Vicky Tagalakis

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 Ginsbergs 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.

The epidemiology of peripheral vein infusion thrombophlebitis: a critical review

We critically assessed studies on the clinical importance, diagnosis, incidence, and pathogenesis of peripheral vein infusion thrombophlebitis, including catheter-related and patient-related risk factors. We reviewed the evidence linking thrombosis, particularly prothrombotic states such as the inherited thrombophilic disorders, with peripheral vein infusion thrombophlebitis. Peripheral vein infusion thrombophlebitis occurs in 25% to 35% of hospitalized patients with peripheral intravenous catheters and has both patient-related implications (e.g., sepsis) and economic consequences (e.g., extra nursing time). Although duration of catheterization, catheter-related infection, and catheter material are important risk factors for peripheral vein infusion thrombophlebitis, patient-related risk factors are not well elucidated.

Incidence of and Mortality from Venous Thromboembolism in a Real-world Population: The Q-VTE Study Cohort

BACKGROUND The public health burden of venous thromboembolism, which includes deep vein thrombosis and pulmonary embolism, is not fully known, and contemporary incidence and mortality estimates are needed. We determined the incidence and case fatality of venous thromboembolism in a general population. METHODS Using the administrative health care databases of the Canadian province of Québec, we identified all incident cases of deep vein thrombosis or pulmonary embolism between 2000 and 2009 and classified them as definite or probable venous thromboembolism. We formed 2 patient cohorts, one with definite cases and the other including cases with definite or probable venous thromboembolism that were followed until December 31, 2009. RESULTS We identified 67,354 definite and 35,123 probable cases of venous thromboembolism. The age- and sex-adjusted incidence rates of definite or probable venous thromboembolism, deep vein thrombosis, and pulmonary embolism were 1.22 (95% confidence interval [CI], 1.22-1.23), 0.78 (95% CI, 0.77-0.79), and 0.45 (95% CI, 0.44-0.45) per 1000 person-years, respectively, while for definite venous thromboembolism it was 0.90 (95% CI, 0.89-0.90) per 1000 person-years. The 30-day and 1-year case-fatality rates after definite or probable venous thromboembolism were 10.6% (95% CI, 10.4-10.8) and 23.0% (95% CI, 22.8-23.3), respectively, and were slightly higher among definite cases. The 1-year survival rate was 0.47 (95% CI, 0.46-0.48) for cases with definite or probable venous thromboembolism and cancer, 0.93 (95% CI, 0.93-0.94) for cases with unprovoked venous thromboembolism, and 0.84 (95% CI, 0.83-0.84) for cases with venous thromboembolism secondary to a major risk factor. Similar survival rates were seen for cases with definite venous thromboembolism. CONCLUSION The risk of venous thromboembolism in the general population remains high, and mortality, especially in cancer patients with venous thromboembolism, is substantial.

Effectiveness of compression stockings to prevent the post-thrombotic syndrome (The SOX Trial and Bio-SOX biomarker substudy): a randomized controlled trial

BackgroundPost thrombotic syndrome (PTS) is a burdensome and costly complication of deep venous thrombosis (DVT) that develops in 20–40% of patients within 1–2 years after symptomatic DVT. Affected patients have chronic leg pain and swelling and may develop ulcers. Venous valve disruption from the thrombus itself or thrombus-associated mediators of inflammation is considered to be a key initiating event for the development of venous hypertension that often underlies PTS. As existing treatments for PTS are extremely limited, strategies that focus on preventing the development of PTS in patients with DVT are more likely to be effective and cost-effective in reducing its burden. Elastic compression stockings (ECS) could be helpful in preventing PTS; however, data on their effectiveness are scarce and conflicting.Methods/DesignThe SOX Trial is a randomized, allocation concealed, double-blind multicenter clinical trial. The objective of the study is to evaluate ECS to prevent PTS. A total of 800 patients with proximal DVT will be randomized to one of 2 treatment groups: ECS or placebo (inactive) stockings worn on the DVT-affected leg daily for 2 years. The primary outcome is the incidence of PTS during follow-up. Secondary outcomes are severity of PTS, venous thromboembolism (VTE) recurrence, death from VTE, quality of life and cost-effectiveness. Outcomes will be evaluated during 6 clinic visits and 2 telephone follow ups. At baseline, 1 and 6 months, blood samples will be obtained to evaluate the role of inflammatory mediators and genetic markers of thrombophilia in the development of PTS (Bio-SOX substudy).DiscussionThe SOX Trial will be the largest study and the first with a placebo control to evaluate the effectiveness of ECS to prevent PTS. It is designed to provide definitive data on the effects of ECS on the occurrence and severity of PTS, as well as DVT recurrence, cost-effectiveness and quality of life. This study will also prospectively evaluate the predictive role of biomarkers that are reflective of putative underlying pathophysiological mechanisms in the development of clinical PTS. As such, our results will impact directly on the care of patients with DVT.Trial RegistrationNCT00143598 and ISRCTN71334751

Use of warfarin and risk of urogenital cancer: a population-based, nested case-control study

BACKGROUND Indirect evidence suggests that prolonged treatment with warfarin might be associated with a decreased incidence of urogenital cancer. We aimed to assess this association in a large population-based study. METHODS Beneficiaries of Saskatchewan Health who were eligible for prescription drug benefits and aged 50 years or over with no history of cancer since 1967 were enrolled into a nested, matched case-control study. 19 412 new cases of urogenital cancer diagnosed between Jan 1, 1981, and Dec 31, 2002, were identified by use of information from the Saskatchewan Cancer Agency registry. For each case, six controls, totalling 116 470, who were matched for age, sex, and time of diagnosis were selected randomly. Conditional logistic regression analysis was used to calculate adjusted incidence rates of urogenital cancer in relation to warfarin use. FINDINGS Compared with men who never used warfarin, men with 4 years of warfarin use had an adjusted incidence rate of 0.80 (95% CI [0.65-0.99]). For warfarin use 76-100% of the time, the adjusted rate ratios were 0.80 (0.66-0.96) during year 2 preceding diagnosis of prostate cancer, 0.76 (0.62-0.94) during year 3, and 0.67 (0.53-0.86) during year 4. No significant association was found between warfarin and risk of other urogenital cancers. INTERPRETATION Our results suggest that warfarin has an antitumour effect that is specific to prostate cancer. Further investigation, with more complete assessment of confounders and that addresses the effect of warfarin on mortality of prostate cancer, is warranted.

Graduated compression stockings to treat acute leg pain associated with proximal DVT. A randomised controlled trial.

Acute deep venous thrombosis (DVT) causes leg pain. Elastic compression stockings (ECS) have potential to relieve DVT-related leg pain by diminishing the diameter of distended veins and increasing venous blood flow. It was our objective to determine whether ECS reduce leg pain in patients with acute DVT. We performed a secondary analysis of the SOX Trial, a multicentre randomised placebo controlled trial of active ECS versus placebo ECS to prevent the post-thrombotic syndrome.The study was performed in 24 hospital centres in Canada and the U.S. and included 803 patients with a first episode of acute proximal DVT. Patients were randomised to receive active ECS (knee length, 30-40 mm Hg graduated pressure) or placebo ECS (manufactured to look identical to active ECS, but lacking therapeutic compression). Study outcome was leg pain severity assessed on an 11-point numerical pain rating scale (0, no pain; 10, worst possible pain) at baseline, 14, 30 and 60 days after randomisation. Mean age was 55 years and 60% were male. In active ECS patients (n=409), mean (SD) pain severity at baseline and at 60 days were 5.18 (3.29) and 1.39 (2.19), respectively, and in placebo ECS patients (n=394) were 5.38 (3.29) and 1.13 (1.86), respectively. There were no significant differences in pain scores between groups at any assessment point, and no evidence for subgroup interaction by age, sex or anatomical extent of DVT. Results were similar in an analysis restricted to patients who reported wearing stockings every day. In conclusion, ECS do not reduce leg pain in patients with acute proximal DVT.

Determining the test characteristics of claims-based diagnostic codes for the diagnosis of venous thromboembolism in a medical service claims database

To determine the test characteristics of diagnostic codes within a medical service claims database for deep vein thrombosis (DVT) and pulmonary embolism (PE).

Inflammation markers and their trajectories after deep vein thrombosis in relation to risk of post-thrombotic syndrome

Post‐thrombotic syndrome (PTS) is a frequent chronic complication of deep vein thrombosis (DVT).

Management of venous thromboembolism in cancer patients and the role of the new oral anticoagulants.

Patients with cancer are at high risk for venous thromboembolism (VTE). Most clinical guidelines agree that low-molecular-weight heparins (LMWHs) are the preferred anticoagulants for the prevention and treatment of VTE in cancer patients. However, LMWHs require daily injections, weight-adjustment of dose, and can be associated with heparin-induced thrombocytopenia; all of which are important considerations in managing cancer-associated VTE. Comparatively, the new oral anticoagulants offer a more attractive option because of their oral administration, fixed-dose, and lack of routine laboratory monitoring. The results of phase III trials support the efficacy and safety of the new oral anticoagulants in the management of VTE. However, generalizing these findings to cancer patients with VTE is difficult since very few cancer patients were included. In this comprehensive review, we provide an overview of the current treatment of VTE, explore anticoagulant thromboprophylaxis in ambulatory cancer patients, and summarize existing evidence on the efficacy and safety of the new oral anticoagulants for the management of VTE in both non-cancer and cancer populations.

Risk factors predictive of occult cancer detection in patients with unprovoked venous thromboembolism

Risk factors predictive of occult cancer detection in patients with a first unprovoked symptomatic venous thromboembolism (VTE) are unknown. Cox proportional hazard models and multivariate analyses were performed to assess the effect of specific risk factors on occult cancer detection within 1 year of a diagnosis of unprovoked VTE in patients randomized in the Screening for Occult Malignancy in Patients with Idiopathic Venous Thromboembolism (SOME) trial. A total of 33 (3.9%; 95% CI, 2.8%-5.4%) out of the 854 included patients received a new diagnosis of cancer at 1-year follow-up. Age ≥ 60 years (hazard ratio [HR], 3.11; 95% CI, 1.41-6.89; ITALIC! P= .005), previous provoked VTE (HR, 3.20; 95% CI, 1.19-8.62; ITALIC! P= .022), and current smoker status (HR, 2.80; 95% CI, 1.24-6.33; ITALIC! P= .014) were associated with occult cancer detection. Age, prior provoked VTE, and smoking status may be important predictors of occult cancer detection in patients with first unprovoked VTE. This trial was registered atwww.clinicaltrials.govas #NCT00773448.