Anticoagulation therapy following endovascular treatment of iliofemoral deep vein thrombosis

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Anticoagulation therapy following endovascular treatment of iliofemoral deep vein thrombosis Tim Sebastian, M.D. University Hospital Zurich Clinic for Angiology

Disclosure Speaker name: Tim Sebastian I have the following potential conflicts of interest to report: Consulting Employment in industry Stockholder of a healthcare company Owner of a healthcare company Other(s) I do not have any potential conflict of interest

Anticoagulation therapy remains first-line therapy for most patients with proximal deep vein thrombosis none invasive widely available Advantages effectively inhibits thrombus propagation low risk of complications reduces risk for recurrence improves VTE morbidity and mortality

80% anatomic abnormalities central to thrombosed vein low recanalization rates in presence of compression Limitations ineffective in preventing the postthrombotic syndrome provides no treatment of underlying anatomic trigger MTS associated with persistent occlusion of left iliac vein and failure of recanalization during anticoagulation therapy

IFDVT PATIENTS ARE HIGH RISK PATIENTS Recurrence rate during active treatment twice as high in patients with iliofemoral DVT compared to patients with proximal DVT without iliac vein involvment 11.8 % versus 5.2% High risk patients most likely beneft from more aggressive therapy: (Douketis JD et al. Am J Med 2001) including early thrombus removal and stent placement Deep vein thrombosis of the common femoral vein or iliac veins predicts a more severe manifestation of the postthrombotic syndrome (Kahn et al.ann Intern Med 2008)

Real World Practise Case Scenario 30 y male First left-leg acute iliofemoral DVT Patient undergoes catheter-directed thrombolysis IVUS: May Thurner lesion -> Covered with a venous stent Good technical result with health leg inflow veins

Current Practise The minority of patients received antithrombotic therapy concistent to published VTE guidelines Proves that antithrombotic management of patients with venous stent implants is highly inconsistent, and no consensus exists. Case scenario sent out to 106 experts 30%: VKA 12 months 15% DOAC 6 months followed by antiplatelet agent 13%: VKA 6 months followed by antiplatelet agent 11%: DOAC 3-6 months 12%: VKA or DOAC for life % refers to the proportion of physicians currently practising the particular antithrombotic regimen VKA = vitamin k antagonist DOAC = direct oral anticoagulant

the optimal duration of anticoagulation after the placement of venous stents in the setting of early thrombus removal has not been adequately studied In patients with acute DVT of the leg who undergo thrombosis removal, we recommend the same intensity and duration of anticoagulant therapy as in similar patients who do not undergo thrombosis removal.

In patients with acute DVT of the leg who undergo thrombosis removal, we recommend the same intensity and duration of anticoagulant therapy as in similar patients who do not undergo thrombosis removal. No mention in ACCP 2016 update

Questions that are unanswered for patients with IFDVT and venous stent implants Can anticoagulation therapy be stopped after some time? Hypothesis 1: Stent may resolve underlying mechanical trigger for recurrence. Hypothesis 2: Stent as foreign body may act as further risk factor for recurrence. Are DOACs as effective as VKA? Is there a need for antiplatelet therapy? If yes, when and in which patients?

Can anticoagulation therapy be stopped after some time? Swiss Venous Stent Registry Subgroup of 113 patients treated for acute iliofemoral DVT (two groups: limited versus extended duration) 72% left leg iliofemoral DVT 88% symptom duration less than 14 days 100% stent rate (19% stents below inguinal ligament) Mean follow-up duration: 26 months Baseline Limited-duration (n = 58) Age (years) 38.1 53.7 Women 43 (74%) 27 (49%) Known previous VTE 5 (9%) 19 (35%) May Thurner Anatomy 38 (66%) 21 (38%) Extended-duration (n = 55)

Can anticoagulation therapy be stopped after some time? Patency Rates at 3 Years Extended vs. Limited Anticoagulation Group Primary Patency Rate Secondary Patency Rate 77% 95% CI 60-87% 71% 95% CI 51-84% 55 58 100% 88% 95% CI 73-95% 55 58 p = 0.16 p = 0.82 Follow-up, months Follow-up, months Total cohort: 73% (95% CI 61-82%) Total cohort: 95% (95% CI 88-98%)

Can anticoagulation therapy be stopped after some time? Recurrent VTE Rates Thrombus removal + Stent (iliofemoral DVT) Swiss Venous Stent Registry 3.5 events per 100 patient years after cessation Carrier et al. 2010. Ann Intern Med. Anticoagulation only (prox. + distal DVT) Metaanalysis (10,050 patients) 7.6 events per 100 patient years after cessation In selected patients (younger, otherwise healthy) with May-Thurner Syndrome, it appears save to discontinue AT 3-12 months after endovascular treatment for IFDVT (RCT necessary!)

Are DOACs as effective as VKA? Patency Rates at 3 Years Rivaroxaban vs. VKA Group Primary Patency Rate Secondary Patency Rate 84% 95% CI 72-96% 62% 95% CI 51-73% 95% 95% CI 88-100 94% 95% CI 86-99% 38 73 38 73 p = 0.11 SE > 10% (VKA) p = 0.83 Follow-up, months Follow-up, months Total cohort: 73% (95% CI 61-82%) Total cohort: 95% (95% CI 88-98%) In patients with acute IFDVT treated with catheter-based thrombus removal and venous stent placement, the effectiveness of rivaroxaban and VKA appeared to be similar.

Is there a need for antiplatelet therapy? Use of AP in VTE disease no stents WARFASA: 403 patients ASPIRE: 822 patients Pat. with first unprovoked DVT and completed anticoagulation therapy Randomized to aspirin or placebo Recurrence rate per year 6.6% aspirin vs 11.2% placebo HR 0.58 (95% CI: 0.36-0.93) p = 0.02 4.8% aspirin vs 6.5% placebo HR 0.74 (95% CI: 0.52-1.05) p = 0.09 Swiss Venous Stent Registry: Only 5% received antiplatelet agents in addition to oral anticoagulation: No subgroup analysis performed

Swiss Venous Stent Registry Patients with Venous Stent Implants Primary Patency Rate Secondary Patency Rate p = 0.003 p = 0.256 95% 95% CI 91-99% 74% 95% CI 66-82% 89% 95% CI 83-95 61% 95% CI 52-70 Acute iliofemoral DVT (n=122) Postthrombotic Syndrome (n=121) Acute iliofemoral DVT (n=122) Postthrombotic Syndrome (n=121) Benefit of antiplatelet agent (aspirin) in addition to anticoagulation (rivaroxaban) will be under investigation in the ARIVA trial for patients with PTS.

Summary Antithrombotic management is inconsistant, and not specified in patients with venous stents. The effectiveness of rivaroxaban and VKA to maintain stent patency appears to be similar. It appears to be safe to discontinue anticoagulation therapy in selected patients. Late stent failure occurs (need for antithrombotic prophylaxis must be evaluated) The benefit of antiplatelet therapy in addition to anticoagulation in PTS patients is currently under investigation (ARIVA trial).

Thank you for your attention! Tim Sebastian, M.D. University Hospital Zurich Clinic for Angiology

Anticoagulation therapy following endovascular treatment of iliofemoral deep vein thrombosis Tim Sebastian, M.D. University Hospital Zurich Clinic for Angiology