Identifying Low-Risk Patients with Pulmonary Embolism Suitable For Outpatient Treatment A VERITY Registry Pilot Study N Scriven, T Farren, S Bacon, T Nokes, P Rose, R Arya, A McManus, A Nieland, D O’Shaughnessy

Five years later, outpatient treatment is not widely accepted, largely because no explicit clinical criteria exist to accurately identify low risk patients

Pulmonary Embolism Severity Index Am J Respir Crit Care Med Vol 172. pp 1041–1046, 2005 Aujesky developed a clinical prediction rule that accurately classifies patients with PE into categories of increasing risk of mortality and other adverse medical outcomes Based on logistic regression analysis, with 30-day mortality as the primary outcome, and patient demographic and clinical data at presentation as potential predictor variables

Points assigned to prognostic variables Score is sum of patient’s age in years and the points for each variable

PESI risk classes Risk class Points Risk category Class I ≤65 very low Class II 66-85 low Class III 86-105 intermediate Class IV 106-125 high Class V >125 very high

VERITY A UK multi-centre observational VTE registry Data collection for >5 years >100,000 patient entries

Features of VERITY National registry – outpatient VTE treatment Full spectrum of VTE – DVT and PE Records information on patients presenting with suspected and confirmed VTE Expanded data on demographics, presentation, management & outcomes Extensive risk factor data

Study design Pilot study - 4 VERITY hospitals participated to assess the accuracy of the PESI to predict 3-month mortality Centres provided completed case report forms after retrospective review of patients’ notes on a total of 176 consecutive PE patients that had been in their care The diagnosis had been confirmed by objective diagnostic testing These patients do not represent an outpatient population, although some of these cases were treated as outpatients Each patient was assigned as low (PESI risk classes I and II) or high-risk (risk classes III–V) Each patient was assigned as low (PESI risk classes I and II) or high-risk (risk classes III–V)

Statistical plan We calculated the sensitivity and specificity of the PESI The accuracy of the index to classify patients was tested by receiver operating characteristic (ROC) curve analysis, plotted as 1–specificity versus sensitivity for 3-month all-cause mortality The c statistic (area under the curve), representing the ability of the model to correctly classify patients, was estimated using the Wilcoxon non-parametric approach

Results Death at 3 months ROC analysis 0% in low-risk group 12.3% in high-risk group Overall mortality at 3 months in all groups 4.5% (8/176) ROC analysis Sensitivity of PESI 1.0 (97.5% one-sided CI, 0.63 to 1) Specificity of PESI 0.64 (95% CI, 0.56 to 0.71)

ROC curve – prediction of 3-month mortality c statistic 0.90 95% CI 0.83–0.96

Very low risk PE (Aujesky score <65) 50 cases 3 cases 35yo female: Number Further VTE Bleeding complication Death 50 cases 3 cases 35yo female: smoker; personal Hx; family Hx; leg paralysis 44yo female: positive thrombophilia; recurrence at 4 months 53yo male: post surgery; recurrence at 16 months 1 minor bleed None A case (2%) had a VTE within 3 months, who was a 35yo female, who smoked, had both personal and familial history of thrombosis and was a recent in patient and hence was immobile due to her surgery.

Low risk PE (Aujesky score 66-85) Number Further VTE Bleeding complication Death 61 cases 4 cases 61yo male: Inpatient; smoker 58yo female Ex-smoker; family Hx; hormonal risk factor 67yo male Ex-smoker; personal Hx 38yo female Smoker; personal Hx; leg paralysis 1 minor bleed (occurred 9 – 17 months after diagnosis) 7.5% cases had a VTE within 3 months. Deaths for low risk patients = 4 cases 51 yo male, died 17 mths after diagnosis 85 yo female, died 9 mths after diagnosis 81 yo female, had minor bleed, died 13 mths after diagnosis 70 yo male, died 12 mths after diagnosis

Intermediate risk PE (Aujesky score 86-105 pts) Number Further VTE Bleeding complication Death 29 cases 4 cases 57yo male: Ex-smoker; ca prostate 67yo female: Hormonal risk factor 48yo male: Smoker; ca 83yo female No risk factors 1 major bleed 5 cases (between 2 weeks and 3 years) 12.5% cases had a VTE within 3 months

High risk PE (Aujesky score 106-125 pts) Number Further VTE Bleeding complication Death 22 cases 2 cases 74yo female: Personal Hx 79yo male: Ca prostate 3 cases (between 1 week* and 2 years) *metastatic ca lung 0 VTE, 0 bleeding events and 3 deaths, with one within 1/52 of admission due to metastatic lung cancer

(Aujesky score >125 pts) Very high risk PE (Aujesky score >125 pts) Number Further VTE Bleeding complication Death 14 cases 1 case 74yo female: personal Hx 1 minor bleed 8 cases (between 6 days and 2.5 yrs) NB: One inpatient died due to a delayed diagnosis of PE (made on PM) 1 case (8% of very high risk group) had a VTE event within 3 months.

Discussion There were no deaths in the low risk group at 3 months, although 4 deaths occurred at 9 – 17 months The c statistic for the risk model (0.90) indicates a very good test for the likelihood of death This pilot study suggests that the PESI accurately identifies PE patients at low risk of death The findings were based on small group (n=176) Outcome was limited to death at 3 months There was a wide variation in the death rate between the 4 hospitals (ranging from 0% - 10.8%)

VERITY PUSH Prospective assessment will be undertaken by VERITY at centres moving to an outpatient (or short hospital stay) model for PE treatment. A follow-up VERITY initiative - PUSH (Prospective follow Up Survey in VERITY Hospitals) was launched on 01/11/08 PUSH will run for a fixed 12-month timescale, with a six-month patient enrollment period and six-month follow-up Major adverse outcomes (death, bleeding, recurrence) will allow accurate prospective assessment of PESI