Benefit of Self-Managed Anticoagulation in Patients with Left Ventricular Assist Device.

BACKGROUND: The exact monitoring of the therapeutic-range international normalized ratio (INR) after left ventricular assist device (LVAD) implantation is an important aim to reduce the risk of thrombosis or bleeding complications. Service providers offer a telemedical anticoagulation service (CS). METHODS: We compared LVAD patients using the CS (n = 15) to those who received regular medical care (RMC; n = 15) to investigate if telemedicine supervision increased the INR-specific time in the therapeutic range (TTR) during anticoagulation. All patients received self-management training for phenprocoumon medication according to their INR value. INR values were documented for 12 months. A survey (scale: 1 = not satisfied and 10 = very satisfied) was used to determine patient's satisfaction and psychological well-being. RESULTS: A total of 1,798 INR measurements were analyzed. The TTRRosendaal was higher in patients undergoing RMC (78.1 ± 14.3%) compared with that in patients using the CS (58.3 ± 28.0%, p = 0.03). The patient's satisfaction with the coagulation setting at the beginning of the study (RMC: 6.7 ± 3.1, CS: 7.2 ± 3.0, p = 0.74) and psychological wellbeing (RMC: 6.5 ± 1.9, CS: 6.5 ± 2.7, p = 0.97) were comparable between both groups. CONCLUSION: We found that INR self-management is superior regarding the efficiency of post-LVAD anticoagulation therapy when compared with telemedical (CS)-based INR management in a small study cohort. Intensive training by experienced staff was able to replace CS.

Risk of traumatic intracranial haemorrhage is increased in older people exposed to oral anticoagulation with phenprocoumon.

BACKGROUND: Hospital admissions resulting from traumatic intracranial haemorrhages (TIH) in older people are increasing. There are concerns regarding an increased risk of a TIH in people taking oral anticoagulants (OAC) like phenprocoumon. AIMS: The aim of this study was to estimate the incremental risk of a TIH associated with OAC in older people. Furthermore, this study explored differences in risk according to functional status. METHODS: The study took data from a large German health insurance provider and combined hospital diagnoses with data regarding drug dispensing to estimate rates of a TIH in people with and without exposure to phenprocoumon. Analyses were stratified by sex and by severe functional impairment as disclosed by the long-term care insurance provider. RESULTS: Overall, exposure to OAC resulted in 2.7 times higher rates of TIH. People with severe functional impairment had a higher baseline risk of TIH than people without severe functional impairment. However, the incremental risk in those exposed to OAC was similar among people with and without severe functional impairment (standardised incidence rate difference 15.73 (95% CI 7.84; 23.61) and 12.10 (95% CI 9.63; 14.57) per 10,000 person-years, respectively). CONCLUSIONS: OAC increases the risk of TIH considerably. The incremental risk of TIH in those exposed to OAC is comparable between people with and without severe functional impairment. The presence of severe functional impairment per se should not exclude such patients from the potential benefits of OAC. For now, the prescription should be personalized based on individual fall risk factors and risk-taking behaviour.

Multistate methodology improves risk assessment under time-varying drug intake-a new view on pregnancy outcomes following coumarin exposure.

PURPOSE: Observational cohort studies are essential to evaluate the risk of adverse pregnancy outcomes associated with drug intake. Besides left truncation and competing events, it is crucial to account for the time-dynamic pattern of drug exposure. In fact, potentially harmful medications are often discontinued, which might affect the outcome. Ignoring these challenges may lead to biased estimation of drug-related risks highlighting the need for adequate statistical techniques. METHODS: We reanalyze updated data of a recently published study provided by the German Embryotox pharmacovigilance institute. The aim of the study was to quantify the effect of discontinuation of vitamin K antagonist phenprocoumon on the risk of spontaneous abortion. RESULTS: We outline multistate methodology as a powerful method removing bias in probability estimation inherent to commonly used crude proportions. We incorporate time-dependent discontinuation and competing pregnancy outcomes as separate states in a multistate model, which enables the formulation of hazard-based Cox proportional hazard models and the application of so-called landmark techniques. Results show that early discontinuation of phenprocoumon substantially reduces the risk of spontaneous abortion, which is of great importance for both pregnant women and treating physicians. CONCLUSIONS: An adequate handling of discontinuation times is essential when analyzing the risk of spontaneous abortion. The proposed concepts are not restricted to pregnancy outcome studies but have broad usage in other fields of epidemiology. Our nontechnical report may provide guidance for the design and analysis of future studies. Example code is provided.

Shorter hospital stays in epistaxis patients with atrial fibrillation when taking rivaroxaban or apixaban versus phenprocoumon.

Patients taking oral anticoagulants (OACs) currently represent one-third of all patients treated for epistaxis and an upward trend is expected. New direct oral anticoagulants (DOACs) have been on the market for approximately 10 years. DOACs are favoured over Vitamin K-Antagonists (VKAs) in the current guidelines. There are barely studies that investigate the impact of DOACs on patients with epistaxis. A retrospective study was performed analysing all patients who had stationary treatment for epistaxis from 01.01.2011 to 01.01.2018 in a tertiary care centre. In a total of 466 patients, 46.1% were on OACs. The main indication was atrial fibrillation (AF, 67.4%).The number of DOACs taken surpassed that of the VKAs during the past 2 years. The length of hospital stay was significantly longer in the phenprocoumon group (3 ± 0.2 days) in comparison to both the rivaroxaban (2.3 ± 0.1) and the apixaban (2.2 ± 0.1) groups (p = 0.005). Posterior epistaxis occurred more frequently in the phenprocoumon group (10.8%) than in the rivaroxaban (0%) and apixaban (0%) groups (p = 0.03). A correlation between CHA2DS2-VASc score (risk score for apoplexy in patients with AF, p = 0.01), HAS-BLED score (score for assessment of major bleeding in patients taking anticoagulants with AF, p = 0.006), and length of hospital stay (p = 0.002) with recurrence of epistaxis was found. Shorter hospital stays and exclusively anterior bleeding was noted in AF patients taking rivaroxaban and apixaban, whereas AF patients taking phenprocoumon stayed in hospital longer and had more posterior bleeding.

Outcome of intracerebral haemorrhage related to non-vitamin K antagonists oral anticoagulants versus vitamin K antagonists: a comprehensive systematic review and meta-analysis.

INTRODUCTION: The characteristics and natural history of acute non-vitamin K antagonists oral anticoagulants (NOAC)-associated intracerebral haemorrhage (ICH) are largely unknown. We performed a comprehensive systematic review and meta-analysis to compare baseline ICH volume, haematoma expansion and clinical outcomes between NOAC-ICH versus vitamin K antagonists-ICH (VKA-ICH). METHODS: We searched PubMed and conference abstracts for observational studies comparing baseline characteristics and outcomes in patients with NOAC-ICH versus VKA-ICH using an appropriate keyword/MeSH term search strategy. Data were extracted following PRISMA and MOOSE guidelines. The main outcome measures were mortality and unfavourable functional outcome (modified Rankin Score: 4-6) at discharge and at 3 months, as well as ICH volumes and haematoma expansion rates in the two groups. Random-effects models with DerSimonian-Laird weights were used for pooled estimates calculation. RESULTS: Twelve studies including 393 NOAC-ICH and 3482 VKA-ICH were pooled in meta-analysis. There was no difference in mean ICH-volume between the two groups (standard mean difference: -0.24; 95% CI -0.52 to 0.04, p=0.093). The rates of haematoma expansion were comparable in NOAC-ICH versus VKA-ICH (OR: 0.76; 95% CI 0.49 to 1.19, p=0.236). We did not find any difference between patients with NOAC-ICH versus VKA-ICH in all-cause mortality at discharge (OR: 0.66; 95% CI 0.42 to 1.05, p=0.077) and unfavourable functional outcome at discharge (OR: 0.77; 95% CI 0.41 to 1.44, p=0.413). The 3-month outcome was also comparable between the two ICH groups. Moderate-to-substantial statistical heterogeneity was noted. CONCLUSION: Our results confirm that ICH volume, haematoma expansion, mortality and functional outcome appear to be similar for NOAC-ICH versus VKA-ICH. Large prospective cohorts and updated meta-analyses are needed to provide more precise estimates.

Non-vitamin K-dependent oral anticoagulants have a positive impact on ischaemic stroke severity in patients with atrial fibrillation.

Aims: Several studies showed reduced stroke severity in patients with atrial fibrillation (AF) if the international normalized ratio (INR) was ≥ 2 at stroke onset. There are no respective data for non-vitamin K-dependent oral anticoagulants (NOACs). The aim of this study was to compare the impact of NOAC or phenprocoumon intake on stroke severity. Methods and results: In this single-centre observational study, 3669 patients with acute ischaemic stroke were retrospectively analysed regarding AF status and medication immediately before admission. Using multivariable regression, we analysed the association of pre-admission anticoagulation with severe stroke (National Institutes of Health Stroke Scale score ≥ 11) on admission and poor outcome at discharge (modified Rankin scale score > 2). Before the index stroke, 655 patients had known AF and a CHA2DS2-VASc score ≥ 2. While 325 (49.6%) patients were anticoagulated, 159 (24.3%) were prescribed a NOAC and 75 (11.5%) phenprocoumon patients had an INR ≥ 2 on admission. Compared with AF patients without medical stroke prevention, an INR ≥ 2 [OR 0.23 (95% CI 0.10-0.53)] or NOAC intake [OR 0.48 (95% CI 0.27-0.86)] were associated with a lower probability of severe stroke after adjustment for confounders, while an INR < 2 [OR 0.62 (95% CI 0.33-1.16)] was not. Adjusted odds ratios for poor functional outcome at hospital discharge were 0.47 (95% CI 0.27-0.84) for NOAC patients, 0.33 (95% CI 0.17-0.65) for INR ≥ 2 and 0.61 (95% CI 0.32-1.16) for INR < 2. Conclusion: NOAC intake before stroke did reduce the probability of severe stroke on hospital admission and poor functional outcome at hospital discharge as similarly demonstrated for phenprocoumon patients with an INR ≥ 2 on admission.

Comparative risks of bleeding, ischemic stroke and mortality with direct oral anticoagulants versus phenprocoumon in patients with atrial fibrillation.

PURPOSE: The pivotal trials for stroke prevention in non-valvular atrial fibrillation (NVAF) compared rivaroxaban, dabigatran, and apixaban with warfarin, as did most claims-based studies. Comparisons with phenprocoumon, the most frequently used vitamin K antagonist (VKA) in Germany, are scarce. METHODS: Risk of bleeding, ischemic stroke, and all-cause mortality in patients with NVAF were analyzed using data for 2010 to 2014 from a large German claims database. New users of oral anticoagulants from January 2012 to December 2013 were included and observed over 1 year. Baseline characteristics were adjusted using propensity score matching and logistic regression. Several sensitivity analyses were carried out. RESULTS: Fifty-nine thousand four hundred forty-nine rivaroxaban, 23,654 dabigatran, 4894 apixaban, and 87,997 matched phenprocoumon users were included. Adjusted hazard ratios (95% confidence intervals) compared with phenprocoumon were as follows: hospitalized bleedings: rivaroxaban 1.04 (0.97; 1.11), dabigatran 0.87 (0.77; 0.98), and apixaban 0.65 (0.50; 0.86); ischemic stroke: rivaroxaban 1.05 (0.94; 1.17), dabigatran 1.14 (0.96; 1.35), and apixaban 1.84 (1.20; 2.84); all-cause mortality: rivaroxaban 1.17 (1.11; 1.22), dabigatran 1.04 (0.95; 1.13), and apixaban 1.14 (0.97; 1.34). CONCLUSIONS: With rivaroxaban, no significant differences were observed compared to phenprocoumon with regard to hospitalized bleedings or ischemic strokes. Dabigatran was associated with fewer bleedings and a similar risk of ischemic strokes compared to phenprocoumon. Apixaban was also associated with fewer bleedings but was unexpectedly associated with more ischemic strokes, possibly reflecting selective prescribing. The association of rivaroxaban with higher all-cause mortality unrelated to bleedings or strokes has been described previously but remains to be explained.

Epistaxis in anticoagulated patients: Fewer hospital admissions and shorter hospital stays on rivaroxaban compared to phenprocoumon.

OBJECTIVES: Treatment of epistaxis in patients on anticoagulants is challenging and associated with higher admission rates and longer hospital stays compared with patients without anticoagulation. However, there is little information about epistaxis in patients taking new direct oral anticoagulants such as rivaroxaban compared with patients on traditional vitamin K antagonists such as phenprocoumon. DESIGN: Retrospective cohort study. SETTING: The study was conducted at the emergency department of the University Hospital Inselspital, Bern, Switzerland. PARTICIPANTS: All admissions to the emergency department of the University Hospital Inselspital, Bern, Switzerland from 1st July 2012 to 30th June 2016 with non-traumatic epistaxis on anticoagulant therapy with phenprocoumon or rivaroxaban were included. MAIN OUTCOME MEASURES: We compared clinical outcome parameters (admission rates, length of hospital stay and mortality) for both anticoagulant groups. RESULTS: We included 440 patients with epistaxis, 123 (28%) on rivaroxaban and 317 (72%) on phenprocoumon. Fewer hospital admissions and shorter hospital stays were found in patients under rivaroxaban (12 (10.4%) vs 57 (18.0%) patients, P=.033; 0.7±2.2 vs 1.5±3.7 days, P=.011) compared with phenprocoumon. Anterior epistaxis was more common in the rivaroxaban group in contrast to posterior epistaxis in patients on phenprocoumon (74 (60.2%) vs 139 (43.8%) patients, P=.002; 7 (5.7%) vs 39 (12.3%) patients, P=.042). CONCLUSIONS: Our data suggests that epistaxis on direct oral anticoagulation with rivaroxaban is associated with shorter hospital stays and fewer hospital admissions than epistaxis on vitamin K antagonist phenprocoumon.

Prospective multicentre cohort study on 9154 surgical procedures to assess the risk of postoperative bleeding - a DESSI study.

BACKGROUND: To date, there is still a debate how to deal with patients receiving antithrombotic agents prior to surgical procedures on the skin. OBJECTIVE: To prospectively assess complications after dermatosurgical interventions, especially bleeding, depending on anticoagulation therapy. METHODS: Patients underwent surgery consecutively as scheduled, without randomization, whether or not they were currently taking anticoagulants. Nine institutions of the DESSI (DErmatoSurgical Study Initiative) working group documented patient data prospectively on a standardized study sheet prior to and after 9154 dermatosurgical interventions. RESULTS: Bleeding complications were observed in 7.14% of cases (654/9154 surgeries). A severe bleed requiring intervention by a physician occurred in 83 surgeries (0.91%). In multivariate analysis, INR, length of the defect, perioperative antibiotic treatment, current treatment with anticoagulation therapy, age and surgery on hidradenitis suppurativa/acne inversa (HS/AI) were significant parameters independently influencing the risk of bleeding. Discontinuation of phenprocoumon therapy and subsequent switching to low molecular weight heparin was associated with the highest risk of bleeding (9.26%). CONCLUSION: Bleeding complications in skin surgery are generally rare. Even if slightly increased complication rates are found in patients taking anticoagulants during skin surgery, platelet inhibitors should not be stopped prior to surgery. If a surgical procedure in patients on a combination therapy of 2 or more antiplatelet cannot be postponed, it should be conducted with the patient remaining on combination therapy. Discontinuation of DOACs is recommended 24 h prior to surgery. Bridging of phenprocoumon should be terminated. In patients with a bleeding history, the INR value should be within the therapeutic range.

Apixaban, Rivaroxaban, and Dabigatran in Patients Undergoing Atrial Fibrillation Ablation.

INTRODUCTION: Data on the novel oral anticoagulants (NOACS) during catheter ablation (CA) of atrial fibrillation (AF) are still limited. This study evaluated the periprocedural major complications (MC) of CA of AF, and compared Apixaban, Dabigatran, and Rivaroxaban with continuous phenoprocoumon. METHODS AND RESULTS: A total of 444 patients (mean age = 65.1 ± 9.4 years; 283 [64%] male) with paroxysmal (n = 180 [41%]), persistent (n = 256 [58%]), or longstanding-persistent AF were enrolled. CA was performed in all patients using radiofrequency energy in conjunction with a 3D-mapping system. MCs were defined according to the current guidelines. Continuous phenprocoumon-therapy was administered in 120/444 (27%) patients (group 1) and 324/444 (73%) patients were treated with NOACs (group 2; Dabigatran: n = 51 [15.7%]; Rivaroxaban: n = 193 [59.6%]; Apixaban: n = 80 [24.7%]). Procedure times were comparable between groups 1 and 2 (128.2 ± 39.7 minutes vs. 129.7 ± 51.2 minutes; P = 0.77). CHA2 DS2-Vasc (3.0 [2.0, 4.0)] vs. 2.0 [1.0, 3.0]; P < 0.01) and HASBLED scores (2.0 [2.0, 2.5] vs. 2.0 [1.0, 2.0]; P = 0.002) were higher in group 1 patients. The incidence of MCs in the overall group was 8/444 (2%) and was equally distributed between groups 1 and 2 (2/120 [2%] vs. 6/324 [2%], P = 0.90). The incidence of MCs was comparable between the three different NOACs. There were no significant differences between patients with and without MCs with regard to age, CHA2 DS2-Vasc-score or HASBLED-score. CONCLUSIONS: The major complication rate between all three NOACs currently available and continuous phenprocoumon during AF ablation seem to be comparable. Complication rates were similar between patients treated with the three different available NOACs.

Antiplatelet therapy for stable coronary artery disease in atrial fibrillation patients taking an oral anticoagulant: a nationwide cohort study.

BACKGROUND: The optimal long-term antithrombotic treatment of patients with coexisting atrial fibrillation and stable coronary artery disease is unresolved, and commonly, a single antiplatelet agent is added to oral anticoagulation. We investigated the effectiveness and safety of adding antiplatelet therapy to vitamin K antagonist (VKA) in atrial fibrillation patents with stable coronary artery disease. METHODS AND RESULTS: Atrial fibrillation patients with stable coronary artery disease (defined as 12 months from an acute coronary event) between 2002 and 2011 were identified. The subsequent risk of cardiovascular events and serious bleeding events (those that required hospitalization) was examined with adjusted Cox regression models according to ongoing antithrombotic therapy. A total of 8700 patients were included (mean age, 74.2 years; 38% women). During a mean follow-up of 3.3 years, crude incidence rates were 7.2, 3.8, and 4.0 events per 100 person-years for myocardial infarction/coronary death, thromboembolism, and serious bleeding, respectively. Relative to VKA monotherapy, the risk of myocardial infarction/coronary death was similar for VKA plus aspirin (hazard ratio, 1.12 [95% confidence interval, 0.94-1.34]) and VKA plus clopidogrel (hazard ratio, 1.53 [95% confidence interval, 0.93-2.52]). The risk of thromboembolism was comparable in all regimens that included VKA, whereas the risk of bleeding increased when aspirin (hazard ratio, 1.50 [95% confidence interval, 1.23-1.82]) or clopidogrel (hazard ratio, 1.84 [95% confidence interval, 1.11-3.06]) was added to VKA. CONCLUSIONS: In atrial fibrillation patients with stable coronary artery disease, the addition of antiplatelet therapy to VKA therapy is not associated with a reduction in risk of recurrent coronary events or thromboembolism, whereas risk of bleeding is increased significantly. The common practice of adding antiplatelet therapy to oral VKA anticoagulation in patients with atrial fibrillation and stable coronary artery disease warrants reassessment.

Hyperglycemia and PPARγ Antagonistically Influence Macrophage Polarization and Infarct Healing After Ischemic Stroke.

BACKGROUND AND PURPOSE: Secondary intracerebral hemorrhage (sICH) is a potentially serious complication of ischemic stroke, in particular under concomitant oral anticoagulation. Previous studies in murine stroke models defined a novel vascular repair function of hematogenous monocytes/macrophages (MO/MP), which proved essential for the prevention of oral anticoagulation-associated sICH. Here, we addressed the question whether hyperglycemia as a clinically relevant prohemorrhagic risk factor and peroxisome proliferator-activated receptor gamma (PPARγ) activation affect MO/MP differentiation and the risk of sICH after ischemic stroke. METHODS: Oral anticoagulation-associated sICH was induced by phenprocoumon feeding to mice undergoing transient middle cerebral artery occlusion. Hyperglycemia was induced by streptozotocin treatment. The role of PPARγ-dependent MO/MP differentiation was addressed in mice with myeloid cell-specific PPARγ-knockout (LysM-PPARγ(KO)). Pharmacological PPARγ activation via pioglitazone was tested as a treatment option. RESULTS: Hyperglycemic mice and normoglycemic LysM-PPARγ(KO) mice exhibited abnormal proinflammatory skewing of their hematogenous MO/MP response and abnormal vascular remodeling in the infarct border zone, leading to an increased rate of oral anticoagulation-associated sICH. Pharmacological PPARγ activation in hyperglycemic mice corrected the inflammatory response toward an anti-inflammatory profile, stabilized neovessels in the infarct border zone, and reduced the rate of sICH. This preventive effect was dependent on the presence of macrophages, but independent from effects on blood glucose levels. CONCLUSIONS: Hyperglycemia and macrophage-specific PPARγ activation exert opposing effects on MO/MP polarization in ischemic stroke lesions and, thereby, critically determine the risk of hemorrhagic infarct transformation.

Possible drug-drug interaction between high-dose esomeprazole and phenprocoumon.

PURPOSE: It is established that omeprazole increases (R)+ warfarin levels with around 10 %. Whether (es)omeprazole also increase the plasma levels of acenocoumarol or phenprocoumon is still uncertain. We analyzed whether addition of (es)omeprazole to acenocoumarol or phenprocoumon increases the international normalized ratio (INR) levels and the risk of overanticoagulation. METHODS: We analyzed all hospital admissions in four teaching hospitals. Patients who used coumarins and pantoprazole or (es)omeprazole simultaneously for at least four consecutive days were included in the study. We analyzed the highest INR level and whether patients had an INR level above six. We compared patients using omeprazole or esomeprazole with patients using pantoprazole, because for pantoprazole, no interaction has been reported. RESULTS: We analyzed 5747 admissions with 4540 patients using one of the drug combinations. For acenocoumarol (4578 admissions), no significant differences were found between users of esomeprazole, omeprazole, and pantoprazole. For phenprocoumon (1169 admissions), the highest INR measured was significantly higher in users of esomeprazole than in users of pantoprazole (4.7 versus 4.3; p = 0.035). No significant difference was found with omeprazole versus pantoprazole (4.3 versus 4.3; p = 0.66). A non-significant association was found between the esomeprazole dose and the highest INR level (p = 0.055). The risk of an INR above six did not differ significantly between esomeprazole and pantoprazole (27.7 % versus 22.9 %; p = 0.34). CONCLUSIONS: The use of esomeprazole simultaneously with phenprocoumon during hospital admissions might increase the anticoagulant effect. The clinical relevance seems to be limited, because no statistically significant increased risk of overanticoagulation was found.

Spontaneous and non-spontaneous bleeding complications in patients with oral vitamin K antagonist therapy.

PURPOSE: The aim of the study was to evaluate potential differences between patients with spontaneous and non-spontaneous bleeding episodes during treatment with vitamin K antagonists which mainly resulted in compartment syndromes. METHODS: The population in this study comprised 116 patients who suffered at least one bleeding complication which required surgical treatment during therapy with an oral vitamin K antagonist. The patients were treated between September 2001 and July 2008. RESULTS: Significant differences were observed between the two patient groups with regard to the presence of renal failure, arterial hypertension, and diabetes mellitus, which occurred more frequently in patients with spontaneous bleeding. Also, significantly more patients with spontaneous bleedings developed compartment syndrome that needed emergency operation. Overall mortality was 9.6 %, was associated with multiorgan failure in all patients, and was not different between the two patient groups. CONCLUSIONS: The identification of high-risk patients before treatment with an oral vitamin K antagonist is of major importance. The existence of over-anticoagulation syndrome and compartment syndrome is associated with significant mortality and morbidity and should not be underestimated.

Comparative effectiveness of factor Xa non-vitamin K antagonist oral anticoagulants versus phenprocoumon in patients with non-valvular atrial fibrillation.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) have largely supplanted vitamin K antagonists (VKAs) for oral anticoagulation in non-valvular atrial fibrillation (NVAF). However, data on the real-world effectiveness of NOACs vs. phenprocoumon, a VKA widely used in Germany, are limited. The RELOADED study aimed to compare effectiveness of factor Xa NOACs and phenprocoumon in NVAF in clinical practice. METHODS: Patients who started on a factor Xa NOAC or phenprocoumon for NVAF during the study period were enrolled from the Institute for Applied Healthcare Research Berlin. Patients were followed from first prescription until the end of exposure or available data. Primary outcomes were analyzed by Cox proportional hazard regression models and included ischemic stroke and systemic embolism for effectiveness, and intracranial hemorrhage (ICH) for safety. Subgroups of interest were patients with diabetes and patients with renal impairment. RESULTS: The total study population was 64,920; 36.3% of patients initiated phenprocoumon, 34.4% initiated rivaroxaban, 25.0% apixaban, and 4.4% edoxaban. Treatment with phenprocoumon is associated with a similar risk of ischemic stroke/systemic embolism as treatment with rivaroxaban or apixaban; while rivaroxaban (adjusted hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.43-0.75) and apixaban (adjusted HR 0.43, 95% CI 0.31-0.6) were associated with a lower risk of ICH compared to phenprocoumon in NVAF patients. The use of rivaroxaban and apixaban was associated with a lower risk of developing kidney failure in patients with diabetes or renal impairment in comparison to those treated with phenprocoumon. CONCLUSION: The factor Xa NOACs rivaroxaban and apixaban demonstrated similar effectiveness and lower rates of ICH compared with phenprocoumon in this study.

Long-term outcome after anticoagulation-associated intracerebral haemorrhage with or without restarting antithrombotic therapy.

BACKGROUND: For patients who survive intracerebral haemorrhage (ICH) during treatment with oral anticoagulation (OAC), the balance between the benefits and risks of restarting OAC is unclear. The decision to restart OAC or to start antiplatelet therapy in these patients therefore poses a dilemma for all physicians involved. We assessed the long-term outcome of patients who did or did not restart antithrombotic therapy after OAC-associated ICH. METHODS: We conducted a retrospective follow-up study of all patients discharged from our institution after OAC-associated ICH over a 10-year period. Data on the use of OAC or platelet inhibitors and the occurrence of vascular events during follow-up were assessed through questionnaires and patient files. The primary outcome was recurrent fatal or non-fatal stroke. Secondary outcomes were the occurrence of other haemorrhagic, thrombotic or thromboembolic events. With patients without antithrombotic treatment as reference, we calculated incidence ratios with corresponding 95% confidence intervals (CI) for treatment with OAC and for treatment with antiplatelet therapy. RESULTS: We included 38 patients, of whom 21 (55%) died during a mean follow-up of 3.5 years. The medication regime changed frequently during follow-up, illustrated by the fact that two thirds of the patients who had resumed OAC within 2 months of ICH terminated this at later points in time. Two recurrent strokes occurred during 35.4 patient-years without antithrombotic medication, 7 during 63.8 patient-years on antiplatelet medication (incidence ratio 1.9; 95% CI, 0.4-9.4), and 3 during 19.5 patient-years on OAC (incidence ratio 2.7; 95% CI, 0.5-16.3). There was only 1 recurrent ICH, which occurred during treatment with OAC. CONCLUSION: In this observational study, no significant difference in the primary outcome measure was found between the treatment groups, but there was a tendency towards a higher long-term risk of any stroke in patients who resumed OAC or started antiplatelet therapy. However, based on these results it is difficult to draw any concrete conclusions or make any strong recommendations. A randomized trial to assess the optimal long-term strategy after OAC-related ICH is warranted. Based on the point estimates of our study, such a trial should involve at least 300 patient-years of follow-up.

Calciphylaxis - a challenging & solvable task for plastic surgery? A case report.

BACKGROUND: Calciphylaxis (calcific uremic arteriolopathy) is rare and its pathogenesis is not fully understood. Indeed, Calciphylaxis presents a challenge through the course of its management which involve different specialities but unfortunately this disease so far has a poor prognosis. We herein present, in this case report, a multidisciplinary approach involving plastic surgeons with special regards to reconstructive approach after debridement procedures. CASE PRESENTATION: We present a 21 years old male with a BMI of 38,2, who was transferred to our department from another hospital. Calciphylaxis has been diagnosed after receiving anticoagulation with phenprocoumon after a single event of pulmonary embolism. The INR on admission was 1,79. He had necrotic spots on both sides of the abdominal wall and on both thighs medially. During this time he underwent several reconstructive procedures in our department. CONCLUSION: It can be suggested that this agonizing disease needs indeed a multidisciplinary approach involving Nephrologists, Dermatologists, Intensive Care Physicians and Plastic Surgeons, taking into consideration that surgical correction can achieve further improvement in a specialized centre. Notwithstanding, further cohort studies should be approached clinically to insight the light on this disease with special regard to the prognosis after this approach.

Quality of Anticoagulation With Phenprocoumon and Warfarin in Left Ventricular Assist Device Patients: A Multicenter Study.

VISUAL ABSTRACT: of key results. INR, international normalized ratio; TTR, time in therapeutic range; PTR, percentage of tests in range; HRAE, hemocompatibility-related adverse event; FFUV, first follow-up visit; GIB, gastrointestinal bleeding; HR, hazard ratio.http://links.lww.com/ASAIO/A961.