRS hemorrhage. The post-SRS hemorrhage rate exceeded 2.2% annually within the diffuse and large (> 40 cm3) bAVMs and the diffuse Spetzler-Martin IV–V bAVMs. These findings may help guide patient selection of SRS for the unruptured bAVMs.

Comparison of early and delayed anticoagulation therapy after ischemic stroke in patients with atrial fibrillation: a systematic review and meta-analysis.

The optimal initiation timing of oral anticoagulants (OACs) remains controversial in patients with atrial fibrillation (AF)-related acute ischemic stroke (AIS). The aim of this study is to compare the efficacy and safety of early OACs initiation with that of the delayed initiation for AIS and AF.We searched systematically the following mainstream databases: PubMed, Embase, and Web of Science from the inception to July 2023 for studies that compared the early initiation with the delayed initiation of OACs for AF-related AIS patients. Outcome measures were the incidence of hemorrhagic events, ischemic events, and combined outcomes, as well as all-cause mortality.There were 12 eligible articles included (10 cohort studies and 2 RCT), involving 11421 patients (5690 patients in the early-initiation group and 5731 in the delayed-initiation group). Meta-analysis revealed that patients receiving OACs at the early stage of stroke had a lower incidence of ischemic events (OR: 0.68; 95% CI: 0.55,0.84; p = 0.0003) and combined outcomes (OR=0.74, 95% CI (0.57,0.95), p=0.02). No significant differences were identified in the incidence of hemorrhagic events (p = 0.26) and all-cause mortality ( p = 0.20) between the groups.Early initiation of anticoagulation therapy would be preferable in lowering the incidence of ischemic events and combined outcomes in AIS patients with AF. It is safe compared to the delayed-initiation strategy. However, the conclusion of this study needs to be further validated by more well-designed RCTs.

Intracranial Bleeding in Deep Brain Stimulation Surgery: A Systematic Review and Meta-Analysis

Background: Deep brain stimulation (DBS) is a neurosurgical treatment used for the treatment of movement disorders. Surgical and perioperative complications, although infrequent, can result in clinically significant neurological impairment. Objectives: In this study, we evaluated the incidence and risk factors of intracranial bleeding in DBS surgery. Method: Medline, EMBASE, and Cochrane were screened in line with PRISMA 2020 guidelines to capture studies reporting on the incidence of hemorrhagic events in DBS. After removing duplicates, the search yielded 1,510 papers. s were evaluated by two independent reviewers for relevance. A total of 386 abstracts progressed to the full-text screen and were assessed against eligibility criteria. A total of 151 studies met the criteria and were included in the analysis. Any disagreement between the reviewers was resolved by consensus. Relevant data points were extracted and analyzed in OpenMeta [Analyst] software. Results: The incidence of intracranial bleeding was 2.5% (95% CI: 2.2–2.8%) per each patient and 1.4% (95% CI: 1.2–1.6%) per each implanted lead. There was no statistically significant difference across implantation targets and clinical indications. Patients who developed an intracranial bleed were on average 5 years older (95% CI: 1.26–13.19), but no difference was observed between the genders (p = 0.891). A nonsignificant trend was observed for a higher risk of bleeding in patients with hypertension (OR: 2.99, 95% CI: 0.97–9.19) (p = 0.056). The use of microelectrode recording did not affect the rate of bleeding (p = 0.79). Conclusions: In this review, we find that the rate of bleeding per each implanted lead was 1.4% and that older patients had a higher risk of hemorrhage.

Hemorrhage Risk after Stereotactic Radiosurgery for Patients with Unruptured Brain Arteriovenous Malformation: Significance of Vascular Compactness

<h3>Purpose/Objective(s)</h3> Our purpose was to investigate whether the morphology (i.e., compact/ diffuse) of brain arteriovenous malformations (bAVMs) correlates with the incidence of hemorrhagic events in patients with unruptured bAVMs after receiving non-invasive stereotactic radiosurgery (SRS). <h3>Materials/Methods</h3> This study retrospectively included 264 adult patients with unruptured bAVMs undergoing upfront SRS from multi-institutions. Two senior neurosurgeons confirmed the unruptured presentation. The follow-ups were performed in a 6-month interval. Hemorrhagic events were defined as bleeding signs on computed tomography (CT) or magnetic resonance images (MRI). The morphology of bAVMs was evaluated using fully automated segmentation, which calculated the proportion of vessel, brain tissue, and cerebrospinal fluid in bAVMs on T2-weighted MRI. Compactness index, defined as a ratio of vessel to brain tissue, was proposed and further dichotomized based on Youden indices to classify the bAVMs into compact or diffuse type. Cox proportional hazard model was used to identify the independent factors for the occurrence of post-SRS hemorrhage. <h3>Results</h3> The median follow-up duration was 62.1 months. Post-SRS hemorrhage occurred in 14 (5.3%) patients with 2 bAVMs bleeding twice, incurring an annual bleeding risk of 0.9%. Multivariable analysis with stepwise backward variable selection method revealed that bAVM morphology (compact versus diffuse), bAVM volume and prescribed margin dose were significant predictors for post-GKRS hemorrhage. The incidence density of post-GKRS hemorrhage in the compact and diffuse bAVMs were 4.9 and 11.8 (hemorrhagic events/ 1000 person-years (P-Ys)). Among the diffuse bAVMs (n=153), the post-GKRS hemorrhage rate was lower for smaller bAVM volume, <15ml versus 15-30ml versus >30ml (2.2 versus 13.5 versus 26.3 hemorrhagic events/ 1000 P-Ys; p=0.044) and for bAVMs receiving margin dose >16.6 Gy versus <16.6 Gy (5.2 versus 25.8 hemorrhagic events/ 1000 P-Ys; p=0.004). For the compact bAVMs (n=111), the post-GKRS hemorrhage rate was not significantly different between the dose and volume groups. <h3>Conclusion</h3> Compact and smaller bAVMs, with higher prescribed margin dose harbor lower risks of post-SRS hemorrhage. Among the diffuse bAVMs, post-GKRS hemorrhage risk varied with bAVM volume and margin dose. The finding could help guide GKRS treatment decision-making for the unruptured bAVMs.

Incidence of Venous Thromboembolism in Hospitalized COVID-19 Patients Receiving Thromboprophylaxis.

The purpose of this study was to investigate the association between anticoagulant dosing intensity in coronavirus disease 2019 (COVID-19) infected patients and its outcomes on venous thromboembolism (VTE) and all-cause mortality. This is a retrospective observational study that examined different anticoagulation regimens among COVID-19 patients for prophylaxis of VTE. Primary outcomes of the study were VTE incidence and all-cause mortality for patients receiving prophylaxis-intensity (PPX) and therapeutic-intensity (TX) anticoagulation. Secondary outcomes were incidence of hemorrhagic events and hospital length of stay. Patients were matched (1:1) based on age and Charlson comorbidity score. Sub-group analyses evaluated outcomes within critically ill patients, between specific anticoagulant agents and comorbid conditions. The primary outcome of VTE occurred in six patients within the prophylactic dose group and eight patients in the therapeutic-intensity dose group (risk ratio (RR): 2.02 (95% confidence interval (CI): 0.7 - 5.2); P = 0.2). Bleeding occurred in 15 (11%) patients in the prophylactic group and 27 (19%) patients in the therapeutic group (RR: 0.5 (95% CI: 0.3 - 1.0); P < 0.049). Hospital length of stay was shorter by 4 days in those treated with prophylactic-intensity anticoagulation (P = 0.003). Intensive care unit admission and ventilation were negatively correlated with mortality in a multivariate analysis. Among hospitalized COVID-19 patients, the use of therapeutic-intensity anticoagulation did not show any benefits in reducing the occurrence of VTE. An increase in mortality and in the incidence of hemorrhagic events was statistically significant in the therapeutic-intensity group. Future prospective studies are warranted to evaluate anticoagulation therapy in COVID-19 infected patients.

Effect of ABCB1 gene variants on rivaroxaban pharmacokinetic and hemorrhage events occurring in patients with non-valvular atrial fibrillation.

Hemorrhage events occur most frequently in anticoagulant therapy for non-valvular atrial fibrillation (NVAF). Rivaroxaban is used widely for routine anticoagulation care. Genetic polymorphisms are thought to contribute to the wide intraindividual variability seen in rivaroxaban metabolism and the anticoagulant response. The aim of this study was to evaluate the effect of drug transport related single-nucleotide polymorphisms (SNPs) on rivaroxaban metabolism and on the risk of a hemorrhage event. A total of 216 Chinese patients with NVAF were enrolled in the study. Rivaroxaban was used for anticoagulation therapy. Rivaroxaban plasma concentrations were detected using a validated ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Seven SNPs in four genes were genotyped using the Sanger dideoxy DNA sequencing method. Associations between genotype variants, the incidence of hemorrhage events, and the time of bleeding were analyzed. ABCB1 2677G (rs2032582) variation was highly associated with the dose-adjusted rivaroxaban peak concentration in plasma (Cmax /D) (p=0.025, FDR=0.042). The ABCB1 G allele carriers had a higher rivaroxaban Cmax /D than non-carriers. Logistic regression showed that rivaroxaban Cmax /D and ABCB1 genotype variants were associated with a higher incidence of hemorrhage events. No statistically significant difference was found between ABCB1 genotypes and the time of bleeding after anticoagulant therapy in 30days. These results indicated that ABCB1 2677G (rs2032582) genetic variant affects the rivaroxaban Cmax /Dose and the incidence of hemorrhage events significantly.

Conventional Versus Minimally Invasive Aortic Valve Replacement Surgery: A Systematic Review, Meta-Analysis, and Meta-Regression.

Objective: To assess the potential benefits of minimally invasive aortic valve replacement (MIAVR) compared with conventional AVR (CAVR) by examining short-term outcomes. Methods: A systematic search identified randomized trials comparing MIAVR with CAVR. To assess study limitations and quality of evidence, we used the Cochrane Risk of Bias tool and GRADE and performed random-effects meta-analysis. We used meta-regression and sensitivity analysis to explore reasons for diversity. Results: Thirteen studies (1,303 patients) were included. For the comparison of MIAVR and CAVR, the risk of bias was judged low or unclear and the quality of evidence ranged from very low to moderate. No significant difference was observed in mortality, stroke, acute kidney failure, infectious outcomes, cardiac events, intubation time, intensive care unit stay, reoperation for bleeding, and blood transfusions. Blood loss (mean difference [MD] = -130.58 mL, 95% confidence interval [CI] = -216.34 to -44.82, I2 = 89%) and hospital stay (MD = -0.93 days, 95% CI = -1.62 to -0.23, I2 = 81%) were lower with MIAVR. There were shorter aortic cross-clamp (MD = 5.99 min, 95% CI = 0.99 to 10.98, I2 = 93%) and cardiopulmonary bypass (CPB) times (MD = 7.75 min, 95% CI = 0.27 to 15.24, I2 = 94%) in the CAVR group. In meta-regression analysis, we found that age was the variable with the greatest influence on heterogeneity. Conclusions: MIAVR seems to be an excellent alternative to CAVR, reducing hospital stay and incidence of hemorrhagic events. Despite significantly greater aortic cross-clamp and CPB times with MIAVR, this did not translate into adverse effects, with no changes in the results found with CAVR.

Role of ethnicity in thrombotic and hemorrhagic complications of myeloproliferative neoplasms.

e18555 Background: Philadelphia-chromosome negative myeloproliferative neoplasms (MPN) are a group of hematologic malignancies with known complications of hemorrhage and thrombosis. Age and a previous history of thrombosis are well-documented risk factors for future vascular events. Variations in the rates of these complications among ethnicities and sexes have not been extensively explored. Methods: Our retrospective analysis included 301 adult patients with a diagnosis of MPN without a history of thrombosis or hemorrhagic event seen at the Indiana University Simon Cancer Center between 1992 and 2019. Relationships between ethno-racial backgrounds and vascular complications and disease outcomes were evaluated using multivariate logistic regression analysis and Cox regression models. Results: Two hundred seventy-one patients (90.0%) were Caucasian and 30 patients (10.0%) were non-Caucasian. Non-Caucasian patients were comprised of African America, Asian, and Middle Eastern ethnicities. Median age at diagnosis was 56 years, and 43.9% were male. No association was found between the incidence of thrombotic complications and ethnicity using the log-rank test ( p 0.68). The incidence of hemorrhagic events was significantly increased in non-Caucasian patients (OR = 4.33; 95% CI [1.15 – 16.36], p 0.03). Patients with higher hemoglobin concentration at diagnosis were at a significantly lower risk of bleeding complications (OR = 0.79; 95% CI [0.65 – 0.95], p 0.01). Non-Caucasian patients were at 2.98 times (95% CI [1.19 – 7.44], p 0.02) higher risk when vascular complications were pooled together. Our models also showed that male sex (OR = 0.14; 95% CI [.02 – .98], p 0.048) and a higher platelet count at the time of diagnosis (OR = 0.99; 95% CI [.993 –.999], p 0.03) had a marginally significant association with decreased rate of progression to acute myeloid leukemia. Conclusions: This study suggests that in patients without a history of thrombosis or bleeding, non-Caucasian ethnicity was associated with an increased adjusted risk of hemorrhagic complications in patients with MPN. This observation may inform future studies to further characterize those disparities in outcomes at the genetic or socioeconomic level.

Five-Year Risk of Major Ischemic and Hemorrhagic Events After Intracerebral Hemorrhage.

Background and Purpose- We aimed to determine incidences and predictors of major vascular events in intracerebral hemorrhage (ICH) survivors. Methods- We did a prospective observational cohort study in patients with spontaneous ICH from the Prognosis of Intracerebral Hemorrhage cohort in Lille, France. We studied incidences and predictors of long-term vascular events (cerebral and extracerebral, ischemic and hemorrhagic) in patients alive at 30 days with a prespecified subgroup analysis according to ICH location. We performed multivariable analyses (competing risk analyses, with death during follow-up as a competing event). Results- From the 560 patients with spontaneous ICH enrolled between November 2004 and March 2009, we included 310 patients (median age, 70 years). Eighty-two patients presented at least 1 major vascular event leading to an incidence rate of 20.0% (95% CI, 15.7-24.7) at 5 years after ICH. In the overall cohort, ischemic events were more frequent than hemorrhagic events. However, the incidence strikingly differed according to ICH location: deep ICH was associated with future ischemic events (subhazard ratio, 1.85; 95% CI, 1.01-3.40), whereas lobar ICH with hemorrhagic events (subhazard ratio, 2.38; 95% CI, 1.17-4.86). In deep ICH, the incidence of ischemic events at 5 years was 6× higher than the incidence of hemorrhagic events. Conclusions- ICH survivors are at high risk of both cerebral and extracerebral vascular events. The ischemic or hemorrhagic risk profile varies according to the index ICH location with a stronger ischemic risk in deep ICH. Secondary prevention, tailored on ICH location, should target not only cerebral recurrences but also extracerebral vascular events.

Abstract WP367: Volume of Intracerebral Hemorrhage Varies According to the Kind of Anticoagulant: Direct Oral Anticoagulants vs Warfarin

Background and Hypothesis: The effectiveness and safety of anticoagulants, which are widely used for preventing stroke recurrence, in stroke prevention is well established, they rarely cause severe adverse events, such as intracerebral hemorrhage (ICH). Direct oral anticoagulants (DOACs) have recently become an option for anticoagulation therapy. The incidence of hemorrhagic events in patients under DOAC therapy has been investigated in several studies, but it is unclear whether the severity of a hemorrhagic event is influenced by the use of DOACs. We hypothesized that the severity of ICH is different in patients under warfarin versus those under DOAC therapy. Method: We retrospectively reviewed medical records and computed tomography images of patients with ICH who were treated at our hospital during April 2011-May 2016. Patients’ clinical characteristics and ICH volume and location were compared between warfarin- and DOAC-treated patients. Result: Of the 1147 patients with ICH, 114 patients were taking anticoagulants on admission. Eighty-nine patients (78.1%) received warfarin, whereas 25 (21.9%) received DOACs. The following DOACs were used: dabigatran (two patients), rivaroxaban (10 patients), apixaban (12 patients), and edoxaban (one patients). Median ICH volume was significantly lesser in DOAC-treated patients than in warfarin-treated patients [8.1 (range, 0.05-160) ml vs 15.9 (range, 0.1-119) ml, respectively; p = 0.048). A significant correlation between ICH volume and HAS-BLED score was found only in the DOACs group (ρ= 0.560 p = 0.004) but not in the warfarin group (ρ= 0.025 p = 0.822). We found two patients with an ICH volume of &gt;150 mL in the DOACs group. Their HAS-BLED score was 3, and they had experienced multiple stroke events (three or six times). Conclusion: ICH volume was lesser in DOAC-treated patients than in warfarin-treated patients. We also found that HAS-BLED can be a predictor of ICH volume in DOAC-treated patients.

Prophylactic Use of a Combination of an Anticoagulant and Ursodeoxycholic Acid for Sinusoidal Obstruction Syndrome after Allogeneic Myeloablative Hematopoietic Stem Cell Transplantation

Introduction:Sinusoidal obstruction syndrome (SOS) is one of the potentially fatal complications of hematopoietic stem cell transplantation (HSCT). In particular, severe SOS frequently leads to multiple organ failure, and a worse prognosis. Thus, prophylaxis against development of SOS could contribute improved survival after HSCT.Previous reports demonstrated the effectiveness of the prophylactic use of ursodeoxycholic acid (UDCA) or certain anticoagulants, including unfractionated and low-molecular-weight heparin, for SOS. In two randomized controlled trials and two meta-analyses it was reported that UDCA, a hydrophilic bile acid, was an effective and safe drug for prophylaxis against SOS. The usefulness and feasibility of prophylactic use of anticoagulants after allogeneic HSCT are however still controversial. In addition, to our knowledge no study has evaluated the feasibility of usage of UDCA combined with an anticoagulant for SOS prevention after allogeneic HSCT in adult patients.To assess the efficacy and safety of use of UDCA combined with an anticoagulant as SOS prophylaxis, we performed a retrospective cohort study to examine the occurrences of SOS and hemorrhagic events in patients who underwent myeloablative allogeneic HSCT at our institution. We examined use of any anticoagulant together with simultaneous administration of UDCA, in comparison with UDCA alone for the prevention of SOS.Patients and methods:We reviewed the charts of consecutive adult patients in whom myeloablative allogeneic HSCT was performed at our hospital from November 1994 to May 2014, and who received either unfractionated heparin or dalteparin (low-molecular-weight heparin) with UDCA (group 1), danaparoid with UDCA (group 2), or UDCA only (group 3), used for prophylaxis against SOS.Results:A total of 280 patients (group 1: n=52; group 2: n=33; and group 3: n=195) were investigated. The proportions of patients with risk factors for SOS-including non-remission at the time of HSCT, a second or subsequent HSCT, high aspartate aminotransferase (AST) levels before HSCT, high ferritin levels before HSCT, a history of receiving gemtuzumab ozogamicin, and HLA disparity-were similar across the three groups. In group 1, a conditioning regimen containing busulfan was used less frequently (P = 0.002).SOS occurred in seven patients (13.7%) in group 1, five patients (15.2%) in group 2, and 28 patients (14.4%) in group 3, all meeting the Seattle criteria. None of the patients in group 1, two (6.1%) in group 2, and nine (4.6%) in group 3 had SOS diagnosed according to the Baltimore criteria. There was no significant difference in the incidence of SOS among the three groups. In addition, with regard to the cumulative incidence of severe SOS, no statistically significant difference was present among the three groups. The incidence of hemorrhagic events within 30 and 100 days following allogeneic HSCT was not significantly different across the three groups (30 days; 5.8%, 3.0%, 5.1%, P = 0.843, 100 days; 17.6%, 15.2%, 14.4%, P=0.843, respectively). Furthermore, the probabilities of OS and NRM until day 100 after allogeneic HSCT were similar among the three groups (P = 0.733 and P = 0.637, respectively).In a univariate model, a history of gemtuzumab ozogamicin treatment, high serum ferritin levels before HSCT, an HLA mismatched donor, and non-complete remission of disease at the time of allogeneic HSCT were found to be significant risk factors for SOS. Multivariate analysis revealed that a history of gemtuzumab ozogamicin therapy, a mismatched HLA donor, and non-complete remission of disease at the time of allogeneic HSCT were significant and independent risk factors for SOS. In the multivariate as well as univariate analyses, combined administration of UDCA and any anticoagulant for SOS prophylaxis did not have a significant effect on the incidence SOS, when compared to prophylaxis with UDCA alone.Conclusion:Our study results suggest that the combined use of UDCA and an anticoagulant for SOS prophylaxis after myeloablative allogeneic HSCT in adult patients was not beneficial. Establishment of an optimal strategy for prophylaxis against SOS after HSCT is still needed. DisclosuresNakane:Mundipharma KK: Research Funding. Koh:Pfizer: Consultancy, Honoraria. Hino:Pfizer: Honoraria, Research Funding; Nippon Shinyaku: Honoraria, Speakers Bureau; Alexion: Honoraria, Research Funding. Nakamae:Mochida Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Novartis Pharma KK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel/accommodation/meeting expenses, Research Funding.

Status of oral anticoagulant treatment in patients with nonvalvular atrial fibrillation in Spain. REACT-AF study

Background and objectivesOral anticoagulant therapy is complex due to the need for control and the hemorrhagic risk the therapy entails. This study aims to determine the standard clinical practice in the treatment for preventing stroke in patients with nonvalvular atrial fibrillation (NVAF) in Spain. Patients and methodThe Real Evidence of Anti Coagulation Treatment in AF is a European, multicenter, multinational, observational, retrospectively monitored cohort of patients with NVAF. This study included patients recruited in Spain with at least one visit during the period of inclusion (May 2010/April 2012). The study evaluated the following: (a) persistence of oral anticoagulant treatment (time to discontinuation); (b) persistence rate (% of patients in treatment) at 6, 12 and 24 months and at 5 years; (c) therapeutic compliance (medication possession ratio); (d) the correlation between the treatment followed and that recommended by the European Society of Cardiology; and the incidence of stroke and hemorrhagic events. ResultsThe patients treated with oral anticoagulants (n=7526) had a median time to discontinuation of treatment of 1.99 years and a persistence rate at 5 years of 26% (discontinuation ≥3 months). The compliance (mean MPR) was 0.54±0.36. The incidence of stroke was 0.3/100 person-years, and the incidence of hemorrhagic events was 2.4/100 person-years. Fifty-eight percent of the patients with NVAF (n=12,514) followed the recommendations of the European Society of Cardiology. ConclusionForty-two percent of the patients with NVAF did not follow the recommendations of the European Society of Cardiology. We detected low persistence and treatment compliance rates for oral anticoagulants.

Abstract 17101: Low-intensity Anticoagulant Treatment in Chinese Patients with Mechanical Heart Valve Prostheses: Early Outcomes of a Prospective, Multicenter Registry in China

Background: Current guidelines recommend vitamin K antagonist treatment with relatively higher international normalized ratio (INR) targets for patients with mechanical heart valve prostheses. However, there is lack of data from large clinical trials about the outcomes of low-intensity anticoagulant treatment in Chinese patients with mechanical heart valves. Methods: The Low-intensity Anticoagulation Therapy after Heart Valve Replacement is an ongoing multicenter, prospective, observational cohort study (ChiCTR-OCH-10001185). Between January 2011 and August 2013, qualified patients from 34 cardiac centers in China mainland were recruited in the Anticoagulation Therapy Database of Chinese Patients after Heart Valve Replacement. Baseline characteristics were collected and patients were followed up for anticoagulant treatment, INRs and adverse events till March 2014. Results: The database recruited 11,769 patients, and 11,040 patients (93.8%) undergoing mechanical heart valve replacement were analyzed in this study. The mean age was 48.9±11.5 years and 6,227 patients (56.4%) were female. A total of 9,870 patients (89.4%) of the baseline population completed at least 6 months follow-up. The median follow-up time was 1.2 years (range 0.5-2.2). For all 9,870 patients, 143,115 measurements of the INR were obtained. The average warfarin dosage was 2.98±1.16mg/d and the mean INR was 1.81±0.46, and 88.7% patients had an INR level≤2.5 during the follow-up period. The incidence of hemorrhagic events was the lowest in patients with an INR≤2.0, whereas the risk of thromboembolic complications in this group of patients was not significantly increased (Table 1). Conclusions: Low-intensity anticoagulation with an INR of 1.5 to 2.5 is safe and effective for Chinese patients with mechanical heart valves in short-term. The optimal INR targets for mechanical valve recipients with different implanting positions and risk factors require further investigation.

Situación del tratamiento anticoagulante oral en pacientes con fibrilación auricular no valvular en España. Estudio REACT-AF

Background and objectivesOral anticoagulant therapy is complex due to the need for control and the hemorrhagic risk the therapy entails. This study aims to determine the standard clinical practice in the treatment for preventing stroke in patients with nonvalvular atrial fibrillation (NVAF) in Spain. Patients and methodThe Real Evidence of Anti Coagulation Treatment in AF is a European, multicenter, multinational, observational, retrospectively monitored cohort of patients with NVAF. This study included patients recruited in Spain with at least one visit during the period of inclusion (May 2010/April 2012). The study evaluated the following: a) persistence of oral anticoagulant treatment (time to discontinuation); b) persistence rate (% of patients in treatment) at 6, 12 and 24 months and at 5 years; c) therapeutic compliance (medication possession ratio); d) the correlation between the treatment followed and that recommended by the European Society of Cardiology; and the incidence of stroke and hemorrhagic events. ResultsThe patients treated with oral anticoagulants (n=7,526) had a median time to discontinuation of treatment of 1.99 years and a persistence rate at 5 years of 26% (discontinuation ≥3 months). The compliance (mean MPR) was 0.54±0.36. The incidence of stroke was 0.3/100 person-years, and the incidence of hemorrhagic events was 2.4/100 person-years. Fifty-eight percent of the patients with NVAF (n=12,514) followed the recommendations of the European Society of Cardiology. ConclusionForty-two percent of the patients with NVAF did not follow the recommendations of the European Society of Cardiology. We detected low persistence and treatment compliance rates for oral anticoagulants.

Abstract T P58: Early Anticoagulant Therapy for Secondary Stroke Prevention in Japanese NVAF Patients With TIA/minor Stroke: The SAMURAI-NVAF Study

Objective: Early anticoagulant therapy is commonly used for acute cardioembolic stroke in Japan, although its usefulness remains undetected. The purpose of this study was to estimate the efficacy and safety of early anticoagulation for the treatment of acute stroke/TIA patients with nonvalvular atrial fibrillation (NVAF). Methods: From September 2011 through June 2013, 697 acute ischemic stroke/TIA patients with NVAF were registered from a multicenter prospective registry (the SAMURAI-NVAF study including 18 Japanese stroke centers, NCT01581502). Of those, the patients who started anticoagulant therapy within 48 hours after the onset were assessed for the incidence of ischemic and hemorrhagic events during the first 30 days. Results: A total of 438 patients (62.8%; 247 men, 77.4±9.8 years old) was evaluated. Of these, 292 patients (66.7%) started anticoagulation with intravenous unfractionated heparin (UFH) mono-therapy, 87 patients (19.9%) with UFH and warfarin, and 2 patients (0.5%) with UFH switched to novel oral anticoagulants (NOACs). As oral anticoagulants mono-therapy, 34 patients (7.8%) started with warfarin, and 23 (5.3%) with NOAC. Ischemic events were developed in 11 patients (2.5%: 11 recurrent ischemic strokes), and hemorrhagic events in 11 patients (2.5%: 6 symptomatic intracranial hemorrhages during the first 7days and 5 extracranial hemorrhages). Patients with major artery occlusion had higher incidence of hemorrhagic events than those without (4.0% versus 0.6%, p=0.02), whereas ischemic events were similar in both groups (2.4% versus 2.7%, p=0.82). In multivariable analysis, major artery occlusion was independently associated with higher rate of major hemorrhagic events (OR 6.19; 95% CI 1.01-119.75) adjusted for age, sex, BMI, HAS-BLED score before index TIA/stroke, and NIHSS on admission. Conclusion: In our cohort, early initiation of anticoagulant therapy is often performed in patients with acute stroke/TIA with NVAF patient, and the frequency of ischemic and hemorrhagic events seems to be low compared with previous reports. Early anticoagulant therapy can be safe for patients without major artery occlusion.

Enteric-Coated Aspirin Versus Other Antiplatelet Drugs in Acute Non-Cardioembolic Ischemic Stroke: Post-marketing Study in Japan

Japanese guidelines recommend aspirin 160-300mg/day, starting within 48h, for patients with acute cerebral infarction. However, there are few reports evaluated in Japanese patients. Our objective was to examine the safety and efficacy of enteric-coated aspirin, compared with other oral antiplatelet drugs, in Japanese patients with acute ischemic stroke. We performed a prospective, non-randomized, observational and multicenter study between June 2005 and December 2007. Patients with symptomatic acute ischemic stroke, including transient ischemic attack (TIA), who started enteric-coated aspirin or other antiplatelet drugs within 7days of hospitalization were registered. Outcome measures evaluated within 3months were incidence of cerebral and non-cerebral hemorrhagic events, recurrence of ischemic stroke or TIA, non-cerebral ischemic events and death from any cause. Overall, 2,548 and 830 patients treated with enteric-coated aspirin (100-300mg/day) or other antiplatelet drugs, respectively, were registered; approximately 60% were male, mean age was 70years, 85% had pre-existing cardiovascular disease or other complications. Enteric-coated aspirin of 100mg was mainly prescribed, and only approximately half of the patients were started on it within 48h after onset of ischemic stroke. Safety and efficacy population excluded patients without follow-up data were 2,521 in enteric-coated aspirin and 807 in other antiplatelets. Hemorrhagic events occurred in 46 (1.8%) in the enteric-coated aspirin group and in 13 (1.6%) in the other antiplatelet drugs group, there was not significant. Recurrent ischemic stroke or TIA occurred in 39 (1.5%) of the enteric-coated aspirin and in 18 (2.2%) of other antiplatelet drugs, and there were any-cause death in 16 (0.6%) and 8 (1.0%). Incidences were slightly lower in the enteric-coated aspirin group compared with the other antiplatelet drugs group, but not statistically significant. It seems that these results showed the safety and efficacy of the enteric-coated aspirin in acute stroke care in Japanese patients. Incidence of hemorrhagic events was comparable between the enteric-coated aspirin group and the other antiplatelet drugs group.

Dabigatran, intracranial hemorrhage, and the neurosurgeon

Dabigatran etexilate (Pradaxa) is a novel oral anticoagulant that has gained FDA approval for the prevention of ischemic stroke and systemic embolism in patients with nonvalvular atrial fibrillation. In randomized trials, the incidence of hemorrhagic events has been demonstrated to be lower in patients treated with dabigatran compared with the traditional anticoagulant warfarin. However, dabigatran does not have reliable laboratory tests to measure levels of anticoagulation and there is no pharmacological antidote. These drawbacks are challenging in the setting of intracerebral hemorrhage. In this article, the authors provide background information on dabigatran, review the existing anecdotal experiences with treating intracerebral hemorrhage related to dabigatran therapy, present a case study of intracranial hemorrhage in a patient being treated with dabigatran, and suggest clinical management strategies. The development of reversal agents is urgently needed given the growing number of patients treated with this medication.

Abstract 2781: Argatroban Anticoagulation for PCI: The E04 European Multi-Center Study

Background —Argatroban is an attractive drug for cardiology because it has a fast onset and offset of anticoagulation, and is hepatically excreted. Argatroban received approval for PCI in patients (pts) with heparin-induced thrombocytopenia (HIT) in the U.S. in 2002. However, data about argatroban in the current PCI setting is limited. Methods –The E04 trial, an open-label, parallel-group, multiple-dose study, included 140 pts undergoing PCI. Pts were randomly assigned to three argatroban- (250, 300 or 350 ìg/kg as a bolus injection before PCI, followed by 15, 20 or 25 ìg/kg/min infusion until the end of the procedure) and one unfractionated heparin (UFH)-treated groups (70 –100 IU/kg as a bolus injection). Efficacy endpoints were the proportion of pts reaching the minimum target ACT (250 sec.) after the initial bolus injection of each anticoagulant; ACT time-course during PCI; number of additional bolus injections; composite incidence of all-cause death, myocardial infarction (MI) and urgent revascularization until Day 30; and incidence of hemorrhagic events during the hospital stay. Results —Argatroban dose-dependently prolonged ACT. Significantly (p &lt; 0.01) more pts reached the minimum target ACT after the initial bolus injection with 86.1%, 89.5% and 96.8% in the low, middle and high dose argatroban groups, respectively, compared to 45.5% in the UFH group. Time to start of PCI after reaching minimum target ACT was significantly (p &lt; 0.01) shortened in the argatroban groups compared to UFH. Composite incidences of death, MI and urgent revascularization were 2.8%, 0.0%, 3.2% and 3.0% in the low, middle and high dose argatroban groups, and the UFH group, respectively (n.s.). Major bleeding was observed only in the UFH group (3.0%), and minor bleeding occurred in the high dose argatroban (3.2%) and the UFH group (6.1%). Conclusions —Argatroban had an adequate anticoagulant effect. More pts reached the minimum target ACT in the argatroban groups than in the UFH group. This resulted in a reduced time to start PCI. Although the sample size was too small to conclude an effect on clinical outcome, the results suggest that argatroban is a safe and effective anticoagulant for PCI in the current clinical setting.