Predictors Of The Post-Thrombotic Syndrome In a Large Cohort Of Patients With Proximal DVT: Secondary Analysis Of The Sox Trial
Authors: Kahn Susan R. , Shapiro Stan , Wells Philip S. , Rodger Marc A , Kovacs Michael J. , Anderson David , Tagalakis Vicky , Houweling Adrielle H , Ducruet Thierry , Solymoss Susan , Miron Marie-José , Yeo Erik , Smith Reginald , D Pharm , Schulman Sam , Kassis Jeannine , Kearon Clive , Chagnon Isabelle , Wong Turnly , Demers Christine , Hanmiah Rajendar , Kaatz Scott , Selby Rita , Rathbun Suman , Desmarais Sylvie , Opatrny Lucie , Ortel Thomas L. , Ginsberg Jeffrey S 
Published: October 2019

Background
The post-thrombotic syndrome (PTS) is a frequent complication of deep venous thrombosis (DVT). Identifying predictors of PTS is important to counsel DVT patients on their expected prognosis and to identify patients who may benefit from closer monitoring or preventive strategies.

Objective
In a secondary analysis of the SOX Trial, we aimed to identify predictors of developing PTS during 2 years follow-up after a first episode of proximal DVT.

Methods
The study cohort consisted of participants in the SOX Trial, a multicenter (24 centres in Canada and U.S.) randomized placebo controlled trial of active elastic compression stockings vs. placebo stockings worn for 2 years after a first, symptomatic proximal DVT. PTS, the primary study endpoint, was diagnosed at or after the 6 month visit based on patient-reported pain and swelling of ≥ 1 month duration that were typical in character, i.e. worse at end of day or after prolonged sitting/standing and improved after rest/leg elevation (Ginsberg criteria). Cumulative incidences of PTS were compared in subgroups defined by sex, age category, body mass index (BMI) category, anatomic extent of index DVT, type of DVT (cancer-associated, secondary risk factor-associated, unprovoked) and 1-month Villalta score category (score 0-4: none; 5-9, mild; 10-14, moderate; >14, severe), using Cox regression. Losses to follow-up, withdrawals and deaths were censored as of last date of follow-up. Results are presented as cumulative incidence by 750 days follow-up and hazard ratios (HR) with 95% confidence intervals (CI).

Results
Among the 803 participants in the SOX Trial, 60% were male, mean age was 55.1 years, and 87% were out-patients. In analyses adjusted for intervention group (i.e. allocation to active vs. placebo stockings), iliac vein DVT (HR 2.26 [95% CI 1.12, 4.53]; reference category: popliteal DVT) and Villalta score category at 1 month after DVT (score 5-9, HR 2.74 [95% CI 1.62, 4.64]; score 10-14, HR 5.81[95% CI 2.99, 11.29]; score >14, HR 7.59 [95% CI 3.31, 17.44]; reference category: score <5) were significant predictors of PTS. In analyses adjusted for intervention group and all predictor variables of interest, Villalta score category at 1 month was a highly statistically significant, independent predictor of PTS (see Table). Age, sex, BMI and type of DVT did not predict development of PTS.

Conclusions
In a large prospective cohort of patients with proximal DVT who were participants in the SOX Trial, Villalta score category (which reflects severity of venous symptoms and signs) at 1 month after DVT was strongly predictive of development of PTS during 2 years follow-up. This confirms a similar finding that we first observed in the VETO cohort study (Kahn SR et. al., Annals Intern Med 2008). More extensive DVT was also associated with PTS. Patients with these risk factors may benefit from closer monitoring after proximal DVT, and in the case of iliac vein DVT, from more aggressive strategies to treat acute DVT.

Disclosures:
No relevant conflicts of interest to declare.