title: Apixaban versus Antiplatelet drugs or no antithrombotic drugs after anticoagulation-associated intraCerebral HaEmorrhage in patients with Atrial Fibrillation (APACHE-AF): study protocol for a randomised controlled trial Left Atrial Appendage Closure in Patients with Atrial Fibrillation and Previous Intracerebral Hemorrhage. Long-Term Outcome after Anticoagulation-Associated Intracerebral Haemorrhage with or without Restarting Antithrombotic Therapy Reinitiation of anticoagulation after warfarin-associated intracranial hemorrhage and mortality risk: the Best Practice for Reinitiating Anticoagulation Therapy After Intracranial Bleeding (BRAIN) study. The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage. Left atrial appendage closure with the Watchman device in patients with a contraindication for oral anticoagulation: the ASAP study (ASA Plavix Feasibility Study With Watchman Left Atrial Appendage Closure Technology). Risk factors for impaired outcome after spontaneous intracerebral hemorrhage. Antiplatelet use after intracerebral hemorrhage Apolipoprotein E genotype and the risk of recurrent lobar intracerebral hemorrhage. Variation in Restarting Antithrombotic Drugs at Hospital Discharge After Intracerebral Hemorrhage Management of anticoagulation following central nervous system hemorrhage in patients with high thromboembolic risk. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Anticoagulant reversal, blood pressure levels, and anticoagulant resumption in patients with anticoagulation-related intracerebral hemorrhage. Left atrial appendage occlusion in atrial fibrillation after intracranial hemorrhage
abstract: Background There is a marked lack of evidence on the optimal prevention of ischaemic stroke and other thromboembolic events in patients with non-valvular atrial fibrillation and a recent intracerebral haemorrhage during treatment with oral anticoagulation .  These patients are currently treated with oral anticoagulants , antiplatelet drugs , or no antithrombotic treatment , depending on personal and institutional preferences . Compared with warfarin , the direct oral anticoagulant apixaban reduces the risk of stroke or systemic embolism , intracranial haemorrhage , and case fatality in patients with atrial fibrillation . Compared with aspirin , apixaban reduces the risk of stroke or systemic embolism in patients with atrial fibrillation , and has a similar risk of intracerebral haemorrhage . Novel oral anticoagulants have not been evaluated in patients with atrial fibrillation and a recent intracerebral haemorrhage . To inform a phase III trial , the phase II Apixaban versus Antiplatelet drugs or no antithrombotic drugs after anticoagulation-associated intraCerebral HaEmorrhage in patients with Atrial Fibrillation ( APACHE-AF ) trial aims to obtain estimates of the rates of vascular death or non-fatal stroke in patients with atrial fibrillation and a recent anticoagulation-associated intracerebral haemorrhage treated with apixaban and in those in whom oral anticoagulation is avoided . Methods / Design APACHE-AF is a phase II , multicentre , open-label , parallel-group , r and omised clinical trial with masked outcome assessment . One hundred adults with a history of atrial fibrillation and a recent intracerebral haemorrhage during treatment with anticoagulation in whom clinical equipoise exists on the optimal stroke prevention strategy will be enrolled in 14 hospitals in The Netherl and s . These patients will be r and omly assigned in a 1:1 ratio to either apixaban or to avoiding oral anticoagulation . Patients in the control group may be treated with antiplatelet drugs at the discretion of the treating physician . The primary outcome is the composite of vascular death or non-fatal stroke during follow-up . We aim to include 100 patients in 2.5 years . All patients will be followed-up for the duration of the study , but at least for 1 year . Recruitment commenced in September 2014 and is ongoing . This trial is funded by the Dutch Heart Foundation ( 2012 T077 ) and ZonMW (015008048).Trial registration NTR4526 ( 16 April 2014 ) BACKGROUND Percutaneous left atrial appendage closure ( LAAC ) may be considered in patients with atrial fibrillation and contraindication for long-term anticoagulation . This study aim ed to assess the safety and efficacy of LAAC followed by single antiplatelet therapy in patients with atrial fibrillation and previous spontaneous intracerebral hemorrhage ( ICH ) . METHODS In this explorative , prospect i ve , single-center study , consecutive patients who underwent LAAC because of previous spontaneous ICH over a period of 4 years were analyzed . Risks of ischemic strokes and hemorrhagic complications were estimated using the CHA2DS2-VASc and HAS-BLED scores , respectively . Single antiplatelet therapy was given for at least 6 months post implantation . Clinical follow-up included cardiological evaluations at 1 , 3 , 6 , and 12 months , and neurological evaluations at 3 and 12 months . RESULTS A total of 46 patients  underwent LAAC with a mean follow-up of 12 ± 7 months . The observed annual rate of ischemic stroke was 4.35 % compared with an expected rate of 7.23 % according to the mean risk of the population based on CHA2DS2-VASc score , which translated into a 40 % risk reduction . The observed annual rate of major bleeding was 4.35 % compared with an expected rate of 8.05 % according to the mean risk of the population based on HAS-BLED score , which translated into a 46 % risk reduction . CONCLUSIONS LAAC followed by single antiplatelet therapy is feasible as an alternative to oral anticoagulation in high-risk patients with previous ICH , with an acceptable periprocedural risk . Longer follow-up in a larger number of patients will be needed to establish the effectiveness of LAAC relative to direct oral anticoagulants Background : For patients who survive intracerebral haemorrhage ( ICH ) during treatment with oral anticoagulation ( OAC )  , the balance between the benefits and risks of restarting OAC is unclear . The decision to restart OAC or to start antiplatelet therapy in these patients therefore poses a dilemma for all physicians involved . We assessed the long-term outcome of patients who did or did not restart antithrombotic therapy after OAC-associated ICH . Methods : We conducted a retrospective follow-up study of all patients discharged from our institution after OAC-associated ICH over a 10-year period . Data on the use of OAC or platelet inhibitors and the occurrence of vascular events during follow-up were assessed through question naires and patient files . The primary outcome was recurrent fatal or non-fatal stroke . Secondary outcomes were the occurrence of other haemorrhagic , thrombotic or thromboembolic events . With patients without antithrombotic treatment as reference , we calculated incidence ratios with corresponding 95 % confidence intervals ( CI ) for treatment with OAC and for treatment with antiplatelet therapy . Results : We included 38 patients , of whom 21 ( 55 % ) died during a mean follow-up of 3.5 years . The medication regime changed frequently during follow-up , illustrated by the fact that two thirds of the patients who had resumed OAC within 2 months of ICH terminated this at later points in time . Two recurrent strokes occurred during 35.4 patient-years without antithrombotic medication , 7 during 63.8 patient-years on antiplatelet medication ( incidence ratio 1.9 ; 95 % CI , 0.4 - 9.4 ) , and 3 during 19.5 patient-years on OAC ( incidence ratio 2.7 ; 95 % CI , 0.5 - 16.3 ) . There was only 1 recurrent ICH , which occurred during treatment with OAC . Conclusion : In this observational study , no significant difference in the primary outcome measure was found between the treatment groups , but there was a tendency towards a higher long-term risk of any stroke in patients who resumed OAC or started antiplatelet therapy . However , based on these results it is difficult to draw any concrete conclusions or make any strong recommendations . A r and omized trial to assess the optimal long-term strategy after OAC-related ICH is warranted . Based on the point estimates of our study , such a trial should involve at least 300 patient-years of follow-up BACKGROUND While warfarin-related intracranial hemorrhage ( ICH ) occurs in 0.25%-1.1 % patients per year , little is known about the practice and outcomes of anticoagulant reinitiation . METHODS We studied a cohort of consecutive patients with warfarin-related ICH ( intracerebral or subarachnoid ) admitted to 13 stroke centres in the Registry of the Canadian Stroke Network between July 2003 and March 2008 . We examined patterns of warfarin reinitiation and variables associated with 30-day and 1-year outcomes . RESULTS Among the 284 patients studied ( mean age 74 ± 12 years ) , warfarin was restarted in-hospital in 91 patients ( 32 % ) . Factors associated with restarting warfarin were lower stroke severity ( adjusted odds ratio [ aOR ] 2.07 , 95 % confidence interval [ CI ] ; 1.20 - 3.57 , P = 0.009 ) or presence of valve prosthesis ( aOR 3.07 , 95 % CI ; 1.29 - 7.27 , P = 0.011 ) . Mortality rates were not higher in those who restarted warfarin in-hospital : 31.9 % vs 54.4 % ( 30-day , P < 0.001 ) and 48 % vs 61 % ( 1-year , P = 0.04 ) , and bleeding was not increased . Multivariable predictors of mortality included initial international normalized ratio > 3.0 ( aOR , 3.28 [ 30-day , P < 0.001 ] and 3.32 [ 1-year , P = 0.003 ] ) , greater stroke severity ( aOR , 6.04 [ 30-day ] and 4.22 [ 1-year ] ; both P < 0.001 ) , and intraventricular hemorrhage ( aOR , 2.19 [ 30-day ; P = 0.03 ] and 2.04 [ 1-year ; P = 0.04 ] ) . In selected patients who reinitiated warfarin , there was no increase in 30-day ( aOR , 0.49 ; P = 0.03 ) or 1-year mortality ( aOR , 0.79 ; P = 0.43 ) . CONCLUSIONS In selected patients at high thrombosis risk , reinitiation of warfarin after ICH did not confer increased mortality or bleeding events BACKGROUND Warfarin sodium is highly effective for prevention of embolic stroke , particularly in nonvalvular atrial fibrillation , but its expected benefit can be offset by risk of intracerebral hemorrhage ( ICH ) . We studied the determinants of ICH outcome to quantify the independent effect of warfarin . METHODS Consecutive patients with supratentorial ICH treated in a tertiary care hospital with a neurointensive care unit were prospect ively identified during a 7-year period , and data on hemorrhage location , clinical characteristics , and warfarin use were collected . Independent predictors of 3-month mortality were determined using multiple logistic regression analysis . RESULTS Of 435 consecutive patients aged 55 years or older , 102 ( 23.4 % ) were taking warfarin at the time of ICH .  Three-month mortality was 25.8 % for those not taking warfarin and 52.0 % for those taking warfarin . Independent predictors of death were warfarin use ( odds ratio [ OR ] , 2.2 ; 95 % confidence interval [ CI ] , 1.3 - 3.8 ) , age 70 years or older ( OR , 2.4 ; 95 % CI , 1.4 - 4.0 ) , and presence of diabetes mellitus ( OR , 1.8 ; 95 % CI , 1.0 - 3.3 ) . Although 68.0 % of all warfarin-related hemorrhages occurred at an international normalized ratio ( INR ) of 3.0 or less , increasing degrees of anticoagulation were strongly associated with increasing risk of death compared with no warfarin use . CONCLUSIONS Patients taking warfarin  had a doubling in the rate of intracerebral hemorrhage mortality in a dose-dependent manner . The data suggest that careful control of the INR , already known to limit the risk of warfarin-related ICH , may also limit its severity OBJECTIVES The purpose of this study was to assess the safety and efficacy of left atrial appendage ( LAA ) closure in nonvalvular atrial fibrillation ( AF ) patients ineligible for warfarin therapy . BACKGROUND The PROTECT AF ( Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation ) trial demonstrated that LAA closure with the Watchman device ( Boston Scientific , Natick , Massachusetts ) was noninferior to warfarin therapy . However , the PROTECT AF trial only included patients who were c and i date s for warfarin , and even patients r and omly assigned to the LAA closure arm received concomitant warfarin  for 6 weeks after Watchman implantation . METHODS A multicenter , prospect i ve , nonr and omized study was conducted of LAA closure with the Watchman device in 150 patients with nonvalvular AF and CHADS₂ ( congestive heart failure , hypertension , age ≥75 years , diabetes mellitus , and prior stroke or transient ischemic attack ) score ≥1 , who were considered ineligible for warfarin . The primary efficacy endpoint was the combined events of ischemic stroke , hemorrhagic stroke , systemic embolism , and cardiovascular/unexplained death . RESULTS The mean CHADS₂ score and CHA₂DS₂-VASc ( CHADS₂ score plus 2 points for age ≥75 years and 1 point for vascular disease , age 65 to 74 years , or female sex ) score were 2.8 ± 1.2 and 4.4 ± 1.7 , respectively . History of hemorrhagic/bleeding tendencies ( 93 % ) was the most common reason for warfarin in eligibility . Mean duration of follow-up was 14.4 ± 8.6 months . Serious procedure- or device-related safety events occurred in 8.7 % of patients ( 13 of 150 patients ) . All-cause stroke or systemic embolism occurred in 4 patients ( 2.3 % per year ) : ischemic stroke in 3 patients ( 1.7 % per year ) and hemorrhagic stroke in 1 patient ( 0.6 % per year ) . This ischemic stroke rate was less than that expected ( 7.3 % per year ) based on the CHADS₂ scores of the patient cohort . CONCLUSIONS LAA closure with the Watchman device can be safely performed without a warfarin transition , and is a reasonable alternative to consider for patients at high risk for stroke but with contraindications to systemic oral anticoagulation . ( ASA Plavix Feasibility Study With Watchman Left Atrial Appendage Closure Technology [ ASAP ] ; NCT00851578 ) OBJECTIVE To search out independent prognostic factors , including preictal variables for outcome of spontaneous intracerebral hemorrhage . DESIGN Prospect i ve follow-up study . PATIENTS One hundred fifty-six consecutive patients ( 96 men and 60 women ) aged 16 to 60 years admitted as emergencies after bleeding . MAIN OUTCOME MEASURES Potential risk factors ( baseline characteristics , health habits , and clinical variables ) for death and impaired outcome were studied prospect ively up to 1 year after hemorrhage . RESULTS One year after hemorrhage , 64 patients ( 41 % ) were independent and 34 patients ( 22 % ) were dependent in the activities of daily living ; 58 patients ( 37 % ) had died . Risk of death was predicted , after adjustment for sex , age , hypertension , and body mass index , by clinical condition at admission according to the Glasgow Coma Scale ( P < .001 ) and the occurrence of subcortical hematoma ( odds ratio [ OR ] , 0.18 ; 95 % confidence interval [ CI ] , 0.04 to 0.91 ; P = .04 ) . Risk of poor outcome ( dependent state or death ) was predicted , after adjustment for sex , hypertension , body mass index , cigarette smoking , presence of intraventricular hemorrhage , and surgery , significantly by the Glasgow Coma Scale ( P < .001 ) ; presence of subcortical hematoma ( OR , 0.04 ; 95 % CI , 0.01 to 0.27 ; P < .001 ) ; volume of hematoma ( P = .03 ) ; age ( P = .004 ) ; amount of alcohol consumed within 1 week before hemorrhage ( P = .03 ) ; and presence of cerebellar hematoma ( OR , 0.13 ; 95 % CI , 0.02 to 0.95 ; P = .04 ) . Significant independent predictors of impaired outcome ( assessed with the Glasgow Outcome Scale ) were the Glasgow Coma Scale ( P < .001 ) ; presence of subcortical hematoma ( OR , 0.26 ; 95 % CI , 0.10 to 0.67 ; P = .006 ) ; alcohol intake within 1 week ( P = .002 ) ; and presence of cerebellar ( OR , 0.16 ; 95 % CI , 0.04 to 0.60 ; P = .008 ) , intraventricular ( OR , 2.74 ; 95 % CI , 1.19 to 6.28 ; P = .02 ) , or cau date hemorrhage ( OR , 0.13 ; 95 % CI , 0.02 to 0.77 ; P = .03 ) . The mean erythrocyte corpuscular volume was directly associated with an impaired outcome ( P < .05 ) . CONCLUSION In addition to severity and location of the hemorrhage , the age of the patient and the amount of alcohol consumed within 1 week seem to be independent determinants of outcome after intracerebral hemorrhage Background : Survivors of intracerebral hemorrhage are at risk for recurrent intracerebral hemorrhage  and ischemic cardiovascular and cerebrovascular disease . Objective : To determine whether antiplatelet therapy increases the risk of recurrent intracerebral hemorrhage . Methods : The authors review ed data from consecutive survivors of primary intracerebral hemorrhage enrolled in a single-center prospect i ve cohort study . Survivors were followed by telephone interview ; recurrent intracerebral hemorrhage and post – index antiplatelet agent use and duration were recorded . Cox proportional hazards models was used with antiplatelet agent exposure as a time-dependent variable to assess the effect of antiplatelet agent use on recurrent intracerebral hemorrhage , stratified by lobar and deep hemispheric location . Results : Recurrent intracerebral hemorrhage was more common in survivors of lobar hemorrhage compared with survivors of deep hemorrhage ( cumulative 2-year rate 22 % vs 4 % ; p = 0.007 ) . Antiplatelet agents were prescribed in 22 % of intracerebral hemorrhage survivors ( 27/127 lobar , 19/80 deep hemispheric ) , most commonly for prevention of ischemic heart disease . Antiplatelet agent use was not associated with intracerebral hemorrhage recurrence in survivors of either lobar hemorrhage ( hazard ratio [ HR ] 0.8 , 95 % CI 0.3 to 2.3 , p = 0.73 ) or of deep hemorrhage ( HR 1.2 , 95 % CI 0.1 to 14.3 , p = 0.88 ) . Conclusion : Antiplatelet agent use is relatively common following intracerebral hemorrhage but did not appear to be associated with a large increased risk of intracerebral hemorrhage recurrence in this observational study BACKGROUND Recurrent lobar intracerebral hemorrhage is the hallmark of cerebral amyloid angiopathy . The factors that predispose patients to early recurrence of lobar hemorrhage are unknown . One c and i date is the apolipoprotein E gene , since both the epsilon2 and the epsilon4 alleles of apolipoprotein E appear to be associated with the severity of amyloid angiopathy . METHODS We performed a prospect i ve , longitudinal study of consecutive elderly patients who survived a lobar intracerebral hemorrhage . The patients were followed for recurrent hemorrhagic stroke by interviews at six-month intervals and review s of medical records and computed tomographic scans . RESULTS Nineteen of 71 enrolled patients had recurrent hemorrhages during a mean follow-up period of 23.9+/-14.8 months , yielding a 2-year cumulative rate of recurrence of 21 percent . The apolipoprotein E genotype was significantly associated with the risk of recurrence . Carriers of the epsilon2 or epsilon4 allele had a two-year rate of recurrence of 28 percent , as compared with only 10 percent for patients with the common apolipoprotein E epsilon3/epsilon3 genotype ( risk ratio , 3.8 ; 95 percent confidence interval , 1.2 to 11.6 ; P=0.01 ) . Early recurrence occurred in eight patients , four of whom had the uncommon epsilon2/epsilon4 genotype . Also at increased risk for recurrence were patients with a history of hemorrhagic stroke before entry into the study ( two-year recurrence , 61 percent ; risk ratio , 6.4 ; 95 percent confidence interval , 2.2 to 18.5 ; P<0.001 ) . CONCLUSIONS The apolipoprotein E genotype can identify patients with lobar intracerebral hemorrhage who are at highest risk for early recurrence . This finding makes possible both the provision of prognostic information to patients with lobar hemorrhage and a method of targeting and assessing potential strategies for prevention Background and Purpose — Whether intracerebral hemorrhage ( ICH ) survivors should restart antithrombotic drugs is unknown . We analyzed the frequency of restarting antithrombotic drugs  in ICH survivors who had taken prophylactic antithrombotic drugs in atrial fibrillation or after thromboembolic disease in 5 cohorts and explored factors associated with doing so . Methods — We compared the characteristics and proportions of patients taking antithrombotic drugs at ICH onset and discharge in 4 hospital-based cohorts ( Lille , France , n=542 ; Utrecht , The Netherl and s , n=389 ; multicenter Clinical Relevance of Microbleeds in Stroke-2 ( CROMIS-2 ) ICH , United Kingdom , n=667 ; and Amsterdam , The Netherl and s , n=403 ) and 1 community-based study ( Lothian , Scotl and , n=137 ) , using bivariate analyses . We sought characteristics associated with restarting using bivariate and multivariable logistic regression analyses . Results — A total of 942 ( 44 % ) patients with ICH took  antithrombotic drugs  at hospital admission ( no difference between cohorts ) .  Antithrombotic drugs  were restarted in 96 ( 20 % ) of the 469 survivors who had taken antithrombotic drugs for secondary prevention or atrial fibrillation , but this proportion differed when stratified by the cohort of origin ( Lille , 18 % ; Utrecht , 45 % ; Lothian , 15 % ; CROMIS-2 ICH , 11 % ; Amsterdam , 20 % ; P<0.001 ) and by type of antithrombotic drug pre-ICH ( 14 % in patients with previous antiplatelet drugs versus 26 % in patients with previous vitamin K antagonists and 41 % in patients with both drugs ; P<0.001 ) . We did not find other consistent , independent associations with restarting antithrombotic drugs . Conclusions — The variation in clinical practice and lack of consistent associations with restarting antithrombotic drugs after ICH reflect current knowledge and support the need for r and omized controlled trials to resolve this dilemma SUMMARY BACKGROUND Patients who present with central nervous system ( CNS ) hemorrhage while on anticoagulation ( AC ) for thromboembolic ( TE ) risk factors are a challenge to manage . OBJECTIVE We sought to inform decisions surrounding the timing and intensity of AC resumption by performing a systematic review . METHODS Three review ers screened publications from Medline and EMBASE and extracted data . Hemorrhagic and TE adverse events that occurred subsequent to the index hemorrhage were recorded , as was their timing relative to presentation and covariates that might influence their occurrence . RESULTS Data were extracted from 63 publications detailing 492 patients ; 7.7 % of patients experienced hemorrhagic complications and 6.1 % experienced TE complications . Hemorrhagic complications were more common within 72 h of presentation while TE complications were more common thereafter . Patients restarted on AC after 72 h were significantly more likely to have a TE complication ( P = 0.006 ) and those restarted before 72 h were more likely to hemorrhage ( P = 0.0727 ) . Factors associated with re-hemorrhage included younger age , traumatic cause , subdural hematomas and failure to reverse AC . TE complications were more common in younger patients and those with spinal hemorrhage , multiple hemorrhages , and non-traumatic causes of the index hemorrhage . Re-initiation of AC at a lower intensity also significantly increased the risk of TE complications . INTERPRETATION Our results suggest that it may be prudent to re-initiate AC earlier than previously thought , with the timing and intensity modified based on predictors of TE and hemorrhagic complications . These findings must be explored in a prospect i ve study because of limitations inherent to the analyzed studies AIMS The impact of some risk factors for stroke and bleeding , and the value of stroke and bleeding risk scores , in atrial fibrillation ( AF ) , has been debated , as clinical trial cohorts have not adequately tested these . Our objective was to investigate risk factors for stroke and bleeding in AF , and application of the new CHA(2)DS(2)-VASc and HAS-BLED schemes for stroke and bleeding risk assessment s , respectively . METHODS AND RESULTS We used the Swedish Atrial Fibrillation cohort study , a nationwide cohort study of 182 678 subjects with a diagnosis of AF at any Swedish hospital between 1 July 2005 and 31 December 2008 , who were prospect ively followed for an average of 1.5 years ( 260 000 years at risk ) . With the use of the National Swedish Drug Registry , all patients who used an oral anticoagulant  anytime during follow-up were identified . Most of the analyses were made on a subset of 90 490 patients who never used anticoagulants .  Risk factors for stroke , the composite thromboembolism endpoint ( stroke , TIA , or systemic embolism ) , and bleeding , and the performance of published stroke and bleeding risk stratification schemes were investigated . On multivariable analysis , significant associations were found between the following ' new ' risk factors and thromboembolic events ; peripheral artery disease [ hazard ratio ( HR ) 1.22 ( 95 % CI 1.12 - 1.32 ) ] , ' vascular disease ' [ HR 1.14 ( 1.06 - 1.23 ) ] , prior myocardial infa rct ion [ HR 1.09 ( 1.03 - 1.15 ) ] , and female gender [ HR 1.17 ( 1.11 - 1.22 ) ] . Previous embolic events , intracranial haemorrhage ( ICH ) , hypertension , diabetes , and renal failure were other independent predictors of the composite thromboembolism endpoint , while thyroid disease ( or hyperthyroidism ) was not an independent stroke risk factor . C-statistics for the composite thromboembolic endpoint with the CHADS(2 ) and CHA(2)DS(2)-VASc schemes were 0.66 ( 0.65 - 0.66 ) and 0.67 ( 0.67 - 0.68 ) , respectively . On multivariable analysis , age , prior ischaemic stroke or thromboembolism , prior major bleeding events , and hypertension were significant predictors of ICH and major bleeding . Heart failure , diabetes , renal failure , liver disease , anaemia or platelet/coagulation defect , alcohol abuse , and cancer were other significant predictors for major bleeding , but not ICH . The ability for predicting ICH and major bleeding with both bleeding risk schemes ( HEMORR(2)HAGES , HAS-BLED ) were similar , with c-statistics of ~0.6 . CONCLUSION Several independent risk factors ( prior ICH , myocardial infa rct ion , vascular disease , and renal failure ) predict ischaemic stroke and /or the composite thromboembolism endpoint in AF , but thyroid disease ( or hyperthyroidism ) was not an independent risk factor for stroke . There is a better performance for CHA(2)DS(2)-VASc over CHADS(2 ) schemes for the composite thromboembolism endpoint . While both tested bleeding risk schemes have similar predictive value , the HAS-BLED score has the advantage of simplicity IMPORTANCE Although use of oral anticoagulants ( OACs ) is increasing , there is a substantial lack of data on how to treat OAC-associated intracerebral hemorrhage ( ICH ) . OBJECTIVE To assess the association of anticoagulation reversal and blood pressure ( BP ) with  hematoma enlargement and the effects of OAC resumption . DESIGN , SETTING , AND PARTICIPANTS Retrospective cohort study at 19 German tertiary care centers ( 2006 - 2012 ) including 1176 individuals for analysis of long-term functional outcome , 853 for analysis of hematoma enlargement , and 719 for analysis of OAC resumption . EXPOSURES Reversal of anticoagulation during acute phase , systolic BP at 4 hours , and reinitiation of OAC for long-term treatment . MAIN OUTCOMES AND MEASURES Frequency of hematoma enlargement in relation to international normalized ratio ( INR ) and BP . Incidence analysis of ischemic and hemorrhagic events with or without OAC resumption . Factors associated with favorable ( modified Rankin Scale score , 0 - 3 ) vs unfavorable functional outcome . RESULTS Hemorrhage enlargement occurred in 307 of 853 patients ( 36.0 % ) . Reduced rates of hematoma enlargement were associated with reversal of INR levels < 1.3 within 4 hours after admission ( 43/217 [ 19.8 % ] ) vs INR of ≥1.3 ( 264/636 [ 41.5 % ] ; P < .001 ) and systolic BP < 160 mm Hg at 4 hours ( 167/504 [ 33.1 % ] ) vs ≥160 mm Hg ( 98/187 [ 52.4 % ] ; P < .001 ) . The combination of INR reversal < 1.3 within 4 hours and systolic BP of < 160 mm Hg at 4 hours was associated with lower rates of hematoma enlargement ( 35/193 [ 18.1 % ] vs 220/498 [ 44.2 % ] not achieving these values ; OR , 0.28 ; 95 % CI , 0.19 - 0.42 ; P < .001 ) and lower rates of in-hospital mortality ( 26/193 [ 13.5 % ] vs 103/498 [ 20.7 % ] ; OR , 0.60 ; 95 % CI , 0.37 - 0.95 ; P = .03 ) . OAC was resumed in 172 of 719 survivors ( 23.9 % ) . OAC resumption showed fewer ischemic complications ( OAC : 9/172 [ 5.2 % ] vs no OAC : 82/547 [ 15.0 % ] ; P < .001 ) and not significantly different hemorrhagic complications ( OAC : 14/172 [ 8.1 % ] vs no OAC : 36/547 [ 6.6 % ] ; P = .48 ) . Propensity-matched survival analysis in patients with atrial fibrillation who restarted OAC showed a decreased HR of 0.258 ( 95 % CI , 0.125 - 0.534 ; P < .001 ) for long-term mortality . Functional long-term outcome was unfavorable in 786 of 1083 patients ( 72.6 % ) . CONCLUSIONS AND RELEVANCE Among patients with OAC-associated ICH , reversal of INR < 1.3 within 4 hours and systolic BP < 160 mm Hg at 4 hours were associated with lower rates of hematoma enlargement , and resumption of OAC therapy was associated with lower risk of ischemic events . These findings require replication and assessment in prospect i ve studies . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01829581 Objective : To evaluate the safety and feasibility of percutaneous left atrial appendage occlusion ( LAAO ) in patients with atrial fibrillation ( AF ) and previous intracranial hemorrhage ( ICH ) . Methods : In an explorative , prospect i ve , single-center , observational study , LAAO was performed in patients with previous ICH and AF using the Amplatzer Cardiac Plug device . Risks of ischemic strokes and hemorrhagic complications were estimated using the CHA2DS2Vasc score and the HAS-BLED score . Before and 1 , 6 , 12 , and 24 months after the procedure , clinical status and complications were recorded . Major complications were predefined as periprocedural stroke , death , pericardial effusion , and device embolism . Results : LAAO was performed in 20 patients . Based on CHA2DS2Vasc score ( mean 4.5 ± 1.4 ) and HAS-BLED score ( mean 4.7 ± 1.0 ) , annual risks of stroke and hemorrhagic complications were 4.0%–6.7 % and 8.7%–12.5 % , respectively . No patient had a procedure-related complication . Minor postprocedural complications were observed in 4/20 patients ( 2 inguinal hematoma , 1 self-limiting asystole , and 1 thrombus formation on device ) . No ischemic or hemorrhagic stroke occurred during a mean follow-up of 13.6 ± 8.2 months . Conclusions : In this first study of LAAO in patients with previous ICH , LAAO appears feasible and safe . A larger , controlled trial is needed to assess the efficacy and safety of the procedure compared to other preventive measures . Classification of evidence : This study provides Class III evidence that in patients with a history of previous ICH and AF  , percutaneous LAAO is safe and feasible
target: In addition , 19 letters to the editor/ review s/editorials/experts ' surveys/experts ' opinion were used for discussion purpose s. Conclusions NVAF is highly prevalent among ICH survivors .
  The risks of IS , recurrent ICH , and mortality are heightened in this group .
  Most published data show a net benefit in terms of IS prevention and mortality when anticoagulation is restarted .
background: Background We summarize the existing evidence on the potential benefit of oral anticoagulation ( OAC ) in intracerebral hemorrhage ( ICH ) survivors with nonvalvular atrial fibrillation ( NVAF ) .