1. Innovative DVT Therapy in 2016: Merely the End of the Beginning
Suresh Vedantham, M.D.
Professor of Radiology & Surgery
Mallinckrodt Institute of Radiology
Washington University in St. Louis

2. DISCLOSURES
NIH-NHLBI: ATTRACT Study (U01-HL088476), Translational Research Center (U54-HL112321), C-TRACT Study Planning Grant (U34-HL123831)
Research Support to Washington University
BSN Medical, Volcano, Cook, Therakos
Off-label: TPA for DVT; stents for iliac vein

3. Anticoagulation prevents fatal PE, recurrent VTE, and clot extension
Traditional Approach
Thrombosis is a “Field Condition” It’s the BIOLOGY
Low Priority:
By reducing recurrence, AC reduces risk of PTS
HIGH PRIORITY
Anticoagulation prevents fatal PE, recurrent VTE, and clot extension
Compression reduces leg symptoms & prevents PTS

4. Health depends on “Open Vein” It’s the ANATOMY & PHYSIOLOGY
Alternative Approach
Health depends on “Open Vein” It’s the ANATOMY & PHYSIOLOGY
AC therapy is necessary but not sufficient
Clot extent and location matter – when large veins are obstructed or refluxing, patient will develop life-limiting symptoms and signs
Compression is necessary but not sufficient

5. December 16, 2014 FULLY ENROLLED
STUDY ENROLLMENT
Patient with proximal DVT meets eligibility criteria and provides informed consent
PRE-RANDOMIZATION PROCEDURES
Initiation of AC (LMWH or UFH) and completion of baseline assessments
RANDOMIZATION (1:1 Ratio)
CONTROL ARM SUBJECTS
Complete 5 days heparin therapy (LMWH or UFH) and immediately bridge to warfarin (INR 2.0 – 3.0)
PCDT ARM SUBJECTS
Complete 5 days heparin therapy (LMWH or UFH) concurrent with performance of PCDT procedure, then bridge to warfarin (INR 2.0 – 3.0)
LONG-TERM TREATMENT - ALL SUBJECTS
Long-term (> 3 months) warfarin therapy and daily use of graduated elastic compression stockings (initiated 10 days post-randomization)
FOLLOW-UP VISITS – ALL SUBJECTS
Early (10 days & 30 days post-randomization)
Late (6, 12, 18, & 24 months post-randomization)
FIGURE 1 – ATTRACT STUDY SCHEMA
December 16, 2014
FULLY ENROLLED

6. Transforming Care Will Demand More

7. Trend: Precision Medicine
Linkage with BIG DATA
Genomic Biomarkers
OUTCOMES of trials and patient care
Imaging Biomarkers
GOAL = TARGET Care to Potential for Benefit

8. TREND: Get More for Less $$$ Risky, Inconvenient, Unproven, COSTLY
Endovenous Ablation for Saphenous Reflux
Moving target – requirement for compression
Gonadal Vein Embolization & Venous Stenting
Reimbursement challenged due to lack of evidence
CDT => risky, increases hospital costs by $58,000
Bashir R et al. JAMA 2014.
If we don’t get actively engaged, others will decide

9. WE Must Re-Define Quality Venous Care
1. Avoidance of fatal PE and symptomatic PE
2. Avoidance of recurrent VTE (PE and DVT)
3. Avoidance of treatment-related bleeding
4. Avoidance of limb amputation (rare)
5. Avoidance of re-hospitalization (30 days)
6. Avoidance of Post-Thrombotic Syndrome
7. Avoidance of Venous Ulcer
8. Avoidance of CTPH and Post-PE Syndrome

10. PTS Must Be Required Study Outcome
2008: VETO Study shows that PTS is the leading determinant of a DVT patient’s 2-year HR-QOL
Kahn SR et al. Ann Intern Med 2008.
Kahn SR et al. J Thromb Haemost 2008.
2016: 4 New Oral Anticoagulants FDA approved
Non-inferior to warfarin for preventing recurrent DVT
More convenient and possibly safer than warfarin
ZERO data on NOAC effect upon PTS prevention

11. We Must Simplify Early Referral
NOACs have accelerated outpatient management
ER discharge, no need for LMWH injection teaching
Physician impetus can become a barrier to referral
Technically possible to leverage EMR systems
Need buy-in from ER physicians and health system
Endovascular provider group must be willing to work closely with medical physicians on proper targeting
Know ACCP guidelines, re-define patient flow

12. Credibility: Avoid Over-Treatment

13. Care Must Be Patient-Centered
Better Communication
resources to help convey balanced benefits and risks
Better Care
close monitoring of patients receiving PCDT
excellent follow-up to ensure good AC therapy
identify recurrences and PTS progression early
Better Innovation
Find ways to dissolve clot that don’t cause bleeds
Explore non-invasive adjuncts (e.g. “venous rehab”)

14. Severe Iliac-Obstructive PTS
PTS: chronic leg aching, fatigue, heaviness, swelling, (skin changes)
Severe PTS: 5-10% of proximal DVT, major impact on daily life and QOL
Thrombosis of iliac or CFV in 20-40% with proximal DVT => chronic phase
Kahn SR et al. Ann Intern Med 2008.
Kahn SR et al. J Thromb Haemost 2008.
Kahn SR et al. Circulation 2014.

15. Clinical Observations & Feasibility

16. Patency & Symptom Relief

17. RANDOMIZATION (1:1 Ratio) FOLLOW-UP VISITS – ALL SUBJECTS
C-TRACT STUDY
STUDY ENROLLMENT
Patient with SIO-PTS meets eligibility criteria, completes run-in period, and provides consent
ALL PATIENTS
Compression, DVT-appropriate AC, local preferences for “allowed” PTS treatments
RANDOMIZATION (1:1 Ratio)
CONTROL ARM SUBJECTS
Continue conservative therapy with adjustments at 2-month and 4-month follow-up visits if non-improving
ENDOVASCULAR ARM SUBJECTS
Iliac vein stent placement Endovenous saphenous vein ablation Same conservative therapy as Control
FOLLOW-UP VISITS – ALL SUBJECTS
Scheduled: 2, 4, 6, 12, 18 months post-RAND Unscheduled: as needed for symptoms & recurrence
OUTCOME ASSESSMENTS
Primary: Change in VEINES-QOL from 0 to 6 months
Secondary: Change VEINES-QOL, VCSS, Villalta
Secondary: Ulcer healing, safety events, costs
Multicenter, open-label, assessor-blind RCT (1:1)
Endorsed: AVF, SIR, SVM, ACP, NATF

18. C-TRACT – Site Selection
Best Chance for Study Success
Strong medical, endovascular, and ulcer care expertise - PTS
ATTRACT best-performing sites (accrual, data, responsiveness)
Access to large volume of PTS patients (clinic and outreach)
Endorsements: ACP, AVF, NATF, SIRF, SVM

19. New Era Collaboration Around DVT
2011 AHA Guidelines include far broader spectrum of DVT researchers and expertise
Jaff M et al. Circulation 2011.
Stronger collaborative track record: ACP, AVF, SIR, SVM
Think globally, act locally

20. The End of the Beginning
Tremendous opportunity to benefit public health will depend upon energy and practice-level collaboration