ALBERT

Description: Background: Previous studies evaluating the simplified Pulmonary Embolism Severity Index (sPESI) for predicting pulmonary embolism (PE) mortality did not consistently report the timing of vital sign measurement (systolic blood pressure [SBP], heart rate [HR] and oxygen [O2] saturation) relative to the PE presentation. Objectives: To evaluate the impact of vital sign measurement timing on sPESI's ability to identify PE patients at low-risk for in-hospital all-cause mortality. Methods: This was a retrospective analysis of PE patients from a large, urban teaching hospital in the Northeastern United States. Consecutive patients, diagnosed with PE between November 2010 and May 2015, were identified using the institution's billing system. To be eligible for inclusion, patients had an International Classification of Diseases, ninth-revision, clinical modification (ICD-9-CM) code of 415.1x in the primary position. Those in whom PE could not be objectively confirmed via chart review and those receiving thrombolysis or embolectomy were excluded. Patients' first and either lowest (SBP, O2 saturation) or highest (HR) value within the first 24 hours from presentation (subsequently referred to as "least favorable" values) were recorded. We then compared sensitivity, specificity and negative predictive values (NPV) and 95% confidence intervals (CIs) and the ability of the sPESI to predict all-cause in-hospital mortality using the first and least favorable vital signs. Results: A total of 562 PE patients (18.9% 〉80 years of age, 28.5% history of cardiopulmonary disease, 29.5% history of cancer) were included and 2.1% died in-hospital. No differences in sPESI's sensitivity, specificity or NPV were observed when scored using the first or least favorable vital sign values. sPESI classified 169 (30.1%) as low-risk (sPESI=0) vs. 153 (27.2%) when the least favorable vital sign value was used. Conclusions: The sensitivity and NPV of sPESI to predict PE patients' risk for all-cause in-hospital mortality is not affected by the timing of vital sign measurement. Using the least favorable value within 24-hours of presentation does result in a smaller proportion of patients being classified as low-risk. Table 1.CharacteristicFirst% (95%CI)Least Favorable% (95%CI)P-valueSensitivity91.7 (59.8-99.6)91.7% (59.8-99.6)〉0.99Specificity30.5 (26.8-34.6)27.6% (24.0-31.6)0.31NPV99.4 (96.2-99.9)99.3% (95.9-99.9)0.94Proportion classified as low-risk, n (%)169 (30.1)153 (27.2)

Description: Background: Both the simplified Pulmonary Embolism Severity Index (sPESI) and the multivariable In-hospital Mortality for Pulmonary embolism using Claims daTa (IMPACT) rule classify patients' risk of early post-pulmonary embolism (PE) complications. Objective: To externally validate sPESI and IMPACT for predicting 90-day all-cause mortality and readmission rates among PE patients treated within the Veterans Health Administration (VHA). Methods: We used VHA data from 10/1/2010-9/30/2015 to identify adult patients with: (1) ≥1 inpatient diagnosis for acute PE (International Classification of Diseases-9th Revision-Clinical Modification codes=415.1x), (2) continuous medical and pharmacy enrollment for ≥12-months prior to the index PE (baseline period), (3) a minimum of 90-days of post-event follow-up or until death (whichever came first), and (4) ≥1 claim for an anticoagulant during the index PE stay. Patients were excluded if they had a claim for PE or an anticoagulant during the baseline period. We classified patients as low-risk for early post-PE complications if their sPESI score=0 or their absolute in-hospital mortality risk estimated by IMPACT was 90% and NPVs 〉96% for all-cause 90-day mortality, but low specificity and PPVs (Table). IMPACT's sensitivity for all-cause readmission was numerically higher than sPESI, but both had comparable NPVs. Similar trends were observed for accuracy in predicting readmissions due to recurrent VTE or major bleeding. Conclusion: In this external validation study utilizing VHA data, IMPACT classified patients for 90-day post-PE outcomes with similar accuracy as sPESI. While not recommended for prospective clinical decision-making, IMPACT appears useful for identification of PE patients at low-risk for early mortality or readmission in retrospective claims-based studies. Table. Test characteristics for sPESI and IMPACT for 90-day post-pulmonary embolism outcomes CI= confidence interval; IMPACT=In-hospital Mortality for Pulmonary embolism using Claims data; NPV=negative predictive value; PPV=positive predictive value; sPESI=simplified Pulmonary Embolism Severity Index; VTE=venous thromboembolism Table. Test characteristics for sPESI and IMPACT for 90-day post-pulmonary embolism outcomes CI= confidence interval; IMPACT=In-hospital Mortality for Pulmonary embolism using Claims data; NPV=negative predictive value; PPV=positive predictive value; sPESI=simplified Pulmonary Embolism Severity Index; VTE=venous thromboembolism Disclosures Kumar: Johnson & Johnson: Employment. Wells:Itreas: Other: Served on a Writing Committee; Janssen Pharmaceuticals: Consultancy; Bayer Healthcare: Other: Speaker Fees and Advisory Board; BMS/Pfizer: Research Funding. Peacock:Comprehensive Research Associates LLC: Equity Ownership; Cardiorentis: Consultancy, Research Funding; The Medicine's Company: Consultancy, Research Funding; Banyan: Research Funding; Emergencies in Medicine LLC: Equity Ownership; Abbott: Research Funding; Alere: Consultancy, Research Funding; Prevencio: Consultancy; Janssen: Consultancy, Research Funding; Portola: Consultancy, Research Funding; Pfizer: Research Funding; Roche: Research Funding; ZS Pharma: Consultancy, Research Funding; Ischemia Care: Consultancy; Phillips: Consultancy. Fermann:Janssen Pharmaceuticals: Other: Advisory Board, Speakers Bureau; Pfizer: Research Funding. Wang:Janssen Pharmaceuticals: Research Funding. Baser:Janssen Pharmaceuticals: Research Funding. Schein:Johnson & Johnson: Employment, Equity Ownership, Other: Own in excess of $10,000 of J&J stock. Crivera:Johnson & Johnson: Employment, Equity Ownership, Other: Owns excess of $10,000 in stock. Coleman:Boehringer-Ingelheim Pharmaceuticals, inc.: Consultancy, Research Funding; Bayer Pharmaceuticals AG: Consultancy, Research Funding; Janssen Pharmaceuticals: Consultancy, Research Funding.

Description: Background: Current guidelines suggest that low risk pulmonary embolism (PE) patients may be managed as outpatients or with an abbreviated hospital stay. There is need for a claims-based prediction rule that payers and hospitals can use to efficiently risk stratify PE patients. The authors recently derived a rule found to have high sensitivity and moderate specificity for predicting in-hospital mortality. Objective: To validate the In-hospital Mortality for PulmonAry embolism using Claims daTa (IMPACT) prediction rule originally developed in a commercial claims database in an all-payer administrative database restricted to inpatient claims. Methods: This study utilized data from the 2012 Healthcare Cost and Utilization Project Nationwide Inpatient Sample (NIS). Adult PE admissions were identified by the presence of an appropriate International Classification of Diseases, ninth edition, Clinical Modification (ICD-9-CM) code either in the primary position or secondary position when accompanied by a primary code for a PE complication. The IMPACT rule, consists of age + 11 weighted comorbidities calculated based upon the maximum of 25 ICD-9-CM diagnosis codes and 25 procedural codes reported for each discharge in the NIS (myocardial infarction, chronic lung disease, stroke, prior major bleeding, atrial fibrillation, cognitive impairment, heart failure, renal failure, liver disease, coagulopathy, cancer), and was used to estimate patients' risk of in-hospital mortality. Low risk was defined as in-hospital mortality ≤1.5%. We present the validity of the rule by calculating prognostic test characteristics and 95% confidence intervals (CIs). In order to estimate the potential cost savings from an early discharge, we calculated the difference in total hospital costs between low-risk patients having and not having an abbreviated hospital stay (defined as ≤1, ≤2 or ≤3 days). Results: A total of 34,108 admissions for PE were included (46.7% male, mean ± standard deviation age of 61.9±17.2); and we observed a 3.4% in-hospital PE case-fatality rate. The IMPACT prediction rule classified 11,025 (32.3%) patient admissions as low-risk; and had a sensitivity of 92.4% (95%CI=90.7-93.8), specificity of 33.2% (95%CI=32.7-33.7), negative and positive predictive values of 99.2% (95%CI=99.0-99.4) and 4.6% (95%CI=4.4-4.9) and a C-statistic of 0.74 (95%CI=0.73-0.76) for in-hospital mortality. Low-risk patients had significantly lower in-hospital mortality (0.8% vs. 4.6%, odds reduction of 83%; 95%CI=79-87), shorter LOSs (-1.2 days, p

Description: Background: Observation stays are intended to assess patients for short periods (i.e., 2-midnights, total hospital costs and risk of readmission for venous thromboembolism (VTE) or major bleeding during the same month or 2 months subsequent to the index event were compared between propensity-score-matched treatment cohorts. Results: A total of 401 rivaroxaban patients were matched to 401 patients receiving parenteral bridging to warfarin.Rivaroxaban use was associated with a shorter LOS (-0.25 days), fewer encounters lasting 〉2 midnights (21.1% vs. 32.7%) and lower total hospital costs (-$240) vs. parenteral bridging to warfarin (p²0.03 for all) (Table). Readmission was similar between cohorts (p〉0.99 for both VTE and major bleeding readmission). Conclusion: Shorter LOS and lower hospital costs occurred with rivaroxaban vs. parenteral bridging to warfarin in PE observation stay patients. This was achieved without increasing short-term risk of VTE or major bleeding readmission. Table Table. Disclosures Peacock: Portola: Consultancy, Research Funding; Janssen Pharmaceuticals: Consultancy, Research Funding. Fermann:Janssen Pharmaceuticals: Other: Advisory Board, Speakers Bureau; Pfizer: Research Funding. Baugh:Janssen Pharmaceuticals: Consultancy; Roche Diagnostics: Other: Advisory Board. Wells:Janssen Pharmaceuticals: Consultancy; Bristol Myers Squib: Research Funding; Pfizer: Research Funding; Bayer Healthcare: Other: Advisory Board, Speakers Bureau; Itreas: Other: Writing Committee. Ashton:Janssen Scientific Affairs, LLC, Raritan, New Jersey: Employment. Crivera:Janssen Scientific Affairs, LLC, Raritan, New Jersey: Employment, Equity Ownership. Wildgoose:Janssen Scientific Affairs, LLC, Raritan, New Jersey: Employment, Equity Ownership. Schein:Johnson & Johnson: Employment, Equity Ownership, Other: Own in excess of $10,000 of J&J stock. Coleman:Boehringer-Ingelheim Pharmaceuticals, inc.: Consultancy, Research Funding; Bayer Pharmaceuticals AG: Consultancy, Research Funding; Janssen Pharmaceuticals: Consultancy, Research Funding.

Description: Introduction: The Hestia criteria has been established as a highly sensitive prognostic tool used by clinicians to identify newly diagnosed pulmonary embolism (PE) patients from the general population at low vs. high risk of early (30 day) mortality. Font et al. applied similar risk stratification criteria in a population restricted to PE patients with cancer. We evaluated the performance of the generic Hestia tool and cancer-specific criteria by Font et al. for predicting 30-day post-PE mortality in patients with active cancer. Methods: We identified consecutive, adult, objectively confirmed PE patients with active cancer presenting to the emergency department at our institution from 11/2010-1/2014. We calculated the proportion of patients categorized as low-risk by each set of criteria and determined the accuracy of the criteria for predicting 30-day all-cause mortality. Mortality was determined through Social Security Death Index searches. Results: A total of 124 patients with PE and active cancer (mean age 66.2 years, 46.0% with concurrent deep vein thrombosis, 49.2% with metastatic disease and 46.8%, 16.9% and 10.4% receiving chemotherapy, radiation or both, respectively) were included. Mortality at 30-days occurred in 25 (20.2%) patients. The Hestia tool had a sensitivity of 100% but classified 90% for 〉24 hours (n=19). Conclusion: In this external validation study, both the generic Hestia tool and cancer-specific Font et al. risk stratification criteria displayed acceptable sensitivity. Compared to Hestia, the Font et al. criteria classified two times as many patients as low-risk. Larger, prospective studies are needed to confirm our results. Disclosures Coleman: Janssen Pharmaceuticals: Consultancy, Research Funding; Bayer Pharmaceuticals AG: Consultancy, Research Funding; Boehringer-Ingelheim Pharmaceuticals, inc.: Consultancy, Research Funding.

Description: INTRODUCTION: Conflicting evidence suggests a person who suffers an index pulmonary embolism (PE) is more likely to develop a recurrent PE than a deep vein thrombosis (DVT). We performed a meta-analysis of randomized controlled trials (RCTs) to determine the proportion of recurrent events that will be PE in such people. METHODS: A literature search of MEDLINE, EMBASE and CENTRAL (through 7/2014) was performed to identify RCTs of acute treatment and prevention of recurrent VTE in persons suffering an index PE, enrolling ≥50 subjects, requiring anticoagulation for ≥3 months and reporting the proportion of recurrent events that were DVT or PE (±DVT). RCTs not in English, enrolling only cancer, surgical or thrombophilia patients, primary prevention and extended treatment trials were excluded. We extracted recurrent VTE event data; and used a random-effects approach to pool the proportion [along with 95% confidence intervals (CIs)] of recurrent events that were PE and fatal PE, as well as, the proportion of recurrent PEs that were fatal. RESULTS: Nine RCTs (n=13,606 subjects; 413 recurrent events) were included. In persons presenting with an index PE, 67%; 95%CI, 62-71% of their recurrent events were PE and 27%; 95%CI, 22-33%) were fatal PE. Of all recurrent PEs observed, 41%; 95%CI, 33-48% resulted in death. No statistical heterogeneity was observed in any analysis (I2

Description: Introduction: Venous thromboembolism (VTE) affects ~20% of patients with cancer prior to death and may be present in up to half of cancer patients upon autopsy. International Society of Thrombosis and Haemostasis (ISTH) guidelines recommend oral factor Xa inhibitors for the acute treatment and secondary prevention of cancer-associated thrombosis (CAT) in patients considered low risk of bleeding and without a potential for drug-drug interactions with current systemic therapy. We sought to evaluate the effectiveness and safety of rivaroxaban versus a low molecular weight heparin (LMWH) for the treatment of CAT in routine practice. Methods: Using United States Surveillance, Epidemiology and End Results (SEER)-Medicare-linked data from 2013 to 2015, we identified adults diagnosed with lung, breast, pancreatic, prostate or ovarian cancer, having at ≥1 hospitalization or emergency department admission (index event) with a primary discharge diagnosis code for VTE (indicating VTE was the foremost reason for admission) , ≥12-months of continuous medical and prescription benefits prior to the index CAT and who received rivaroxaban or a LMWH as their first outpatient anticoagulant. Patients with primary or metastatic gastrointestinal cancers, stage 4 or worse chronic kidney disease or liver failure were excluded. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the composite outcome of recurrent VTE or major bleeding, each of these outcomes alone as well as all-cause mortality in the subsequent 12-months were calculated using a multivariable Fine-Gray (competing risk) Cox regression model adjusted for baseline covariates and propensity score decile (c-index=0.76) estimated using generalized boosted models on the basis of 10,000 regression trees. Results: We included 259 rivaroxaban- and 559 LMWH-managed patients with CAT. The median age (25%, 75% range) of patients was 73 (68, 79) years, 62.5% were men and 43.6% had pulmonary embolism. The incident cancer diagnosis was made between 2010 and 2013 in 87.8% of patients. Primary cancer locations included lung (41.8%), breast (21.8%), pancreatic (12.1%), prostate (11.9%), ovarian (5.3%) and other (7.1%). Nearly all patients (96.5%) were diagnosed with stage 2 or 3 disease. During the 12-month follow-up period, the incidence of the composite of recurrent VTE or major bleeding was 13.8%, recurrent VTE alone occurred in 11.4% and major bleeding alone in 2.9% of patients and all-cause mortality occurred in 48.4%. No significant difference in patients' relative hazard of the experiencing the composite outcome (HR=0.86, 95%CI=0.52-1.41), recurrent VTE (HR=0.91, 95%CI=0.51-1.62), major bleeding (HR=0.90, 95%CI=0.29-2.83) or all-cause mortality (HR=0.86, 95%CI=0.62-1.21) were observed between the rivaroxaban and LMWH-managed cohorts. Conclusions: In this real-world study of rivaroxaban- and LMWH-managed CAT patients, no significant difference in patients' relative hazard of experiencing the composite outcome, recurrent thrombosis, major bleeding or all-cause mortality were observed between the two cohorts. These data are consistent with recommendation that the oral factor Xa inhibitor, rivaroxaban, is a reasonable alternative to LMWH for the treatment of CAT and prevention of recurrent thrombosis. Disclosures Lyman: Amgen Inc.: Other: Research support, Research Funding; Janssen Scientific Affairs, LLC: Research Funding; Generex Biotechnology: Membership on an entity's Board of Directors or advisory committees; G1 Therapeutics, Halozyme Therapeutics, Partners Healthcare, Hexal, Bristol-Myers Squibb, Helsinn Therapeutics, Amgen Inc., Pfizer, Agendia, Genomic Health, Inc.: Consultancy. Kuderer:Mylan: Consultancy, Other: Travel, Accommodations, Expenses; Celldex: Consultancy; Myriad Genetics: Consultancy; Coherus Biosciences: Consultancy, Other: Travel, Accommodations, Expenses; Pfizer: Consultancy; Halozyme: Consultancy; Janssen Scientific Affairs, LLC: Consultancy, Other: Travel, Accommodations, Expenses. Coleman:Bayer AG: Consultancy, Honoraria, Research Funding; Janssen Scientific Affairs LLC: Consultancy, Honoraria, Research Funding.