[Prolongation of anti vitamin K treatment for 18 months versus placebo after 6 months treatment of a first episode of ideopathic pulmonary embolism: a mutlicentre, randomised double blind trail. The PADIS-EP Trial]. / Prolongation d'un traitement par antivitamine K pendant dix-huit mois versus placebo au décours d'un premier épisode d'embolie pulmonaire idiopathique traité six mois: un essai randomisé multicentrique en double aveugle. Essai "PADIS-EP".

BACKGROUND: After stopping a 3 to 6 months course of oral anticoagulation for a first episode of idiopathic venous thromboembolism (VTE), the risk of recurrent VTE is high (10% per year). In this setting, international guidelines recommend at least 6 months treatment. However, this recommendation is not satisfactory for the following reasons: (1) no randomized trial has compared 6 months to extended duration (2 years) anticoagulation; and (2), even though the frequency of recurrent VTE is similar after pulmonary embolism (PE) and deep vein thrombosis (DVT), the fatality rate of recurrent VTE after PE is higher than that after DVT. METHODS: A French multicentre double blind randomized trial. The main objective is to demonstrate, after a first episode of symptomatic idiopathic PE treated for 6 months using a vitamin K antagonist, that extended anticoagulation for 18 months (INR between 2 and 3) is associated with an increased benefit / risk ratio (recurrent VTE and severe anticoagulant-related bleeding) compared to placebo. The double blind evaluation is ensured using by active warfarin and placebo, and blinded INR. The protocol was approved by the ethics board of the Brest Hospital on the 7th of March 2006. For an alpha risk of 5% and a beta risk of 20%, the estimated sample size is 374 patients. EXPECTED RESULTS: This study has the potential to: (1) demonstrate that the benefit / risk ratio of extended anticoagulation for 18 months is higher than that observed with placebo in patients with a first episode of idiopathic PE initially treated for 6 months, during and after the treatment period; and (2) to validate or invalidate the contribution of isotope lung scans, lower limb Doppler ultrasound and D-Dimer at 6 months of treatment as predictors of recurrent VTE (medico-economic analysis included).

[Readability of informed consent forms for subjects participating in biomedical research: updating is required]. / Lisibilité de l'information écrite destinée aux sujets se prêtant à une recherche biomédicale: une nécessaire remise en question.

OBJECTIVE: We compared informed consent forms of subjects participating in biomedical research with those of references texts in order to determine the factors that influence readability. METHODS: We assessed the readability of 73 informed consent forms of research protocols conducted in the clinical investigation centres in the Rhone-Alpes area, and then compared them with 33 reference texts corresponding to 5 French school grades (first year infant, primary school, GCS level, high school, and classics aggregation), using the Flesch test and Cordial" analyser. RESULTS: Median Flesch scores were 66 for the first year infant level, 62 for the primary school level, 58 for the GCS level, 42 for the high school level, and 43 for the aggregation level. It was 22 for the informed consent forms. Median Cordial scores were 86 for the first year infant level, 77 for the second, 74 for the third, 49 for the fourth, 43 for the fifth. It was 1 for the informed consent forms. No methodological factor correlated with Flesch and Cordial" results. CONCLUSION: The quantitative readability scores for informed consent forms for subjects participating in biomedical research are low, lower than those proposed to aggregation candidates, whatever the type of protocol. Some thought must be given to the impact of the reduced readability on patients' understanding, and steps should be taken to improve the readability of the forms.

Heparin-associated thrombocytopenia in 24,401 patients with venous thromboembolism: findings from the RIETE Registry.

BACKGROUND: Whether the treatment of venous thromboembolism (VTE) with unfractionated heparin (UFH) confers a higher risk of thrombocytopenia than does treatment with low molecular weight heparin (LMWH) remains controversial, and very few data are available from routine clinical practice. OBJECTIVES: We assessed the incidence, risk factors and prognosis of heparin-associated thrombocytopenia (HAT) according to the type of heparin therapy, UFH or LMWH. PATIENTS/METHODS: Data were obtained from the international prospective Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE), which included 25,369 patients with confirmed VTE until February 2009. Among them, 24,401 patients were treated either with UFH or with LMWH, and had available information about the 6-month occurrence of confirmed thrombocytopenia, defined as a platelet count ≤ 150,000 mm(-3) . RESULTS: One hundred and forty-one patients receiving UFH and/or LMWH developed thrombocytopenia within a 6-month period. The incidence of HAT was significantly higher in the UFH group (1.36%, 95% confidence interval [CI] 0.79-2.17) than in the LMWH group (0.54%, 95% CI 0.44-0.64). As compared with LMWH, UFH significantly increased the risk of HAT in female patients (adjusted hazard ratio [HR] 4.90%, 95% CI 2.58-9.31, P = 0.001) but not in male patients (adjusted HR 1.60%, 95% CI 0.64-3.97, P = 0.31); P = 0.027 for comparison. In each gender, the UFH-associated excess risk was confined to patients with VTE unrelated to cancer. The poor prognosis of patients with thrombocytopenia was not influenced by the type of heparin therapy. CONCLUSIONS: In routine clinical practice, treatment of VTE with UFH seems to confer a higher risk of thrombocytopenia than does treatment with LMWH, especially in women and non-cancerous patients.

Comparison of the clinical history of symptomatic isolated distal deep-vein thrombosis vs. proximal deep vein thrombosis in 11 086 patients.

BACKGROUND: The clinical significance of symptomatic isolated distal deep vein thrombosis (DVT) is uncertain. Consequently, this leads to important disparities in its management. OBJECTIVE: To examine the clinical history of isolated distal DVT and to compare it with that of proximal DVT. METHODS: Using data from the international, prospective, RIETE registry on patients with confirmed symptomatic venous thromboembolism (VTE), we compared the risk factors and 3-month outcome in patients with isolated distal DVT vs. proximal DVT. RESULTS: Eleven thousand and eighty-six patients with symptomatic DVT, but without pulmonary embolism, were included between 2001 and 2008; 1921 (17.3%) exhibited isolated distal DVT. Anticoagulant treatment was received by 89.1% (1680/1885) of isolated distal DVT and 91.8% (7911/8613) of proximal DVT patients for the entire follow-up period. Isolated distal DVTs were more associated with transient risk factors (i.e. recent travel, hospitalization, recent surgery), whereas proximal DVTs were more associated with chronic states (i.e. > or =75 years or with active cancer). At 3 months, major bleeding rate was lower in patients with isolated distal DVT (1.0% vs. 2.2%, P < 0.01), whereas VTE recurrence rate was equivalent (2.0% vs. 2.7%, P = 0.07). The mortality rate was lower in patients with isolated distal DVT (2.7% vs. 7.5%; P < 0.001); this was mainly due to a lower rate of non-VTE-related deaths (2.2% vs. 6.3%; P < 0.001). Active cancer was the main predictive factor of death in patients with isolated distal DVT. CONCLUSIONS: Proximal and isolated distal DVT patients differ in terms of risk factors and clinical outcomes, suggesting different populations. In the short term, the life expectancy of patients with isolated distal DVT depended chiefly on their cancer status.

[Vena cava filters and treatment of venous thromboembolism in cancer patients]. / Place des filtres caves dans le traitement de la maladie thromboembolique veineuse chez les patients cancéreux.

Despite numerous publications, there is still only one randomised clinical trial with vena cava filter in the treatment of venous thromboembolism (VTE). This study has shown a potential and early benefit on the risk of pulmonary embolism (PE) (the first three months) but a late negative effect on the risk of deep vein thrombosis (DVT) recurrences (beyond the sixth month) especially on the risk of filter thrombosis. Consequently, the international recommendations are against a systematic use of vena cava filter to treat VTE (grade 1A) and they suggest to use them in case of a recurrence despite adequate treatment or in case of a contra-indication to anticoagulants (grade 2C). But these two conditions are frequent with VTE associated with cancer since, the risk of VTE recurrences is about 5 to 10% despite prolonged low-molecular-weight heparins (LMWH) treatment and the major bleeding risk is also about 5 to 10% in this case. These VTE recurrences are frequently early (first month of treatment) and contra-indications to anticoagulants due to major bleeding are mostly temporary. In this way, retrievable vena cava filters (possible retrieval until six months after placement) could be useful in order, to prevent recurrences during the thromboembolic risk period without any prolonged increasing risk of vena cava thrombosis. However, vena cava filters could be associated with some complications (tilt, migration sepsis...). So without any strong validation, they have still to be considered as a therapeutic strategy needing to be evaluated especially in cancer patient.

Clinical outcome in patients with venous thromboembolism and hidden cancer: findings from the RIETE Registry.

INTRODUCTION: Although extensive screening in patients with venous thromboembolism (VTE) may result in early identification of hidden cancer, it is unknown whether the prognosis of these patients may be favorably influenced. PATIENTS AND METHODS: RIETE is an ongoing, prospective registry of consecutive patients with objectively confirmed, symptomatic, acute VTE. We compared the 3-month outcome of patients with hidden cancer with that in patients in whom no symptoms of cancer were noted. RESULTS: Of 17,475 patients with acute VTE, 2852 (16%) had cancer diagnosed before VTE or during admission. Hidden cancer was detected in 178 (1.2%) of the remaining 14,623 patients. The most common sites were lung, prostate, colorectum, or hematologic, and 51% had metastases. As compared with patients in whom no symptoms of cancer were noted, those with hidden cancer had an increased incidence of recurrent VTE (11.4% vs. 2.1%; P < 0.001), major bleeding (5.1% vs. 2.1%; P = 0.007), and mortality (20% vs. 5.4%; P < 0.001). In the multivariate analysis, patients aged 60-75 years [odds ratio 1.8; 95% CI 1.2-2.7], with idiopathic VTE (odds ratio 3.0; 95% CI 2.2-4.2), with bilateral thrombosis (odds ratio 2.3; 95% CI 1.3-4.1) or with anemia (odds ratio 1.9; 95% CI 1.4-2.6) were at an increased risk for hidden cancer. CONCLUSIONS: VTE patients with hidden cancer have an increased incidence of recurrences, major bleeding or death during the first 3 months of therapy. With four simple, easily obtainable variables, it is possible to identify a subgroup of VTE patients with a higher risk for hidden cancer.