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[EN] Background: The introduction of direct-acting oral anticoagulants (DOACs) has shown to decrease atrial fibrillation (AF)-related stroke and bleeding rates in clinical studies, but there is no certain evidence about their effects at the population level. Our aim was to assess changes in AF-related stroke and major bleeding rates between 2012 and 2019 in Andalusia (Spain), and the association between DOACs use and events rates at the population level. Methods: All patients with an AF diagnosis from 2012 to 2019 were identified using the Andalusian Health Population Base, that provides clinical information on all Andalusian people. Annual ischemic and hemorrhagic stroke, major bleeding rates, and used antithrombotic treatments were determined. Marginal hazard ratios (HR) were calculated for each treatment. Results: A total of 95,085 patients with an AF diagnosis were identified. Mean age was 76.1 ± 10.2 years (49.7% women). An increase in the use of DOACs was observed throughout the study period in both males and females (p < 0.001). The annual rate of ischemic stroke decreased by one third, while that of hemorrhagic stroke and major bleeding decreased 2–3-fold from 2012 to 2019. Marginal HR was lower than 0.50 for DOACs compared to VKA for all ischemic or hemorrhagic events. Conclusions: In this contemporary population-based study using clinical and administrative databases in Andalusia, a significant reduction in the incidence of AF-related ischemic and hemorrhagic stroke and major bleeding was observed between 2012 and 2019. The increased use of DOACs seems to be associated with this reduction., [EN] Introducción: La introducción de los anticoagulantes orales de acción directa (ACOD) ha demostrado disminuir las tasas de accidentes cerebrovasculares y hemorragias relacionados con fibrilación auricular (FA) en estudios clínicos, pero no hay tanta evidencia sobre sus efectos a nivel poblacional. Nuestro objetivo fue evaluar los cambios en la incidencia de ictus y hemorragias mayores relacionados con FA entre 2012 y 2019 en Andalucía (España), y estudiar la asociación entre el uso de ACOD y estos eventos a nivel poblacional. Métodos: Se incluyeron pacientes con diagnóstico de FA entre los años 2012 y 2019 en la Base de Población Sanitaria de Andalucía, que proporciona información clínica de todos los andaluces. Se determinaron los accidentes cerebrovasculares isquémicos y hemorrágicos anuales, las tasas de sangrado mayor y los tratamientos antitrombóticos utilizados. Se estimaron los hazard ratio para cada tratamiento. Resultados: Se identificaron un total de 95.085 pacientes con diagnóstico de FA. La edad media fue de 76,1 ± 10,2 años (49,7% mujeres). Se observó un aumento en el uso de ACOD a lo largo del período de estudio, tanto en varones como en mujeres (p < 0,001). La tasa anual de ictus isquémico disminuyó en un tercio, mientras que la de ictus hemorrágico y hemorragia mayor se redujo de 2 a 3 veces entre 2012 y 2019. Los hazard ratio fueron inferiores a 0,50 para los ACOD en comparación con los antivitamina K para todos los eventos isquémicos o hemorrágicos. Conclusiones: En este estudio poblacional contemporáneo, se observó, utilizando bases de datos clínicas y administrativas de Andalucía, una reducción significativa en la incidencia de ictus isquémico y hemorrágico, y hemorragia mayor relacionados con FA entre los años 2012 y 2019. El mayor uso de ACOD parece estar asociado con esta reducción.

Aims: Ticagrelor is associated with a lower risk of ischemic events than clopidogrel. However, it is uncertain whether the benefits of more intensive anti-ischemic therapy outweigh the risks of major bleeding in patients who have a high bleeding risk (HBR). Therefore, this study compared ticagrelor and clopidogrel in myocardial infarction (MI) patients with HBR. Methods and results: This study included all patients enrolled in the SWEDEHEART registry who were discharged with dual antiplatelet therapy using ticagrelor or clopidogrel following MI between 2010 and 2017. High bleeding risk was defined as a PRECISE-DAPT score & GE;25. Information on ischemic events, major bleeding, and mortality was obtained from national registries, with 365 days of follow-up. Additional outcomes include major adverse cardiovascular events (MACE), a composite of MI, stroke and all-cause mortality, and net adverse clinical events (NACE), a composite of MACE and bleeding. This study included 25 042 HBR patients, of whom 11 848 were treated with ticagrelor. Ticagrelor was associated with a lower risk of MI, stroke, and MACE, but a higher risk of bleeding compared to clopidogrel. There were no significant differences in mortality and NACE. Additionally, when examining the relationship between antiplatelet therapy and bleeding risk in 69 040 MI patients, we found no statistically significant interactions between the PRECISE-DAPT score and treatment effect. Conclusions: We observed no difference in NACE when comparing ticagrelor and clopidogrel in HBR patients. Moreover, we found no statistically significant interactions between bleeding risk and the comparative effectiveness of clopidogrel and ticagrelor in a larger population of MI patients.

Aims: Ticagrelor is associated with a lower risk of ischemic events than clopidogrel. However, it is uncertain whether the benefits of more intensive anti-ischemic therapy outweigh the risks of major bleeding in patients who have a high bleeding risk (HBR). Therefore, this study compared ticagrelor and clopidogrel in myocardial infarction (MI) patients with HBR. Methods and results: This study included all patients enrolled in the SWEDEHEART registry who were discharged with dual antiplatelet therapy using ticagrelor or clopidogrel following MI between 2010 and 2017. High bleeding risk was defined as a PRECISE-DAPT score & GE;25. Information on ischemic events, major bleeding, and mortality was obtained from national registries, with 365 days of follow-up. Additional outcomes include major adverse cardiovascular events (MACE), a composite of MI, stroke and all-cause mortality, and net adverse clinical events (NACE), a composite of MACE and bleeding. This study included 25 042 HBR patients, of whom 11 848 were treated with ticagrelor. Ticagrelor was associated with a lower risk of MI, stroke, and MACE, but a higher risk of bleeding compared to clopidogrel. There were no significant differences in mortality and NACE. Additionally, when examining the relationship between antiplatelet therapy and bleeding risk in 69 040 MI patients, we found no statistically significant interactions between the PRECISE-DAPT score and treatment effect. Conclusions: We observed no difference in NACE when comparing ticagrelor and clopidogrel in HBR patients. Moreover, we found no statistically significant interactions between bleeding risk and the comparative effectiveness of clopidogrel and ticagrelor in a larger population of MI patients.

Aims: Ticagrelor is associated with a lower risk of ischemic events than clopidogrel. However, it is uncertain whether the benefits of more intensive anti-ischemic therapy outweigh the risks of major bleeding in patients who have a high bleeding risk (HBR). Therefore, this study compared ticagrelor and clopidogrel in myocardial infarction (MI) patients with HBR. Methods and results: This study included all patients enrolled in the SWEDEHEART registry who were discharged with dual antiplatelet therapy using ticagrelor or clopidogrel following MI between 2010 and 2017. High bleeding risk was defined as a PRECISE-DAPT score & GE;25. Information on ischemic events, major bleeding, and mortality was obtained from national registries, with 365 days of follow-up. Additional outcomes include major adverse cardiovascular events (MACE), a composite of MI, stroke and all-cause mortality, and net adverse clinical events (NACE), a composite of MACE and bleeding. This study included 25 042 HBR patients, of whom 11 848 were treated with ticagrelor. Ticagrelor was associated with a lower risk of MI, stroke, and MACE, but a higher risk of bleeding compared to clopidogrel. There were no significant differences in mortality and NACE. Additionally, when examining the relationship between antiplatelet therapy and bleeding risk in 69 040 MI patients, we found no statistically significant interactions between the PRECISE-DAPT score and treatment effect. Conclusions: We observed no difference in NACE when comparing ticagrelor and clopidogrel in HBR patients. Moreover, we found no statistically significant interactions between bleeding risk and the comparative effectiveness of clopidogrel and ticagrelor in a larger population of MI patients.

Aims: Ticagrelor is associated with a lower risk of ischemic events than clopidogrel. However, it is uncertain whether the benefits of more intensive anti-ischemic therapy outweigh the risks of major bleeding in patients who have a high bleeding risk (HBR). Therefore, this study compared ticagrelor and clopidogrel in myocardial infarction (MI) patients with HBR. Methods and results: This study included all patients enrolled in the SWEDEHEART registry who were discharged with dual antiplatelet therapy using ticagrelor or clopidogrel following MI between 2010 and 2017. High bleeding risk was defined as a PRECISE-DAPT score & GE;25. Information on ischemic events, major bleeding, and mortality was obtained from national registries, with 365 days of follow-up. Additional outcomes include major adverse cardiovascular events (MACE), a composite of MI, stroke and all-cause mortality, and net adverse clinical events (NACE), a composite of MACE and bleeding. This study included 25 042 HBR patients, of whom 11 848 were treated with ticagrelor. Ticagrelor was associated with a lower risk of MI, stroke, and MACE, but a higher risk of bleeding compared to clopidogrel. There were no significant differences in mortality and NACE. Additionally, when examining the relationship between antiplatelet therapy and bleeding risk in 69 040 MI patients, we found no statistically significant interactions between the PRECISE-DAPT score and treatment effect. Conclusions: We observed no difference in NACE when comparing ticagrelor and clopidogrel in HBR patients. Moreover, we found no statistically significant interactions between bleeding risk and the comparative effectiveness of clopidogrel and ticagrelor in a larger population of MI patients.

Background: Patients with chronic kidney disease (CKD) and atrial fibrillation (AF) are at high risk of ischemic stroke. Evidence is lacking if patients with advanced CKD or on dialysis benefit from oral anticoagulants (OAC) as stroke prophylaxis. There is also no clear evidence on the safety and efficacy of prophylactic anticoagulants (PAC) in the prothrombotic state nephrotic syndrome (NS). Aims: To investigate effectiveness and risks of oral anticoagulants as stroke prophylaxis in chronic kidney disease with atrial fibrillation To examine the role of warfarin treatment quality as a predictor for ischemic stroke and bleeding in CKD To investigate benefits and risks with prophylactic anticoagulants in patients with nephrotic syndrome and elucidate risk factors for thrombosis and bleeding Methods: A cohort of patients with non-valvular atrial fibrillation (NVAF) and CKD GFR category 3–5 (G3–G5) or on dialysis (G5D) was created by combining data from national health care- and quality registries between 2009-2018. Included registries were the Swedish Renal Registry, AuriculA, The Stroke Register and The Swedish National Patient Register. G3 was defined as GFR 30-59ml/min/1.73m2, G4: 15-29, G5: <15, G5D: on dialysis. Paper I compared patient time on warfarin with patient time on no OAC treatment using Cox regression. Paper II compared DOAC and warfarin using the same methods. Paper III investigated the effect of increasing warfarin treatment quality, measured as individual time in therapeutic range (iTTR). Primary outcomes in paper I-III were ischemic stroke and major bleeding. Paper IV, a retrospective medical records study included adults with NS between 2010-2019 in the county of Västernorrland, Sweden. Outcomes were venous thromboembolism (VTE), bleeding and death. Patients divided into PAC- and no PAC group were compared using Fisher’s exact test. Patient time was divided into serum/plasma (S/P)-albumin intervals and VTE- and bleeding rates were calculated. Re, Bakgrund: Kronisk njursjukdom, CKD, definieras som ihållande nedsatt njurfunktion, mätt som nedsatt filtrationshastighet i njurens små kärlnystan eller andra tecken på njurskada, såsom äggviteläckage i urinen. CKD kan orsakas av flera olika sjukdomar som till exempel diabetes, högt blodtryck eller inflammation i de små kärlnystanen (glomerulonefrit). CKD delas in i stadier där stadium 3 innebär moderat nedsatt njurfunktion, stadium 4 är allvarligt nedsatt njurfunktion och stadie 5 innebär att patienten så småningom behöver njurtransplanteras eller starta dialys (stadium 5D). CKD drabbar upp till 10% av befolkningen och bidrar till ökad risk för en rad följdsjukdomar inklusive hjärtrytmrubbningen förmaksflimmer. Av patienter med CKD stadium 4–5 har upp till 20-25% förmaksflimmer. När hjärtats förmak flimrar står blodet mer still och får chans att levra sig, bilda blodproppar. Detta kan leda till att små proppar lossnar, far i väg från hjärtat till hjärnan och orsakar stroke. Patienter med förmaksflimmer i den allmänna befolkningen behandlas ofta med blodförtunnande läkemedel, antikoagulantia, för att förhindra stroke. Traditionellt sett har man använt den blodförtunnande medlet warfarin. Det senaste decenniet har nya blodförtunnande läkemedel, DOAK, börjat dominera. Patienter med mer än moderat nedsatt njurfunktion har till största del uteslutits från stora randomiserade läkemedelsprövningar (RCTs) av antikoagulantia. Detta beror delvis på att CKD i sig medför ökad blödningsrisk. Därför är det oklart om patienter med allvarligt nedsatt njurfunktion och förmaksflimmer ska ha blodförtunnande, eller om den ökade blödningsrisken medför att antikoagulantia ska undvikas. Nefrotiskt syndrom är ett specialfall av njursjukdom som innebär ökad risk för venösa proppar. Traditionellt sett har dessa patienter behandlats med förebyggande blodförtunning, men det saknas studier på dess effekt och säkerhet. Syftet med våra studier var att undersöka nytta och risk med blodförtunning

Aims: Ticagrelor is associated with a lower risk of ischemic events than clopidogrel. However, it is uncertain whether the benefits of more intensive anti-ischemic therapy outweigh the risks of major bleeding in patients who have a high bleeding risk (HBR). Therefore, this study compared ticagrelor and clopidogrel in myocardial infarction (MI) patients with HBR. Methods and results: This study included all patients enrolled in the SWEDEHEART registry who were discharged with dual antiplatelet therapy using ticagrelor or clopidogrel following MI between 2010 and 2017. High bleeding risk was defined as a PRECISE-DAPT score & GE;25. Information on ischemic events, major bleeding, and mortality was obtained from national registries, with 365 days of follow-up. Additional outcomes include major adverse cardiovascular events (MACE), a composite of MI, stroke and all-cause mortality, and net adverse clinical events (NACE), a composite of MACE and bleeding. This study included 25 042 HBR patients, of whom 11 848 were treated with ticagrelor. Ticagrelor was associated with a lower risk of MI, stroke, and MACE, but a higher risk of bleeding compared to clopidogrel. There were no significant differences in mortality and NACE. Additionally, when examining the relationship between antiplatelet therapy and bleeding risk in 69 040 MI patients, we found no statistically significant interactions between the PRECISE-DAPT score and treatment effect. Conclusions: We observed no difference in NACE when comparing ticagrelor and clopidogrel in HBR patients. Moreover, we found no statistically significant interactions between bleeding risk and the comparative effectiveness of clopidogrel and ticagrelor in a larger population of MI patients.

Background: Patients with chronic kidney disease (CKD) and atrial fibrillation (AF) are at high risk of ischemic stroke. Evidence is lacking if patients with advanced CKD or on dialysis benefit from oral anticoagulants (OAC) as stroke prophylaxis. There is also no clear evidence on the safety and efficacy of prophylactic anticoagulants (PAC) in the prothrombotic state nephrotic syndrome (NS). Aims: To investigate effectiveness and risks of oral anticoagulants as stroke prophylaxis in chronic kidney disease with atrial fibrillation To examine the role of warfarin treatment quality as a predictor for ischemic stroke and bleeding in CKD To investigate benefits and risks with prophylactic anticoagulants in patients with nephrotic syndrome and elucidate risk factors for thrombosis and bleeding Methods: A cohort of patients with non-valvular atrial fibrillation (NVAF) and CKD GFR category 3–5 (G3–G5) or on dialysis (G5D) was created by combining data from national health care- and quality registries between 2009-2018. Included registries were the Swedish Renal Registry, AuriculA, The Stroke Register and The Swedish National Patient Register. G3 was defined as GFR 30-59ml/min/1.73m2, G4: 15-29, G5: <15, G5D: on dialysis. Paper I compared patient time on warfarin with patient time on no OAC treatment using Cox regression. Paper II compared DOAC and warfarin using the same methods. Paper III investigated the effect of increasing warfarin treatment quality, measured as individual time in therapeutic range (iTTR). Primary outcomes in paper I-III were ischemic stroke and major bleeding. Paper IV, a retrospective medical records study included adults with NS between 2010-2019 in the county of Västernorrland, Sweden. Outcomes were venous thromboembolism (VTE), bleeding and death. Patients divided into PAC- and no PAC group were compared using Fisher’s exact test. Patient time was divided into serum/plasma (S/P)-albumin intervals and VTE- and bleeding rates were calculated. Re, Bakgrund: Kronisk njursjukdom, CKD, definieras som ihållande nedsatt njurfunktion, mätt som nedsatt filtrationshastighet i njurens små kärlnystan eller andra tecken på njurskada, såsom äggviteläckage i urinen. CKD kan orsakas av flera olika sjukdomar som till exempel diabetes, högt blodtryck eller inflammation i de små kärlnystanen (glomerulonefrit). CKD delas in i stadier där stadium 3 innebär moderat nedsatt njurfunktion, stadium 4 är allvarligt nedsatt njurfunktion och stadie 5 innebär att patienten så småningom behöver njurtransplanteras eller starta dialys (stadium 5D). CKD drabbar upp till 10% av befolkningen och bidrar till ökad risk för en rad följdsjukdomar inklusive hjärtrytmrubbningen förmaksflimmer. Av patienter med CKD stadium 4–5 har upp till 20-25% förmaksflimmer. När hjärtats förmak flimrar står blodet mer still och får chans att levra sig, bilda blodproppar. Detta kan leda till att små proppar lossnar, far i väg från hjärtat till hjärnan och orsakar stroke. Patienter med förmaksflimmer i den allmänna befolkningen behandlas ofta med blodförtunnande läkemedel, antikoagulantia, för att förhindra stroke. Traditionellt sett har man använt den blodförtunnande medlet warfarin. Det senaste decenniet har nya blodförtunnande läkemedel, DOAK, börjat dominera. Patienter med mer än moderat nedsatt njurfunktion har till största del uteslutits från stora randomiserade läkemedelsprövningar (RCTs) av antikoagulantia. Detta beror delvis på att CKD i sig medför ökad blödningsrisk. Därför är det oklart om patienter med allvarligt nedsatt njurfunktion och förmaksflimmer ska ha blodförtunnande, eller om den ökade blödningsrisken medför att antikoagulantia ska undvikas. Nefrotiskt syndrom är ett specialfall av njursjukdom som innebär ökad risk för venösa proppar. Traditionellt sett har dessa patienter behandlats med förebyggande blodförtunning, men det saknas studier på dess effekt och säkerhet. Syftet med våra studier var att undersöka nytta och risk med blodförtunning

Background: Patients with chronic kidney disease (CKD) and atrial fibrillation (AF) are at high risk of ischemic stroke. Evidence is lacking if patients with advanced CKD or on dialysis benefit from oral anticoagulants (OAC) as stroke prophylaxis. There is also no clear evidence on the safety and efficacy of prophylactic anticoagulants (PAC) in the prothrombotic state nephrotic syndrome (NS). Aims: To investigate effectiveness and risks of oral anticoagulants as stroke prophylaxis in chronic kidney disease with atrial fibrillation To examine the role of warfarin treatment quality as a predictor for ischemic stroke and bleeding in CKD To investigate benefits and risks with prophylactic anticoagulants in patients with nephrotic syndrome and elucidate risk factors for thrombosis and bleeding Methods: A cohort of patients with non-valvular atrial fibrillation (NVAF) and CKD GFR category 3–5 (G3–G5) or on dialysis (G5D) was created by combining data from national health care- and quality registries between 2009-2018. Included registries were the Swedish Renal Registry, AuriculA, The Stroke Register and The Swedish National Patient Register. G3 was defined as GFR 30-59ml/min/1.73m2, G4: 15-29, G5: <15, G5D: on dialysis. Paper I compared patient time on warfarin with patient time on no OAC treatment using Cox regression. Paper II compared DOAC and warfarin using the same methods. Paper III investigated the effect of increasing warfarin treatment quality, measured as individual time in therapeutic range (iTTR). Primary outcomes in paper I-III were ischemic stroke and major bleeding. Paper IV, a retrospective medical records study included adults with NS between 2010-2019 in the county of Västernorrland, Sweden. Outcomes were venous thromboembolism (VTE), bleeding and death. Patients divided into PAC- and no PAC group were compared using Fisher’s exact test. Patient time was divided into serum/plasma (S/P)-albumin intervals and VTE- and bleeding rates were calculated. Re, Bakgrund: Kronisk njursjukdom, CKD, definieras som ihållande nedsatt njurfunktion, mätt som nedsatt filtrationshastighet i njurens små kärlnystan eller andra tecken på njurskada, såsom äggviteläckage i urinen. CKD kan orsakas av flera olika sjukdomar som till exempel diabetes, högt blodtryck eller inflammation i de små kärlnystanen (glomerulonefrit). CKD delas in i stadier där stadium 3 innebär moderat nedsatt njurfunktion, stadium 4 är allvarligt nedsatt njurfunktion och stadie 5 innebär att patienten så småningom behöver njurtransplanteras eller starta dialys (stadium 5D). CKD drabbar upp till 10% av befolkningen och bidrar till ökad risk för en rad följdsjukdomar inklusive hjärtrytmrubbningen förmaksflimmer. Av patienter med CKD stadium 4–5 har upp till 20-25% förmaksflimmer. När hjärtats förmak flimrar står blodet mer still och får chans att levra sig, bilda blodproppar. Detta kan leda till att små proppar lossnar, far i väg från hjärtat till hjärnan och orsakar stroke. Patienter med förmaksflimmer i den allmänna befolkningen behandlas ofta med blodförtunnande läkemedel, antikoagulantia, för att förhindra stroke. Traditionellt sett har man använt den blodförtunnande medlet warfarin. Det senaste decenniet har nya blodförtunnande läkemedel, DOAK, börjat dominera. Patienter med mer än moderat nedsatt njurfunktion har till största del uteslutits från stora randomiserade läkemedelsprövningar (RCTs) av antikoagulantia. Detta beror delvis på att CKD i sig medför ökad blödningsrisk. Därför är det oklart om patienter med allvarligt nedsatt njurfunktion och förmaksflimmer ska ha blodförtunnande, eller om den ökade blödningsrisken medför att antikoagulantia ska undvikas. Nefrotiskt syndrom är ett specialfall av njursjukdom som innebär ökad risk för venösa proppar. Traditionellt sett har dessa patienter behandlats med förebyggande blodförtunning, men det saknas studier på dess effekt och säkerhet. Syftet med våra studier var att undersöka nytta och risk med blodförtunning

Background Severe trauma represents a major global public health burden and the management of post-traumatic bleeding continues to challenge healthcare systems around the world. Post-traumatic bleeding and associated traumatic coagulopathy remain leading causes of potentially preventable multiorgan failure and death if not diagnosed and managed in an appropriate and timely manner. This sixth edition of the European guideline on the management of major bleeding and coagulopathy following traumatic injury aims to advise clinicians who care for the bleeding trauma patient during the initial diagnostic and therapeutic phases of patient management. Methods The pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma included representatives from six European professional societies and convened to assess and update the previous version of this guideline using a structured, evidence-based consensus approach. Structured literature searches covered the period since the last edition of the guideline, but considered evidence cited previously. The format of this edition has been adjusted to reflect the trend towards concise guideline documents that cite only the highest-quality studies and most relevant literature rather than attempting to provide a comprehensive literature review to accompany each recommendation. Results This guideline comprises 39 clinical practice recommendations that follow an approximate temporal path for management of the bleeding trauma patient, with recommendations grouped behind key decision points. While approximately one-third of patients who have experienced severe trauma arrive in hospital in a coagulopathic state, a systematic diagnostic and therapeutic approach has been shown to reduce the number of preventable deaths attributable to traumatic injury. Conclusion A multidisciplinary approach and adherence to evidence-based guidelines are pillars of best practice in the management of, Background: Severe trauma represents a major global public health burden and the management of post-traumatic bleeding continues to challenge healthcare systems around the world. Post-traumatic bleeding and associated traumatic coagulopathy remain leading causes of potentially preventable multiorgan failure and death if not diagnosed and managed in an appropriate and timely manner. This sixth edition of the European guideline on the management of major bleeding and coagulopathy following traumatic injury aims to advise clinicians who care for the bleeding trauma patient during the initial diagnostic and therapeutic phases of patient management. Methods: The pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma included representatives from six European professional societies and convened to assess and update the previous version of this guideline using a structured, evidence-based consensus approach. Structured literature searches covered the period since the last edition of the guideline, but considered evidence cited previously. The format of this edition has been adjusted to reflect the trend towards concise guideline documents that cite only the highest-quality studies and most relevant literature rather than attempting to provide a comprehensive literature review to accompany each recommendation. Results: This guideline comprises 39 clinical practice recommendations that follow an approximate temporal path for management of the bleeding trauma patient, with recommendations grouped behind key decision points. While approximately one-third of patients who have experienced severe trauma arrive in hospital in a coagulopathic state, a systematic diagnostic and therapeutic approach has been shown to reduce the number of preventable deaths attributable to traumatic injury. Conclusion: A multidisciplinary approach and adherence to evidence-based guidelines are pillars of best practice in the management of severely injured trauma patients. F

Background: direct oral anticoagulants (DOACs) are an alternative to conventional antagonist of vitamin-K (AVK). However, immune suppressive drugs (ISDs) may interfere with DOACs pharmacokinetic. Aim of this study: evaluate safety and efficacy profile of DOACs compared to AVK in kidney transplant recipients (KTRs) treated with ISDs. Methods: a multi-center study from 4 Italian University hospitals enrolling consecutive KTRs on DOACs or AVK was carried out. Sixty-six patients on DOACs were compared with fifty patients on AVK with similar clinical features. Serial evaluation of renal function and serum levels of ISDs during 18 months follow-up (FU) was performed. Results: Mean age of DOACs patients was 67±9 and mean eGFR was 58,3± 30,4mL/min/1.73m2. ISDs included tacrolimus (n=47, 71%), cyclosporin (n=13, 20%), everolimus (n=10, 7%) and sirolimus (n=4, 6%). After 14 days of DOACs therapy initiation there was a slight increase of serum levels of tacrolimus (+0.19±0.67 p=0.80) and cyclosporine (+0.12±0.25 p=0.94) not statistically significant. Levels of Tacrolimus and cyclosporin were stable at serial evaluation during 18-months follow-up. There were no thromboembolic events among patients treated with DOACs or AVK and no differences in term of major bleeding (6% vs 4% p=0.69), at long-term follow-up. There was no difference in term of eGFR decline from start therapy to 18 months FU between DOACs vs AVK therapy (-3.9±1 vs -3.8±2 p=0.82). Conclusion: DOACs have similar safety and efficacy than AVK among KTRs treated with ISDs. However, careful evaluation of potential drug interaction and ISDs serum levels is needed.

Background: Severe trauma represents a major global public health burden and the management of post-traumatic bleeding continues to challenge healthcare systems around the world. Post-traumatic bleeding and associated traumatic coagulopathy remain leading causes of potentially preventable multiorgan failure and death if not diagnosed and managed in an appropriate and timely manner. This sixth edition of the European guideline on the management of major bleeding and coagulopathy following traumatic injury aims to advise clinicians who care for the bleeding trauma patient during the initial diagnostic and therapeutic phases of patient management. Methods: The pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma included representatives from six European professional societies and convened to assess and update the previous version of this guideline using a structured, evidence-based consensus approach. Structured literature searches covered the period since the last edition of the guideline, but considered evidence cited previously. The format of this edition has been adjusted to reflect the trend towards concise guideline documents that cite only the highest-quality studies and most relevant literature rather than attempting to provide a comprehensive literature review to accompany each recommendation. Results: This guideline comprises 39 clinical practice recommendations that follow an approximate temporal path for management of the bleeding trauma patient, with recommendations grouped behind key decision points. While approximately one-third of patients who have experienced severe trauma arrive in hospital in a coagulopathic state, a systematic diagnostic and therapeutic approach has been shown to reduce the number of preventable deaths attributable to traumatic injury. Conclusion: A multidisciplinary approach and adherence to evidence-based guidelines are pillars of best practice in the management of severely injured trauma patients. Furt, SCOPUS: ar.j, info:eu-repo/semantics/published

Background Severe trauma represents a major global public health burden and the management of post-traumatic bleeding continues to challenge healthcare systems around the world. Post-traumatic bleeding and associated traumatic coagulopathy remain leading causes of potentially preventable multiorgan failure and death if not diagnosed and managed in an appropriate and timely manner. This sixth edition of the European guideline on the management of major bleeding and coagulopathy following traumatic injury aims to advise clinicians who care for the bleeding trauma patient during the initial diagnostic and therapeutic phases of patient management. Methods The pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma included representatives from six European professional societies and convened to assess and update the previous version of this guideline using a structured, evidence-based consensus approach. Structured literature searches covered the period since the last edition of the guideline, but considered evidence cited previously. The format of this edition has been adjusted to reflect the trend towards concise guideline documents that cite only the highest-quality studies and most relevant literature rather than attempting to provide a comprehensive literature review to accompany each recommendation. Results This guideline comprises 39 clinical practice recommendations that follow an approximate temporal path for management of the bleeding trauma patient, with recommendations grouped behind key decision points. While approximately one-third of patients who have experienced severe trauma arrive in hospital in a coagulopathic state, a systematic diagnostic and therapeutic approach has been shown to reduce the number of preventable deaths attributable to traumatic injury. Conclusion A multidisciplinary approach and adherence to evidence-based guidelines are pillars of best practice in the management of, Background: Severe trauma represents a major global public health burden and the management of post-traumatic bleeding continues to challenge healthcare systems around the world. Post-traumatic bleeding and associated traumatic coagulopathy remain leading causes of potentially preventable multiorgan failure and death if not diagnosed and managed in an appropriate and timely manner. This sixth edition of the European guideline on the management of major bleeding and coagulopathy following traumatic injury aims to advise clinicians who care for the bleeding trauma patient during the initial diagnostic and therapeutic phases of patient management. Methods: The pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma included representatives from six European professional societies and convened to assess and update the previous version of this guideline using a structured, evidence-based consensus approach. Structured literature searches covered the period since the last edition of the guideline, but considered evidence cited previously. The format of this edition has been adjusted to reflect the trend towards concise guideline documents that cite only the highest-quality studies and most relevant literature rather than attempting to provide a comprehensive literature review to accompany each recommendation. Results: This guideline comprises 39 clinical practice recommendations that follow an approximate temporal path for management of the bleeding trauma patient, with recommendations grouped behind key decision points. While approximately one-third of patients who have experienced severe trauma arrive in hospital in a coagulopathic state, a systematic diagnostic and therapeutic approach has been shown to reduce the number of preventable deaths attributable to traumatic injury. Conclusion: A multidisciplinary approach and adherence to evidence-based guidelines are pillars of best practice in the management of severely injured trauma patients. F

Background Observational data comparing warfarin with no treatment for patients with non-valvular atrial fibrillation (NVAF) and severely reduced glomerular filtration rate (GFR) are conflicting and randomized controlled trials (RCTs) are lacking. Most studies do not provide information on warfarin treatment quality, making them difficult to compare. Methods This national cohort study investigates the risk of ischaemic stroke and major bleeding during warfarin treatment compared with no oral anticoagulants in patients with NVAF, GFR category 3-5 (G3-G5) or on dialysis (G5D), with kidney transplant recipients excluded, between 2009 and 2018. Data extracted from high-quality Swedish national healthcare registries, including the Swedish Renal Registry, AuriculA-the Swedish national quality registry for atrial fibrillation and anticoagulation-and the Stroke Registry. Results At enrolment of 12 106 patients, 21.4% were G3, 43.5% were G4, 11.6% were G5 and 23.6% were G5D. The mean time in the therapeutic range was 70%. Warfarin compared with no treatment showed a lower risk for ischaemic stroke for G3 {hazard ratio [HR] 0.37 [95% confidence interval (CI) 0.18-0.76]}, G4 [0.53 (0.38-0.74)] and G5 [0.49 (0.30-0.79)] and an increased risk of major bleeding in G4 [HR 1.22 (1.02-1.46)], G5 [1.52 (1.15-2.01)] and G5D [1.23 (1.00-1.51)]. All-cause mortality was more than halved on warfarin compared with no treatment in all GFR categories. Conclusions Warfarin treatment is associated with a lower risk of ischaemic stroke for patients with NVAF and G3, G4 and G5D at the cost of a higher risk of major bleeding for G4-G5D. Existing observational data are conflicting, stressing the need for RCTs on warfarin compared with no treatment in G4-G5D. Awaiting RCTs, it seems reasonable to treat selected patients on dialysis and NVAF with warfarin.

Background Observational data comparing warfarin with no treatment for patients with non-valvular atrial fibrillation (NVAF) and severely reduced glomerular filtration rate (GFR) are conflicting and randomized controlled trials (RCTs) are lacking. Most studies do not provide information on warfarin treatment quality, making them difficult to compare. Methods This national cohort study investigates the risk of ischaemic stroke and major bleeding during warfarin treatment compared with no oral anticoagulants in patients with NVAF, GFR category 3-5 (G3-G5) or on dialysis (G5D), with kidney transplant recipients excluded, between 2009 and 2018. Data extracted from high-quality Swedish national healthcare registries, including the Swedish Renal Registry, AuriculA-the Swedish national quality registry for atrial fibrillation and anticoagulation-and the Stroke Registry. Results At enrolment of 12 106 patients, 21.4% were G3, 43.5% were G4, 11.6% were G5 and 23.6% were G5D. The mean time in the therapeutic range was 70%. Warfarin compared with no treatment showed a lower risk for ischaemic stroke for G3 {hazard ratio [HR] 0.37 [95% confidence interval (CI) 0.18-0.76]}, G4 [0.53 (0.38-0.74)] and G5 [0.49 (0.30-0.79)] and an increased risk of major bleeding in G4 [HR 1.22 (1.02-1.46)], G5 [1.52 (1.15-2.01)] and G5D [1.23 (1.00-1.51)]. All-cause mortality was more than halved on warfarin compared with no treatment in all GFR categories. Conclusions Warfarin treatment is associated with a lower risk of ischaemic stroke for patients with NVAF and G3, G4 and G5D at the cost of a higher risk of major bleeding for G4-G5D. Existing observational data are conflicting, stressing the need for RCTs on warfarin compared with no treatment in G4-G5D. Awaiting RCTs, it seems reasonable to treat selected patients on dialysis and NVAF with warfarin.

BACKGROUND: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. METHODS: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. RESULTS: A total of 9,306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30.0% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment,p<0.001. Over 24 months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07[95% CI,1.01-1.14] per 10 mL/min/1.73m2 decrease), that was most notable in patients with eGFR <30mL/min/1.73m2 (HR 2.21[95% CI,1.23-3.99] compared to eGFR ≥90mL/min/1.73m2 ). CONCLUSION: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF.

BACKGROUND: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. METHODS: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. RESULTS: A total of 9,306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30.0% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment,p<0.001. Over 24 months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07[95% CI,1.01-1.14] per 10 mL/min/1.73m2 decrease), that was most notable in patients with eGFR <30mL/min/1.73m2 (HR 2.21[95% CI,1.23-3.99] compared to eGFR ≥90mL/min/1.73m2 ). CONCLUSION: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF.

Background Observational data comparing warfarin with no treatment for patients with non-valvular atrial fibrillation (NVAF) and severely reduced glomerular filtration rate (GFR) are conflicting and randomized controlled trials (RCTs) are lacking. Most studies do not provide information on warfarin treatment quality, making them difficult to compare. Methods This national cohort study investigates the risk of ischaemic stroke and major bleeding during warfarin treatment compared with no oral anticoagulants in patients with NVAF, GFR category 3-5 (G3-G5) or on dialysis (G5D), with kidney transplant recipients excluded, between 2009 and 2018. Data extracted from high-quality Swedish national healthcare registries, including the Swedish Renal Registry, AuriculA-the Swedish national quality registry for atrial fibrillation and anticoagulation-and the Stroke Registry. Results At enrolment of 12 106 patients, 21.4% were G3, 43.5% were G4, 11.6% were G5 and 23.6% were G5D. The mean time in the therapeutic range was 70%. Warfarin compared with no treatment showed a lower risk for ischaemic stroke for G3 {hazard ratio [HR] 0.37 [95% confidence interval (CI) 0.18-0.76]}, G4 [0.53 (0.38-0.74)] and G5 [0.49 (0.30-0.79)] and an increased risk of major bleeding in G4 [HR 1.22 (1.02-1.46)], G5 [1.52 (1.15-2.01)] and G5D [1.23 (1.00-1.51)]. All-cause mortality was more than halved on warfarin compared with no treatment in all GFR categories. Conclusions Warfarin treatment is associated with a lower risk of ischaemic stroke for patients with NVAF and G3, G4 and G5D at the cost of a higher risk of major bleeding for G4-G5D. Existing observational data are conflicting, stressing the need for RCTs on warfarin compared with no treatment in G4-G5D. Awaiting RCTs, it seems reasonable to treat selected patients on dialysis and NVAF with warfarin.

Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p < .001. Over 24 months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01-1.14] per 10 ml/min/1.73 m decrease), that was most notable in patients with eGFR <30 ml/min/1.73 m (HR 2.21 [95% CI, 1.23-3.99] compared to eGFR ≥90 ml/min/1.73 m ). A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF.

BACKGROUND: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. METHODS: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. RESULTS: A total of 9,306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30.0% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment,p<0.001. Over 24 months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07[95% CI,1.01-1.14] per 10 mL/min/1.73m2 decrease), that was most notable in patients with eGFR <30mL/min/1.73m2 (HR 2.21[95% CI,1.23-3.99] compared to eGFR ≥90mL/min/1.73m2 ). CONCLUSION: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF.

BACKGROUND: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. METHODS: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. RESULTS: A total of 9,306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30.0% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment,p<0.001. Over 24 months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07[95% CI,1.01-1.14] per 10 mL/min/1.73m2 decrease), that was most notable in patients with eGFR <30mL/min/1.73m2 (HR 2.21[95% CI,1.23-3.99] compared to eGFR ≥90mL/min/1.73m2 ). CONCLUSION: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF.

Background Observational data comparing warfarin with no treatment for patients with non-valvular atrial fibrillation (NVAF) and severely reduced glomerular filtration rate (GFR) are conflicting and randomized controlled trials (RCTs) are lacking. Most studies do not provide information on warfarin treatment quality, making them difficult to compare. Methods This national cohort study investigates the risk of ischaemic stroke and major bleeding during warfarin treatment compared with no oral anticoagulants in patients with NVAF, GFR category 3-5 (G3-G5) or on dialysis (G5D), with kidney transplant recipients excluded, between 2009 and 2018. Data extracted from high-quality Swedish national healthcare registries, including the Swedish Renal Registry, AuriculA-the Swedish national quality registry for atrial fibrillation and anticoagulation-and the Stroke Registry. Results At enrolment of 12 106 patients, 21.4% were G3, 43.5% were G4, 11.6% were G5 and 23.6% were G5D. The mean time in the therapeutic range was 70%. Warfarin compared with no treatment showed a lower risk for ischaemic stroke for G3 {hazard ratio [HR] 0.37 [95% confidence interval (CI) 0.18-0.76]}, G4 [0.53 (0.38-0.74)] and G5 [0.49 (0.30-0.79)] and an increased risk of major bleeding in G4 [HR 1.22 (1.02-1.46)], G5 [1.52 (1.15-2.01)] and G5D [1.23 (1.00-1.51)]. All-cause mortality was more than halved on warfarin compared with no treatment in all GFR categories. Conclusions Warfarin treatment is associated with a lower risk of ischaemic stroke for patients with NVAF and G3, G4 and G5D at the cost of a higher risk of major bleeding for G4-G5D. Existing observational data are conflicting, stressing the need for RCTs on warfarin compared with no treatment in G4-G5D. Awaiting RCTs, it seems reasonable to treat selected patients on dialysis and NVAF with warfarin.

Background: Observational data comparing warfarin with no treatment for patients with non-valvular atrial fibrillation (NVAF) and severely reduced glomerular filtration rate (GFR) are conflicting and randomized controlled trials (RCTs) are lacking. Most studies do not provide information on warfarin treatment quality, making them difficult to compare. Methods: This national cohort study investigates the risk of ischaemic stroke and major bleeding during warfarin treatment compared with no oral anticoagulants in patients with NVAF, GFR category 3-5 (G3-G5) or on dialysis (G5D), with kidney transplant recipients excluded, between 2009 and 2018. Data extracted from high-quality Swedish national healthcare registries, including the Swedish Renal Registry, AuriculA-the Swedish national quality registry for atrial fibrillation and anticoagulation- A nd the Stroke Registry. Results: At enrolment of 12 106 patients, 21.4% were G3, 43.5% were G4, 11.6% were G5 and 23.6% were G5D. The mean time in the therapeutic range was 70%. Warfarin compared with no treatment showed a lower risk for ischaemic stroke for G3 {hazard ratio [HR] 0.37 [95% confidence interval (CI) 0.18-0.76]}, G4 [0.53 (0.38-0.74)] and G5 [0.49 (0.30-0.79)] and an increased risk of major bleeding in G4 [HR 1.22 (1.02-1.46)], G5 [1.52 (1.15-2.01)] and G5D [1.23 (1.00-1.51)]. All-cause mortality was more than halved on warfarin compared with no treatment in all GFR categories. Conclusions: Warfarin treatment is associated with a lower risk of ischaemic stroke for patients with NVAF and G3, G4 and G5D at the cost of a higher risk of major bleeding for G4-G5D. Existing observational data are conflicting, stressing the need for RCTs on warfarin compared with no treatment in G4-G5D. Awaiting RCTs, it seems reasonable to treat selected patients on dialysis and NVAF with warfarin.

Background: Observational data comparing warfarin with no treatment for patients with non-valvular atrial fibrillation (NVAF) and severely reduced glomerular filtration rate (GFR) are conflicting and randomized controlled trials (RCTs) are lacking. Most studies do not provide information on warfarin treatment quality, making them difficult to compare. Methods: This national cohort study investigates the risk of ischaemic stroke and major bleeding during warfarin treatment compared with no oral anticoagulants in patients with NVAF, GFR category 3-5 (G3-G5) or on dialysis (G5D), with kidney transplant recipients excluded, between 2009 and 2018. Data extracted from high-quality Swedish national healthcare registries, including the Swedish Renal Registry, AuriculA-the Swedish national quality registry for atrial fibrillation and anticoagulation- A nd the Stroke Registry. Results: At enrolment of 12 106 patients, 21.4% were G3, 43.5% were G4, 11.6% were G5 and 23.6% were G5D. The mean time in the therapeutic range was 70%. Warfarin compared with no treatment showed a lower risk for ischaemic stroke for G3 {hazard ratio [HR] 0.37 [95% confidence interval (CI) 0.18-0.76]}, G4 [0.53 (0.38-0.74)] and G5 [0.49 (0.30-0.79)] and an increased risk of major bleeding in G4 [HR 1.22 (1.02-1.46)], G5 [1.52 (1.15-2.01)] and G5D [1.23 (1.00-1.51)]. All-cause mortality was more than halved on warfarin compared with no treatment in all GFR categories. Conclusions: Warfarin treatment is associated with a lower risk of ischaemic stroke for patients with NVAF and G3, G4 and G5D at the cost of a higher risk of major bleeding for G4-G5D. Existing observational data are conflicting, stressing the need for RCTs on warfarin compared with no treatment in G4-G5D. Awaiting RCTs, it seems reasonable to treat selected patients on dialysis and NVAF with warfarin.

Background: Observational data comparing warfarin with no treatment for patients with non-valvular atrial fibrillation (NVAF) and severely reduced glomerular filtration rate (GFR) are conflicting and randomized controlled trials (RCTs) are lacking. Most studies do not provide information on warfarin treatment quality, making them difficult to compare. Methods: This national cohort study investigates the risk of ischaemic stroke and major bleeding during warfarin treatment compared with no oral anticoagulants in patients with NVAF, GFR category 3-5 (G3-G5) or on dialysis (G5D), with kidney transplant recipients excluded, between 2009 and 2018. Data extracted from high-quality Swedish national healthcare registries, including the Swedish Renal Registry, AuriculA-the Swedish national quality registry for atrial fibrillation and anticoagulation- A nd the Stroke Registry. Results: At enrolment of 12 106 patients, 21.4% were G3, 43.5% were G4, 11.6% were G5 and 23.6% were G5D. The mean time in the therapeutic range was 70%. Warfarin compared with no treatment showed a lower risk for ischaemic stroke for G3 {hazard ratio [HR] 0.37 [95% confidence interval (CI) 0.18-0.76]}, G4 [0.53 (0.38-0.74)] and G5 [0.49 (0.30-0.79)] and an increased risk of major bleeding in G4 [HR 1.22 (1.02-1.46)], G5 [1.52 (1.15-2.01)] and G5D [1.23 (1.00-1.51)]. All-cause mortality was more than halved on warfarin compared with no treatment in all GFR categories. Conclusions: Warfarin treatment is associated with a lower risk of ischaemic stroke for patients with NVAF and G3, G4 and G5D at the cost of a higher risk of major bleeding for G4-G5D. Existing observational data are conflicting, stressing the need for RCTs on warfarin compared with no treatment in G4-G5D. Awaiting RCTs, it seems reasonable to treat selected patients on dialysis and NVAF with warfarin.

Background: Observational data comparing warfarin with no treatment for patients with non-valvular atrial fibrillation (NVAF) and severely reduced glomerular filtration rate (GFR) are conflicting and randomized controlled trials (RCTs) are lacking. Most studies do not provide information on warfarin treatment quality, making them difficult to compare. Methods: This national cohort study investigates the risk of ischaemic stroke and major bleeding during warfarin treatment compared with no oral anticoagulants in patients with NVAF, GFR category 3-5 (G3-G5) or on dialysis (G5D), with kidney transplant recipients excluded, between 2009 and 2018. Data extracted from high-quality Swedish national healthcare registries, including the Swedish Renal Registry, AuriculA-the Swedish national quality registry for atrial fibrillation and anticoagulation- A nd the Stroke Registry. Results: At enrolment of 12 106 patients, 21.4% were G3, 43.5% were G4, 11.6% were G5 and 23.6% were G5D. The mean time in the therapeutic range was 70%. Warfarin compared with no treatment showed a lower risk for ischaemic stroke for G3 {hazard ratio [HR] 0.37 [95% confidence interval (CI) 0.18-0.76]}, G4 [0.53 (0.38-0.74)] and G5 [0.49 (0.30-0.79)] and an increased risk of major bleeding in G4 [HR 1.22 (1.02-1.46)], G5 [1.52 (1.15-2.01)] and G5D [1.23 (1.00-1.51)]. All-cause mortality was more than halved on warfarin compared with no treatment in all GFR categories. Conclusions: Warfarin treatment is associated with a lower risk of ischaemic stroke for patients with NVAF and G3, G4 and G5D at the cost of a higher risk of major bleeding for G4-G5D. Existing observational data are conflicting, stressing the need for RCTs on warfarin compared with no treatment in G4-G5D. Awaiting RCTs, it seems reasonable to treat selected patients on dialysis and NVAF with warfarin.

BACKGROUND: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. METHODS: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. RESULTS: A total of 9,306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30.0% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment,p<0.001. Over 24 months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07[95% CI,1.01-1.14] per 10 mL/min/1.73m2 decrease), that was most notable in patients with eGFR <30mL/min/1.73m2 (HR 2.21[95% CI,1.23-3.99] compared to eGFR ≥90mL/min/1.73m2 ). CONCLUSION: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF.

Background Observational data comparing warfarin with no treatment for patients with non-valvular atrial fibrillation (NVAF) and severely reduced glomerular filtration rate (GFR) are conflicting and randomized controlled trials (RCTs) are lacking. Most studies do not provide information on warfarin treatment quality, making them difficult to compare. Methods This national cohort study investigates the risk of ischaemic stroke and major bleeding during warfarin treatment compared with no oral anticoagulants in patients with NVAF, GFR category 3-5 (G3-G5) or on dialysis (G5D), with kidney transplant recipients excluded, between 2009 and 2018. Data extracted from high-quality Swedish national healthcare registries, including the Swedish Renal Registry, AuriculA-the Swedish national quality registry for atrial fibrillation and anticoagulation-and the Stroke Registry. Results At enrolment of 12 106 patients, 21.4% were G3, 43.5% were G4, 11.6% were G5 and 23.6% were G5D. The mean time in the therapeutic range was 70%. Warfarin compared with no treatment showed a lower risk for ischaemic stroke for G3 {hazard ratio [HR] 0.37 [95% confidence interval (CI) 0.18-0.76]}, G4 [0.53 (0.38-0.74)] and G5 [0.49 (0.30-0.79)] and an increased risk of major bleeding in G4 [HR 1.22 (1.02-1.46)], G5 [1.52 (1.15-2.01)] and G5D [1.23 (1.00-1.51)]. All-cause mortality was more than halved on warfarin compared with no treatment in all GFR categories. Conclusions Warfarin treatment is associated with a lower risk of ischaemic stroke for patients with NVAF and G3, G4 and G5D at the cost of a higher risk of major bleeding for G4-G5D. Existing observational data are conflicting, stressing the need for RCTs on warfarin compared with no treatment in G4-G5D. Awaiting RCTs, it seems reasonable to treat selected patients on dialysis and NVAF with warfarin.

Background: Observational data comparing warfarin with no treatment for patients with non-valvular atrial fibrillation (NVAF) and severely reduced glomerular filtration rate (GFR) are conflicting and randomized controlled trials (RCTs) are lacking. Most studies do not provide information on warfarin treatment quality, making them difficult to compare. Methods: This national cohort study investigates the risk of ischaemic stroke and major bleeding during warfarin treatment compared with no oral anticoagulants in patients with NVAF, GFR category 3-5 (G3-G5) or on dialysis (G5D), with kidney transplant recipients excluded, between 2009 and 2018. Data extracted from high-quality Swedish national healthcare registries, including the Swedish Renal Registry, AuriculA-the Swedish national quality registry for atrial fibrillation and anticoagulation- A nd the Stroke Registry. Results: At enrolment of 12 106 patients, 21.4% were G3, 43.5% were G4, 11.6% were G5 and 23.6% were G5D. The mean time in the therapeutic range was 70%. Warfarin compared with no treatment showed a lower risk for ischaemic stroke for G3 {hazard ratio [HR] 0.37 [95% confidence interval (CI) 0.18-0.76]}, G4 [0.53 (0.38-0.74)] and G5 [0.49 (0.30-0.79)] and an increased risk of major bleeding in G4 [HR 1.22 (1.02-1.46)], G5 [1.52 (1.15-2.01)] and G5D [1.23 (1.00-1.51)]. All-cause mortality was more than halved on warfarin compared with no treatment in all GFR categories. Conclusions: Warfarin treatment is associated with a lower risk of ischaemic stroke for patients with NVAF and G3, G4 and G5D at the cost of a higher risk of major bleeding for G4-G5D. Existing observational data are conflicting, stressing the need for RCTs on warfarin compared with no treatment in G4-G5D. Awaiting RCTs, it seems reasonable to treat selected patients on dialysis and NVAF with warfarin.

Adults with congenital heart disease (ACHD) are a completely new and rapidly growing specialty comprising patients who require specialist knowledge regarding their care and treatment. Challenges involve diagnostics and treatment as studies are scarce and include small and heterogenous study populations.The first aim with this thesis was to evaluate the relationship between the systemic right ventricular function determined by cardiac magnetic resonance (CMR) imaging, biomarkers, echocardiographic parameters, New York Heart Association class and performance on stress test.The second aim of this thesis was to evaluate anticoagulation treatment with vitamin K antagonists (VKA) in ACHD. This involved determining the quality of VKA therapy by evaluating time in therapeutic range (TTR) and variability of international normalised ratio of prothrombin time. Furthermore, studying the efficacy and safety of VKA and non-vitamin K oral antagonists (NOAC) in ACHD by evaluating the incidence of thromboembolism (TE), major bleeding and potential risk factors.Paper I A correlation was observed between the systemic ventricular function determined with CMR and echocardiographic ventricular global longitudinal strain in patients with systemic right ventricle.Paper II-III Anticoagulation with VKA was of high quality in ACHD in the South of Sweden. A low incidence of TE and major bleeding events was seen in ACHD patients with high quality VKA treatment. Younger age, female gender and cardiac failure were risk factors for poor anticoagulation and thus may be cause for cautiosness and when suitable, consideration of alternative non-VKA anticoagulants. History of TE was associated with complcations (TE and major bleeding).Paper IV In this retrospective study reports a single-center experience of NOAC use in ACHD patients we found no thromboembolic and one major bleeding events during a median duration of 17 months of therapy.In conclusion, right ventricular global longitudinal strain by ec

Objective: To establish the risk of major bleeding in direct oral anticoagulant (DOAC) users (overall and by class) versus vitamin K antagonist (VKA) users, using health care databases from four European countries and six provinces in Canada. Methods: A retrospective cohort study was performed according to a similar protocol. First-users of VKAs or DOACs with a diagnosis of non-valvular atrial fibrillation (NVAF) were included. The main outcome of interest was major bleeding and secondary outcomes included gastrointestinal (GI) bleeding and intracranial haemorrhage (ICH). Incidence rates of events per 1000 person years were calculated. Hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated using a Cox proportional hazard regression model. Exposure and confounders were measured and analysed in a time-dependant way. Risk estimates were pooled using a random effect model. Results: 421 523 patients were included. The risk of major bleeding for the group of DOACs compared to VKAs showed a pooled HR of 0.94 (95% CI: 0.87–1.02). Rivaroxaban showed a modestly increased risk (HR 1.11, 95% CI: 1.06–1.16). Apixaban and dabigatran showed a decreased risk of respectively HR 0.76 (95% CI: 0.69–0.84) and HR 0.85 (95% CI: 0.75–0.96). Conclusions: This study confirms that the risk of major bleeding of DOACs compared to VKAs is not increased when combining all DOACs. However, we observed a modest higher risk of major bleeding for rivaroxaban, whereas for apixaban and dabigatran lower risks of major bleeding were observed compared to VKAs.

AIMS: The introduction of direct oral anticoagulants (DOACs) has broadened the treatment arsenal for nonvalvular atrial fibrillation, but observational studies on the benefit-risk balance of DOACs compared to vitamin K antagonists (VKAs) are needed. The aim of this study was to characterize the risk of major bleeding in DOAC users using longitudinal data collected from electronic health care databases from 4 different EU-countries analysed with a common study protocol.METHODS: A cohort study was conducted among new users (≥18 years) of DOACs or VKAs with nonvalvular atrial fibrillation using data from the UK, Spain, Germany and Denmark. The incidence of major bleeding events (overall and by bleeding site) was compared between current use of DOACs and VKAs. Cox regression analysis was used to calculate hazard ratios and 95% confidence intervals (CI) and adjust for confounders.RESULTS/CONCLUSION: Overall, 251 719 patients were included across the 4 study cohorts (mean age ~75 years, % females between 41.3 and 54.3%), with overall hazard ratios of major bleeding risk for DOACs vs VKAs ranging between 0.84 (95% CI: 0.79-0.90) in Denmark and 1.13 (95% CI 1.02-1.25) in the UK. When stratifying according to the bleeding site, risk of gastrointestinal bleeding was increased by 48-67% in dabigatran users and 30-50% for rivaroxaban users compared to VKA users in all data sources except Denmark. Compared to VKAs, apixaban was not associated with an increased risk of gastrointestinal bleeding in all data sources and seemed to be associated with the lowest risk of major bleeding events compared to dabigatran and rivaroxaban.

New oral anticoagulants (NOACs) is the preferred treatment in secondary prophylaxis of venous thromboembolic events (VTE). The aim of this study was to investigate possible risk factors associated with major bleeding in VTE-patients treated with NOACs. In this retrospective register-based study we screened the Swedish anticoagulation register Auricula (during 2012.01.01-2017.12.31) to find patients and used other national registers for outcomes. Primary endpoint was major bleeding defined as bleeding leading to hospital care. Multivariate Cox-regression analysis was used to reveal risk factors. 18 219 patients with NOAC due to VTE were included. 85.6% had their first VTE, mean age was 69.4 years and median follow-up time was 183 days. The most common NOAC was rivaroxaban (54.8%), followed by apixaban (42.0%), dabigatran (3.2%) and edoxaban (0.1%). The rate of major bleeding was 6.62 (95% CI 6.19-7.06) per 100 treatment years in all patients and 11.27 (CI 9.96-12.57) in patients above 80 years of age. Statistically independent risk factors associated with major bleeding were age (normalized HR 1.38, CI 1.27-1.50), earlier major bleeding (HR 1.58, Cl 1.09-2.30), COPD (HR 1.28, CI 1.04-1.60) and previous stroke (HR 1.28, Cl 1.03-1.58) or transient ischemic attack (TIA) (HR 1.33, Cl 1.01-1.76). Prior warfarin treatment was protective (HR 0.67, CI 0.58-0.78). This real world cohort shows a high bleeding rate especially among the elderly and in patients with previous major bleeding, COPD and previous stroke or TIA. This should be considered when deciding on treatment duration and NOAC dose in these patients., First published online: 2 November 2020

New oral anticoagulants (NOACs) is the preferred treatment in secondary prophylaxis of venous thromboembolic events (VTE). The aim of this study was to investigate possible risk factors associated with major bleeding in VTE-patients treated with NOACs. In this retrospective register-based study we screened the Swedish anticoagulation register Auricula (during 2012.01.01-2017.12.31) to find patients and used other national registers for outcomes. Primary endpoint was major bleeding defined as bleeding leading to hospital care. Multivariate Cox-regression analysis was used to reveal risk factors. 18 219 patients with NOAC due to VTE were included. 85.6% had their first VTE, mean age was 69.4 years and median follow-up time was 183 days. The most common NOAC was rivaroxaban (54.8%), followed by apixaban (42.0%), dabigatran (3.2%) and edoxaban (0.1%). The rate of major bleeding was 6.62 (95% CI 6.19-7.06) per 100 treatment years in all patients and 11.27 (CI 9.96-12.57) in patients above 80 years of age. Statistically independent risk factors associated with major bleeding were age (normalized HR 1.38, CI 1.27-1.50), earlier major bleeding (HR 1.58, Cl 1.09-2.30), COPD (HR 1.28, CI 1.04-1.60) and previous stroke (HR 1.28, Cl 1.03-1.58) or transient ischemic attack (TIA) (HR 1.33, Cl 1.01-1.76). Prior warfarin treatment was protective (HR 0.67, CI 0.58-0.78). This real world cohort shows a high bleeding rate especially among the elderly and in patients with previous major bleeding, COPD and previous stroke or TIA. This should be considered when deciding on treatment duration and NOAC dose in these patients., First published online: 2 November 2020

New oral anticoagulants (NOACs) is the preferred treatment in secondary prophylaxis of venous thromboembolic events (VTE). The aim of this study was to investigate possible risk factors associated with major bleeding in VTE-patients treated with NOACs. In this retrospective register-based study we screened the Swedish anticoagulation register Auricula (during 2012.01.01-2017.12.31) to find patients and used other national registers for outcomes. Primary endpoint was major bleeding defined as bleeding leading to hospital care. Multivariate Cox-regression analysis was used to reveal risk factors. 18 219 patients with NOAC due to VTE were included. 85.6% had their first VTE, mean age was 69.4 years and median follow-up time was 183 days. The most common NOAC was rivaroxaban (54.8%), followed by apixaban (42.0%), dabigatran (3.2%) and edoxaban (0.1%). The rate of major bleeding was 6.62 (95% CI 6.19-7.06) per 100 treatment years in all patients and 11.27 (CI 9.96-12.57) in patients above 80 years of age. Statistically independent risk factors associated with major bleeding were age (normalized HR 1.38, CI 1.27-1.50), earlier major bleeding (HR 1.58, Cl 1.09-2.30), COPD (HR 1.28, CI 1.04-1.60) and previous stroke (HR 1.28, Cl 1.03-1.58) or transient ischemic attack (TIA) (HR 1.33, Cl 1.01-1.76). Prior warfarin treatment was protective (HR 0.67, CI 0.58-0.78). This real world cohort shows a high bleeding rate especially among the elderly and in patients with previous major bleeding, COPD and previous stroke or TIA. This should be considered when deciding on treatment duration and NOAC dose in these patients.

New oral anticoagulants (NOACs) is the preferred treatment in secondary prophylaxis of venous thromboembolic events (VTE). The aim of this study was to investigate possible risk factors associated with major bleeding in VTE-patients treated with NOACs. In this retrospective register-based study we screened the Swedish anticoagulation register Auricula (during 2012.01.01-2017.12.31) to find patients and used other national registers for outcomes. Primary endpoint was major bleeding defined as bleeding leading to hospital care. Multivariate Cox-regression analysis was used to reveal risk factors. 18 219 patients with NOAC due to VTE were included. 85.6% had their first VTE, mean age was 69.4 years and median follow-up time was 183 days. The most common NOAC was rivaroxaban (54.8%), followed by apixaban (42.0%), dabigatran (3.2%) and edoxaban (0.1%). The rate of major bleeding was 6.62 (95% CI 6.19-7.06) per 100 treatment years in all patients and 11.27 (CI 9.96-12.57) in patients above 80 years of age. Statistically independent risk factors associated with major bleeding were age (normalized HR 1.38, CI 1.27-1.50), earlier major bleeding (HR 1.58, Cl 1.09-2.30), COPD (HR 1.28, CI 1.04-1.60) and previous stroke (HR 1.28, Cl 1.03-1.58) or transient ischemic attack (TIA) (HR 1.33, Cl 1.01-1.76). Prior warfarin treatment was protective (HR 0.67, CI 0.58-0.78). This real world cohort shows a high bleeding rate especially among the elderly and in patients with previous major bleeding, COPD and previous stroke or TIA. This should be considered when deciding on treatment duration and NOAC dose in these patients.

New oral anticoagulants (NOACs) is the preferred treatment in secondary prophylaxis of venous thromboembolic events (VTE). The aim of this study was to investigate possible risk factors associated with major bleeding in VTE-patients treated with NOACs. In this retrospective register-based study we screened the Swedish anticoagulation register Auricula (during 2012.01.01-2017.12.31) to find patients and used other national registers for outcomes. Primary endpoint was major bleeding defined as bleeding leading to hospital care. Multivariate Cox-regression analysis was used to reveal risk factors. 18 219 patients with NOAC due to VTE were included. 85.6% had their first VTE, mean age was 69.4 years and median follow-up time was 183 days. The most common NOAC was rivaroxaban (54.8%), followed by apixaban (42.0%), dabigatran (3.2%) and edoxaban (0.1%). The rate of major bleeding was 6.62 (95% CI 6.19-7.06) per 100 treatment years in all patients and 11.27 (CI 9.96-12.57) in patients above 80 years of age. Statistically independent risk factors associated with major bleeding were age (normalized HR 1.38, CI 1.27-1.50), earlier major bleeding (HR 1.58, Cl 1.09-2.30), COPD (HR 1.28, CI 1.04-1.60) and previous stroke (HR 1.28, Cl 1.03-1.58) or transient ischemic attack (TIA) (HR 1.33, Cl 1.01-1.76). Prior warfarin treatment was protective (HR 0.67, CI 0.58-0.78). This real world cohort shows a high bleeding rate especially among the elderly and in patients with previous major bleeding, COPD and previous stroke or TIA. This should be considered when deciding on treatment duration and NOAC dose in these patients.

New oral anticoagulants (NOACs) is the preferred treatment in secondary prophylaxis of venous thromboembolic events (VTE). The aim of this study was to investigate possible risk factors associated with major bleeding in VTE-patients treated with NOACs. In this retrospective register-based study we screened the Swedish anticoagulation register Auricula (during 2012.01.01-2017.12.31) to find patients and used other national registers for outcomes. Primary endpoint was major bleeding defined as bleeding leading to hospital care. Multivariate Cox-regression analysis was used to reveal risk factors. 18 219 patients with NOAC due to VTE were included. 85.6% had their first VTE, mean age was 69.4 years and median follow-up time was 183 days. The most common NOAC was rivaroxaban (54.8%), followed by apixaban (42.0%), dabigatran (3.2%) and edoxaban (0.1%). The rate of major bleeding was 6.62 (95% CI 6.19-7.06) per 100 treatment years in all patients and 11.27 (CI 9.96-12.57) in patients above 80 years of age. Statistically independent risk factors associated with major bleeding were age (normalized HR 1.38, CI 1.27-1.50), earlier major bleeding (HR 1.58, Cl 1.09-2.30), COPD (HR 1.28, CI 1.04-1.60) and previous stroke (HR 1.28, Cl 1.03-1.58) or transient ischemic attack (TIA) (HR 1.33, Cl 1.01-1.76). Prior warfarin treatment was protective (HR 0.67, CI 0.58-0.78). This real world cohort shows a high bleeding rate especially among the elderly and in patients with previous major bleeding, COPD and previous stroke or TIA. This should be considered when deciding on treatment duration and NOAC dose in these patients.

New oral anticoagulants (NOACs) is the preferred treatment in secondary prophylaxis of venous thromboembolic events (VTE). The aim of this study was to investigate possible risk factors associated with major bleeding in VTE-patients treated with NOACs. In this retrospective register-based study we screened the Swedish anticoagulation register Auricula (during 2012.01.01-2017.12.31) to find patients and used other national registers for outcomes. Primary endpoint was major bleeding defined as bleeding leading to hospital care. Multivariate Cox-regression analysis was used to reveal risk factors. 18 219 patients with NOAC due to VTE were included. 85.6% had their first VTE, mean age was 69.4 years and median follow-up time was 183 days. The most common NOAC was rivaroxaban (54.8%), followed by apixaban (42.0%), dabigatran (3.2%) and edoxaban (0.1%). The rate of major bleeding was 6.62 (95% CI 6.19-7.06) per 100 treatment years in all patients and 11.27 (CI 9.96-12.57) in patients above 80 years of age. Statistically independent risk factors associated with major bleeding were age (normalized HR 1.38, CI 1.27-1.50), earlier major bleeding (HR 1.58, Cl 1.09-2.30), COPD (HR 1.28, CI 1.04-1.60) and previous stroke (HR 1.28, Cl 1.03-1.58) or transient ischemic attack (TIA) (HR 1.33, Cl 1.01-1.76). Prior warfarin treatment was protective (HR 0.67, CI 0.58-0.78). This real world cohort shows a high bleeding rate especially among the elderly and in patients with previous major bleeding, COPD and previous stroke or TIA. This should be considered when deciding on treatment duration and NOAC dose in these patients., First published online: 2 November 2020

ObjectiveTo establish the risk of major bleeding in direct oral anticoagulant (DOAC) users (overall and by class) versus vitamin K antagonist (VKA) users, using health care databases from four European countries and six provinces in Canada.MethodsA retrospective cohort study was performed according to a similar protocol. First-users of VKAs or DOACs with a diagnosis of non-valvular atrial fibrillation (NVAF) were included. The main outcome of interest was major bleeding and secondary outcomes included gastrointestinal (GI) bleeding and intracranial haemorrhage (ICH). Incidence rates of events per 1000 person years were calculated. Hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated using a Cox proportional hazard regression model. Exposure and confounders were measured and analysed in a time-dependant way. Risk estimates were pooled using a random effect model.Results421 523 patients were included. The risk of major bleeding for the group of DOACs compared to VKAs showed a pooled HR of 0.94 (95% CI: 0.87–1.02). Rivaroxaban showed a modestly increased risk (HR 1.11, 95% CI: 1.06–1.16). Apixaban and dabigatran showed a decreased risk of respectively HR 0.76 (95% CI: 0.69–0.84) and HR 0.85 (95% CI: 0.75–0.96).ConclusionsThis study confirms that the risk of major bleeding of DOACs compared to VKAs is not increased when combining all DOACs. However, we observed a modest higher risk of major bleeding for rivaroxaban, whereas for apixaban and dabigatran lower risks of major bleeding were observed compared to VKAs.

Aims The introduction of direct oral anticoagulants (DOACs) has broadened the treatment arsenal for nonvalvular atrial fibrillation, but observational studies on the benefit-risk balance of DOACs compared to vitamin K antagonists (VKAs) are needed. The aim of this study was to characterize the risk of major bleeding in DOAC users using longitudinal data collected from electronic health care databases from 4 different EU-countries analysed with a common study protocol. Methods A cohort study was conducted among new users (>= 18 years) of DOACs or VKAs with nonvalvular atrial fibrillation using data from the UK, Spain, Germany and Denmark. The incidence of major bleeding events (overall and by bleeding site) was compared between current use of DOACs and VKAs. Cox regression analysis was used to calculate hazard ratios and 95% confidence intervals (CI) and adjust for confounders. Results/Conclusion Overall, 251 719 patients were included across the 4 study cohorts (mean age similar to 75 years, % females between 41.3 and 54.3%), with overall hazard ratios of major bleeding risk for DOACsvsVKAs ranging between 0.84 (95% CI: 0.79-0.90) in Denmark and 1.13 (95% CI 1.02-1.25) in the UK. When stratifying according to the bleeding site, risk of gastrointestinal bleeding was increased by 48-67% in dabigatran users and 30-50% for rivaroxaban users compared to VKA users in all data sources except Denmark. Compared to VKAs, apixaban was not associated with an increased risk of gastrointestinal bleeding in all data sources and seemed to be associated with the lowest risk of major bleeding events compared to dabigatran and rivaroxaban.

ObjectiveTo establish the risk of major bleeding in direct oral anticoagulant (DOAC) users (overall and by class) versus vitamin K antagonist (VKA) users, using health care databases from four European countries and six provinces in Canada.MethodsA retrospective cohort study was performed according to a similar protocol. First-users of VKAs or DOACs with a diagnosis of non-valvular atrial fibrillation (NVAF) were included. The main outcome of interest was major bleeding and secondary outcomes included gastrointestinal (GI) bleeding and intracranial haemorrhage (ICH). Incidence rates of events per 1000 person years were calculated. Hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated using a Cox proportional hazard regression model. Exposure and confounders were measured and analysed in a time-dependant way. Risk estimates were pooled using a random effect model.Results421 523 patients were included. The risk of major bleeding for the group of DOACs compared to VKAs showed a pooled HR of 0.94 (95% CI: 0.87–1.02). Rivaroxaban showed a modestly increased risk (HR 1.11, 95% CI: 1.06–1.16). Apixaban and dabigatran showed a decreased risk of respectively HR 0.76 (95% CI: 0.69–0.84) and HR 0.85 (95% CI: 0.75–0.96).ConclusionsThis study confirms that the risk of major bleeding of DOACs compared to VKAs is not increased when combining all DOACs. However, we observed a modest higher risk of major bleeding for rivaroxaban, whereas for apixaban and dabigatran lower risks of major bleeding were observed compared to VKAs.

New oral anticoagulants (NOACs) is the preferred treatment in secondary prophylaxis of venous thromboembolic events (VTE). The aim of this study was to investigate possible risk factors associated with major bleeding in VTE-patients treated with NOACs. In this retrospective register-based study we screened the Swedish anticoagulation register Auricula (during 2012.01.01-2017.12.31) to find patients and used other national registers for outcomes. Primary endpoint was major bleeding defined as bleeding leading to hospital care. Multivariate Cox-regression analysis was used to reveal risk factors. 18 219 patients with NOAC due to VTE were included. 85.6% had their first VTE, mean age was 69.4 years and median follow-up time was 183 days. The most common NOAC was rivaroxaban (54.8%), followed by apixaban (42.0%), dabigatran (3.2%) and edoxaban (0.1%). The rate of major bleeding was 6.62 (95% CI 6.19-7.06) per 100 treatment years in all patients and 11.27 (CI 9.96-12.57) in patients above 80 years of age. Statistically independent risk factors associated with major bleeding were age (normalized HR 1.38, CI 1.27-1.50), earlier major bleeding (HR 1.58, Cl 1.09-2.30), COPD (HR 1.28, CI 1.04-1.60) and previous stroke (HR 1.28, Cl 1.03-1.58) or transient ischemic attack (TIA) (HR 1.33, Cl 1.01-1.76). Prior warfarin treatment was protective (HR 0.67, CI 0.58-0.78). This real world cohort shows a high bleeding rate especially among the elderly and in patients with previous major bleeding, COPD and previous stroke or TIA. This should be considered when deciding on treatment duration and NOAC dose in these patients.

Aims The introduction of direct oral anticoagulants (DOACs) has broadened the treatment arsenal for nonvalvular atrial fibrillation, but observational studies on the benefit-risk balance of DOACs compared to vitamin K antagonists (VKAs) are needed. The aim of this study was to characterize the risk of major bleeding in DOAC users using longitudinal data collected from electronic health care databases from 4 different EU-countries analysed with a common study protocol. Methods A cohort study was conducted among new users (>= 18 years) of DOACs or VKAs with nonvalvular atrial fibrillation using data from the UK, Spain, Germany and Denmark. The incidence of major bleeding events (overall and by bleeding site) was compared between current use of DOACs and VKAs. Cox regression analysis was used to calculate hazard ratios and 95% confidence intervals (CI) and adjust for confounders. Results/Conclusion Overall, 251 719 patients were included across the 4 study cohorts (mean age similar to 75 years, % females between 41.3 and 54.3%), with overall hazard ratios of major bleeding risk for DOACsvsVKAs ranging between 0.84 (95% CI: 0.79-0.90) in Denmark and 1.13 (95% CI 1.02-1.25) in the UK. When stratifying according to the bleeding site, risk of gastrointestinal bleeding was increased by 48-67% in dabigatran users and 30-50% for rivaroxaban users compared to VKA users in all data sources except Denmark. Compared to VKAs, apixaban was not associated with an increased risk of gastrointestinal bleeding in all data sources and seemed to be associated with the lowest risk of major bleeding events compared to dabigatran and rivaroxaban.

New oral anticoagulants (NOACs) is the preferred treatment in secondary prophylaxis of venous thromboembolic events (VTE). The aim of this study was to investigate possible risk factors associated with major bleeding in VTE-patients treated with NOACs. In this retrospective register-based study we screened the Swedish anticoagulation register Auricula (during 2012.01.01-2017.12.31) to find patients and used other national registers for outcomes. Primary endpoint was major bleeding defined as bleeding leading to hospital care. Multivariate Cox-regression analysis was used to reveal risk factors. 18 219 patients with NOAC due to VTE were included. 85.6% had their first VTE, mean age was 69.4 years and median follow-up time was 183 days. The most common NOAC was rivaroxaban (54.8%), followed by apixaban (42.0%), dabigatran (3.2%) and edoxaban (0.1%). The rate of major bleeding was 6.62 (95% CI 6.19-7.06) per 100 treatment years in all patients and 11.27 (CI 9.96-12.57) in patients above 80 years of age. Statistically independent risk factors associated with major bleeding were age (normalized HR 1.38, CI 1.27-1.50), earlier major bleeding (HR 1.58, Cl 1.09-2.30), COPD (HR 1.28, CI 1.04-1.60) and previous stroke (HR 1.28, Cl 1.03-1.58) or transient ischemic attack (TIA) (HR 1.33, Cl 1.01-1.76). Prior warfarin treatment was protective (HR 0.67, CI 0.58-0.78). This real world cohort shows a high bleeding rate especially among the elderly and in patients with previous major bleeding, COPD and previous stroke or TIA. This should be considered when deciding on treatment duration and NOAC dose in these patients., First published online: 2 November 2020

Background The benefit of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) on major bleeding was less prominent among atrial fibrillation (AF) patients with polypharmacy in post-hoc randomized controlled trials analyses. Whether this phenomenon also exists in routine care is unknown. The aim of the study is to investigate whether the number of concomitant drugs prescribed modifies safety and effectiveness of DOACs compared with VKAs in AF patients treated in general practice. Study Design Adult, nonvalvular AF patients with a first DOAC or VKA prescription between January 2010 and July 2018 were included, using data from the United Kingdom Clinical Practice Research Datalink. Primary outcome was major bleeding, secondary outcomes included types of major bleeding, nonmajor bleeding, ischemic stroke, and all-cause mortality. Effect modification was assessed using Cox proportional hazard regression, stratified for the number of concomitant drugs into three strata (0-5, 6-8, ≥9 drugs), and by including the continuous variable in an interaction term with the exposure (DOAC vs. VKA). Results A total of 63,600 patients with 146,059 person-years of follow-up were analyzed (39,840 person-years of DOAC follow-up). The median age was 76 years in both groups, the median number of concomitant drugs prescribed was 7. Overall, the hazard of major bleeding was similar between VKA-users and DOAC-users (hazard ratio [HR] 0.98; 95% confidence interval [CI] 0.87-1.11), though for apixaban a reduction in major bleeding was observed (HR 0.81; 95% CI 0.68-0.98). Risk of stroke was comparable, while risk of nonmajor bleeding was lower in DOAC users compared with VKA users (HR 0.92; 95% CI 0.88-0.97). We did not observe any evidence for an impact of polypharmacy on the relative risk of major bleeding between VKA and DOAC across our predefined three strata of concomitant drug use ( p -value for interaction = 0.65). For mortality, however, risk of mortality was hig

OBJECTIVES: To compare effectiveness of warfarin and antiplatelet exposure regarding both thrombotic and bleeding events, following surgical aortic valve replacement with a biological prosthesis(bioSAVR). METHODS: The study included all patients in Sweden undergoing a bioSAVR during 2008-2014 who were alive at discharge from the index hospital stay. Exposure was analysed and defined as postdischarge dispension of any antithrombotic pharmaceutical, updated at each following dispensions and categorised as single antiplatelet (SAPT), warfarin, warfarin combined with SAPT, dual antiplatelet (DAPT) or no antithrombotic treatment. Exposure to SAPT was used as comparator. Outcome events were all-cause mortality, ischaemic stroke, haemorrhagic stroke, any thromboembolism and major bleedings. We continuously updated adjustments for comorbidities with any indication for antithrombotic treatment by Cox regression analysis. RESULTS: We identified 9539 patients with bioSAVR (36.8% women) at median age of 73 years with a mean follow-up of 3.13 years. As compared with SAPT, warfarin alone was associated with a lower incidence of ischaemic stroke (HR 0.49, 95% CI 0.35 to 0.70) and any thromboembolism (HR 0.75, 95% CI 0.60 to 0.94) but with no difference in mortality (HR 0.94, 95% CI 0.78 to 1.13). The incidence of haemorrhagic stroke (HR 1.94, 95% CI 1.07 to 3.51) and major bleeding (HR 1.67, 95% CI 1.30 to 2.15) was higher during warfarin exposure. As compared with SAPT, DAPT was not associated with any difference in ischaemic stroke or any thromboembolism. Risk-benefit analyses demonstrated that 2.7 (95% CI 1.0 to 11.9) of the ischaemic stroke cases could potentially be avoided per every haemorrhagic stroke caused by warfarin exposure instead of SAPT during the first year. CONCLUSION: In patients discharged after bioSAVR, warfarin exposure as compared with SAPT exposure was associated with lower long-term risk of ischaemic stroke and thromboembolic events, and with a higher incid

New oral anticoagulants (NOACs) is the preferred treatment in secondary prophylaxis of venous thromboembolic events (VTE). The aim of this study was to investigate possible risk factors associated with major bleeding in VTE-patients treated with NOACs. In this retrospective register-based study we screened the Swedish anticoagulation register Auricula (during 2012.01.01-2017.12.31) to find patients and used other national registers for outcomes. Primary endpoint was major bleeding defined as bleeding leading to hospital care. Multivariate Cox-regression analysis was used to reveal risk factors. 18 219 patients with NOAC due to VTE were included. 85.6% had their first VTE, mean age was 69.4 years and median follow-up time was 183 days. The most common NOAC was rivaroxaban (54.8%), followed by apixaban (42.0%), dabigatran (3.2%) and edoxaban (0.1%). The rate of major bleeding was 6.62 (95% CI 6.19-7.06) per 100 treatment years in all patients and 11.27 (CI 9.96-12.57) in patients above 80 years of age. Statistically independent risk factors associated with major bleeding were age (normalized HR 1.38, CI 1.27-1.50), earlier major bleeding (HR 1.58, Cl 1.09-2.30), COPD (HR 1.28, CI 1.04-1.60) and previous stroke (HR 1.28, Cl 1.03-1.58) or transient ischemic attack (TIA) (HR 1.33, Cl 1.01-1.76). Prior warfarin treatment was protective (HR 0.67, CI 0.58-0.78). This real world cohort shows a high bleeding rate especially among the elderly and in patients with previous major bleeding, COPD and previous stroke or TIA. This should be considered when deciding on treatment duration and NOAC dose in these patients.

OBJECTIVES: To compare effectiveness of warfarin and antiplatelet exposure regarding both thrombotic and bleeding events, following surgical aortic valve replacement with a biological prosthesis(bioSAVR). METHODS: The study included all patients in Sweden undergoing a bioSAVR during 2008-2014 who were alive at discharge from the index hospital stay. Exposure was analysed and defined as postdischarge dispension of any antithrombotic pharmaceutical, updated at each following dispensions and categorised as single antiplatelet (SAPT), warfarin, warfarin combined with SAPT, dual antiplatelet (DAPT) or no antithrombotic treatment. Exposure to SAPT was used as comparator. Outcome events were all-cause mortality, ischaemic stroke, haemorrhagic stroke, any thromboembolism and major bleedings. We continuously updated adjustments for comorbidities with any indication for antithrombotic treatment by Cox regression analysis. RESULTS: We identified 9539 patients with bioSAVR (36.8% women) at median age of 73 years with a mean follow-up of 3.13 years. As compared with SAPT, warfarin alone was associated with a lower incidence of ischaemic stroke (HR 0.49, 95% CI 0.35 to 0.70) and any thromboembolism (HR 0.75, 95% CI 0.60 to 0.94) but with no difference in mortality (HR 0.94, 95% CI 0.78 to 1.13). The incidence of haemorrhagic stroke (HR 1.94, 95% CI 1.07 to 3.51) and major bleeding (HR 1.67, 95% CI 1.30 to 2.15) was higher during warfarin exposure. As compared with SAPT, DAPT was not associated with any difference in ischaemic stroke or any thromboembolism. Risk-benefit analyses demonstrated that 2.7 (95% CI 1.0 to 11.9) of the ischaemic stroke cases could potentially be avoided per every haemorrhagic stroke caused by warfarin exposure instead of SAPT during the first year. CONCLUSION: In patients discharged after bioSAVR, warfarin exposure as compared with SAPT exposure was associated with lower long-term risk of ischaemic stroke and thromboembolic events, and with a higher incid