Keywords
venous thrombosis - deep vein thrombosis - pulmonary embolism
Introduction
Venous thromboembolism (VTE) is an important preventable cause of in-hospital death.[1]
[2]
[3] VTE including deep vein thrombosis (DVT) and pulmonary embolism (PE) afflicts an
estimated 1,000,000 new cases annually in Europe and the United States, combined.[4]
[5]
[6] Among survivors, VTE is associated with recurrent events, post-thrombotic syndrome,
pulmonary hypertension and bleeding events (as a result of anticoagulant therapy),
all of which contribute to the high burden of the disease.[7]
[8]
However, contemporary aspects of VTE presentation, pattern of care, and outcomes are
understudied. Published epidemiological studies are generally limited by small size,
data age (representing a different era of diagnosis and treatment)[9]
[10] or lack of detailed clinical data.[11]
[12] Clinical trials have also faced challenges in providing adequate evidence base,
with ethical and feasibility issues limiting recruitment for some important conditions
(e.g. PE with hemodynamic instability, or VTE among those with recent bleeding),[13] and underrepresentation of many key subgroups (such as the elderly, pregnant patients,
and those with high risk of bleeding) that limit the availability and generalizability
of the evidence. These issues have led to a growing unmet imperative for evidence
from large groups of patients without numerous exclusions.[14] Contemporary information to characterize the modern-day presentation, risk factor
profile, treatment and outcomes of patients can inform practice and policy, preventing
unnecessary harm, and bringing novel hypotheses for future research and improving
quality and outcomes.[15]
[16]
[17]
[18]
The Registro Informatizado Enfermedad TromboEmbolica (RIETE) is a large prospective registry initiated to address these unmet needs
and has been enrolling patients with objectively confirmed VTE since 2001. Several
of the resultant studies have provided a better understanding of the epidemiology,[19]
[20] common treatment patterns,[21]
[22] and outcomes[23]
[24] of patients with VTE and the key understudied clinical subgroups.[25]
[26]
[27] In response to continued and expanding investigations from RIETE, herein we provide
an overview of the design, methodology, possible and future directions of the registry.
Methods
RIETE is an ongoing, prospective multicentre multinational observational study of
patients with objectively confirmed acute VTE. The registry was originally started
in Spain in 2001 with the goal of gathering a large sample of patients with VTE, with
specific attention to those excluded from the typical randomized trials of anticoagulant
therapy (e.g. those with severe renal insufficiency, liver failure, recent major bleeding,
pregnancy, disseminated cancer, thrombocytopenia and the elderly) with an aim to understand
their common presentation, management pattern and outcomes, as well as factors associated
with better or worse patient outcomes. The hope was also to use the hypothesis-generating
findings to help design new randomized clinical studies.
With successful recruitment of an increasing number and diversity of patients over
time, the numbers of retrieved variables and data elements were progressively increased.
The platform, including the electronic data entry system, was translated to English
from 2006 and the network expanded to other participating centres. As of June 30,
2017, RIETE includes 207 investigators from 179 participating centres. RIETE is registered
at Clinicaltrials.gov (NCT: 02832245). Detailed information about participating centres
is also available at the registry Web site: https://www.riete.org/.
Patients, Inclusion and Exclusion Criteria
At each participating site, patients are screened by the site investigators and checked
for eligibility ([Table 1]). All patients are objectively confirmed with acute symptomatic or asymptomatic
VTE (i.e. DVT, PE, or both). More recently, in an attempt to similarly understand
the presentation, treatment pattern, and outcomes of other thrombotic conditions,
RIETE has also started to enrol patients with superficial vein thrombosis, splanchnic
vein thrombosis (i.e. thrombosis involves the mesenteric, splenic or portal veins),
retinal vein thrombosis and cerebral vein thrombosis. At each participating centre,
every attempt is made to enrol consecutive patients and RIETE investigators are committed,
by contract agreement, to enrol consecutive patients. Periodic audits of the sites
have confirmed consecutiveness. Further, comparison against the Spanish Ministry of
Health database has shown that patients in RIETE have similar characteristics to the
data from all-comers with VTE in that database.[28] No duplicate entries are permitted and patients who are enrolled in blinded treatment
trials are ineligible.
Table1
Inclusion and exclusion criteria for RIETE
|
Inclusion criteria
|
|
Acute objectively confirmed DVT or acute objectively confirmed PE[a]
[b]
|
|
Availability of data for at least 54 core variables and minimum of 3-mo follow-up
|
|
Exclusion criteria
|
|
Enrolment in any treatment trial (VTE or other conditions) in a blinded fashion
|
|
Previous enrolment in the registry
|
|
Lack or withdrawal of patient consent
|
Abbreviations: DVT, deep vein thrombosis; PE, pulmonary embolism; RIETE, Registro Informatizado Enfermedad TromboEmbolica (also known as the Computerized Registry of Patients with Venous Thromboembolism);
VTE, venous thromboembolism.
a Not mutually exclusive (i.e. patients may have both DVT and PE but will not be double
counted).
b In more recent years, those with superficial vein thrombosis, splanchnic vein thrombosis
(i.e. thrombosis involves thrombosis in the mesenteric, splenic or portal veins),
retinal vein thrombosis and cerebral vein thrombosis have been separately enrolled.
Methods of DVT diagnosis include contrast venography, ultrasonography, magnetic resonance
or, rarely in the past, plethysmography (only 172 patients in the entire cohort).
PE is diagnosed on the basis of pulmonary angiography, contrast-enhanced computed
tomography (CT) of the chest (specifically CT pulmonary angiography), lung scintigraphy
or rarely on the basis of confirmed DVT in patients with signs and symptoms of PE.
RIETE, by design, does not currently enrol patients with intracardiac thrombi in the
absence of VTE. As of 30 June 2017, a total of 72,107 valid patients with acute VTE
have been enrolled in RIETE. Currently, RIETE has 179 participating sites from 24
countries and across 3 continents. There has been a growth, over time, in the number
of involved sites and countries ([Fig. 1A, B]).
Fig. 1 Participating countries in RIETE in 2001 (A) and 2017 (B).
Data Elements
Key data elements in RIETE include demographics, VTE risk factors and comorbidities
(such as presence or absence of immobility, hormonal therapies, pregnancy and puerperal
state, recent surgery, active cancer, heart failure, chronic lung disease, renal and
liver function, prior VTE, prior bleeding episodes, dementia, depression, autoimmune
disorders, gastroduodenal ulcer, inflammatory bowel disease and others). It also includes
concomitant medications (such as antiplatelet agents, corticosteroids, nonsteroidal
anti-inflammatory drugs, erythropoietin, statins and psychotropic drugs) and disposition
status (inpatient vs. outpatient). Test results (common blood tests [including plasma
haematocrit, platelet count, creatinine and others], cardiac biomarkers [including
troponin, CK-MB and B-type natriuretic peptide], electrocardiography [including the
rhythm, presence of right bundle branch block, S1Q3T3 patter and others], ultrasonography,
echocardiography, CT scan) and therapies (including antithrombotic medications and
advanced therapies such as thrombolytic therapy, surgical thrombectomy and inferior
vena caval filter placement; [Table 2]) are separately recorded.
Table 2
Select list of data elements
|
Patients with available values (N)
|
DVT cohort
|
PE cohort
|
Other patients[a]
|
Total
|
|
Patients (%)
|
72,107
|
33,150
|
35,745
|
3,212
|
72,107 (100%)
|
|
Disposition (inpatient vs. outpatient)
|
70,122
|
8,228 (25.5%)
|
10,872 (31.3%)
|
794 (25.4%)
|
19,894 (28.4%)
|
|
Demographics
|
|
Male (%)
|
72,107
|
17,019 (51.3%)
|
16,668 (46.6%)
|
1,684 (52.4%)
|
35,371 (49.1%)
|
|
Age (y ± SD)
|
72,107
|
63.5 ± 18
|
67.3 ± 17
|
63.5 ± 15.4
|
65.4 ± 17.5
|
|
Body mass index (kg/m2)
|
50,118
|
27.6 ± 5.2
|
28.2 ± 5.7
|
27 ± 5.2‡
|
27.8 ± 5.5
|
|
Underlying conditions
|
|
Chronic lung disease
|
72,107
|
2,800 (8.4%)
|
5,112 (14.3%)
|
326 (10.1%)
|
8,238 (11.4%)
|
|
Chronic heart failure
|
72,107
|
1,455 (4.4%)
|
3,263 (9.1%)
|
137 (4.3%)
|
4,855 (6.7%)
|
|
Diabetes
|
45,033
|
2,778 (14.8%)
|
3,693 (16%)
|
585 (18.7%)
|
7,056 (15.7%)
|
|
Hypertension
|
45,263
|
8,117 (43%)
|
11,869 (51%)
|
1,409 (44.9%)
|
21,395 (47.3%)
|
|
Prior myocardial infarction
|
45,002
|
1,224 (6.5%)
|
1,918 (8.3%)
|
176 (5.7%)
|
3,318 (7.4%)
|
|
Prior ischemic stroke
|
44,981
|
1,095 (5.8%)
|
1,800 (7.8%)
|
170 (5.5%)
|
3,065 (6.8%)
|
|
Recent major bleeding
|
72,107
|
678 (2%)
|
836 (2.3%)
|
125 (3.9%)
|
1,639 (2.3%)
|
|
Anaemia
|
72,107
|
11,883 (35.8%)
|
11,680 (32.7%)
|
1,410 (43.9%)
|
24,973 (34.6%)
|
|
Platelet count <150,000
|
71,990
|
885 (2.7%)
|
823 (2.3%)
|
144 (4.6%)
|
1,852 (2.6%)
|
|
Platelet count >450,000
|
71,990
|
1,113 (3.4%)
|
1,264 (3.5%)
|
155 (4.9%)
|
2,532 (3.5%)
|
|
Recent surgery
|
72,107
|
3,476 (10.5%)
|
4,241 (11.9%)
|
316 (9.8%)
|
8,033 (11.1%)
|
|
Recent immobility
|
72,107
|
7,530 (22.7%)
|
7,642 (21.4%)
|
464 (14.4%)
|
15,636 (21.7%)
|
|
Active cancer
|
72,107
|
7,655 (23.1%)
|
7,974 (22.3%)
|
1,612 (50.2%)
|
17,241 (23.9%)
|
|
Prior VTE
|
72,107
|
5,336 (16.1%)
|
5,258 (14.7%)
|
272 (8.5%)
|
10,866 (15.1%)
|
|
Pregnancy/Puerperium
|
72,107
|
561 (1.7%)
|
314 (0.9%)
|
31 (1%)
|
906 (1.3%)
|
|
Hormonal use
|
72,107
|
1,779 (5.4%)
|
1,916 (5.4%)
|
158 (4.9%)
|
3,853 (5.3%)
|
|
Initial therapy
|
|
Low-molecular-weight heparin
|
72,107
|
30,634 (92.4%)
|
30,138 (84.3%)
|
2,504 (78%)
|
63,276 (87.8%)
|
|
Unfractionated heparin
|
72,107
|
877 (2.6%)
|
3413 (9.5%)
|
94 (2.9%)
|
4,384 (6.1%)
|
|
Fondaparinux
|
72,107
|
736 (2.2%)
|
613 (1.7%)
|
92 (2.9%)
|
1,441 (2%)
|
|
NOACs
|
20,792
|
579 (7.1%)
|
417 (4%)
|
35 (1.6%)
|
1,031 (5.0%)
|
|
Thrombolytic therapy
|
72,107
|
54 (0.2%)
|
882 (2.5%)
|
3 (0.1%)
|
939 (1.3%)
|
|
Vena cava filter use
|
72,107
|
720 (2.2%)
|
1,042 (2.9%)
|
80 (2.5%)
|
1,842 (2.6%)
|
|
Clinical presentation
|
|
SBP levels <90 mm Hg
|
69,286
|
268 (0.9%)
|
1,253 (3.5%)
|
37 (1.3%)
|
1,558 (2.2%)
|
|
Syncope
|
69,108
|
195 (0.6%)
|
5,211Z (15%)
|
46 (1.6%)
|
5,452 (7.9%)
|
|
Heart rate ≥110 mm Hg
|
67,212
|
1,374 (4.6%)
|
7,272 (21%)
|
169 (6.1%)
|
8,815 (13.1%)
|
|
Sat O2 levels <90%
|
27,097
|
289 (6.9%)
|
6,618 (29.6%)
|
64 (12%)
|
6,971 (25.7%)
|
Abbreviations: DVT, deep vein thrombosis; NOAC, non–vitamin K antagonist oral anticoagulant;
PE, pulmonary embolism; VTE, venous thromboembolism.
Note: Data include patients enrolled until 30 June 2017.
a Those with superficial vein thrombosis, splanchnic vein thrombosis (i.e. thrombosis
involves thrombosis in the mesenteric, splenic or portal veins), retinal vein thrombosis
and cerebral vein thrombosis.
Outcomes
The main outcomes of interest in RIETE include all-cause death, PE-specific death,
recurrent DVT, recurrent PE, major bleeding, non-major (but clinically relevant) bleeding,
arterial ischemic events (myocardial infarction, ischemic stroke or leg amputation),
thrombocytopenia, bone fractures and other side-effects of the prescribed therapies.
In recent years, development of post-thrombotic syndrome (since 2008) and chronic
thromboembolic pulmonary hypertension (since 2015) are also ascertained in those with
reported long-term follow-up ([Table 3]). RIETE, by design, does not require universal screening for asymptomatic events.
Table 3
Main study outcomes and their definitions
|
Outcomes
|
Definition
|
|
All-cause mortality
|
|
|
PE-specific mortality
|
Autopsy-confirmed. In the absence of autopsy, fatal PE is defined as any death appearing
within 10 d after symptomatic PE diagnosis, in the absence of any alternative cause
of death
|
|
Recurrent VTE
|
Recurrent DVT is defined as a new non-compressible vein segment, or an increase of
the vein diameter of >4 mm compared with the last available measurement on venous
ultrasonography. Recurrent PE is defined as a new ventilation–perfusion mismatch on
lung scan or a new intraluminal filling defect on spiral computed tomography or pulmonary
angiography
|
|
Major bleeding
|
Bleeding events that are overt and required a transfusion of two units or more of
blood, or are retroperitoneal, spinal or intracranial, or when they are fatal
|
|
Clinically relevant non-major bleeding
|
Bleeding events that are overt and require medical assistance but not fulfilling criteria
for major bleeding
|
|
Fatal bleeding
|
Any death occurring within 10 d of a major bleeding episode, in the absence of an
alternative cause of death
|
|
Post-thrombotic syndrome
|
Evaluated every 12 mo according to the Villalta score
|
|
Chronic thromboembolic pulmonary hypertension
|
Diagnosed by site investigators based on assessment of clinical information and tests
including echocardiography, ventilation–perfusion lung scan, pulmonary angiography,
pulmonary functional tests and right heart catheterization
|
|
Bone fractures
|
Confirmed by adequate image testing
|
|
Myocardial infarction
|
Presence of typical chest pain in combination with a transient increase of creatine
kinase-MB or troponin and/or typical electrocardiographic signs (development of pathologic
Q-waves or ST-segment elevation or depression) that are not otherwise explained
|
|
Arterial ischemic events
|
Diagnosed in the setting of acute neurological event not resolving completely within
24 hours, confirmed by computed tomography or magnetic resonance imaging
|
Abbreviations: PE, pulmonary embolism; VTE, venous thromboembolism.
Note: Outcomes are assessed in various time intervals including during the inpatient
stay, 30 days after the event, 3 months after the even and longer term in a subset
of patients with available data.
Follow-up
The minimum follow-up duration for patients in RIETE is at least 3 months.[13] Since 2010, collaborators have been requested to extend follow-up to at least 12
months. As for June 30 2017, a total of 24,828 patients have followed up for at least
12 months and 11,304 for at least 24 months ([Fig. 2]).
Fig. 2 Cumulative number of enrolled patients over time. The top-five recruiting countries
are Spain (n = 54,525), Italy (n = 5,910), France (n = 4,233), Israel (n = 2,650) and Switzerland (n = 1,144). (A) Cumulative number of enrolled patients over time. (B) Amount of patients followed-up for >3, 6, 9, 12, 15, 18 and 24 months.
Ethics
All enrolees provide written or verbal informed consent according to the local ethics
protocols of enrolling centres. The institutional review board at each enrolling centre
approves participation in RIETE for the site investigators and allows the entry of
de-identified patient information into the RIETE database.
Data Entry
Data are entered into electronic case report forms through an electronic portal and
submitted to the coordinating centre via secure Web site[13] ([Fig. 3], https://www.riete.org/login.php).
Fig. 3 Screenshot from the electronic data entry platform.
Quality Control and Oversight
S & H Medical Science Service serves as the coordinating centre for RIETE. The study
coordinating centre assigns a unique identification number for each patient to avoid
duplicate entries and ensure the security of protected health information. The coordinating
centre ensures the completeness of data entry by site investigators. In order for
a patient to count in the registry, a minimum of 54 core data elements (variables)
related to the first 3 months of care need to be completed. Of the main items in these
54 elements, age, gender, weight, date of diagnosis, recent major bleeding, characteristics
of DVT/PE (diagnostic method), risk factors (cancer, surgery, immobilization, history
of DVT/PE, pregnancy), laboratory (haemoglobin, leukocytes, platelets), clinical symptoms,
treatments (drug, dose, onset and finishing date), IVC filter use (yes/no and timing),
date of last follow-up and events (death, thromboembolic recurrence, bleeding) could
be named. The number of variables has been progressively increasing over the years.
Recently, depending on the events, ancillary tests, therapies and follow-up duration,
each patient may be represented by up to 1,000 variables filled out; yet as discussed
earlier, there are only 54 core mandatory variables per patient. Data quality is electronically
monitored by S & H Medical Science Service on a weekly basis. In case of identification
of several inconsistencies from any enrolling centre, a full audit of all the data
from that centre is performed. In addition, trained staffs from S & H Medical Science
Service make periodic visits to participating centres and compare the information
in a randomly selected sample of patients entered by the site investigators. In the
most recent audit, RIETE staff assessed 4,100 randomly chosen records that included
1,230,000 measurements. The data showed 95% overall agreement between the registered
information by site investigators and patients' original records (with no difference
between key data elements and others, and no specific patterns that undermined a group
of variables disproportionately). The audits also included ascertainment of inclusion
of consecutive patients via cross-checking by available medical records at enrolling
hospitals. The RIETE leadership and steering committee (led by Dr. Monreal) is in
charge of overseeing the registry, ensuring the collaboration between the investigators
and the S & H Medical Science Service, and proposing, soliciting and overseeing the
process for development, and publication of new research projects based on RIETE.
All active members are permitted to propose new studies. The proposals are reviewed
by the leadership and steering committee and, if not overlapping with prior or ongoing
projects, would be enlisted.
Statistical Analysis
A dedicated team of statisticians conducts the statistical analyses. The main data
warehouse for RIETE is in Madrid, Spain, and managed by S & H Medical Science Service.
RIETE analyses are either performed by statisticians at the S & H Medical Science
Service or by other RIETE statisticians who have signed confidentiality contracts
and downloaded de-identified portions of the data into secure platforms. Patients
whose entered data do not fulfil the minimum available variables criteria will not
be entered in any of the analyses. Categorical variables are reported as frequencies
and percentages. Continuous variables are reported as means with standard deviation.
Tests of comparison, association, survival analysis, multivariable adjustment, propensity-score
matching and others are contingent on hypotheses and questions per each individual
study from the RIETE database. Large numbers would enable the investigators to explore
the regional variations, and to determine the robustness of analyses by factors such
as sites and volume. Multi-level modelling could help minimize errors related to potential
clustering of observations, if one occurs at certain centres. Although RIETE does
not have a study-wide statistical approach for missing data (e.g. multiple imputations),
the coordinating centre makes study-wide efforts to help minimize missing data elements
by frequent communications with each of the enrolling centres.
Discussion
RIETE is a large multicentric multinational registry of patients with acute VTE. Over
the past 15 years, it has provided data for more than 100 original research studies,
some of which have been among the seminal studies related to epidemiology, prognostication
or comparative effectiveness of strategies for management of VTE.[19]
[21]
[29]
[30]
[31] Investigations from RIETE have provided novel information about VTE risk factors,
therapies and outcomes among understudied subgroups such as pregnant patients, those
at high risk of bleeding, those with morbid obesity and the elderly persons.[25]
[26]
[32]
[33] Other studies revealed distinct risk gradients across key subgroups, including differential
presentation and outcomes based on primary cancer site.[34] Some others provided evidence from observational studies in areas where randomized
trials are extremely difficult to conduct, if not impossible, including for those
with VTE and high bleeding risk,[24]
[35] or patients with PE and hypotension.[23] RIETE investigators have also contributed to studies related to prognostication,
including for the simplified PE severity index.[29] Other studies have shown the contemporary trends in hospitalizations, clinical presentation
and outcomes of patients with DVT and with PE.[21]
[22] With continued enrolment and increase in the number and diversity of collaborating
centres, in part via better recognition of the registry by other investigators and
in part by active advocacy from existing RIETE investigators and the steering committee,
it is expected that the registry continues to provide a greater breadth and depth
of information related to presentation, treatment pattern and outcomes of patients
with VTE.
There are several functions in the usage of registries for cardiovascular conditions[15]
[16]
[17] including VTE. Registries enable us to look into VTE epidemiology (including hospitalizations,
and in many cases outpatients), common treatment patterns, trends, variations in practice
and also to address some questions related to comparative effectiveness, especially
in areas where randomized trials are unfeasible or unlikely to occur (including efficacy
studies related to the oldest old, patients with morbid obesity or severe renal insufficiency,
or for conditions where equipoise is questioned because of existing grandfathered
therapies, or where enrolment is technically challenging because of the high acuity
of medical illness [such as the case of massive PE, disseminated cancer and others];
[Table 4]).[36]
[37]
[38]
[39]
[40]
[41]
[42] Registry data complement the findings from randomized trials and are a critical
element for contemporary knowledge generation, and quality control. Findings can reflect
on routine practice results for newly approved or existing health interventions and
may unravel new signals for benefits or harms that were previously understudied in
randomized trials. Further, they can reflect on variations in care, temporal trends
over time and adherence to guidelines recommendations, among many other utilities.
Table 4
Summary information about some of the large VTE registries and their key features
|
Setting
|
Enrolment timeline
|
Study population (DVT, PE, VTE)
|
Sample size
|
Follow-up period
|
Main objectives
|
|
MASTER[36]
|
25 centres from Italy
|
January 2002 to October 2004
|
Adults with objectively confirmed VTE
|
2,111
|
All patients were followed up for 24 mo. Patient management was at the discretion
of the attending physicians
|
To describe the demographics, risk factors, clinical features and outcomes of patients
with VTE during short-term and long-term follow-up
|
|
EMPEROR[37]
|
Emergency departments from 22 academic and community hospitals in the United States
|
January 2005 to December 2008
|
Adults with objectively confirmed PE
|
1,880
|
Main follow-up was up to 30 d
|
To define the presenting symptoms, signs, risk factor profile, treatments (including
use of anticoagulants) and short-term outcomes of patients with PE presenting to emergency
departments
|
|
IPER[38]
|
47 hospitals from Italy
|
September 2006 to 2010
|
Adults with objectively confirmed PE
|
1,716
|
NA, follow-up ended in August 2014
|
Similar to MASTER (see above)
|
|
SWIVTER[39]
|
18 hospitals in Switzerland
|
January 2009 to May 2010
|
Adults with objectively confirmed VTE
|
1,247
|
No systematic follow-up beyond hospital discharge
|
A study to determine characteristics of patients with VTE, and key subgroups, including
the elderly, and those with cancer
|
|
VTEval[40]
|
Started as a single-centre study in Germany with plan to involve more centres
|
April 2013 to ongoing
|
Adults with objectively confirmed VTE
|
2,000 planned, unclear details
|
Active follow-up is planned for 36 mo
|
To determine the symptoms, risk factors as well as psychosocial, environmental and
lifestyle factors associated with VTE. The study is also collecting blood samples
for future ‘omics’ studies, on genome, transcriptome, proteome, metabolome and phenome
|
|
PREFER in VTE[41]
|
381 centres from 7 European countries
|
January 2013 to July 2014
|
Adults with objectively confirmed VTE
|
3,545
|
Up to 12 mo (by phone calls)
|
To determine the clinical characteristics, management and outcomes, and also health
care resource utilization and costs of care for 12 mo of treatment
|
|
GARFIELD-VTE[42]
|
500 sites from 28 countries
|
July 2014 to ongoing
|
Adults with objectively confirmed acute VTE
|
10,000 planned, recruitment recently completed
|
Minimum follow-up for 36 mo
|
To describe the global treatment patterns and outcomes for VTE. Utilization and outcomes
of patients receiving non–vitamin K antagonist oral anticoagulants, descriptions about
regional variations in care and description of long-term outcomes such as post-thrombotic
syndrome and chronic thromboembolic pulmonary hypertension could be named
|
|
RIETE
|
179 centres from 24 countries
|
2001 to ongoing
|
Adults with objectively confirmed VTE. In recent years, also enrolling patients with
thrombosis at unusual sites
|
72,107 patients as of June 2017. Still recruiting
|
Minimum follow-up for 3 mo, but many have longer follow-up (see [Fig. 1B])
|
Detailed in the text. In brief, to describe the epidemiology, treatment patterns and
outcomes of a large group of patients with VTE, including many of the understudied
subgroups. Also to provide a platform for several additional investigations, including
pragmatic trials
|
Abbreviations: EMPEROR, Emergency Medicine Pulmonary Embolism in the Real World Registry;
GARFIELD, Global Anticoagulant Registry in the FIELD; IPER, Italian Pulmonary Embolism
Registry; MASTER, Multicenter Advanced Study for a ThromboEmbolism Registry; NA, not
available; PE, pulmonary embolism; SWIVTER, SWIss Venous ThromboEmbolism Registry;
VTE, venous thromboembolism.
Note: Only dedicated VTE registries with >1,000 patients are discussed. The list is
not meant to be exhaustive and did not include several of the registries from the
prior years.
RIETE encompasses several distinct features[18] compared with other existing and ongoing VTE registries.[10]
[36]
[37]
[38]
[42] The large sample size (to our knowledge, the largest prospective patient-level VTE
registry) enables the investigators to study questions that are not feasibly addressed
in single-centre studies.[19]
[21]
[29]
[30]
[31] Patient enrolment is from many centres with various levels of acuity of care, making
it a representative sample and providing opportunities for evaluation of care in ambulatory
setting, general hospitals, and centres of excellence. Other future specific areas
of interest include (but are not limited to) identification of risk factor profiles
related to VTE recurrence that can help determine the duration of anticoagulation,
and identification of factors based on VTE presentation and comorbidities that could
provide hints at tailored therapy for specific drugs, doses and duration (which would
be subsequently tested in trial platforms). RIETE also plans to provide additional
empiric evidence on non–vitamin-K antagonist oral anticoagulants. Although such patients
are currently under-represented in the registry, in part because of slow uptake of
this class in Spain due to reimbursement issues, with increasing enrolment of patients
from the rest of the world, and possibility of adjustments in the reimbursement regulations
in Spain, we anticipate that the breadth and depth of data related to this class of
medications in RIETE will be further enriched. The registry also aims to pay attention
to understudied subgroups of patients such as those with splanchnic vein thrombosis,
superficial vein thrombosis and others. RIETE is gaining additional information to
help better characterize the significance and risk factor profile for long-term complications,
such as post-thrombotic syndrome and chronic thromboembolic pulmonary hypertension.
Furthermore, unlike several other registries, continuation of the registry over time
makes it possible for assessment of temporal trends. Finally, the platform will also
bring possibilities for future patient-oriented research investigations related to
VTE, including pragmatic intervention trials,[43] and quality improvement initiatives. In fact, some such randomized trials are under
way using the RIETE platform.[44]
[45]
[46] In large part driven by the data from the RIETE and tools created based on original
such data, RIETE investigators have also created Web site that provides information
related to VTE for physicians and patients, including risk estimation models (http://trombo.info/?lang=en). Also, contrary to some of the other existing registries, despite receiving funding
from various groups, RIETE is independently investigator driven. The data are entirely
managed by the investigators. The funders (including industry funders) have no rights
in reviewing the protocols, abstracts or manuscripts, or about decisions to submit
them.
In conclusion, RIETE is a large existing and ongoing VTE registry. It is expected
that RIETE will continue to provide clinical evidence for understudied subgroups with
thrombotic disease, and will have more prominent role for facilitation of multicentre
(and multinational studies) that could be used for assessment of variations and disparities
in care, quality improvement and conducting comparative effectiveness research. The
overarching goal is to improve the management of VTE through better understanding
of prevention, as well as demographics, comorbidities, treatment patterns and outcomes
of patients with VTE.
Appendix A
Coordinator of the RIETE Registry:
Dr. Manuel Monreal (Spain).
RIETE Steering Committee Members:
Dr. Hervè Decousus (France).
Dr. Paolo Prandoni (Italy).
Dr. Benjamin Brenner (Israel).
RIETE National Coordinators:
Dr. Raquel Barba (Spain).
Dr. Pierpaolo Di Micco (Italy).
Dr. Laurent Bertoletti (France).
Dr. Inna Tzoran (Israel).
Dr. Abilio Reis (Portugal).
Dr. Henri Bounameaux (Switzerland).
Dr. Radovan Malý (Czech Republic).
Dr. Philip Wells (Canada).
Dr. Peter Verhamme (Belgium).
Dr. Marijan Bosevski (Republic of Macedonia).
Dr. Joseph A. Caprini (United States).
RIETE Registry Coordinating Centre:
S & H Medical Science Service.
Appendix B
Members of the RIETE Group:
Spain: Adarraga MD, Aibar MA, Alfonso M, Arcelus JI, Ballaz A, Baños P, Barba R, Barrón
M, Barrón-Andrés B, Bascuñana J, Blanco-Molina A, Camon AM, Carrasco C, Cruz AJ, de
Miguel J, del Pozo R, del Toro J, Díaz-Pedroche MC, Díaz-Peromingo JA, Falgá C, Fernández-Capitán
C, Fernández-Muixi J, Fidalgo MA, Font C, Font L, Furest I, García MA, García-Bragado
F, García-Morillo M, García-Raso A, García-Sánchez AI, Gavín O, Gómez C, Gómez V,
González J, Grau E, Guijarro R, Gutiérrez J, Hernando E, Isern V, Jara-Palomares L,
Jaras MJ, Jiménez D, Jiménez R, Joya MD, Lima J, Llamas P, Lobo JL, López-Jiménez
L, López-Reyes R, López-Sáez JB, Lorente MA, Lorenzo A, Loring M, Lumbierres M, Madridano
O, Maestre A, Marchena PJ, Martín M, Martín-Martos F, Mestre B, Monreal M, Morales
MV, Nieto JA, Núñez MJ, Olivares MC, Otero R, Pedrajas JM, Pellejero G, Pérez-Ductor
C, Peris ML, Pons I, Porras JA, Riera-Mestre A, Rivas A, Rodríguez-Dávila MA, Rosa
V, Rubio CM, Ruiz-Artacho P, Sahuquillo JC, Sala-Sainz MC, Sampériz A, Sánchez-Martínez
R, Sancho T, Soler S, Soto MJ, Suriñach JM, Tolosa C, Torres MI, Trujillo-Santos J,
Uresandi F, Usandizaga E, Valero B, Valle R, Vela J, Vidal G, Villalobos A, Xifre
B.
Argentina: Vázquez FJ, Vilaseca A.
Belgium: Vanassche T, Vandenbriele C, Verhamme P.
Brazil: Yoo HHB.
Canada: Wells P.
Czech Republic: Hirmerova J, Malý R.
Ecuador: Salgado E.
France: Benzidia I, Bertoletti L, Bura-Riviere A, Falvo N, Farge-Bancel D, Hij A, Merah A,
Mahé I, Moustafa F, Quere I.
Israel: Braester A, Brenner B, Ellis M, Tzoran I.
Italy: Bilora F, Brandolin B, Bucherini E, Camerota A, Cattabiani C, Ciammaichella M, Dentali
F, Di Micco P, Giorgi-Pierfranceschi M, Grandone E, Imbalzano E, Lessiani G, Maida
R, Mastroiacovo D, Pace F, Pesavento R, Pinelli M, Prandoni P, Quintavalla R, Rocci
A, Siniscalchi C, Tiraferri E, Visonà A, Zalunardo B.
Latvia: Gibietis V, Kigitovica D, Skride A.
Republic of Macedonia: Bosevski M, Zdraveska M.
Switzerland: Bounameaux H, Erdmann A, Fresa M, Mazzolai L.
United States: Bikdeli B, Caprini J.
