M.-A. Sevestre

Effect of a Retrievable Inferior Vena Cava Filter Plus Anticoagulation vs Anticoagulation Alone on Risk of Recurrent Pulmonary Embolism: A Randomized Clinical Trial

IMPORTANCE Although retrievable inferior vena cava filters are frequently used in addition to anticoagulation in patients with acute venous thromboembolism, their benefit-risk ratio is unclear. OBJECTIVE To evaluate the efficacy and safety of retrievable vena cava filters plus anticoagulation vs anticoagulation alone for preventing pulmonary embolism recurrence in patients presenting with acute pulmonary embolism and a high risk of recurrence. DESIGN, SETTING, AND PARTICIPANTS Randomized, open-label, blinded end point trial (PREPIC2) with 6-month follow-up conducted from August 2006 to January 2013. Hospitalized patients with acute, symptomatic pulmonary embolism associated with lower-limb vein thrombosis and at least 1 criterion for severity were assigned to retrievable inferior vena cava filter implantation plus anticoagulation (filter group; n = 200) or anticoagulation alone with no filter implantation (control group; n = 199). Initial hospitalization with ambulatory follow-up occurred in 17 French centers. INTERVENTIONS Full-dose anticoagulation for at least 6 months in all patients. Insertion of a retrievable inferior vena cava filter in patients randomized to the filter group. Filter retrieval was planned at 3 months from placement. MAIN OUTCOMES AND MEASURES Primary efficacy outcome was symptomatic recurrent pulmonary embolism at 3 months. Secondary outcomes were recurrent pulmonary embolism at 6 months, symptomatic deep vein thrombosis, major bleeding, death at 3 and 6 months, and filter complications. RESULTS In the filter group, the filter was successfully inserted in 193 patients and was retrieved as planned in 153 of the 164 patients in whom retrieval was attempted. By 3 months, recurrent pulmonary embolism had occurred in 6 patients (3.0%; all fatal) in the filter group and in 3 patients (1.5%; 2 fatal) in the control group (relative risk with filter, 2.00 [95% CI, 0.51-7.89]; P = .50). Results were similar at 6 months. No difference was observed between the 2 groups regarding the other outcomes. Filter thrombosis occurred in 3 patients. CONCLUSIONS AND RELEVANCE Among hospitalized patients with severe acute pulmonary embolism, the use of a retrievable inferior vena cava filter plus anticoagulation compared with anticoagulation alone did not reduce the risk of symptomatic recurrent pulmonary embolism at 3 months. These findings do not support the use of this type of filter in patients who can be treated with anticoagulation. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00457158.

Predictive factors for concurrent deep-vein thrombosis and symptomatic venous thromboembolic recurrence in case of superficial venous thrombosis. The OPTIMEV study.

Superficial venous thrombosis (SVT) prognosis is debated and its management is highly variable. It was the objective of this study to assess predictive risk factors for concurrent deep-vein thrombosis (DVT) at presentation and for three-month adverse outcome. Using data from the prospective multicentre OPTIMEV study, we analysed SVT predictive factors associated with concurrent DVT and three-month adverse outcome. Out of 788 SVT included, 227 (28.8%) exhibited a concurrent DVT at presentation. Age >75years (odds ratio [OR]=2.9 [1.5-5.9]), active cancer (OR=2.6 [1.3-5.2]), inpatient status (OR=2.3 [1.2-4.4]) and SVT on non-varicose veins (OR=1.8 [1.1-2.7]) were significantly and independently associated with an increased risk of concurrent DVT. 39.4% of SVT on non-varicose veins presented a concurrent DVT. However, varicose vein status did not influence the three-month prognosis as rates of death, symptomatic venous thromboembolic (VTE) recurrence and major bleeding were equivalent in both non-varicose and varicose SVTs (1.4% vs. 1.1%; 3.4% vs. 2.8%; 0.7% vs. 0.3%). Only male gender (OR=3.5 [1.1-11.3]) and inpatient status (OR=4.5 [1.3-15.3]) were independent predictive factors for symptomatic VTE recurrence but the number of events was low (n=15, 3.0%). Three-month numbers of deaths (n=6, 1.2%) and of major bleedings (n=2, 0.4%) were even lower, precluding any relevant interpretation. In conclusion, SVT on non-varicose veins and some classical risk factors for DVT were predictive factors for concurrent DVT at presentation. As SVT remains mostly a clinical diagnosis, these data may help selecting patients deserving an ultrasound examination or needing anticoagulation while waiting for diagnostic tests. Larger studies are needed to evaluate predictive factors for adverse outcome.

Incidence and predictors of venous thromboembolism recurrence after a first isolated distal deep vein thrombosis

Isolated distal deep vein thrombosis (iDDVT) (i.e. without proximal DVT or pulmonary embolism) represents half of all cases of lower limb DVT. Its clinical significance and management are controversial. Data on long‐term follow‐up are scarce, especially concerning risk and predictors of venous thromboembolism (VTE) recurrence.

Predictive factors for concurrent deep-vein thrombosis and symptomatic venous thromboembolic recurrence in case of superficial venous thrombosis. The OPTIMEV study

Superficial venous thrombosis (SVT) prognosis is debated and its management is highly variable. It was the objective of this study to assess predictive risk factors for concurrent deep-vein thrombosis (DVT) at presentation and for three-month adverse outcome. Using data from the prospective multicentre OPTIMEV study, we analysed SVT predictive factors associated with concurrent DVT and three-month adverse outcome. Out of 788 SVT included, 227 (28.8%) exhibited a concurrent DVT at presentation. Age >75years (odds ratio [OR]=2.9 [1.5-5.9]), active cancer (OR=2.6 [1.3-5.2]), inpatient status (OR=2.3 [1.2-4.4]) and SVT on non-varicose veins (OR=1.8 [1.1-2.7]) were significantly and independently associated with an increased risk of concurrent DVT. 39.4% of SVT on non-varicose veins presented a concurrent DVT. However, varicose vein status did not influence the three-month prognosis as rates of death, symptomatic venous thromboembolic (VTE) recurrence and major bleeding were equivalent in both non-varicose and varicose SVTs (1.4% vs. 1.1%; 3.4% vs. 2.8%; 0.7% vs. 0.3%). Only male gender (OR=3.5 [1.1-11.3]) and inpatient status (OR=4.5 [1.3-15.3]) were independent predictive factors for symptomatic VTE recurrence but the number of events was low (n=15, 3.0%). Three-month numbers of deaths (n=6, 1.2%) and of major bleedings (n=2, 0.4%) were even lower, precluding any relevant interpretation. In conclusion, SVT on non-varicose veins and some classical risk factors for DVT were predictive factors for concurrent DVT at presentation. As SVT remains mostly a clinical diagnosis, these data may help selecting patients deserving an ultrasound examination or needing anticoagulation while waiting for diagnostic tests. Larger studies are needed to evaluate predictive factors for adverse outcome.

ICD-10 hospital discharge diagnosis codes were sensitive for identifying pulmonary embolism but not deep vein thrombosis

OBJECTIVE To estimate the sensitivity of International Classification of Diseases, Tenth revision (ICD-10) hospital discharge diagnosis codes for identifying deep vein thrombosis (DVT) and pulmonary embolism (PE). STUDY DESIGN AND SETTING We compared predefined ICD-10 discharge diagnosis codes with the diagnoses that were prospectively recorded for 1,375 patients with suspected DVT or PE who were enrolled at 25 hospitals in France. Sensitivity was calculated as the percentage of patients identified by predefined ICD-10 codes among positive cases of acute symptomatic DVT or PE confirmed by objective testing. RESULTS The sensitivity of ICD-10 codes was 58.0% (159 of 274; 95% CI: 51.9, 64.1) for isolated DVT and 88.9% (297 of 334; 95% CI: 85.6, 92.2) for PE. Depending on the hospital, the median values for sensitivity were 57.7% for DVT (interquartile range, IQR, 48.6-66.7; intracluster correlation coefficient, 0.02; P=0.31) and 88.9% for PE (IQR, 83.3-96.3; intracluster correlation coefficient, 0.11; P=0.03). The sensitivity of ICD-10 codes was lower for surgical patients and for patients who developed PE or DVT while they were hospitalized. CONCLUSION ICD-10 discharge diagnosis codes yield satisfactory sensitivity for identifying objectively confirmed PE. A substantial proportion of DVT cases are missed when using hospital discharge data for complication screening or research purposes.

Compliance with recommendations of clinical practice in the management of venous thromboembolism in cancer: the CARMEN study.

UNLABELLED Cancer is associated with venous thromboembolism in 20% of patients. In such patients, thrombosis is difficult to treat, associated with bleeding, recurrence, and death. Specific treatments for venous thromboembolism in cancer are recommended. Guidelines have been implemented in many countries and international guidelines have been recently developed. We evaluated the adhesion to national French guidelines via a survey of cancer patients treated for venous thromboembolism. METHODS A national cross-sectional observational study evaluated the adhesion to guidelines in hospitalized patients. Good clinical practice was defined as initial 10-day treatment with injectable molecules followed by long-term treatment with low molecular weight heparin for at least 3 months. Demographic data, cancer type, stage, treatment, risk factors and type of thrombosis, were recorded. RESULTS Five patients were included in 47 centers. Overall adhesion to guidelines was present in 59% (55-63%) of patients (295/500). During initial treatment, adhesion was high (487/496; 98%) but dropped (296/486; 62%) during the long-term maintenance. In patients with renal insufficiency, only a fourth of them received the adequate treatment. A majority of patients had metastatic disease (64%). Cancer sites were gastro-intestinal (25%), gynecologic (23%), pulmonary (21%), hematological (14%), urologic (10%), or other (8%). Lung and hematological malignancies were significantly associated with the highest and lowest rates of adhesion. CONCLUSION Adhesion to national guidelines for treatment of venous thromboembolism in cancer is not optimal. Good compliance is observed during initial treatment, but drops after 10 days, underlying the need for further education to achieve a better implementation on a national level.

Accuracy of complete compression ultrasound in ruling out suspected deep venous thrombosis in the ambulatory setting - A prospective cohort study

Evidence on the safety of complete compression ultrasound for ruling out deep venous thrombosis (DVT) is derived from studies conducted in tertiary care centers, although most patients with suspected DVT are managed in the ambulatory office setting. It was the objective of this study to estimate the rate of venous thromboembolism when anticoagulant therapy is withheld from ambulatory patients with normal findings on a single complete compression ultrasound. As part of a prospective cohort study, 3,871 ambulatory patients with clinically suspected DVT were enrolled by 255 board-certified vascular medicine physicians practicing in private offices in France. Compression ultrasound of the entire lower extremities was performed using a standardised examination protocol. Anticoagulant therapy was withheld from patients with negative findings on compression ultrasound, and 1,254 of them were randomly selected for follow-up. The main outcome measure was the three-month incidence of symptomatic venous thromboembolic events confirmed by objective testing. DVT was detected in 1,023 patients (26.4%), including 454 (11.7%) and 569 (14.7%) cases of proximal and isolated distal DVT, respectively. Of the 1,254 patients with negative results sampled for follow-up, six received anticoagulant therapy during follow-up and five were lost to follow-up. Five of 1,243 patients (0.4%, 95% confidence interval [CI], 0.1-0.9) experienced non-fatal symptomatic venous thromboembolic events (pulmonary embolism in two patients and DVT in three patients) and eight of 1,254 patients (0.6%, 95% CI, 0.3-1.2) died during the three-month follow-up. In conclusion, anticoagulant therapy can be safely withheld after negative complete compression ultrasound without further testing in the ambulatory office setting.

Superficial vein thrombosis and recurrent venous thromboembolism: a pooled analysis of two observational studies

Summary.  Background:  The management strategies for symptomatic isolated superficial vein thrombosis (SVT) (without concomitant deep vein thrombosis [DVT] or pulmonary embolism [PE]) have yet to achieve widespread consensus. Concerns have been raised regarding the usefulness of prescribing anticoagulant treatments to all patients with isolated SVT. Determining the isolated SVT subgroups who have the highest risks of venous thromboembolism (VTE) recurrence (composite of DVT, PE, and new SVT) may facilitate the identification of patients who are likely to benefit from anticoagulant treatment.

Impact of anatomical location of lower limb venous thrombus on the risk of subsequent cancer

After a proximal deep-vein thrombosis (P-DVT), the risk of diagnosis of a previously unsuspected cancer is high. Isolated distal DVT (iD-DVT; i.e. infra-popliteal DVT without pulmonary embolism [PE]) and isolated superficial-vein thrombosis (iSVT; i.e. without concomitant DVT and PE) are at least as frequent as P-DVT but their association with subsequent cancer is uncertain. We exploited data from the OPTIMEV prospective, observational, multicentre study to i) compare the risk of subsequent cancer three years after a first objectively confirmed iSVT, iD-DVT and iP-DVT in patients without a prior history of cancer or of venous thromboembolism, ii) assess predictors of subsequent cancer in cases of iD-DVT. The overall cumulative rates of cancer among the 304 patients with iSVT, 536 patients with iD-DVT, and 327 patients with iP-DVT were similar (3.4% 95% confidence interval [1.8-6.2], 3.9% [2.5-5.9] and 3.9% [2.3-6.8], respectively), regardless of whether the index venous thromboembolic event was unprovoked or associated with a major transient risk factor. Neither anatomical (muscular vs deep-calf DVT) nor ultrasound scan characteristics (number of thrombosed veins, clot diameter under compression) seemed strongly associated with the risk of cancer in cases of iD-DVT. In patients managed in routine practice, all the different clinical expressions of lower limb venous thromboembolism are associated with a similar risk of subsequent cancer. From a clinical practice point of view, this suggests that cancer screening, without discussing the necessity, or not, of such screening, should not differ between a deep-proximal, deep-distal or superficial location of thrombosis.

Optimisation de l'interrogatoire dans l'évaluation du risque de maladie thromboembolique veineuse : L'étude optimev

Resume La maladie thrombo-embolique veineuse est une affection repandue. Bien que les formes cliniques, les methodes diagnostiques, et les traitements de cette pathologie aient recemment evolue, la plupart des etudes concernant ses facteurs de risque sont anciennes, conduites en milieu hospitalier et souvent non adaptees aux formes actuelles de la maladie. Dans cet article, nous decrivons le rationnel, les objectifs et la methodologie de l’etude OPTIMEV (OPTimisation de l’Interrogatoire pour la Maladie thromboEmbolique Veineuse). Rationnel Les facteurs de risque de la maladie thromboembolique veineuse (MTEV) sont multiples, complexes, associes entre eux, la question de leur signification clinique se pose. Nous avons effectue une analyse bibliographique systematique entre 1972 et 2005 des articles originaux, essais, description de cohortes ou meta-analyses decrivant les facteurs de risque et avons choisi les themes de travail suivants : l’antecedent de MTEV, la chirurgie, le cancer, l’immobilisation, l’âge, les facteurs biologiques ainsi que d’autres facteurs moins valides ou des facteurs protecteurs. Quatre-vingt-quatre articles ont ete retenus et analyses. Pour chacun de ces themes, une evaluation du risque a ete presentee (odds ratio) et les questions non resolues ont ete posees. Objectifs L’objectif principal de l’etude OPTIMEV est de redefinir et preciser la place actuelle des differents facteurs de risque de MTEV accessibles a l’interrogatoire pour prendre en compte les changements survenus depuis leur identification. Les objectifs secondaires sont 1) de determiner si les memes facteurs de risque doivent etre recherches a l’interrogatoire pour l’evaluation du risque de MTEV quelle que soit sa topographie (thrombose veineuse profonde TVP. distale, proximale, musculaire, ou embolie pulmonaire) ; 2) si les facteurs de risque different entre les patients vus en ville et ceux vus a l’hopital. Une des hypotheses de l’etude est que les facteurs de risque communement admis ne s’appliquent pas aux TVP distales. Methodes L’etude OPTIMEV est une etude prospective multicentrique avec suivi longitudinal de 10 000 patients inclus par les medecins vasculaires francais liberaux et hospitaliers. Sont eligibles tous les patients avec une suspicion de MTEV adresses dans les centres participants sur une periode donnee. Les caracteristiques, facteurs de risque, et les resultats des examens paracliniques sont recueillis a l’inclusion par l’investigateur a l’aide d’un cahier d’observation electronique. Le 1er juin 2005, 4 173 patients ont ete inclus. Un suivi longitudinal avec recueil de criteres de jugement cliniques (deces, recidive de MTEV, accident hemorragique, cancer) est effectue a 3 mois et un an par telephone. Le promoteur de l’etude est la Societe Francaise de Medecine Vasculaire. L’organisation a ete confiee au Centre d’Investigation Clinique du CHU de Grenoble. Cette etude a recu un soutien financier du Programme Hospitalier de Recherche Clinique et du Laboratoire Sanofi Aventis France qui fournit egalement un soutien logistique. Un comite scientifique independant a ete mis en place pour veiller au bon deroulement de l’etude et pour decider de l’utilisation des donnees obtenues. Discussion Les resultats de l’etude OPTIMEV montreront comment apprehender le risque thrombo-embolique veineux en consultation. De nouveaux outils seront developpes pour evaluer la probabilite clinique de MTEV en tenant compte de sa topographie. Les resultats finaux seront presentes courant 2006. (J Mal Vasc 2005 ; 30 : 217-227).