Resumption Of Anticoagulation Research Articles

Clinical events after interruption of anticoagulation in patients with atrial fibrillation: An analysis from the ENGAGE AF-TIMI 48 trial

BackgroundPatients with atrial fibrillation (AF) who interrupt anticoagulation are at high risk of thromboembolism and death. Methods and resultsPatients enrolled in the ENGAGE AF-TIMI 48 trial (randomized comparison of edoxaban vs. warfarin) who interrupted study anticoagulant for >3 days were identified. Clinical events (ischemic stroke/systemic embolism, major cardiac and cerebrovascular events [MACCE]) were analyzed from day 4 after interruption until day 34 or study drug resumption. During 2.8 years median follow-up, 13,311 (63%) patients interrupted study drug for >3 days. After excluding those who received open-label anticoagulation during the at-risk window, the population for analysis included 9148 patients. The rates of ischemic stroke/systemic embolism and MACCE post interruption were substantially greater than in patients who never interrupted (15.42 vs. 0.26 and 60.82 vs. 0.36 per 100 patient-years, respectively, padj < .001). Patients who interrupted study drug for an adverse event (44.1% of the cohort), compared to those who interrupted for other reasons, had an increased risk of MACCE (HRadj 2.75; 95% CI 2.02–3.74, p < .0001), but similar rates of ischemic stroke/systemic embolism. Rates of clinical events after interruption of warfarin and edoxaban were similar. ConclusionInterruption of study drug was frequent in patients with AF and was associated with a substantial risk of major cardiac and cerebrovascular events over the ensuing 30 days. This risk was particularly high in patients who interrupted as a result of an adverse event; these patients deserve close monitoring and resumption of anticoagulation as soon as it is safe to do so.

Oral anticoagulant re-initiation following intracerebral hemorrhage in non-valvular atrial fibrillation: Global survey of the practices of neurologists, neurosurgeons and thrombosis experts.

BackgroundWhile oral anticoagulants (OACs) are highly effective for ischemic stroke prevention in atrial fibrillation, intracerebral hemorrhage (ICH) remains the most feared complication of OAC. Clinical controversy remains regarding OAC resumption and its timing for ICH survivors with atrial fibrillation because the balance between risks and benefits has not been investigated in randomized trials.Aims/HypothesisTo survey the practice of stroke neurologists, thrombosis experts and neurosurgeons on OAC re-initiation following OAC-associated ICH.MethodsAn online survey was distributed to members of the International Society for Thrombosis and Haemostasis, Canadian Stroke Consortium, NAVIGATE-ESUS trial investigators (Clinicatrials.gov identifier NCT02313909) and American Association of Neurological Surgeons. Demographic factors and 11 clinical scenarios were included.ResultsTwo hundred twenty-eight participants from 38 countries completed the survey. Majority of participants were affiliated with academic centers, and >20% managed more than 15 OAC-associated ICH patients/year. Proportion of respondents suggesting OAC anticoagulant resumption varied from 30% (for cerebral amyloid angiopathy) to 98% (for traumatic ICH). Within this group, there was wide distribution in response for timing of resumption: 21.4% preferred to re-start OACs after 1–3 weeks of incident ICH, while 25.3% opted to start after 1–3 months. Neurosurgery respondents preferred earlier OAC resumption compared to stroke neurologists or thrombosis experts in 5 scenarios (p<0.05 by Kendall’s tau).ConclusionsWide variations in current practice exist among management of OAC-associated ICH, with decisions influenced by patient- and provider-related factors. As these variations likely reflect the lack of high quality evidence, randomized trials are direly needed in this population.

Abstract TP349: Clinical Outcomes of Direct Oral Anticoagulants versus Warfarin in Patients With Atrial Fibrillation Who Have Had an Intracerebral Hemorrhage

Introduction: It has recently been demonstrated in a meta-analysis that patients with a history of intracerebral hemorrhage (ICH) and atrial fibrillation have a reduced risk of ischemic stroke (IS) with the initiation or resumption of oral anticoagulation (OAC). It remains uncertain if there is a difference in clinical outcomes between direct oral anticoagulants (DOAC) compared to warfarin (WF) in this patient population. We aimed to compare these two populations using data from the Southern California Kaiser Permanente (SCKP) health care system. Methods: Patient records with ICH and AF diagnosis were obtained from the SCKP Database, and divided into two cohorts: WF or DOAC. Subjects were included if the OAC was started after the index ICH. CT scans within 24 hours of symptom onset were examined for: ICH location, ICH size (Using the ABC/2 method), and leukoariosis. If available, an axial gradient echo sequence MRI scan taken within 180 days, either before or after the index ICH was examined for microbleeds. Differences in demographics, concurrent medications with an antithrombotic effect and statins, and traditional vascular risk factors were assessed using Kruskal-Wallis and Chi-Square tests. Results: Eighty-one subjects were identified (53 WF and 28 DOAC). In the DOAC group, 18 patients were on dabigatran, 9 on apixaban and 1 on rivaroxaban. There was no difference between WF and DOAC in baseline demographics, concurrent medications and location of ICH. The mean ICH volume was 15.4cc in DOAC and 5.6cc in WF (P=0.09). Time to start drug from ICH was 15.0 and 24.5 months for DOAC and WF respectively (P=0.26). More patients died in WF (28.3%) vs DOAC (10.7%) (P=0.0478). There was no difference in time to IS, ICH and major hemorrhage between the two groups. The composite outcome of IS, ICH, Major Hemorrhage and death was 35.8 % in WF vs 25% in DOAC group (P=0.32). Conclusion: Our results, while limited in size, suggest that patients with a previous ICH with AF, who are started on a DOAC have lower mortality compared to WF. There was a higher percentage of patients in the WF group who met the composite outcome of IS, ICH, major hemorrhage and death, but this did not reach statistical significance.

Outcome on Reinstitution of Anticoagulation Following Intracranial Hemorrhage: A Single Institutional Analysis

Introduction: Arterial and venous thromboembolic events, including stroke and myocardial infarction, are a leading cause of morbidity and mortality in the United States. Anticoagulation therapies including but not limited to vitamin K anticoagulant (VKA) and direct oral anticoagulants (DOACs) are critical in preventing such morbidity and/or mortality. Adversely, studies have shown an increased risk of bleeding associated with anticoagulation. For instance, there is a two-fivefold increase risk of intracranial hemorrhage (ICH) with warfarin use. On the other hand, 6.5% to 19.6% of all strokes result in ICH which increases mortality. For patients who were on anticoagulation prior to ICH, there seems to be no consensus on the appropriate timing to resume anticoagulation if at all. Most reported observational studies reveal that the decision on whether and when to resume anticoagulation is based on several clinical factors, such as the size and location of the ICH, the recurrence rate of the particular type of ICH, the underlying indication for anticoagulation and social factors. We performed a single institutional analysis on the correlation of anticoagulation resumption with subsequent risk of ICH recurrence and/or thromboembolismMethod: We retrospectively reviewed medical records of 600 adults [mean age 69 (22-79)] at Beaumont Hospital, an academic community center from May 2015 to May 2016 with confirmed ICH, of which 125 patients were on prior anticoagulation. Our aim was to determine whether there is correlation between timing of re-institution of anticoagulant post ICH and eventual outcome with regards to recurrent ICH and/or thrombosis. We also compared outcome in patients on VKA to those on DOACs. Statistical analysis was performed by an independent investigator.Results: Demographic distribution of studied patients were 97(77.6%) white, 10 (8.0%) African Americans and 18 (14.4%) others. Among these patients, 75 (60.0%) were on VKA, 18 (14.4%) on Enoxaparin, 26(20.8%) were on one of the DOACs, and 6(4.8%) were on unknown anticoagulant prior to intracranial hemorrhage (ICH) (Table 1). Although anticoagulation was not reinstituted in 71(56.8%) patients following ICH; 5 (4.0%) patients had anticoagulant restarted within 7 days of diagnosis of ICH; 27 (21.6%) patients were restarted between 7-30days and 18 (14.4%) patients were restarted after 30 days. All patients restarted within 7 days of diagnosis were on warfarin due to severe cardiac dysfunction requiring mechanical valves. Using SAS System for Windows version 9.3, statistical analysis was performed on 32 (25.6%) patients who restarted on anticoagulation within 30 days of initial diagnosis to determine the risk of recurrent ICH or thromboembolism. Results showed that 11 (37.5%) patients had recurrent ICH when anticoagulation was restarted within 14 days from initial diagnosis. Of these, 2 (6.25%) patients were on DOACs (specifically, rivaroxaban) while 9 (28.1%) patients were on VKA. Within 30 days of initial ICH diagnosis, 19 (15.2%) patients developed thrombosis. Of those, 16 (12.8%) patients were restarted more than twenty-one days from initial diagnosis; 3 (2.4%) were restarted between fourteen and twenty-one days post diagnosis. Subgroup analysis of the thrombosis arm revealed that 2 (10.5%) were restarted on rivaroxaban while 17 (89.5%) were restarted on VKA. Forty-one (32.8%) patients were alive within the studied time period and the outcome of 28 (22.4%) patients could not be ascertained from our database.Conclusion: Given the rising national trend on the use of anticoagulants for various medical necessities, it is imperative that a safe and efficient process be devised on reinstitution of anticoagulation post ICH. Although our study represents a single institutional analysis, it concurs with recent studies that early resumption of anticoagulant following stable ICH is associated with lower thromboembolic events and similar risk of ICH recurrence. Our study further reveals that the risk of recurrent ICH and/or thromboembolism may be less in patients on DOACs. Nonetheless, randomized clinical trials are needed to evaluate the true risk-benefit profile of anticoagulation resumption after ICH. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Resumption of oral anticoagulation following traumatic injury and risk of stroke and bleeding in patients with atrial fibrillation: a nationwide cohort study.

We examined the risks of all-cause mortality, stroke, major bleeding, and recurrent traumatic injury associated with resumption of vitamin K antagonists (VKAs) and non-VKAs oral anticoagulants (NOACs) following traumatic injury in atrial fibrillation (AF) patients. This was a Danish nationwide registry-based study (2005-16), including 4541 oral anticoagulant (OAC)-treated AF patients experiencing traumatic injury (defined as traumatic brain injury, hip fracture, or traumatic torso or abdominal injury). Within 90 days following discharge from traumatic injury, 60.6% resumed VKA (median age = 80, CHA2DS2-VASc = 4, HAS-BLED = 2), 16.7% resumed NOAC (median age = 81, CHA2DS2-VASc = 4, HAS-BLED = 2), and 22.7% did not resume OAC treatment (median age = 81, CHA2DS2-VASc = 4, HAS-BLED = 3). Switch from VKA to NOAC occurred among 9.5%. Since 2009, the trend in OAC resumption increased (P-value <0.0001), in particular with NOACs (P-value <0.0001). Follow-up started 90 days after discharge, and time-varying multiple Cox regression analyses were used for comparisons. Compared with non-resumption, VKA and NOAC resumption were associated with lower hazard [95% confidence interval (CI)] of all-cause mortality [hazard ratio (HR) 0.48 (0.42-0.53) and HR 0.55 (0.47-0.66), respectively] and ischaemic stroke [HR 0.56 (0.43-0.72) and HR 0.54 (0.35-0.82), respectively], increased major bleeding hazard [HR 1.30 (1.03-1.64) and HR 1.15 (0.81-1.63), respectively], and similar hazard of recurrent traumatic injury [HR 0.93 (0.73-1.18) and HR 0.87 (0.60-1.27), respectively]. AF patients resuming VKA and NOAC treatment following traumatic injury have lower hazard of all-cause mortality and ischaemic stroke, increased hazard of major bleeding but without additional hazards of recurrent traumatic injury. Withholding OAC following a traumatic injury in AF patients may not be warranted.

Resumption of Oral Anticoagulation after Intracerebral Hemorrhage is Associated with Decreased Mortality and Favorable Functional Outcome

Resumption of Oral Anticoagulation after Intracerebral Hemorrhage is Associated with Decreased Mortality and Favorable Functional Outcome

Resumption of Anticoagulation After Intracranial Hemorrhage.

Anticoagulation is a vital therapy in a number of different disease processes, and is strongly recommended for the prevention of stroke in patients with atrial fibrillation and/or with mechanical prosthetic heart valves. Studies involving patients on oral anticoagulants (OACs) have revealed that ICH can occur eight times more frequently in this population, with an annual estimated incidence of 0.25 to 1.1%. The decision of whether and when to resume anticoagulation following intracranial hemorrhage is challenging and requires an assessment of associated risks and benefits. Clinical data, imaging, and risk factors for both ischemic and hemorrhagic complications may aid in decision-making. Baseline functional status, life expectancy, compliance with therapy, and family support also impact decision analyses. Currently available data suggest that anticoagulation could be safely restarted in select groups of OAC-ICH patients within 4weeks of intracranial hemorrhage; however, high-quality randomized, clinical trials are needed.

The hemorrhagic transformation index score: a prediction tool in middle cerebral artery ischemic stroke

BackgroundWe aimed to develop a tool, the hemorrhagic transformation (HT) index (HTI), to predict any HT within 14 days after middle cerebral artery (MCA) stroke onset regardless of the intravenous recombinant tissue plasminogen activator (IV rtPA) use. That is especially important in the light of missing evidence-based data concerning the timing of anticoagulant resumption after stroke in patients with atrial fibrillation (AF).MethodsWe retrospectively analyzed 783 consecutive MCA stroke patients. Clinical and brain imaging data at admission were recorded. A follow-up period was 2 weeks after admission. The patients were divided into derivation (DC) and validation (VC) cohorts by generating Bernoulli variates with probability parameter 0.7. Univariate/multivariate logistic regression, and factor analysis were used to extract independent predictors. Validation was performed with internal consistency reliability and receiver operating characteristic (ROC) analysis. Bootstrapping was used to reduce bias.ResultsThe HTI was composed of 4 items: Alberta Stroke Program Early CT score (ASPECTS), National Institutes of Health Stroke Scale (NIHSS), hyperdense MCA (HMCA) sign, and AF on electrocardiogram (ECG) at admission. According to the predicted probability (PP) range, scores were allocated to ASPECTS as follows: 10–7 = 0; 6–5 = 1; 4–3 = 2; 2–0 = 3; to NIHSS: 0–11 = 0; 12–17 = 1; 18–23 = 2; >23 = 3; to HMCA sign: yes = 1; to AF on ECG: yes = 1. The HTI score varied from 0 to 8. For each score, adjusted PP of any HT with 95% confidence intervals (CI) was as follows: 0 = 0.027 (0.011–0.042); 1 = 0.07 (0.043–0.098); 2 = 0.169 (0.125–0.213); 3 = 0.346 (0.275–0.417); 4 = 0.571 (0.474–0.668); 5 = 0.768 (0.676–0.861); 6 = 0.893 (0.829–0.957); 7 = 0.956 (0.92–0.992); 8 = 0.983 (0.965–1.0). The optimal cutpoint score to differentiate between HT-positive and negative groups was 2 (95% normal-based CI, 1–3) for the DC and VC alike. ROC area/sensitivity/specificity with 95% normal-based CI for the DC and VC were 0.85 (0.82–0.89)/0.82 (0.73–0.9)/0.89 (0.8–0.97) and 0.83 (0.78–0.88)/0.8 (0.66–0.94)/0.87 (0.73–1.0) respectively. McDonald’s categorical omega with 95% bias-corrected and accelerated CI for the DC and VC was 0.81 (0.77–0.84) and 0.82 (0.76–0.86) respectively.ConclusionsThe HTI is a simple yet reliable tool to predict any HT within 2 weeks after MCA stroke onset regardless of the IV rtPA use.

Stroke : Highlights of Selected Articles

<i>Stroke</i> : Highlights of Selected Articles

Resumption of Oral Anticoagulation after Intracerebral Hemorrhage is Associated with Decreased Mortality and Favorable Functional Outcome (CCI.003)

Resumption of Oral Anticoagulation after Intracerebral Hemorrhage is Associated with Decreased Mortality and Favorable Functional Outcome (CCI.003)

Restarting Anticoagulant Therapy After Intracranial Hemorrhage: A Systematic Review and Meta-Analysis.

The safety and efficacy of restarting anticoagulation therapy after intracranial hemorrhage (ICH) remain unclear. We performed a systematic review and meta-analysis to summarize the associations of anticoagulation resumption with the subsequent risk of ICH recurrence and thromboembolism. We searched published medical literature to identify cohort studies involving adults with anticoagulation-associated ICH. Our predictor variable was resumption of anticoagulation. Outcome measures were thromboembolic events (stroke and myocardial infarction) and recurrence of ICH. After assessing study heterogeneity and publication bias, we performed a meta-analysis using random-effects models to assess the strength of association between anticoagulation resumption and our outcomes. Eight studies were eligible for inclusion in the meta-analysis, with 5306 ICH patients. Almost all studies evaluated anticoagulation with vitamin K antagonists. Reinitiation of anticoagulation was associated with a significantly lower risk of thromboembolic complications (pooled relative risk, 0.34; 95% confidence interval, 0.25-0.45; Q=5.12, P for heterogeneity=0.28). There was no evidence of increased risk of recurrent ICH after reinstatement of anticoagulation therapy, although there was significant heterogeneity among included studies (pooled relative risk, 1.01; 95% confidence interval, 0.58-1.77; Q=24.68, P for heterogeneity <0.001). No significant publication bias was detected in our analyses. In observational studies, reinstitution of anticoagulation after ICH was associated with a lower risk of thromboembolic complications and a similar risk of ICH recurrence. Randomized clinical trials are needed to determine the true risk-benefit profile of anticoagulation resumption after ICH.

Bleeding Complications and Management on anticoagulant therapy.

Patients treated with anticoagulants have an unavoidable risk of bleeding complications. There are, for all oral anticoagulants, several potential options for management of major bleeding. The first action is to assess the causative role of the anticoagulant in the current bleeding. Supportive measures have been assessed in several post hoc analyses of the phase III pivotal trials with the non-vitamin K antagonist oral anticoagulants (NOACs). Those results will be reviewed here together with emerging data on the efficacy and safety of the specific antidotes idarucizumab (for dabigatran) and andexanet-α (for factor Xa inhibitors). Regular or activated prothrombin complex concentrates are also evaluated and might have a role as alternatives for management of NOAC-associated major bleeding if the "specific" antidote is not available. Once hemostasis has been achieved, it is imperative to assess the possibility and timing of resumption of anticoagulation, as these patients have an inherent prothrombotic state and a non-negligible proportion of patients will have thromboembolic complications during the first month after the hemorrhage. Many factors will have to be taken into account for this decision and unfortunately the guidelines in this respect are very weak if at all available. This review will hopefully provide some assistance in the management of major bleeding and posthemorrhage care.

Abstract TP340: Resumption of Anticoagulation after Intracerebral Hemorrhage: Risks, Benefits and Impact on Outcome

Introduction: The risks, benefits and impact on outcome of anticoagulation following spontaneous intracerebral hemorrhage (ICH) are not well established. Methods: Prospectively collected data of ICH patients on full-dose anticoagulation at ictus or after ICH were reviewed between 5/2013 and 4/2016. Composite ischemic (ischemic stroke, venous thromboembolism or myocardial infarction) and hemorrhagic (GI bleed, anemia requiring transfusion, new intracerebral hemorrhage) complications and 12-month modified Rankin scores were compared between those anticoagulated versus not post-ICH. Results: Of 174 ICH patients, 54 (31%) were anticoagulated at ictus (N=38 on warfarin; N=13 on heparin/LMWH, N=9 on novel oral anticoagulant [NOAC]). Twenty-five patients were anticoagulated post-ICH in a median of 22 days (range 3-271); 16/54 [30%] resumed anticoagulation, 9 patients started anticoagulation de novo (N=17 warfarin, N=7 NOAC and N=1 LMWH) and 38/54 (70%) did not resume anticoagulation. Compared to those who did not resume anticoagulation, anticoagulated patients were younger, had better ICH and APACHE-2 scores and were more likely to undergo ICH evacuation (all P&lt;0.05). Composite ischemic events trended lower in anticoagulated patients (0.03 versus 0.73 events per patient-year in non-anticoagulated, P=0.093) and there was no difference in composite hemorrhage events (0.17 in anti-coagulated versus 0.63 events per patient-year in non-anticoagulated, P=0.417). Recurrent intracerebral hemorrhage post-discharge occurred in 3 (12%) anticoagulated versus 0 non-anticoagulated patients (P=0.03) in a median of 102 days (range 24-263). In multivariable logistic regression analysis adjusting for ICH score and ICH evacuation, and excluding those who underwent withdrawal of life-sustaining therapy, resumption of anticoagulation was protective against death at 12-months (aOR 0.1, 95% CI 0.02-0.9, P=0.047). Conclusions: Anticoagulation post-ICH is associated with fewer ischemic events, but more recurrent ICH post-discharge compared to non-resumption in previously anticoagulated patients. However, mortality rates were lower at 12-months in those who were anticoagulated, even after adjusting for ICH score and ICH evacuation.

Haemorrhagic Transformation after Ischaemic Stroke in Patients Taking Non-vitamin K Antagonist Oral Anticoagulants.

Background and Purpose To evaluate the frequency and outcome of haemorrhagic transformation (HT) after ischaemic stroke in patients treated with non-vitamin K antagonist oral anticoagulants (NOACs).Methods Patients with stroke on treatment with a NOAC were prospectively enrolled in this multicentre observational study between February 2012 and 2015. Brain imaging at admission and follow-up imaging until day 7 were reviewed for HT. Functional outcome was assessed by the modified Rankin scale (mRS) before the index event, at discharge, and at 3-months.Results 231 patients without recanalisation therapy (no-RT), and 32 patients with RT were eligible for analysis. Any HT was present at admission in 9/231 no-RT patients (3.9%, 95% CI 2.0 to 7.3) and in none of the patients with RT. In patients with follow-up imaging (no-RT, n=129, and RT, n=32), HT was present in 14.0% (no-RT; 95% CI, 8.9 to 21.1), and 40.6% (RT, 95% CI, 25.5 to 57.8), respectively. After adjustment for stroke severity, this difference between the no-RT and RT groups became non-significant. Symptomatic ICH was observed in 1 patient per group. HT was not associated with unfavourable outcome (mRS 3-6) at 3-months in multivariable analysis. Resumption of OAC after stroke was delayed in patients with HT compared to those without (15 d [IQR, 5–26] vs. 1 d [0–4], P<0.001).Conclusions The frequency and severity of HT after stroke on NOAC appears similar to previous reports for vitamin K antagonists and no anticoagulation. Whether asymptomatic HT should delay resumption of preventive anticoagulation requires further investigation.

脳出血患者の抗凝固薬再開の時期と経過についての検討

脳出血患者の抗凝固薬再開の時期と経過についての検討

Influence of antithrombotic agents on the recurrence of chronic subdural hematomas and the quest about the recommencement of antithrombotic agents: A meta-analysis

Antithrombotic agents (AT), including anticoagulants and antiplatelets, are risk factors of chronic subdural hematomas (CSDHs). However, the use of AT has not been clearly associated with postoperative recurrence (PR) in the literature before. Furthermore, the association between the resumption of AT and postoperative complications also requests research. Databases including Pubmed, Embase and Cochrane were searched for patients presenting with CSDH on anticoagulant or antiplatelet medication. Ten studies were included to analyze the association between the use of AT and PR: The meta-analysis showed that the use of AT, both anticoagulants (OR=2.20, 95%CI [1.45, 3.33]; P=0.0002) and antiplatelets (OR=1.64, 95%CI [1.17, 2.30]; P=0.004), could increase the PR rate. Two studies were included to analyze the relationship between the resumption of AT and postoperative complications. The meta-analysis showed that after the patients on AT resumed their medication, the risk of PR did not increase (OR=0.33, 95%Cl [0.13, 0.80]; P=0.01), and the occurrence of thromboembolism events had no statistical significance (OR=1.30, 95%CI [0.26, 6.50]; P=0.75). This meta-analysis demonstrated that AT were risk factors for the recurrence of CSDH. Recommencement of AT did not appear to increase the risk of postoperative hemorrhage, and could reduce the risk of thromboembolism. Thus, appropriate postoperative resumption of anticoagulants or antiplatelets may be safe. Still, more evidence is needed to answer the question about whether and how to resume AT.

What to do after the bleed: resuming anticoagulation after major bleeding.

Resuming anticoagulation therapy after a potentially life-threatening bleeding complication evokes high anxiety levels among clinicians and patients trying to decide whether resuming oral anticoagulation to prevent devastating and potentially fatal thromboembolic events or discontinuing anticoagulation in hopes of reducing the risk of recurrent bleeding is best. The available evidence favors resumption of anticoagulation therapy for gastrointestinal tract bleeding and intracranial hemorrhage survivors, and it is reasonable to begin postbleeding decision making with resuming anticoagulation therapy as the default plan. After considering factors related to the index bleeding event, the underlying thromboembolic risk, and comorbid conditions, a decision to accept or modify the default plan can be made in collaboration with other care team members, the patient, and their caregivers. Although additional information is needed regarding the optimal timing of anticoagulation resumption, available evidence indicates that waiting ∼14 days may best balance the risk of recurrent bleeding, thromboembolism, and mortality after gastrointestinal tract bleeding. When to resume anticoagulation after intracranial hemorrhage is less clear, but most studies indicate that resumption within the first month of discharge is associated with better outcomes.

Anticoagulation Use and Clinical Outcomes After Major Bleeding on Dabigatran or Warfarin in Atrial Fibrillation.

Little is known about the clinical outcomes associated with posthemorrhage anticoagulation resumption for atrial fibrillation. This study had 2 objectives: first, to evaluate anticoagulation use after a first major bleed on warfarin or dabigatran and, second, to compare effectiveness and safety outcomes between patients discontinuing anticoagulation after a major bleed and patients restarting warfarin or dabigatran. Using 2010 to 2012 Medicare Part D data, we identified atrial fibrillation patients who experienced a major bleeding event while using warfarin (n=1135) or dabigatran (n=404) and categorized them by their posthemorrhage use of anticoagulation. We followed them until an ischemic stroke, recurrent hemorrhage, or death through December 31, 2012. We constructed logistic regression models to evaluate factors affecting anticoagulation resumption and Cox proportional hazard models to compare the combined risk of ischemic stroke and all-cause mortality and the risk of recurrent bleeding between treatment groups. Resumption of anticoagulation with warfarin (hazard ratio [HR] 0.76; 95% confidence interval [CI] 0.59-0.97) or dabigatran (HR 0.66; 95% CI 0.44-0.99) was associated with lower combined risk of ischemic stroke and all-cause mortality than anticoagulation discontinuation. The incidence of recurrent major bleeding was higher for patients prescribed warfarin after the event than for those prescribed dabigatran (HR 2.31; 95% CI 1.19-4.76) or whose anticoagulation ceased (HR 1.56; 95% CI 1.10-2.22), but did not differ between patients restarting dabigatran and those discontinuing anticoagulation (HR 0.65; 95% CI 0.32-1.33). Dabigatran was associated with a superior benefit/risk ratio than warfarin and anticoagulation discontinuation in the treatment of atrial fibrillation patients who have survived a major bleed.

Abstract 12209: Anticoagulation Use and Clinical Outcomes Following Major Bleeding on Dabigatran or Warfarin in Atrial Fibrillation

Introduction: Little is known about the patterns of anticoagulation use and clinical outcomes associated with the resumption of anticoagulation after a major hemorrhage. Hypothesis: We hypothesized that the discontinuation of anticoagulation would be associated with higher thromboembolic risk but lower risk of recurrent bleeding than the post-hemorrhage resumption of anticoagulation with warfarin or dabigatran. Methods: Using 2010-2012 Medicare Part D data, we identified atrial fibrillation patients who experienced a major bleeding while using warfarin (n=1135) or dabigatran (n=404) and categorized them by their post-hemorrhage use of anticoagulation. We followed them until a clinical event of ischemic stroke, recurrent hemorrhage, or death through December 31, 2012. We constructed logistic regression models to evaluate factors impacting anticoagulation resumption, and Cox Proportional Hazard models to compare the risk of ischemic stroke, all-cause mortality, and recurrent bleeding between treatment groups. Results: CHA2DS2-Vasc and HAS-BLED scores did not affect the odds of post-hemorrhage anticoagulation resumption. The odds of resuming anticoagulation decreased however by 11% (95%CI, 4%-18%) and 24% (95%CI, 9%-37%) for every 5 years increase in age for warfarin and dabigatran users, respectively. Resumption of anticoagulation with warfarin (hazard ratio (HR) 0.76; 95%CI, 0.59-0.97) or dabigatran (HR0.66; 95%CI 0.44-0.99) was associated with lower combined risk of ischemic stroke and all-cause mortality than anticoagulation discontinuation. The incidence of recurrent major bleeding was higher for patients who were prescribed warfarin after the bleeding event than for those prescribed dabigatran (HR2.31; 95%CI, 1.19-4.76) or whose anticoagulation ceased (HR1.56; 95%CI, 1.10-2.22), but did not differ between patients restarting dabigatran and those discontinuing anticoagulation. Conclusions: The benefit/risk ratio of dabigatran among atrial fibrillation patients who have survived a major hemorrhage is superior to that of warfarin and of anticoagulation discontinuation.

Timing of vitamin K antagonist re-initiation following intracranial hemorrhage in mechanical heart valves: Systematic review and meta-analysis

BackgroundWhile evidence supports resumption of vitamin K antagonists (VKAs) among mechanical heart valve (MHV) patients presenting with anticoagulant-associated intracranial hemorrhage (ICH), ideal timing of resumption is uncertain. ObjectiveTo determine the optimal timing of VKA re-initiation and its associated clinical outcomes. MethodsWe performed a systematic review and a meta-analysis of studies published from January 1950 to August 2015. We extracted data on the location of initial ICH, use of cranial surgery, presence of atrial fibrillation, MHV type and position, number of MHVs, and timing of VKA resumption. Outcomes including valve thrombosis, thromboembolic events or ICH recurrence were recorded. Meta-regression analysis was conducting with controlling for covariates. We calculated absolute risks, and assessed the effect of anticoagulant resumption timing on ICH recurrence. Results23 case-series and case-reports were identified. Overall ICH recurrence was 13% (95% confidence interval [CI], 7%–25%), while valve thrombosis and ischemic strokes occurred at 7% (95% CI, 3%–17%) and 12% (95% CI, 5%–23%) respectively. A trend towards lower ICH recurrence was observed with delayed VKA resumption (slope estimate −0.2154, p=0.10). Recurrence rate ranged from 50% with VKA resumption at 3days to 0% with resumption at 16days. ConclusionAmong patients with MHV, there is inadequate data to suggest an optimal timing of VKA re-initiation following an ICH, though delayed restart appears to be protective against recurrence but is associated with higher risk of thrombosis. Our analysis suggests 4–7days might be an ideal time with least risk of thrombosis or ICH recurrence.