The management and outcome of acute venous thromboembolism: a prospective registry including 4011 patients☆
Article Outline
Abstract
Objective
To obtain a realistic overview of management and clinical outcomes of patients with venous thromboembolism (VTE) in Spain on the basis of data from a national multicenter registry.
Methods
A prospective registry was initiated in Spain in March 2001. Data were collected from patients with objectively confirmed deep vein thrombosis (DVT) and/or pulmonary embolism (PE) and entered into the online registry by physicians who were responsible for the management of these patients.
Results
As of August 2002, 4011 patients with confirmed VTE were included in the registry: 60% with DVT, 23% with PE, and 17% with both DVT and PE. Diagnostic methods for VTE included compression ultrasonography (86%), venography (10%), V/Q lung scans (42%), computed tomography scan (28%), and pulmonary angiography (0.9%). D-dimer testing was performed in 61% of cases and was positive in 92% of patients with confirmed VTE. The majority of DVT (95%) were located in the lower extremities (82% proximal and 4% bilateral), while 4.8% were located in the upper extremities or neck veins. Most patients (90.5%) were admitted to hospital. In the acute phase, treatment consisted of low molecular weight heparin (LMWH) in 88%, unfractionated heparin (UFH) in 11%, and fibrinolysis in 0.8%. Cava filters were inserted in 2% of patients, mainly because of active bleeding (13%), increased hemorrhagic risk (38%), or recurrent VTE (29%). Absolute bed rest was recommended to 63% of patients. Secondary prevention of VTE included oral anticoagulants (75%) and LMWH (24.5%). Therapeutic compression stockings were prescribed to 53% of patients at the time of hospital discharge. Regarding the main clinical outcomes during an average (±SD) follow-up period of 156 ± 95 days, 19% had adverse events: 12.5% of patients died, 5.5% had clinically confirmed VTE recurrence, and 9.8% suffered bleeding complications (44% with major bleeding).
Conclusions
This prospective observational multicenter registry provides a large database reflecting the actual day-to-day clinical practice regarding VTE management in a European country. The most important findings were the increasing use of spiral computed tomography for PE diagnosis, the unexpectedly high proportion of patients admitted to hospital despite the use of LMWH in almost 90% of cases in the acute phase, and the utilization of LMWH for secondary prevention in almost 25% of cases. On the other hand, this large-scale prospective registry permits on-line consultation of high-risk situations to assess how difficult cases were treated and what their outcomes were. This will provide a most useful tool for the practicing physician responsible for the management of VTE patients.
Venous thromboembolism (VTE) remains an important cause of morbidity and mortality in western countries. According to population-based studies conducted in North America and Europe,1, 2, 3, 4 the annual incidence of this disease is between 1000 and 2000 per year, and more than one third of these cases represent recurrent disease.3 A 25-year population-based study has reported that although the incidence of pulmonary embolism (PE) has decreased over time, the incidence of deep vein thrombosis (DVT) remains unchanged for men and is increasing for older women.5
The natural course of untreated VTE is unfavorable, especially in patients with PE; in a trial performed in 1960, approximately 25% of these patients died, whereas another 25% experienced nonfatal recurrent VTE .6 The introduction of anticoagulant therapy with heparin and warfarin has substantially reduced the mortality and morbidity associated with this disorder, as shown by many randomized controlled trials.7 However, inclusion of patients into controlled studies entails a careful screening process that results in the exclusion of patients at very high risk of developing complications,8, 9 as well as selection bias.
At the present time, there is limited information on how patients with VTE are currently managed in Spain10, 11 and how consistently the recommendations from clinical trials are implemented in clinical practice. The National Registry of Venous Thromboembolism in Spain or RIETE (Registro Informatizado de la Enfermedad TromboEmbólica) is an ongoing national, prospective, and observational study that, since March 2001, has tracked practice patterns and outcomes of more than 4000 patients with acute symptomatic VTE enrolled at 81 selected hospitals throughout Spain.
Methods
Objectives of the registry
The main objective of this registry is to collect prospective data on the epidemiologic characteristics, management, and outcomes of patients with acute symptomatic VTE that can be used to (1) obtain a realistic profile and overview of patients with VTE and data on existing and evolving patterns in clinical practice in the management of patients with this disorder; (2) identify gaps between recommendations based on clinical trials and real day-to-day practice; (3) locally assess individual hospital practice and outcomes to facilitate quality improvement; and (4) create predictive models to assist physicians in making decisions in difficult cases.
Registry design
The RIETE initiative is a national, multicenter, prospective, and observational registry sponsored by Aventis Pharma (Madrid, Spain) that gathers and analyzes data on patients with confirmed VTE (DVT or PE) initially diagnosed in any of the 81 participating hospitals, which represent approximately 8.8% of the 900 Spanish hospitals. These hospitals were selected by the scientific advisory committee on the basis of the presence in these institutions of physicians with experience in the management of VTE patients. These physicians were invited to be local clinical coordinators for the study. Hospitals of all levels and those distributed geographically in all Spanish regions were included in the study.
Patient management is decided by the physicians without any imposed intervention in order to collect data reflecting the actual clinical approach to the management of VTE. The database consists of different sections that include patient demographics; symptoms upon presentation; presence of DVT, PE, or both; location of thrombi; diagnostic methods used and their results; risk factors; and treatment, in both the acute phase (first 10 days of therapy) and for subsequent secondary prevention.
Outcomes
Main outcomes from March 2001 to August 2002 were recurrent VTE, bleeding complications, and mortality. All adverse events occurring during at least a 3-month follow-up period were analyzed. Local coordinators at each participating hospital were responsible for the 3-month follow-up after VTE diagnosis. In most cases, they reviewed the hospital charts and examined patients in the outpatient clinic. If this was not possible, they talked to the patients by phone and, when this was not feasible, contacted their family physicians by phone, fax, or e-mail to get reliable information on the development of adverse events. After discharge, each patient was followed up by a family physician and was contacted by letter or phone at 3 months.
Diagnostic studies were performed only in clinically suspicious cases and not on selective cases or symptom-free patients. Diagnosis of DVT was based on the absence of full compression on venous ultrasound scan or on the presence of a filling defect on venography. Diagnosis of PE was based on high-probability ventilation-perfusion scan, spiral computed tomography (CT), or contrast pulmonary angiography. Recurrent DVT was defined as an extension of thrombus or development of new thrombus in a previously unaffected vein segment detected by ultrasound scan or venography. Recurrent PE was defined by the presence of new segmental perfusion defects compared with the previous studies. Bleeding complications were classified as major if transfusion of more than two units of packed red blood cells was required, if the patient had to be admitted to hospital for this reason, or if the patient's life was at risk. As this is an observational prospective registry, there is not a central clinical events committee. However, all of the adverse events (recurrent VTE, bleeding, and death) are entered into the database by the coordinator at each hospital and analyzed by the Study Coordinating Center.
Data collection
Patients with symptomatic, acute DVT or PE confirmed by objective testing who meet the predefined enrollment criteria are considered eligible for inclusion into the registry. A registry coordinator at each participating hospital records data from each patient onto a computer-based case report form (CRF). They interact with the physicians who are responsible for the management of VTE patients and who have volunteered to participate in the study. In addition, coordinators are instructed to ensure that consecutive patients with confirmed VTE are included in the registry. Once completed, the information is transferred online to the Study Coordinating Center (S & H Medical Science Service, Madrid, Spain) responsible for all data management. Patient identities remain confidential because they are identified by a unique number assigned at the time of enrollment by the Study Coordinating Center. The Study Coordinating Center is not connected in any way with Aventis, which serves only as sponsor to the study by means of an educational grant and does not have access to the data. Data submitted through the Internet are sent via a secure website. This website (http://www.riete.com) is currently written in Spanish, but there are plans to translate it into English in the near future.
The need to obtain informed consent from patients to participate in the registry varies depending on the requirements of individual hospital ethics committees. Participation in the registry is voluntary, and hospitals are encouraged to enter consecutive patients with confirmed DVT (venography, ultrasound scan, or plethysmography) or PE (ventilation/perfusion lung scans, spiral CT angioscan, or pulmonary angiography), irrespective of management strategy and outcome. During the enrollment period, hospitals are asked not to enter patients participating in clinical trials, so that the registry will reflect actual clinical practice rather than management mandated by a clinical trial protocol. Patients for whom a 3-month follow-up would not be possible are also excluded.
Quality control
Before entering data into the registry, the clinical coordinator at each participating hospital receives a training manual explaining how to complete the CRF and how to define each variable. Periodic meetings of registry coordinators, members of the Study Coordinating Center, and a scientific advisory committee are held.
Data quality is monitored electronically to detect abnormal variables, inconsistencies, and errors, and questions are either sent via e-mail or telephoned to the local coordinators for resolution. In addition, full audits are periodically performed.
Statistical methods
Differences between groups are assessed by the χ2 test or Fisher exact test for categorical variables and by the two-sided t test for continuous variables. For all analyses, a two-tailed P value of less than .05 is considered to indicate statistical significance.
Results
From March 2001 to August 2002, 4011 patients with confirmed symptomatic VTE were enrolled from 81 contributing hospitals throughout Spain. Enrollment continues and is currently proceeding at a rate of approximately 300 new patients per month. Of the 4011 consecutive VTE patients included in the registry, 2017 (50.3%) were women and 1994 (49.7%) were men. The average age was 66 ± 17 years, and weight and height were 74 ± 14 kg and 164 ± 9 cm, respectively.
To date, 2402 patients (60%) were found to have isolated DVT, 922 (23%) were found to have isolated PE, and 687 (17%) were found to have both PE and DVT. The most common signs and symptoms upon presentation to hospital were limb swelling and pain for DVT and dyspnea and chest pain for PE. Among patients with confirmed PE without DVT symptoms, a diagnostic test for DVT was performed in 54% and had positive results in 36%. On the other hand, among patients with confirmed symptomatic DVT without symptoms of PE, a diagnostic test for PE was completed in 16% and confirmed the presence of PE in 30%.
At the time of VTE diagnosis, 264 patients (6.6%) were inpatients and the remaining 3747 (93.4%) were outpatients. Of these, 3394 (90.5%) were admitted to hospital and 353 (9.5%) were discharged from the emergency department without hospital admission. Table I shows the proportion of patients admitted and discharged and the final diagnosis.
Table I. Distribution of admitted and ambulatory patients and VTE diagnosis
| Admitted to hospital | Ambulatory treatment | |
|---|---|---|
| DVT alone | 1934 (85%) | 335 (15%) |
| PE alone | 882 (99%) | 8 (0.89%) |
| DVT and PE | 578 (98.2%) | 10 (1.7%) |
Thrombi were located in the lower extremities in 2941 cases (95.2%) and in the upper extremities in 148 patients (4.8%). Among those with leg DVT, 55% were in the left limb, 42% were in the right limb, and 3% were bilateral. In the upper extremities, 50% were located in the right arm, 45% in the left arm, and 5% were bilateral (P = .05). Forty-one percent of upper-extremity DVTs were related to the presence of a central catheter, and 29% were considered idiopathic. Among patients with leg DVT, 82.5% were proximal (affecting the popliteal, femoral or iliac veins) and 17.5% were limited to the calf veins.
Ventilation-perfusion lung scanning was performed in 1246 patients (31%) with suspected PE. The results were high probability in 63%, nondiagnostic in 27%, and normal in 10%. Spiral CT was performed in 821 cases (20%) and was high probability for PE in 87%. Conventional contrast pulmonary artery angiography was completed in 27 patients (0.6%) and was considered high probability in 81.3%.
Ultrasound scanning of the lower or upper extremities was done in 3270 patients (81%) and was diagnostic for DVT in 87%. Venography was performed in 338 patients (0.8%) and confirmed DVT in 91%. Impedance plethysmography was used in 16 cases (0.4%) for diagnosis.
D-dimer was analyzed in 2263 patients (56%) with confirmed VTE and was positive in 2087 (92.2%) and negative in 176 cases (7.8%). D-dimer was positive in 79.3% of patients with upper extremity DVT and in 93.3% in those with leg DVT (P = .001). Approximately 10 different D-dimer tests were used in the participating hospitals; 56% were based on immunologic assays and 44% on agglutination techniques.
The main risk factors detected in patients with confirmed VTE (PE, DVT, or both) were immobilization lasting more than 4 days in the previous 2 months (31%), cancer (20.5%), varicose veins (20%), history of VTE (17.5%), surgery in the past 2 months (14.6%), travel by plane or car lasting longer than 6 hours in the past 3 weeks (0.9%), estrogen therapy (6.1%), pregnancy (5%), postpartum (5.5%), and known thrombophilia (2.1%). The main reasons for nonsurgical immobilization were neurologic problems (7%), lower extremity trauma (5%), acute infection (3.5%), respiratory problems (3%), and cancer (2%).
Among surgical patients with VTE, 66% received prophylaxis. Only 23% of immobilized patients presenting with VTE had received prophylaxis. The doses and duration of prophylactic low molecular weight heparin (LMWH) in patients who developed VTE were 3824 units per day for an average of 19.8 days for immobilized nonsurgical patients and 3870 units per day for 14.5 days in patients with previous surgery. Venous thromboembolism was considered idiopathic in 46% of patients because risk factors were not identified. Thrombophilia was sought in 18% of patients and identified in 35%. The distribution of risk factors in patients with upper-extremity or leg DVT (without PE) is shown in Table II. No significant differences were identified for varicose veins, travel, and pregnancy.
Table II. Risk factors in patients with upper- and lower-extremity deep vein thrombosis
| Lower- extremity | Upper- extremity | P | |
|---|---|---|---|
| Age | 66 ± 2 | 55 ± 3 | <.001 |
| Immobility | 31% | 14% | <.001 |
| Cancer | 20% | 32% | <.01 |
| Colorectal | 14% | 14.4% | .8 |
| Breast | 28% | 45% | .11 |
| Lung | 8% | 18.5% | .02 |
| Prostate | 21% | 15% | .38 |
| Surgery | 13.3% | 13.9% | .83 |
| Previous VTE | 18.7% | 5.4% | <.01 |
| Estrogens | 5.5% | 13% | <.05 |
| Pregnancy | 11.5% | 0 | <.05 |
In the acute phase, during the first 10 days of treatment, most patients received therapy with LMWH (88%); 485 were treated with unfractionated heparin (11%) and 35 with fibrinolysis (0.8%). Among patients with confirmed PE, 24 (1.5%) received fibrinolysis. Cava filters were inserted in 85 patients (2%), of which 86% were permanent and 14% removable. The main reasons for using filters in this phase were high risk of bleeding (38%), recurrent VTE (28.6%), bleeding during treatment (13%), and need for surgery (11.7%). Pulmonary artery thromboembolectomy was performed in 8 cases (0.02%). With respect to ambulation, 63% of patients were kept at absolute bed rest, 31% were allowed limited mobility, and 6% were fully ambulated.
During the subsequent chronic phase of treatment (secondary prevention), 2813 patients (74.8%) received oral anticoagulants, 921 (24.5%) patients received LMWH, and 26 (0.7%) received subcutaneous unfractionated heparin. In this phase, 46 patients (1.3%) had cava filters placed. The main reasons for filter placement were active bleeding (36%), recurrent VTE (25%), need for surgery (19.4%), and high risk of bleeding (8.3%). Elastic stockings were prescribed for 1548 patients (53% of 2921, with information about stocking use). The pharmacologic treatment used in upper- and lower-extremity DVT is detailed in Table III.
Table III. Pharmacologic treatment used in the acute and chronic phases in patients with upper- and lower- extremity deep vein thrombosis
| Acute phase | Upper-extremity | Lower-extremity | P |
|---|---|---|---|
| LMWH | 91% | 93% | .3 |
| Unfractionated heparin | 7% | 6.3% | .9 |
| Fibrinolysis | 2% | 0.2% | .001 |
| Chronic phase | Upper-extremity | Lower-extremity | P |
| LMWH | 43.8% | 28% | .001 |
| Unfractionated heparin | 0 | 0.2% | .001 |
| Oral anticoagulation | 56% | 71.4% | .001 |
As of August 2002, 2408 patients had completed the 3-month follow-up and 1603 had not completed the follow-up or the data were in the course of being uploaded. During the 3-month follow-up period, 237 patients had bleeding complications (9.8% of 2408 patients with complete follow-up). Major hemorrhage occurred in 43.7% and minor in 56.3% of patients with bleeding. In more than half of these patients, bleeding was located in the gastrointestinal or urinary tracts.
During the chronic treatment phase, 60% of bleeding complications occurred in patients receiving oral anticoagulants and 40% in patients receiving LMWH.
Recurrent VTE was diagnosed in 130 patients (5.5% of 2378 with complete follow-up information). Overall, 301 patients died during follow-up for different reasons (12.5% of 2413 with complete information). Of these, 21 patients died as a result of PE (7%) and 60 because of bleeding problems (20%). Table IV details the proportion of adverse events documented in patients with isolated DVT or with PE (alone or with DVT). There was a significantly higher incidence of death and bleeding in patients who were found to have PE at presentation than in those who presented with isolated DVT without concomitant PE.
Table IV. Rates of adverse events in patients with isolated DVT or with PE (alone or with DVT)
| DVT alone | PE (± DVT) | P | |
|---|---|---|---|
| Death | 10.6% | 14.8% | .03 |
| Recurrent VTE | 6.5% | 5.2% | .7 |
| Bleeding | 8.5% | 11.7% | .01 |
Discussion
To our knowledge, this registry is the largest prospective database collecting patients with confirmed VTE. As there is not a selection process, all patients with DVT or PE are included irrespective of the location of DVT, comorbid conditions, prognosis, treatment, or outcome.
The RIETE initiative consists of a registry, and the data reported are not from a prospective, randomized, controlled trial. As in most similar registries,8, 9, 12, 13, 14 neither diagnostic evaluations nor therapy are controlled. Therefore, the strength of this ongoing registry is the prospective collection of data reflecting real practice from a very large sample of patients with documented VTE management in hospitals throughout Spain.
There are several limitations of the RIETE registry that should be acknowledged. First, the participating registry hospitals are not necessarily representative of all Spanish hospitals and probably reflect practice from physicians with particular interest in VTE who volunteered to participate in the registry. However, 40% of the participating hospitals are the largest hospitals in Spain and responsible for the care of approximately 25% of the Spanish population. This could provide a good estimate of current clinical management of VTE. Second, the registry is an observational database, and accordingly, its value is to document practice patterns and temporal trends rather than to compare outcomes of patient subgroups. The main interest of this study is to provide information on current “real world” practice, which may be important to recognize gaps between information obtained from clinical trials and real practice.
The age of patients in our registry is similar to the age reported in other series from Sweden,1 France,2 and the United States.8 With respect to the distribution of DVT and PE in our series, it matches the distribution reported in a recent French population-based study2 with 627 patients, where 67% had isolated DVT, 14% had isolated PE, and 19% had DVT and PE. An interesting finding has been the low rate of patients admitted to hospital for other reasons at the time of VTE diagnosis (6.6%), which indicates that most patients are at home (or discharged from hospital) when VTE occurs.
Data on diagnostic testing reflect the relative use of these tests in cases with confirmed VTE, but they do not provide any information regarding their accuracy. The use of ultrasound scans in 86% of patients for the diagnosis of DVT is in agreement with published reports that demonstrate that this test is very reliable for the diagnosis of symptomatic DVT.15, 16 Venography was used in 36% of patients with confirmed upper-extremity thrombosis. This invasive test remains the most valuable diagnostic tool for this problem, although experience with noninvasive techniques, such as duplex ultrasound scanning, is rapidly evolving. The low incidence of calf DVT in this study could be attributed to the fact that most early calf thrombi are initially asymptomatic. Those thrombi progressing to proximal veins are responsible for most of the symptoms.
Most patients underwent lung scintigraphy (perfusion or ventilation-perfusion scans) for PE diagnosis. The results of this test in our patients, with 62% high-probability scans, is slightly lower than the 77% reported by the International Cooperative Pulmonary Embolism Registry (ICOPER) registry.12 The recent advent of spiral or helical CT is gradually replacing pulmonary angiography, and data from our registry reflect this new approach.17 D-dimer testing was negative in almost 8% of patients with confirmed VTE (sensitivity 92%). These results are similar to other reports that show sensitivities between 80% and 95% for agglutination techniques and up to 97% for ELISA testing.18
The high proportion (46%) of VTE patients without detectable thrombosis clinical risk factors is similar to the 50% reported by Cogo in Italy in a group of symptomatic DVT outpatients.19 The risk factors more frequently found in our patients were immobility, cancer, previous VTE, and recent surgery, which are comparable with the factors reported in population-based series from Sweden1 and the United States.20
Two thirds of patients with VTE and recent surgery and less than one quarter of nonsurgical immobilized patients who were bedridden received prophylaxis. This indicates that prophylaxis failed in many surgical patients and that most nonsurgical patients at risk do not receive any prophylaxis. The problem of low implementation of prophylaxis in surgical patients has been reported recently by other investigators from the United States21, 22 and Brazil.14 On the basis of these data, quality improvement should emphasize the importance of implementing more intensive prophylaxis among high-risk patients.
A surprisingly low number of patients received inferior vena cava filters (2%), which is noticeably lower than the 18% reported for patients with DVT in Boston8 or the 10% from the ICOPER study in patients with PE.12 In the only randomized study of filter placement in patients with isolated proximal DVT,23 the device did not prolong survival after a first episode of DVT, although it reduced the rate of PE. This benefit was offset by a higher recurrent DVT rate.
During the initial acute treatment phase, most patients received LMWH, as these heparin fragments have become the standard therapy for VTE in most European countries and North America. Yet, we were surprised by the high proportion of patients who were admitted to the hospital for VTE treatment, despite evidence supporting the home treatment of both DVT and PE.7, 24, 25, 26 However, it is possible that a few patients with isolated DVT could have been discharged from the emergency department in some of the participating hospitals for ambulatory treatment. Therefore, the actual percentage of patients with isolated DVT being admitted to hospital could be lower.
We estimate that almost 25% of patients included in the registry had underlying conditions or comorbidities (recent bleeding, cancer, pregnancy, and renal failure) that put them at risk to develop bleeding complications. This could explain the high rate of patients—56% of upper-extremity DVT and 71% of lower-extremity DVT—who received secondary prophylaxis with LMWH instead of oral anticoagulation. Besides, these fractionated heparins are also safe and effective for the long-term treatment of these difficult cases.
Another significant gap between published studies and current practice in the registry hospitals was the high proportion of VTE patients who were kept bedridden. According to the results of two prospective studies, early ambulation is safe to recommend as routine in most DVT patients.27, 28
The incidence of adverse events during the 3-month follow-up period is similar to the rates reported by Prandoni et al29 in a prospective cohort study of patients with a first episode of symptomatic DVT. The incidence of bleeding complications and recurrent VTE in that study was 9.8% and 4.9% 3 months after DVT diagnosis. In our registry, these events were reported in 9.8% and 5.5% of patients, respectively. Major bleeding occurred in 4% of patients in our series, which is slightly higher than the .5% to 3% reported in controlled trials, where some high-risk patients were excluded.30 The mortality rate in our patients (12.5% at 3 months) is lower than the 14% in-hospital mortality rate from a Japanese registry of patients with PE31 and 17.4% from the ICOPER study.12 In our patients, only 25% of deaths were attributed to VTE or bleeding complications and most patients died from reasons unrelated to VTE. This has also been reported by another study that indicated that 15% of deaths in patients with suspected PE were attributable to PE.32 Factors associated with adverse outcome are cancer, heart failure, previous VTE, hypotension, and hypoxemia.33 Other studies have suggested that patients who are initially found to have PE have a higher risk of developing recurrent pulmonary embolism compared with patients with DVT alone.10, 34, 35 Although in our patients the rate of recurrent VTE was similar in patients with DVT and PE, the incidence of mortality and bleeding complications during the 3-month follow-up was significantly higher in patients with confirmed PE (with or without DVT) than in patients with isolated symptomatic DVT. It is important to notice that in this registry, the incidence of adverse events reflects early symptomatic problems developing within 3 months of VTE diagnosis. A longer follow-up would probably increase the incidence of VTE recurrences, bleeding complications, and mortality.
On the basis of the initial success of our registry, with more patients enrolled than we initially anticipated, an international registry could be organized with a similar structure to undertake a more representative investigation of unselected patients with VTE, to elucidate the risk factor profiles for this disorder, and to find predictors for the outcome of a thromboembolic event in different types of patients.
Acknowledgements
Members of the RIETE Group who have included at least 20 patients in the registry are as follows: D. Adarraga (Jaén), J. Alegre, J. Bugés, C. Falgá, J. Mateo, M. Monreal, E. Raguer, A. Raventós, J.M. Segalés, C. Tolosa (Barcelona), J. .I Arcelus, J. Trujillo (Málaga), R. Barba, I Candel, J. del Toro, C. Cervera, C. Fernández Capitán, P. Rondón, C. Suárez (Madrid), J. L. Beato (Albacete), A. Blanco, L. López (Córdoba), T. Bosch (Palma de Mallorca), J. Bosco, P. Gallego, M.J. Soto (Cádiz), F. Gabriel, E. Grau, P. Román, J.A. Todolí (Valencia), F. García Bragado, S. Soler (Girona), J.A. González-Fajardo (Valladolid), S. Herrera, M.A. Page (Murcia), J.M. Llaneza, J. López, I. López, S. Rubio (Asturias), J. Lasierra (Logroño), J.L. Lobo (Vitoria), P. López-Beret (Toledo), A. Maestre, S. Reus (Alicante), C. Panizo, A.L. Sampériz, G. Tiberio (Navarra), J. Portillo (Ciudad Real), J. Montes (Vigo), J. Moreno (Segovia), J.A. Nieto (Cuenca), R. Otero (Sevilla), J.L. Pérez Burkhardt (Tenerife), J. Rodríguez (Gran Canaria), D. Sánchez (Avila), JF. Sánchez (Cáceres), A. Sánchez (Salamanca), R. Segura (Coruña), F. Uresandi (Bilbao), R. Valle (Santander), and F. Pajuelo (Medical Department, Aventis Pharma, Madrid).
We express our gratitude to “S & H Medical Science Service” for its logistic and administrative support.
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☆ Competition of interest: Drs Arcelus, Suárez, Monreal, and González-Fajardo are occasionally consultants for Aventis.Supported by Aventis Pharma with an unrestricted educational grant.
PII: S0741-5214(03)00789-4
doi:10.1016/S0741-5214(03)00789-4
© 2003 The Society for Vascular Surgery and The American Association for Vascular Surgery. Published by Elsevier Inc. All rights reserved.
