Compression stockings to prevent post-thrombotic syndrome: a randomised placebo-controlled trial.

BACKGROUND: Post-thrombotic syndrome (PTS) is a common and burdensome complication of deep venous thrombosis (DVT). Previous trials suggesting benefit of elastic compression stockings (ECS) to prevent PTS were small, single-centre studies without placebo control. We aimed to assess the efficacy of ECS, compared with placebo stockings, for the prevention of PTS. METHODS: We did a multicentre randomised placebo-controlled trial of active versus placebo ECS used for 2 years to prevent PTS after a first proximal DVT in centres in Canada and the USA. Patients were randomly assigned to study groups with a web-based randomisation system. Patients presenting with a first symptomatic, proximal DVT were potentially eligible to participate. They were excluded if the use of compression stockings was contraindicated, they had an expected lifespan of less than 6 months, geographical inaccessibility precluded return for follow-up visits, they were unable to apply stockings, or they received thrombolytic therapy for the initial treatment of acute DVT. The primary outcome was PTS diagnosed at 6 months or later using Ginsberg's criteria (leg pain and swelling of ≥1 month duration). We used a modified intention to treat Cox regression analysis, supplemented by a prespecified per-protocol analysis of patients who reported frequent use of their allocated treatment. This study is registered with ClinicalTrials.gov, number NCT00143598, and Current Controlled Trials, number ISRCTN71334751. FINDINGS: From 2004 to 2010, 410 patients were randomly assigned to receive active ECS and 396 placebo ECS. The cumulative incidence of PTS was 14·2% in active ECS versus 12·7% in placebo ECS (hazard ratio adjusted for centre 1·13, 95% CI 0·73-1·76; p=0·58). Results were similar in a prespecified per-protocol analysis of patients who reported frequent use of stockings. INTERPRETATION: ECS did not prevent PTS after a first proximal DVT, hence our findings do not support routine wearing of ECS after DVT. FUNDING: Canadian Institutes of Health Research.

Determinants and time course of the postthrombotic syndrome after acute deep venous thrombosis.

BACKGROUND: The reason some patients with deep venous thrombosis (DVT) develop the postthrombotic syndrome is not well understood. OBJECTIVE: To determine the frequency, time course, and predictors of the postthrombotic syndrome after acute DVT. DESIGN: Prospective, multicenter cohort study. SETTING: 8 Canadian hospital centers. PATIENTS: 387 outpatients and inpatients who received an objective diagnosis of acute symptomatic DVT were recruited from 2001 to 2004. MEASUREMENTS: Standardized assessments for the postthrombotic syndrome using the Villalta scale at 1, 4, 8, 12, and 24 months after enrollment. Mean postthrombotic score and severity category at each interval was calculated. Predictors of postthrombotic score profiles over time since diagnosis of DVT were identified by using linear mixed modeling. RESULTS: At all study intervals, about 30% of patients had mild (score, 5 to 9), 10% had moderate (score, 10 to 14), and 3% had severe (score >14 or ulcer) postthrombotic syndrome. Greater postthrombotic severity category at the 1-month visit strongly predicted higher mean postthrombotic scores throughout 24 months of follow-up (1.97, 5.03, and 7.00 increase in Villalta score for mild, moderate, and severe 1-month severity categories, respectively, vs. none; P < 0.001). Additional predictors of higher scores over time were venous thrombosis of the common femoral or iliac vein (2.23 increase in score vs. distal [calf] venous thrombosis; P < 0.001), higher body mass index (0.14 increase in score per kg/m(2); P < 0.001), previous ipsilateral venous thrombosis (1.78 increase in score; P = 0.001), older age (0.30 increase in score per 10-year age increase; P = 0.011), and female sex (0.79 increase in score; P = 0.020). LIMITATIONS: Decisions to prescribe compression stockings were left to treating physicians rather than by protocol. Because international normalized ratio data were unavailable, the relationship between anticoagulation quality and Villalta scores could not be assessed. CONCLUSION: The postthrombotic syndrome occurs frequently after DVT. Patients with extensive DVT and those with more severe postthrombotic manifestations 1 month after DVT have poorer long-term outcomes.

VEINES-QOL/Sym questionnaire was a reliable and valid disease-specific quality of life measure for deep venous thrombosis.

OBJECTIVE: To assess the validity of VEINES-QOL/Sym, a patient-reported questionnaire to evaluate quality of life and symptoms in patients with deep venous thrombosis (DVT). STUDY DESIGN AND SETTING: Psychometric study within the Venous Thrombosis Outcomes (VETO) Study, a prospective cohort study of long-term outcomes after DVT. A total of 359 English- and French-speaking patients with acute, objectively diagnosed DVT were recruited at seven hospitals in Quebec, Canada. The VEINES-QOL/Sym questionnaire, a 26-item patient-reported measure that generates separate summary scores for symptoms (VEINES-Sym) and quality of life (VEINES-QOL) was evaluated for acceptability, reliability, validity, and responsiveness in VETO Study subjects. RESULTS: Standard psychometric tests confirmed the acceptability (missing data, item endorsement frequencies, floor and ceiling effects), reliability (internal consistency, item-total and inter-item correlations, test-retest), validity (content, construct, convergent, discriminant, known groups), and responsiveness to clinical change of the VEINES-QOL/Sym in patients with DVT. CONCLUSION: The VEINES-QOL/Sym is a practical and scientifically sound patient-reported measure of outcomes that was developed using gold-standard methods. VEINES-QOL/Sym is valid and reliable for use as a measure of quality of life and symptoms in patients with acute DVT and provides a rigorous tool to allow more comprehensive evaluation of outcomes in clinical trials and epidemiological studies of patients with DVT.

Prospective evaluation of health-related quality of life in patients with deep venous thrombosis.

BACKGROUND: To our knowledge, the burden of deep venous thrombosis from the patient's perspective has not been quantified. We evaluated health-related quality of life (QOL) after deep vein thrombosis and compared results with general population norms. METHODS: This was a multicenter prospective cohort study of 359 consecutive eligible patients with deep vein thrombosis recruited at 7 Canadian hospital centers. Quality of life was assessed at baseline and at 1 and 4 months after diagnosis using generic (36-Item Short-Form Health Survey) and disease-specific (Venous Insufficiency Epidemiological and Economic Study [VEINES]-QOL and VEINES symptom [VEINES-Sym] questionnaires) measures. Changes in QOL scores during the 4-month period were calculated, and determinants of lack of improvement in QOL were evaluated. RESULTS: During the 4 months, mean 36-Item Short-Form Health Survey physical and mental component summary scores improved by 5.1 and 4.6 points, respectively, and VEINES-QOL and VEINES-Sym scores improved by 3.1 and 2.2 points, respectively (P < .001 for time trend for all measures). However, about one third of patients had worsening of QOL during follow-up. Multivariate analyses showed that worsening of the postthrombotic syndrome score was an independent predictor of worsening of 36-Item Short-Form Health Survey physical component summary (P = .04), VEINES-QOL (P < .001), and VEINES-Sym (P < .001) scores. The 36-Item Short-Form Health Survey physical component summary scores were lower than population norms at all points assessed. CONCLUSIONS: On average, QOL improves during the 4 months following deep vein thrombosis. However, in about one third of patients, QOL deteriorates, and at 4 months, average QOL remains poorer than population norms. Worsening of the postthrombotic syndrome score is associated with worsening of QOL.

Management and adherence to VTE treatment guidelines in a national prospective cohort study in the Canadian outpatient setting. The Recovery Study.

Documenting patterns and outcomes of venous thromboembolism (VTE) management and degree of adherence by clinicians to treatment guidelines could help identify remediable gaps in patient care. Prospective, clinical practice-based data from Canadian outpatient settings on management of VTE, degree of adherence with treatment guidelines and frequency of recurrent VTE and bleeding during follow-up was obtained in a multicentre, prospective observational study. From 12 Canadian centres, we assessed 868 outpatients with acute symptomatic VTE who received the low-molecular-weight heparin (LMWH) enoxaparin alone or with vitamin K antagonists (VKA), at baseline and at six months (or at the end of treatment, whichever came first). Index VTE was limb deep venous thrombosis (DVT) in 583 (67.2%) patients, pulmonary embolism (PE) with or without DVT in 262 (30.2%) patients, and unusual site DVT in 23 (2.6%) patients. VTE was unprovoked in 399 (46.0%) patients, associated with cancer in 74 (8.5%) patients, transient risk factors in 327 (37.7%) patients and hormonal factors in 68 (7.8%) patients.With regard to guideline adherence, 58 (7.3%) patients received <5 days LMWH and 114 (14.5%) had overlap <1 day. Among patients with cancer-related VTE, 59.5% were prescribed LMWH monotherapy and 43.2% received such treatment for >3 months. Only 38.1% of patients with transient VTE risk factors had received thromboprophylaxis. Our study provides useful information on clinical presentation, management and related outcomes in Canadian outpatients with VTE. Our results suggest there may be important gaps in use of thromboprophylaxis to prevent VTE and use of LMWH monotherapy to treat cancer-related VTE.