1. Provoked VTE vs. Unprovoked VTE
Perspectives from GARFIELD-VTE
Professor Walter Ageno
University of Insubria,
Varese, Italy

2. Disclosures
Honoraria from Boehringer Ingelheim, Bayer Pharmaceuticals, BMS-Pfizer, Portola, Sanofi, Aspen, and Daiichi-Sankyo.
Research support from Bayer Pharmaceuticals

3. Aim
Compare the clinical characteristics, anticoagulant treatment patterns and 12-month outcomes between patients with transient provoking risk factors, persistent provoking risk factors and unprovoked VTE
Reference Ageno, W et al, Thromb Haemost 2019;119(2):

4. Definitions of Transient and Persistent Risk Factors
Transient provoking risk factors
(within 3 months preceding VTE diagnosis)
• Surgery
• Hospitalization
• Pregnancy
• Hormone replacement
• Oral contraception
• Acute medical illness
• Trauma of the lower limb
Persistent provoking risk factors
(within -90 to + 30 days of VTE diagnosis)
• Active cancer
Unprovoked VTE
No transient or persistent risk factor at baseline

5. Patient Population Excluded after screening (n=972)
Assessed for eligibility
(n=11,842)
Excluded after screening (n=972)
Declined to participate (n=474)
Not meeting protocol-defined inclusion/exclusion criteria (n=389)
Deceased before consent (n=68)
Physician decision (n=41)
Enrolled (n=10,870)
Patients with objectively confirmed diagnosis of VTE (n=10,685)
Persistent provoking risk factor (N=1062)
Transient provoking risk factor (N=3282)
Unprovoked VTE (n=6341)
Data cut: May 2018

6. Baseline Demographics
Variable
Persistent (N=1062)
Transient (N=3282)
Unprovoked (N=6341)
Male, n (%)
502 (47.2)
1274 (38.8)
3606 (56.9)
Age at diagnosis, years, median (IQR)
64.8 ( )
52 ( )
61.9 ( )
BMI, kg/m2, median (IQR)
25.7 (22.3 to 29.4)
27.1 (23.6 to 31.2)
27.7 (24.6 to 31.7)
Site of VTE, n (%)
DVT alone
642 (60.5)
2146 (65.4)
3799 (59.9)
PE ± DVT
420 (39.5)
1136 (34.6)
2541 (40.0)
Site of DVT
Upper limb
71 (9.2)
136 (5.2)
230 (4.8)
Lower limb
664 (85.7)
2431 (93.6)
4507 (93.6)
Caval vein
40 (5.2)
29 (1.1)
80 (1.7)
Data cut: May 2018

7. Anticoagulation treatment over 12 months
Up to 30 days
3 months
6 months
12 months
Percentage of patients (%)
Data cut: May 2018

8. Anticoagulation treatment over 12 months
Up to 30 days
3 months
6 months
12 months
Percentage of patients (%)
Data cut: May 2018

9. Event rates during 12 months follow up
Persistent (n=1056)
Transient (n=3260)
Unprovoked (n=6293)
Number of events
Rate (95% CI)
All-cause mortality
364
48.5 ( )
129
4.3 ( )
214
3.6 ( )
Recurrent VTE 67
9.3 ( )
4.6 ( )
281
4.9 ( )
Major bleed 49
6.7 ( )
1.7 ( ) 75
1.3 ( )
Any bleeding
164
24.4 ( )
10.8 ( )
506
9.1 ( )
New cancer* 63
8.7 ( )
1.2
1.2 ( )
125
2.1 ( )
Stroke/TIA 17
2.3 ( ) 5
0.6 ( ) 38
0.6 ( ) MI
0.7 ( )
0.7 ( ) 43
0.7 ( )
Event rate is shown per 100 person-years
*Cancer diagnosed >30 days after VTE diagnosis
Data cut: May 2018

10. Adjusted† Hazard Ratios
Unprovoked vs. Persistent
Unprovoked vs. Transient
Death
9.94 ( )
0.97 ( )
Recurrent VTE
1.35 ( )
0.87 ( )
Major bleeding
2.45 ( )
1.19 ( )
Any bleeding
2.14 ( )
1.11 ( )
New Cancer*
4.04 ( )
0.7 ( ) 1 2 4 8
0.5 1 2
Increased risk with persistent risk factors
Increased risk with transient risk factors
*Cancer diagnosed >30 days after VTE diagnosis
†Adjusted for age, gender, ethnicity, BMI, site of VTE, recent bleed/anaemia, chronic heart failure, chronic immobilization, family history of VTE, history of cancer, known thrombophilia, prior episode of VTE, chronic kidney disease stage, and treatment at baseline.
Data cut: May 2018

11. Cumulative incidence of primary outcomes
All-cause mortality
Recurrent VTE
Major bleed
Cumulative Incidence
Time (days)
Cumulative Incidence
Time (days)
Cumulative Incidence
Time (days)
Data cut: May 2018

12. Summary
VTE patients with transient provoking risk factors were more likely to be younger, and female, than patients with unprovoked VTE
Anticoagulant treatment at baseline was similar between patients with transient provoking factors and unprovoked VTE. However, treatment duration was not.
Event rates were comparable between patients with transient provoking factors and unprovoked VTE. Patients with a persistent provoking factor had an increased incidence of death and major bleeding.