Prior Warfarin Use Research Articles

Hematoma expansion in spontaneous intracerebral hemorrhage: predictors and outcome

Background: Hematoma growth is an independent determinant of outcome in patients with intracerebral hemorrhage (ICH). Predictors of hematoma expansion are poorly defined. Our aim is to determine predictors of hematoma expansion in patients with ICH. Methods: We reviewed our prospective database of patients with ICH between January 2009 and June 2012. Patients were divided into two groups based on the presence or absence of hematoma expansion. Hematoma volume was calculated by thin volumetric cuts using special software. Expansion was defined as 33% increase in hematoma volume over 24 hours. We compared risk factors, laboratory parameters, medications and CT findings between the two groups using Fisher's exact test. A multivariate regression analysis was performed to identify predictors of expansion. Results: We identified 200 patients with ICH. On univariate analysis, patients with hematoma expansion were more likely to have Warfarin use (37% vs. 11% p = 0.001), low admission GCS (9 ± 4, 11 ± 4, p = 0.003), intraventricular hemorrhage (IVH) (79% vs. 45% p = 0.002) and hydrocephalus (43% vs. 22% p = 0.032). On multivariate regression analysis, prior Warfarin use (OR = 3.6, 95% CI: 1.3,10.3; p = 0.016) and IVH (OR = 5.7, 95% CI: 1.5,20.9; p = 0.009) were significant predictors of hematoma expansion. The ICU length of stay (8 ± 8 vs. 4 ± 6, p = 0.004), intubation rate (82% vs. 32%, p = 0.034), and hospital mortality (68% vs. 20%, p = < 0.001) were significantly higher among patients with hematoma expansion. Conclusion: Patient with prior Warfarin use and IVHs are at risk of hematoma expansion. Aggressive measures to prevent hematoma growth are important in these patients.

Apixaban versus warfarin in patients with atrial fibrillation according to prior warfarin use: Results from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial

Patients with atrial fibrillation who are vitamin K antagonist (VKA)-naive may have a higher risk of thrombosis and/or bleeding than VKA-experienced patients. Using data from ARISTOTLE, we assessed baseline characteristics and the treatment effect of apixaban versus warfarin in the VKA-naive and VKA-experienced cohorts. We compared rates of study drug discontinuation and time-in-therapeutic range. Overall, 7,800 (43%) were VKA naive, and 10,401 were VKA experienced. At baseline, both groups were similar with respect to age and congestive heart failure, hypertension, age, diabetes, stroke score (CHADS2). Fewer VKA-naive patients had a history of prior stroke (18% vs 21%) or prior bleeding (10% vs 22%) and were more often female (39% vs 33%). The effect of apixaban on the primary efficacy and safety outcomes was similar in VKA-naive (stroke/systemic embolism: hazard ratio [HR] 0.86, 95% CI 0.67-1.11 and major bleeding: HR 0.73, 95% CI 0.59-0.91) and VKA-experienced populations (stroke/systemic embolism: HR 0.73, 95% CI 0.57-0.95, P value for interaction = 0.39 and major bleeding: HR 0.66, 95% CI 0.55-0.80, P value for interaction = 0.50). Permanent study drug discontinuation was numerically less likely in patients receiving apixaban whether they were VKA naive (HR for discontinuation: 0.87, 95% CI 0.79-0.95) or VKA experienced (HR for discontinuation: 0.93, 95% CI 0.85-1.02). Among patients receiving warfarin, the mean/median times in therapeutic range were lower in the VKA-naive group (VKA-naive: 57.5/61.4, VKA-experienced: 66.0/69.1, P < .001). The treatment effects of apixaban (vs warfarin) were not modified by VKA naivety. The rates of stroke/systemic embolism and major bleeding were numerically lower among the patients assigned to apixaban, irrespective of prior VKA use.

Design of a randomized clinical trial of concurrent treatment with vitamin K2 and risedronate compared to risedronate alone in osteoporotic patients: Japanese Osteoporosis Intervention Trial-03 (JOINT-03)

Concurrent treatments with bisphosphonates and vitamin K are promising given that bisphosphonates possibly interfere with vitamin K activation. This is a prospective, multi-center, open-labeled, randomized trial of the efficacy of concurrent treatment with vitamin K2 and risedronate compared with risedronate alone and to explore subsets of patients for which concurrent treatment is particularly efficacious (trial identification number UMIN000000991). Inclusion criteria are women who meet the criteria for pharmacological therapy for osteoporosis, aged ≥65 years, have any of pre-specified risk factors, can walk unassisted, and are able to answer questionnaires. Exclusion criteria are prior warfarin use, secondary osteoporosis or non-osteoporotic metabolic bone diseases, contraindication for vitamin K2 and risedronate, hyper- or hypoparathyroidism, mental disorders, prevalent vertebral fracture at ≥6 sites, severe degenerative spinal deformation between T4 and L4, serious heart, liver, or kidney disease, or bisphosphonate use within the previous 6 months. Patients were recruited from 123 institutes between January 2008 and February 2010, and allocated to vitamin K2 (45 mg/day) and risedronate (2.5 mg/day or 17.5 mg/week) or risedronate alone (2.5 mg/day or 17.5 mg/week) groups. Primary endpoint is a vertebral or non-vertebral fracture. Secondary endpoints are bone mineral density, height, undercarboxylated osteocalcin, JOQOL, EQ-5D and safety. A sample size of 910 subjects per group and 2-year follow-up will provide 80 % power to detect 35 % risk reduction for fracture, with a two-sided significance level of 5 %. Subgroup analysis stratified to adjustment factors for random allocation, body mass index, 25-hydroxyvitamin D, estimated glomerular filtration rate, grade of vertebral fracture, JOQOL, EQ-5D, and co-morbidity is pre-specified.

Warfarin treatment and thrombolysis

The study by Xian et al.,1 published in JAMA (June 27, 2012), adds to the growing literature on the safety of IV thrombolysis among stroke patients undergoing anticoagulation treatment. This study, which uses data from the American Heart Association Get With The Guidelines (GWTG)–Stroke Registry, concluded that there was no association between IV thrombolysis and symptomatic intracranial hemorrhage (SICH).1 These findings are in agreement with some2–4 but contrast with other studies (including 2 meta-analyses).5–8 The study by Xian et al. is the largest study to date drawing from hospitals throughout the United States, including 23,437 patients who received IV thrombolysis.1 Nearly 8% of these patients had prior warfarin use and 48.6% of the warfarin-treated patients who met the eligibility criteria did not receive IV thrombolysis.1

Abstract 18466: Anemia is Associated with an Adverse Outcome in Patients with Atrial Fibrillation: Insights Form the Re-ly Trial

Background: Anemia may predispose to cardiovascular events. While patients with atrial fibrillation (AF) may be particularly prone to anemia, the impact of anemia on outcome in patients with AF is unclear. Methods: We retrospectively analyzed the RE-LY trial that randomized 18,113 patients with AF to receive dabigatran or warfarin for a median follow-up of 2 years.The association between anemia (Hb &lt;13.0 g/dL in men and &lt;12.0 g/dL in women) and the incidence of cardiovascular and bleeding events was assessed with multivariable Cox regression analysis. Results: Anemia was present in 12% of the population at baseline and the presence of anemia was associated with an increased incidence of all cause mortality or myocardial infarction (adjusted hazard ratio (adj. HR) 1.50, 95% confidence interval (CI) 1.32-1.71). Anemia was also associated with an increased incidence of the primary RE-LY endpoints of stroke or systemic embolism (adj. HR 1.41 95% CI (1.12-1.78)) and major bleeding (adj. HR 2.14, 95% CI 1.87-2.46). The association between anemia and outcome did not differ according to major cardiovascular comorbidities, treatment allocation or prior use of warfarin. After 6 months, anemia had resolved in 35% of anemic patients, while anemia had developed in 10% of patients without prior anemia. Resolution of anemia was associated with a more favorable outcome than sustained anemia (adj HR. 0.71, 95%CI 0.97-0.52), or new onset anemia (adj HR. 0.68, 95%CI 0.50-0.93) Conclusions: Anemia is associated with an increased risk of cardiovascular events and bleeding complications in patients with AF. Accordingly, resolution of anemia is associated with a more favourable outcome than sustained anemia.

Pre‐ICH warfarin use, not antiplatelets, increased case fatality in spontaneous ICH patients

Anticoagulant and antiplatelets for prevention of ischaemic stroke and cardiovascular diseases may increase the risk of intracerebral hemorrhage (ICH). This study aimed to investigate the influence of pre-ICH use of anticoagulant and antiplatelets on ICH patients. Consecutive patients with acute spontaneous ICH registered in a single-center stroke registry during 2001 to 2010 were analyzed and categorized according to their pre-ICH use of warfarin (Group I), antiplatelets (Group II), or neither (Group III). Survival analysis and the Cox proportional hazard model were used to compare between the three groups and the predictors. Of 2021 ICH patients (male, 63.3%; mean age, 62.6 ± 14.4 years) included, there were 94 (4.7%) in Group I, 232 (11.4%) in Group II, and 1695 (83.9%) in Group III. Warfarin users had larger hematoma volume, more intraventricular extension, higher frequencies of lobar ICH, and higher case fatality than non-warfarin users (Groups II and III). The Cox proportional hazard model showed increased 6-month case fatality in pre-ICH warfarin users (adjusted hazard ratio 2.75, 95% confidence interval 2.04-3.72, P < 0.001), but not in pre-ICH antiplatelet users (adjusted hazard ratio 0.95, 95% confidence interval 0.72-1.26). Intracerebral hemorrhage patients with prior warfarin use, but not antiplatelet use, had significantly higher case fatality at 6 months.

Thrombolytic therapy for ischaemic stroke in patients using warfarin: a systematic review and meta-analysis

BackgroundIt is uncertain whether thrombolytic therapy is safe in patients with acute ischaemic stroke who are treated with warfarin and have a subtherapeutic international normalised ratio (INR) at stroke onset.MethodsThe...

Abstract 187: Electrocardiographic Heart Rate-corrected Qt Interval And Risk Of Stroke In The REasons For Geographic And Racial Differences In Stroke (REGARDS) Study

Background: Prolongation of heart rate-corrected QT interval (QTc) is a well established predictor of cardiovascular morbidity and mortality. Little is known, however, about the relationship between this simple electrocardiographic (ECG) marker and risk of stroke. Methods: A total of 27,411 participants aged &gt; 45 years without prior stroke from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study were included in this analysis. QTc was calculated using Framingham formula (QTcFram). Stroke cases were identified and adjudicated during an up to 7 years of follow-up (median 2.7 years). Cox proportional hazards analysis was used to estimate the hazard ratios for incident stroke associated with prolonged QTcFram interval (vs. normal) and per 1 standard deviation (SD) increase, separately, in a series of incremental models. Results: The risk of incident stroke in the study participants with baseline prolonged QTcFram was almost 3 times the risk in those with normal QTcFram [HR (95% CI): 2.88 (2.12, 3.92), p&lt;0.0001]. After adjustment for age, race, sex, antihypertensive medication use, systolic blood pressure, current smoking, diabetes, left ventricular hypertrophy, atrial fibrillation, prior cardiovascular disease, QRS duration, warfarin use, and QT-prolonging drugs (full model), the risk of stroke remained significantly high [HR (95% CI): 1.67 (1.16, 2.41), p=0.0060)], and was consistent across several subgroups of REGARDS participants. When the risk of stroke was estimated per 1 SD increase in QTcFram, a 24% increased risk was observed [HR (95% CI): 1.24 (1.16, 1.33), p&lt;0.0001)]. This risk remained significant in the fully adjusted model [HR (95% CI): 1.12 (1.03, 1.21), p=0.0055]. Similar results were obtained when other QTc correction formulas including Hodge’s, Bazett’s and Fridericia’s were used. Conclusions: QTc prolongation is associated with a significantly increased risk of incident stroke independently from known stroke risk factors. In light of our results, examining the risk of stroke associated with QT-prolonging drugs may be warranted.

The Association Between Prior Use of Aspirin and/or Warfarin and the In-hospital Management and Outcomes in Patients Presenting With Acute Coronary Syndromes: Insights From the Global Registry of Acute Coronary Events (GRACE)

Background The role of acetylsalicylic acid (ASA [aspirin]) and warfarin in secondary prevention after acute coronary syndromes (ACS) is well established. However, there are sparse data comparing the presentation and outcomes of patients who present with ACS while on ASA and/or warfarin therapy and those on neither. Methods Using data from the Canadian Global Registry of Acute Coronary Events (GRACE), we stratified 14,090 ACS patients into 4 groups according to prior use of antithrombotic therapies and compared in-hospital management and outcomes. Results Among 14,090 ACS patients, 7411 (52.6%) were not on prior ASA or warfarin therapy, 5724 (40.6%) were on ASA only, 593 (4.2%) were on warfarin only, and 362 (2.6%) were on both ASA and warfarin. ACS patients taking ASA and/or warfarin were older with more comorbidities than the patients on neither drug. Patients receiving prior warfarin only or ASA and warfarin were less likely to receive guideline-recommended therapies. Patients who were taking prior warfarin only had higher unadjusted rates of death, death and/or reinfarction (re-MI), congestive heart failure (CHF), and major bleeding as compared with patients on no prior therapy. Furthermore, patients who were taking ASA and warfarin had higher unadjusted rates of death and/or re-MI and CHF than patients on prior ASA only. Conclusions ACS patients on prior warfarin are a high-risk population, yet they receive less guideline-recommended therapies and have higher unadjusted adverse event rates during their index hospitalization. With the increasing use of oral anticoagulants, clinical trials are needed to guide the optimal management of these ACS patients.

Effectiveness and Safety of Warfarin Initiation in Older Hemodialysis Patients with Incident Atrial Fibrillation

Although generally recommended in atrial fibrillation (AF) patients, the effectiveness and safety of oral anticoagulation in dialysis patients with AF is unknown. We assembled a cohort of older hemodialysis patients who initiated dialysis without prior record of AF and who had prescription drug benefits through three state-administered programs. The index event was a first hospitalization with diagnosed AF; patients with any recorded prior warfarin use were excluded. Eligible patients survived ≥30 days from discharge, and new warfarin use was recorded from prescription records during that 30-day window. Propensity-matched warfarin users and nonusers were compared using Cox regression. Outcomes included ischemic stroke, hemorrhagic stroke, and mortality. Among 2313 patients with new AF who survived 30 days from discharge, 249 (10.8%) filled a prescription for warfarin. Comparing 237 warfarin users and 948 propensity-matched nonusers over 2287 person-years of follow-up, the occurrence of ischemic stroke was similar (HR = 0.92; 95% CI, 0.61 to 1.37), whereas warfarin users experienced twice the risk of hemorrhagic stroke (HR = 2.38; 95% CI, 1.15 to 4.96). The risks of stroke, gastrointestinal hemorrhage, and mortality did not differ between groups. As-treated analyses yielded similar findings, as did analyses restricted to patients with CHADS(2) scores ≥2. Although we confirmed association between warfarin use and hemorrhagic stroke in dialysis patients with AF, we found no association between warfarin use and ischemic stroke. Adequately powered randomized trials are required to conclusively determine the risks and benefits of the studied warfarin indication in hemodialysis patients.

Risk factors for 1-year mortality in patients with nontraumatic intracranial hemorrhage requiring intensive care

Mortality in patients with intracranial hemorrhage remains high. The aim of this study was to determine the 1-year survival and potential risk factors for 1-year mortality in patients with nontraumatic intracranial hemorrhage requiring intensive care. This was a 3-year (2005-2007) retrospective study in a university-level intensive care unit (ICU). Patient characteristics, level of consciousness, and radiological findings of the primary head computed tomography were recorded on admission. Sequential Organ Failure Assessment scores were recorded during the ICU stay. Patients were divided into two groups: subarachnoid hemorrhage (SAH) group and intracerebral hemorrhage (ICH) group. Kaplan-Meier survival curves were constructed, and independent risk factors were determined using Cox proportional hazards regression analyses. Two hundred twenty-nine patients were analyzed. The 1-year mortality rate was 32% in patients with SAH and 44% in patients with ICH. The risk factors for 1-year mortality in both groups were unconsciousness on admission [SAH: hazard ratio (HR) 6.2, P = 0.017 and ICH: HR 3.0, P = 0.004] and renal failure during the ICU stay (SAH: HR 2.5, P = 0.021 and ICH: HR 3.6, P = 0.021). Risk factors specific to the type of hemorrhage were the presence of ICH (HR 2.0, P = 0.033) and diffuse cerebral edema (HR 2.3, P = 0.017) in the SAH group and a prior use of warfarin (HR 5.1, P = 0.016) in the ICH group. In addition to decreased level of consciousness on admission, renal failure during the ICU stay is an independent risk factor for 1-year mortality in nontraumatic SAH as well as ICH.

Subtherapeutic International Normalized Ratio in Warfarin-Treated Patients Increases the Risk for Symptomatic Intracerebral Hemorrhage After Intravenous Thrombolysis

There is uncertainty whether warfarin-treated patients (despite international normalized ratio < 1.7) have increased risks of symptomatic intracerebral hemorrhage after intravenous thrombolysis. Vascular risk factors, stroke subtype, and outcome measures were compared between warfarin- and nonwarfarin-treated patients undergoing acute thrombolysis within 3 hours of symptom onset. From 212 patients (mean age, 74 ± 14 years; 50% men) studied, 14 (6.5%) had prior warfarin use. After adjusting for age, baseline National Institutes of Health Stroke Scale, and stroke subtype, warfarin-treated patients had significantly increased risks of developing symptomatic intracerebral hemorrhage (adjusted OR, 14.7; 95% CI, 1.3 to 54.3). A trend for poorer stroke recovery and increased mortality was observed in warfarin-treated patients on univariate, but not on multivariable, analyses. Warfarin-treated patients with stroke have increased risks of symptomatic intracerebral hemorrhage after thrombolytic treatment. These data raise safety concerns of thrombolytic treatment in warfarin-treated patients with subtherapeutic international normalized ratio.

Warfarin: Implementing Its Safe Use in Hospitalized Patients from Nursing Homes and Community Through a Performance Improvement Initiative

Warfarin is increasingly used to prevent thromboembolism but adverse drug events (ADEs) are common. The National Safety Goals (3E) 2008 recommend that institutions develop processes to monitor the safe use of warfarin. Despite these guidelines, adverse events (bleeding) are common. This initiative, in an academic hospital, tracked warfarin use before and after using a PI process aimed at improving safe use of warfarin in hospitalized adults. Retrospective (PRE-initiative, September-December 2007) and prospective (POST-initiative, January-December 2008) data were collected on in-hospital and prior warfarin use, demographics, medical history, initial and in-hospital warfarin maintenance dosing, hematocrit, International Normalized Ratio (INR), hepatic and renal function and adverse events related to warfarin use. Education on the appropriate use of warfarin was provided through formal and informal sessions and during daily hand-off sessions. A total of 308 patients receiving oral warfarin were examined (mean age 70 ± 17(SD) years, 47% males, 36% from nursing homes). Age, sex ratios, and place of residence were similar PRE- versus POST-initiative. Overall initial and maintenance warfarin doses were significantly lower POST-initiative (P = .0129 and P = .0319, respectively) and these decreases occurred exclusively in patients with supratherapeutic INR levels (>3.0). During the POST-period, the prevalence of high INR levels and bleeding events during hospitalization also decreased significantly (P = .015 and P < .0005, respectively). Finally, concomitant use of anticoagulant and/or antiplatelet drugs was significantly decreased POST-initiative (P = .028). Most hospitalized patients (PRE- and POST-) presented with INRs in the sub- or supratherapeutic ranges (<2 and >3, respectively), requiring warfarin dose adjustments. Education through this initiative resulted in significantly lower average maintenance doses of warfarin, less use of concomitant anticoagulant or antiplatelet drugs, fewer supratherapeutic range INRs, and fewer adverse events during warfarin therapy. Education through a PI initiative is a simple and effective means to implement safer use of warfarin in the in-hospital setting.

Safety and outcome after thrombolytic treatment in ischemic stroke patients with high-risk cardioembolic sources and prior subtherapeutic warfarin use

Background Hemorrhage is a major complication of thrombolytic treatment. Concerns have been raised about the risk of hemorrhage in patients having received warfarin. Therefore, different indications for thrombolytic treatment are in use for stroke patients on warfarin. However, it remains uncertain whether the prior warfarin use actually increases their risk of bleeding in patients treated with thrombolysis. Methods This study included 179 consecutive patients who had high-risk cardioembolic sources and received thrombolytic treatment. Patients were treated with intravenous thrombolytic agents, or underwent intraarterial thrombolysis if their international normalized ratio (INR) was ≤ 1.7. We compared the frequency of bleeding complications between patients with prior warfarin use and those without. We also investigated whether there were differences in functional outcome and recanalization rates between them. Results A prior warfarin use was present in 28 patients (15.6%). Although INR levels were higher in the prior warfarin group, the frequency of bleeding complications was not different between patients who received prior warfarin and those who did not. No differences were observed in patients with or without prior warfarin use, for successful recanalization rate (Thrombolysis in Myocardial Infarction grade 2 or 3), mortality, or modified Rankin score (≤ 2) at 3 months. Conclusions Thrombolytic therapy for patients who previously received warfarin and had an INR ≤ 1.7 did not affect bleeding risk, clinical outcome, or recanalization rate. Our data suggest that patients with a history of prior warfarin use may be safely treated with thrombolytic agents when their INR levels are low.

Retrospective study of total healthcare costs associated with chronic nonvalvular atrial fibrillation and the occurrence of a first transient ischemic attack, stroke or major bleed

Objective:To determine the direct healthcare costs associated with the onset of chronic nonvalvular atrial fibrillation (CNVAF), warfarin utilization and the occurrence of cerebrovascular events in a commercially-insured population.Research design and methods:This retrospective, observational cohort study utilized medical and pharmacy claims from a large, geographically diverse managed-care organization (N = 18.5 million) to identify continuously benefit-eligible CNVAF patients ≥45 years of age without prior valvular disease or warfarin use between January 1, 2001 and June 1, 2002. All patients were followed at least 6 months, until plan termination or the end of study follow-up. Stroke risk was assessed using the CHADS2 (stroke-risk) index; warfarin use was defined as having filled at least one pharmacy claim. Inpatient and outpatient cost benchmarks were utilized to estimate total direct healthcare costs (pre- and post-AF index claim). For patients with transient ischemic attacks (TIA), ischemic stroke (IS) and major bleed (MB) total direct healthcare costs were also assessed. The limitations of this study included a descriptive retrospective study design without a comparison group or adjustment for baseline disease severity and drug exposure, as well as, the reliance upon administrative claims data and use of a standardized reference costing methodology.Results:The pre- and post-AF onset total direct healthcare costs (pmpm) for 3891 incidence CNVAF patients were $412 and $1235, respectively, a 200% increase. Of the 448 (12%) patients with a cerebrovascular event, pmpm costs post-AF ranged from $2235 to $3135 correlating with CHADS2 stroke-risk status and exposure to warfarin. Total cohort pmpm costs pre and post event increased 24% from $3446.91 to $4262.12. Approximately 20% of all events occurred <2 days and 46% within 1 month after the index AF claim. Any warfarin exposure, regardless of CHADS2 risk had an 18% to 29 % decrease in pmpm costs.Conclusions:Post-AF total direct healthcare costs were 3 times greater than pre-AF costs. For those with a TIA, IS or MB, post-AF total direct healthcare costs increased 4.5 times from pre-AF costs; overall post-event costs in this cohort increased ∼25% over pre-event costs. Nearly half of the events occurred within 1 month of a claim associated with an AF diagnosis. Warfarin exposure appeared to be associated with lower pmpm costs in this population.

W1028 Validation of a Survey Methodology for the Systematic Investigation of Gastrointestinal Diseases in China (SILC) Epidemiological Study

ALBI epidemiology is poorly known, selection bias limits published clinical data, and few follow-up data exist. Aims: To study the epidemiology, clinical aspects, care and long-term outcome of patients (Ps) with ALBI.Methods: Among 500,000 HMO members, we reviewed records of Ps ≥ 20 yrs of age with ICD-9 code 557.0, 557.1 or 557.9 from 2000 through 2006 and identified ALBI by specified criteria. Results: There were 424 hospitalizations (Hs) among 401 Ps (25-97 yrs [median, 69]; 303 females [Fs], 98 males [Ms]); 17 and 3 Ps (19 Fs, 1 M) had 2 and 3 Hs, respectively. Annual incidence /100,000 was: 16.4 Hs and 15.6 Ps (Fs, 22.6; Ms, 8.0); Hs rose 16-fold from 40-49 to 80+ yrs. ALBI preceded 400 (94%) Hs and followed surgery/admission for another disease in 24 (6%) Hs. Symptoms were abdominal pain, 368 (87%); rectal bleeding, 355 (84%); diarrhea, 238 (56%); vomiting, 130 (31%); dizziness, 43 (10%); syncope, 26 (6%); and constipation before other symptoms, 32 (8%) of Hs. In 417 Hs with a known ALBI site, the site was rectum only, 1 ( 100/min (4.4, 1.5-13.3, .008), prior warfarin use (4.3, 1.2-15.5, .02), antibiotic therapy (3.9, 1.2-12.6, .02), male sex (2.7, 1.0-7.0, .05), prior NSAID use (0.2, 0.04-0.52, .003), and rectal bleeding (0.2, 0.09-0.65, .005). During 2.6 ± 1.9 yrs (mean ± SD) follow-up of survivors, only 1 (<1%) P needed stricture dilation. Cumulative ALBI recurrence (Kaplan-Meier) was 3%, 5%, 6% and 10% at yrs 1, 2/3, 4 and 5/6, respectively. Conclusions: ALBI predominates in Fs. Demographic/clinical factors predict resection and/or death, especially right side/bilateral ALBI and onset after surgery or admission for another disease. Symptomatic post-ALBI stricture is rare. The ALBI recurrence rate is 10% at 5 yrs.

W1027 Gastrointestinal Disorders in Adults with Down Syndrome

ALBI epidemiology is poorly known, selection bias limits published clinical data, and few follow-up data exist. Aims: To study the epidemiology, clinical aspects, care and long-term outcome of patients (Ps) with ALBI.Methods: Among 500,000 HMO members, we reviewed records of Ps ≥ 20 yrs of age with ICD-9 code 557.0, 557.1 or 557.9 from 2000 through 2006 and identified ALBI by specified criteria. Results: There were 424 hospitalizations (Hs) among 401 Ps (25-97 yrs [median, 69]; 303 females [Fs], 98 males [Ms]); 17 and 3 Ps (19 Fs, 1 M) had 2 and 3 Hs, respectively. Annual incidence /100,000 was: 16.4 Hs and 15.6 Ps (Fs, 22.6; Ms, 8.0); Hs rose 16-fold from 40-49 to 80+ yrs. ALBI preceded 400 (94%) Hs and followed surgery/admission for another disease in 24 (6%) Hs. Symptoms were abdominal pain, 368 (87%); rectal bleeding, 355 (84%); diarrhea, 238 (56%); vomiting, 130 (31%); dizziness, 43 (10%); syncope, 26 (6%); and constipation before other symptoms, 32 (8%) of Hs. In 417 Hs with a known ALBI site, the site was rectum only, 1 ( 100/min (4.4, 1.5-13.3, .008), prior warfarin use (4.3, 1.2-15.5, .02), antibiotic therapy (3.9, 1.2-12.6, .02), male sex (2.7, 1.0-7.0, .05), prior NSAID use (0.2, 0.04-0.52, .003), and rectal bleeding (0.2, 0.09-0.65, .005). During 2.6 ± 1.9 yrs (mean ± SD) follow-up of survivors, only 1 (<1%) P needed stricture dilation. Cumulative ALBI recurrence (Kaplan-Meier) was 3%, 5%, 6% and 10% at yrs 1, 2/3, 4 and 5/6, respectively. Conclusions: ALBI predominates in Fs. Demographic/clinical factors predict resection and/or death, especially right side/bilateral ALBI and onset after surgery or admission for another disease. Symptomatic post-ALBI stricture is rare. The ALBI recurrence rate is 10% at 5 yrs.

Prophylactic Antiepileptic Drug Use is Associated with Poor Outcome Following ICH

Intracerebral hemorrhage (ICH) is associated with a risk of early seizure and guidelines recommend consideration of prophylactic antiepileptic drugs (AEDs) for some patients, although the utility is uncertain. We analyzed data from the placebo arm of the Cerebral Hemorrhage and NXY-059 Trial (CHANT), an international multicenter randomized trial of a potential neuroprotectant that enrolled patients within 6 h of the onset of acute ICH. Logistic regression analyses were performed to determine whether early AED use was associated with poor outcome at day 90, defined as a modified Rankin Scale of 5 or 6 (severely disabled or dead). Excluding patients who were previously on AEDs, the primary analysis included 295 patients. The median ICH volume at admission was 14.9 (interquartile range, IQR 7.9-32.7) ml and the mean was 23.3 (+/-SD 22.8) ml. Seizures occurred in 5 patients (1.7%) after enrollment and 82 patients (28%) had a poor outcome at day 90. AEDs were initiated on 23 patients (8%) without documented seizure during the first 10 days of the trial. In logistic regression, initiation of AEDs was robustly associated with poor outcome (OR 6.8; 95% CI: 2.2-21.2, P = 0.001) after adjustment for other known predictors of outcome after ICH (age, initial hematoma volume, presence of intraventricular blood, initial Glasgow coma score, and prior warfarin use). In this clinical trial cohort, seizures were rare after the first few hours following ICH. In addition, prophylactic AED use was associated with poor outcome independent of other established predictors. Given the potential for residual confounding in this cohort, a randomized trial needs to be performed.

Admission international normalized ratio and acute infarct volume in ischemic stroke

The level of anticoagulation at the time of stroke onset may influence the size, composition, and dissolution rate of the occlusive clot. We explored the relation between admission international normalized ratio (INR) and acute infarct volume in patients with ischemic stroke. We studied 93 consecutive patients with preadmission warfarin use who had INR measurement and diffusion-weighted imaging performed within 24 hours of stroke onset. Ninety-three etiologic stroke subtype-matched patients without prior warfarin use served as control patients. Linear regression analysis was used to test for independence of INR as a predictor of infarct volume. In patients with preadmission warfarin use, admission INR was inversely correlated with lesion volume on diffusion-weighted imaging (r = -0.38). This relation was retained after adjustment for potential covariates (p = 0.014). INR less than 2.0 was associated with 3.5-fold (95% confidence interval, 2.9-4.2) greater lesion volume on diffusion-weighted imaging as compared with INR of 2.0 or more. Patients who were on therapeutic INR (>or=2.0) had smaller infarcts compared with patients without preadmission warfarin use (p = 0.001). Admission INR was inversely correlated with acute perfusion defect (r = -0.33), chronic infarct volume (r = -0.42), National Institutes of Health Stroke Scale score at admission (r = -0.27), and modified Rankin score at discharge (r = -0.28). These results suggest that preadmission warfarin use associated with therapeutic level of anticoagulation can offer a benefit in limiting the extent of ischemic injury in an event of acute stroke.

Predictors of Early Neurological Deterioration after Ischaemic Stroke: A Case-Control Study

Background: Early neurological deterioration after ischaemic stroke (stroke in progression) is reported to be common and associated with poor outcome or death. The causes of progressing stroke are, however, uncertain. Objective: To determine whether prior drug treatment (with anticoagulant or antiplatelet agents) or early adverse physiological features (pyrexia, hypoxia, dehydration or hyperglycaemia) are associated with progressing ischaemic stroke. Methods: The study used a case-control design. From a database of 873 consecutive acute stroke admissions, 196 cases of progressing ischaemic stroke (defined by point deterioration in components of the Scandinavian Stroke Scale or death over the first 72 h after hospital admission) were matched to 196 controls on the basis of age and stroke type. Univariate and conditional logistic regression techniques were used to explore predictors of progressing stroke. Results: Cases and controls were well matched for baseline stroke severity. Warfarin use prior to admission was associated with a reduced risk of progressing stroke [odds ratio (OR) 0.10, p = 0.005]. Prior antiplatelet use was not related. A previous history of diabetes (OR 2.11, p = 0.039) and elevated systolic blood pressure on admission (OR 1.01 for each 1 mm Hg rise, p = 0.017) predicted progressing stroke. Although there were no differences in time to presentation or to brain imaging, a visible causative lesion on CT scanning was more common in the progressing stroke group (OR 2.30, p = 0.022). We found no evidence that adverse physiological features were associated with progressing stroke. Outcomes were worse in the progressing stroke group with 70% being dead or dependent by 30 days compared to 55% in the control group (p = 0.002). Conclusion: Prior warfarin use may be protective against progressing ischaemic stroke. A previous history of diabetes along with elevated admission systolic blood pressure predict deterioration. We found no evidence for an association between adverse physiological features and progressing stroke.