Clinical predictors of adverse outcome in VTE outpatients – the VERITY PUSH (Prospective Follow-Up Survey in Verity Hospitals) study Peter Rose, Aidan McManus, Shankaranarayana Paneesha, Nicholas Scriven, Timothy Farren, Sue Bacon, Roopen Arya, Olatunde Falode, Denise O'Shaughnessy & Tim Nokes for the VERITY Investigators

Background Outpatient VTE treatment with LMWH is now commonplace in the UK Factors predictive of VTE recurrence have been reported including age, cancer, immobility and thrombophilic mutations, but there are few data describing risk factors associated with recurrence, or adverse outcome in unselected VTE patients treated in outpatient clinics

PUSH study objectives To determine the frequency of major adverse outcomes (death, recurrence of VTE, and bleeding) in patients diagnosed with VTE and treated as outpatients with low molecular weight heparin To establish risk factors for adverse outcome after VTE

PUSH study design Patients negative for VTE Exclusion algorithms and diagnostic tests Recurrence Bleeds Death Patients with suspected VTE Consecutive patients with confirmed VTE Day 0 Day 180 Timeline VERITY databaseVERITY PUSH database EnrolmentFollow-up Day 0 Day 360 Logistic regression

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

VERITY and PUSH centres

PUSH centres

Enrolment (Nov 2008 – Apr 2009) Seven hospitals enrolled 843 consecutive patients

Study population 221 patients were excluded –75 = no follow-up entry –50 = no record if treated as an outpatient –96 = not treated as outpatient Final study population n=622 Patients were followed for up to 388 days (mean duration of 195 days)

Baseline characteristics (risk factors)

RESULTS Major adverse outcomes (n=34) (n=16) (n=36) Major bleed 1.2%

Home treatment with LMWH Levine et al. N Engl J Med. 1996;334:677-81; Koopman et al. N Engl J Med. 1996;334:682-7.

RISK MODELING 1. Major surgery (last 4 weeks) (AND type of major surgery: general/orthopaedic/other) 2. Hormonal risk factor (yes or no) 3. Family history 4. Personal history 5. History of thrombophilia 6. Age (≥50 or ≥70 years on day of diagnosis of VTE) 7. Cancer 8. IVDU 9. Cancer surgery in last 6 months Univariate and multivariate logistic regression analyses were conducted to determine if any of the known risk factors predicted for recurrence or adverse outcome. 10. Indwelling catheter 11. Metastatic cancer 12. New cancer diagnosis after VTE diagnosis 13. Type of VTE (DVT or PE or DVT+PE) 14. High (quantitative) D-dimer at diagnosis 15. Gender

Clinical predictors of adverse outcome in VTE outpatients Univariate logistic regression showed that recurrence was related to younger age (<50 years, p=0.007) but to none of the 14 other parameters assessed Cancer (p<0.001) and a diagnosis of cancer subsequent to VTE (p=0.037) were predictive of an adverse event

Clinical predictors of adverse outcome in VTE outpatients Multivariate logistic regression confirmed these cancer factors were independent predictors of adverse outcome with high odds ratios –Cancer:OR 4.3, 95% CI 2.4–7.5 –New cancer:OR 4.3, 95% CI 1.2–15

Clinical predictors of adverse outcome in VTE outpatients Non-cancer patients Restricting the univariate logistic regression analysis to non-cancer outpatients: –age <50 years (p=0.033) was related to the risk of VTE recurrence –new cancer diagnosis (p=0.007) was a predictor of adverse outcome

Clinical predictors of adverse outcome in VTE outpatients ‘First event’ VTE Restricting the univariate logistic regression analysis to first event VTE outpatients: –age <50 years (p=0.033) was related to the risk of VTE recurrence –cancer (p<0.001), new cancer diagnosis (p=0.008), metastatic cancer (p=0.02) and high D-dimer at diagnosis (p=0.023) were all predictors of adverse outcome

Clinical predictors of adverse outcome in VTE outpatients ‘First event’ VTE Multivariate logistic regression confirmed three factors were independent predictors of adverse outcome with high odds ratios –Cancer:OR 6.3, 95% CI 2.8–14.1 –New cancer:OR 13.0, 95% CI 3.0–57.5 –High D-dimer:OR 2.7, 95% CI 1.0–6.8

Clinical predictors of adverse outcome in VTE outpatients Previous history of VTE Restricting the univariate logistic regression analysis to outpatients with previous history of VTE: –Cancer (p=0.002) and a hormonal risk factor (p=0.029) were predictors of adverse outcome Cancer was an independent predictor of adverse outcome on multivariate analysis –Cancer:OR 6.9, 95% CI 1.8–27.0)

Clinical implication From the perspective of routine outpatient treatment of VTE, these results identify cancer as an overriding risk for adverse outcome irrespective of VTE history, and show that high D-dimer at diagnosis is predictive of adverse outcome in patients experiencing a first VTE event.

The VERITY PUSH study was funded by sanofi-aventis