JAMDA 19 (2018) 497e503

JAMDA
journal homepage: www.jamda.com

Original Study

Prophylaxis of Venous Thromboembolism in Geriatric Settings:

A Cluster-Randomized Multicomponent Interventional Trial
Jean Paul Rwabihama MD, PhD a, b, *, y, Etienne Audureau MD, PhD a, c, y,
Marie Laurent MD, PhD a, d, Lalaina Rakotoarisoa MD e, Marc Jegou MD f,
Sofiane Saddedine MD f, Sébastien Krypciak MD g, Stéphane Herbaud MD g,
Hind Benzengli PharmD h, Lauriane Segaux MS a, c, Esther Guery MS c, Gabin Ambime MD b,
Marie-Thérèse Rabus MD b, Jean-Guy Perilliat MD b, Jean-Philippe David MD, PhD a, f,
Elena Paillaud MD, PhD a, g , for the améliorer la prophylaxie de la Maladie
ThromboEmbolique veineuse en milieu gériatrique (MATEV) Study Groupz
a
Université Paris-Est, UPEC, DHU A-TVB, IMRB-EA 7376 CEpiA (Clinical Epidemiology and Aging Unit), Créteil, France
b
Assistance Publique-Hôpitaux de Paris, Service de Gériatrie, Hôpital Joffre-Dupuytren, Draveil, France
c
Assistance Publique-Hôpitaux de Paris, Service de Santé Publique, Hôpital Henri Mondor, Créteil, France
d
Assistance Publique-Hôpitaux de Paris, Service de Gériatrie, Hôpital Albert Chenevier-Henri Mondor, Créteil, France
e
Assistance Publique-Hôpitaux de Paris, Service de Gériatrie, Hôpital George Clemenceau, Champceuil, France
f
Assistance Publique-Hôpitaux de Paris, Service de Gériatrie, Hôpital Emile Roux, Limeil Brévannes, France
g
Assistance Publique-Hôpitaux de Paris, Service de Gériatrie, Hôpital Henri Mondor, Créteil, France
h
Assistance Publique-Hôpitaux de Paris, Service de Pharmacie, Hôpital Joffre-Dupuytren, Draveil, France

a b s t r a c t

Keywords: Objectives: To evaluate the efficacy of an intervention on the practice of venous thromboembolism
Thromboprophylaxis prevention.
educational intervention Design: A multicenter, prospective, controlled, cluster-randomized, multifaceted intervention trial
older patients
consisting of educational lectures, posters, and pocket cards reminding physicians of the guidelines for
cluster-randomized trial
thromboprophylaxis use.
Settings: Twelve geriatric departments with 1861 beds total, of which 202, 803, and 856 in acute care,
post-acute care, and long-term care wards, respectively.
Participants: Patients hospitalized between January 1 and May 31, 2015, in participating departments.
Measurements: The primary endpoint was the overall adequacy of thromboprophylaxis prescription at
the patient level, defined as a composite endpoint consisting of indication, regimen, and duration of
treatment. Geriatric departments were divided into an intervention group (6 departments) and control
group (6 departments). The preintervention period was 1 month to provide baseline practice levels, the
intervention period 2 months, and the postintervention period 1 month in acute care and post-acute care
wards or 2 months in long-term care wards. Multivariable regression was used to analyze factors
associated with the composite outcome.
Results: We included 2962 patients (1426 preintervention and 1536 postintervention), with median age
85 [79;90] years. For the overall 18.9% rate of inadequate thromboprophylaxis, 11.1% was attributable to
underuse and 7.9% overuse. Intervention effects were more apparent in post-acute and long-term care
wards although not significantly [odds ratio 1.44 (95% confidence interval 0.78;2.66), P ¼ .241; and

This research did not receive any specific grant from funding agencies in the
public, commercial, or not-for-profit sector
The authors declare no conflicts of interest.
* Address correspondence to Jean Paul Rwabihama MD, PhD, Hôpitaux
Universitaires Henri Mondor, Pôle gériatrique de l’Essonne, site Joffre-Dupuytren,
1 rue Eugène Delacroix 91210, Draveil, France.
E-mail address: jean-paul.rwabihama@aphp.fr (J.P. Rwabihama).
y
These authors contributed equally to this work.
z
The MATEV Study Group is composed of Jean Paul Rwabihama MD, PhD,
Etienne Audureau MD, PhD, Marie Laurent MD, PhD, Lalaina Rakotoarisoa MD,
Marc Jegou, MD, Sofiane Saddedine MD, Sebastien Krypciak MD, Stéphane Herbaud
MD, Hind Benzengli PharmD, Lauriane Segaux MS, Esther Guery MS, Gabin Ambime
MD, Marie-Thérèse Rabus MD, Jean-Guy Perilliat MD, Jean-Philippe David MD, PhD,
Elena Paillaud MD, PhD, Anh Thu Le Quang MD, Michèle Dicko MD, Bahieddine
Bouabdelli MD, Mohand Mazouzi MD, Hélène Biault MD, Fattima Abdallah MD,
Hoby Razafimbelo MD, Kamel Hadj Mahfoud MD, Mourad Menaa MD, Andry
Razakarivony MD, De Rozier Rakotoarisoa MD, Mohammed Haichour MD, Sylvie
Haulon MD, Olivier Henry MD, Olivier Bouillanne MD, Eric Ballanger MD, Muriel
Palisson MD, Isabelle Perilliat MD, Nathalie Baptiste MD

https://doi.org/10.1016/j.jamda.2018.02.004
1525-8610/Ó 2018 AMDA e The Society for Post-Acute and Long-Term Care Medicine.
498 J.P. Rwabihama et al. / JAMDA 19 (2018) 497e503

1.44 (0.68, 3.06), P ¼ .345]. Adequacy rates significantly improved in the postintervention period for the
intervention group overall (from 78.9% to 83.4%; P ¼ .027) and in post-acute care (from 75.4% to 86.3%;
P ¼ .004) and long-term care (from 87.0% to 91.7%; P ¼ .050) wards, with no significant trend observed in
the control group.
Conclusions/Implications: This study failed to demonstrate improvement in prophylaxis adequacy with
our intervention. However, the intervention seemed to improve practices in post-acute and long-term
care but not acute care wards.
Ó 2018 AMDA e The Society for Post-Acute and Long-Term Care Medicine.

Venous thromboembolism (VTE), which includes deep venous
thrombosis (DVT) and pulmonary embolism, is one of the common
causes of preventable mortality in hospitalized patients.1 The
proportion of severe and fatal VTE events is increased in older
patients.2 VTE risk significantly increases with advancing age, and age
75 years has been found an independent risk factor.3e6 Other
important risk factors in hospitalized patients include active cancer
and/or cancer therapy, ongoing hormonal treatment, previous history
of VTE, reduced mobility, recent trauma and/or surgery, heart and/or
respiratory failure, acute myocardial infarction or ischemic stroke,
acute infection and/or rheumatologic disorder, central venous
catheter use, and obesity.7,8 Almost all older inpatients have at least 1
risk factor for VTE, and approximately 21% have 3 or more risk factors.9
The use of primary thromboprophylaxis for inpatients at risk for VTE is
effective in reducing DVT and pulmonary embolism,10 and systematic
assessment of VTE risk at admission has been shown to improve
prophylaxis practice and reduce the risk of VTE.11,12
Consensus guidelines published by the American College of Chest
Physicians recommend prophylaxis with unfractionated heparin or
low-molecular-weight heparin (LMWH) in hospitalized patients at
risk for VTE.10 At the French national level, the Agence Française de
Sécurité Sanitaire des Produits de Santé recommends prophylaxis for
patients 40 years and older who are hospitalized for an expected
duration of more than 3 days because of (1) acute cardiac or
respiratory decompensation or (2) severe infection, acute
inflammatory rheumatic disease, or inflammatory bowel disease,
when associated with a risk factor for VTE including age >75 years,
cancer, VTE history, hormone therapy, chronic heart or respiratory
failure, and myeloproliferative syndrome. Of note, the recommenda-
tions do not include any mention of the mobility status of patients.
However, despite these recommendations, recent studies have
demonstrated that VTE prophylaxis for patients at risk remains
underutilized13e15 and/or misused,16 especially in older patients in
geriatric settings.17e20 In the last 10 years, various system-wide
measures have been implemented to increase the use of thrombo-
prophylaxis in hospitalized patients. These measures include the
distribution of guidelines, educational events, or multifaceted
interventions, audit and feedback, and the use of automatic
reminders.11,21 A recent meta-analysis suggested that alerts or
multifaceted interventions increase prophylaxis prescription.22
We hypothesized that geriatricians lacking updated knowledge on
preventing VTE may explain the widespread underuse or inappropriate
use of pharmacologic thromboprophylaxis in older patients. To
improve this practice, we performed a multicomponent interventional
study to remind geriatricians of the main guidelines of VTE prevention.
The primary objective was to evaluate the efficacy of a multifaceted
intervention for VTE prevention practice in geriatric settings.
Methods
Study Population
We conducted the “améliorer la prophylaxie de la Maladie
ThromboEmbolique veineuse en milieu gériatrique” (MATEV) trial at 4
teaching hospitals in the Paris region, France, from January 1, 2015 to
May 31, 2015. Participating hospitals comprised 12 geriatric
departments, with 202, 803, and 856 beds of acute care, post-acute
care (or rehabilitation), and long-term care wards, respectively. We
prospectively enrolled all patients hospitalized for a medical illness in
one of the participating geriatric departments during the period study.
Patients were excluded from the analysis if they were admitted after a
surgical condition or a traumatic event, if venous thrombosis or
pulmonary embolism was diagnosed within 48 hours after admission,
if they already received anticoagulant treatment at a therapeutic
dosage, or if they were hospitalized for palliative care.
Study Design and Oversight
We performed a multicenter, prospective, controlled, cluster-
randomized interventional trial. Geriatric departments in partici-
pating hospitals were randomly assigned to an intervention group
(6 departments) and a control group (6 departments). Considering the
nature of the intervention designed for health professionals, geriatric
departments were designated as the units of randomization to ensure
that all patients within a given geriatric ward unit were assigned to
the same intervention or control group, hence, reducing the risk of
contamination of the intervention effect. The study included a
1-month preintervention period (January 2015) to provide baseline
practice levels, a 2-month intervention period (February-March 2015)
to implement the intervention, and a postintervention period of
1 month (May 2015) in acute care and post-acute care wards or
2 months (April-May 2015) in long-term care wards to account for the
reduced turnover of patients in long-term care wards. No specific
intervention was performed in the wards allocated to the control
group, where physicians were instructed to continue their practice as
usual. A steering committee was set up and composed of 14 senior
geriatricians (including 12 heads of geriatric departments),
1 biostatistician, and 1 coordinating investigator. This group defined
the scientific basis, the design of the study, and the components of the
multifaceted intervention. This study was approved by the Ethics
Committee of Paris-Ile-de-France IV and registered at the European
Union Clinical Trials website (EudraCT: 2014-A00547-40). Given the
cluster-randomized design and the nature of the intervention, the
need for informed consent was waived; all patients or their surrogate
decision-makers received an information sheet with contact details,
and authorization to use data could be withdrawn at any time.
Randomization and Masking
Because a potential imbalance may still occur across groups
despite randomization with respect to important prognostic factors,
an optimized allocation procedure was applied following the “best
balance” strategy.23e25 In a nutshell, a census is first taken of all
possible intervention allocations (n ¼ 924), calculating for each one an
imbalance statistic for a prespecified set of prognostic factors of
interest. Randomization is then performed on a subset of all
allocations with the highest degree of balance (ie, 5% lowest measures
of imbalance). For the MATEV study, all units were enrolled before
 J.P. Rwabihama et al. / JAMDA 19 (2018) 497e503 499

randomization, allowing the prospective collection of the following confidence interval for the interaction between group (intervention vs
ward characteristics over a 1-month prestudy period: mean patient control) and period (postintervention vs preintervention) measuring
age, mean hospital stay duration, and proportion of good practices. the intervention effect with the difference-in-differences approach for
Randomization was computer-generated with an allocation list clustered binary outcomes.26 Crude ORs were computed and were
prepared by an independent statistician not involved in patient adjusted for age, sex, and care sector. Additional analyses were
enrollment or in the final analysis. Because the nature of the conducted to document overall adequacy and underuse/overuse rates
intervention precluded blinding patients and participating physicians, by care sector and to investigate potential determinants of inadequate
the trial was an open-label study. practices by multivariable logistic mixed-effects modeling with a
stepwise backward procedure. All tests were 2-sided, and a P value of
Data Collection and Endpoints <.05 was considered statistically significant. Analyses involved use of
Stata v14.2 (StataCorp, College Station, TX).
In-hospital data were abstracted from the medical records of
patients and included characteristics of patients (age, sex, acute Results
medical event and background, comorbidities, and VTE risk factors)
and information on thromboprophylaxis use. We included 1426 patients in the control and intervention groups
The primary endpoint was the overall adequacy at the patient level (n ¼ 706 and n ¼ 720) during the preintervention period and 1563
of the decision and modalities of thromboprophylaxis prescription, (n ¼ 779 and n ¼ 784) in the postintervention period. General
defined as a composite endpoint by the presence of all of the 3 characteristics of patients from the 12 participating geriatric
following criteria: (1) Appropriate indication: justified indications for departments are shown in Table 1 by study group and period.
VTE prophylaxis in patients with major criteria including congestive
heart failure (New York Heart Association class III or IV), acute
respiratory failure, recent myocardial infarction, recent ischemic Table 1
General Characteristics of Patients by Randomized Groups
stroke, or with minor criteria (ie, sepsis, acute rheumatic disorders,
acute inflammatory bowel disease, acute inflammatory disease) with Preintervention Postintervention
at least an additional risk factor such as age 75 years, active cancer, Control Intervention Control Intervention
previous VTE event, varicose veins, chronic heart or respiratory failure,
(N ¼ 706) (N ¼ 720) (N ¼ 779) (N ¼ 784)
reduced mobility (bed rest >3 days), and hormonal treatment;
(2) Suitable dosage: the available drugs in the study hospitals with Patients
Age, y
recommended dose once daily: enoxaparin, 40 mg; dalteparin, Median [IQR] 85 [79;90] 84 [78;89] 85 [79;89] 84 [78;89]
5000 IU; fondaparinux 2.s5 mg; or unfractionated heparin, 5000 IU, <80 184 (26.1) 205 (28.5) 205 (26.3) 226 (28.9)
twice daily; (3) Appropriate treatment duration: 7e14 days of [80‒85] 163 (23.1) 161 (22.4) 174 (22.3) 184 (23.5)
prophylaxis is the common duration; however, an extension from 15 85 359 (50.8) 354 (49.2) 400 (51.3) 373 (47.6)
Sex, women 439 (62.2) 486 (67.5) 491 (63.0) 533 (68.0)
to 30 days is allowed. Components of the composite endpoint were
Creatinine clearance,
further assessed as secondary endpoints, including (1) thrombopro- mL/min
phylaxis underuse, defined as patients for whom thromboprophylaxis Median [IQR] 50 [36;64] 53 [41;67] 50 [39;65] 53 [40;70]
was not prescribed or was prescribed at insufficient dosage and/or 60 228 (32.4) 279 (38.9) 257 (33.0) 304 (38.9)
duration despite a proper indication and (2) thromboprophylaxis <60 476 (67.6) 439 (61.1) 522 (67.0) 478 (61.1)
Signs of dehydration 157 (22.2) 175 (24.3) 173 (22.2) 186 (29.9)
overuse defined as patients for whom thromboprophylaxis was VTE risk factors
prescribed but not indicated or at too-high dosage and/or duration. Chronic heart failure 165 (23.4) 149 (20.7) 184 (23.6) 131 (16.7)
Chronic respiratory 66 (9.3) 46 (6.4) 59 (7.6) 46 (5.9)
Educational Program in the Intervention Group failure
Active cancer 86 (12.2) 51 (7.1) 86 (11.0) 60 (7.7)
Hormone 12 (1.7) 6 (0.8) 7 (0.9) 2 (0.3)
The multifaceted intervention consisted of educational lectures, replacement
posters, and pocket cards. Between February and March 2015, the therapy
guidelines for thromboprophylaxis use for hospitalized patients were VTE history 53 (7.5) 46 (6.4) 55 (7.1) 39 (5.0)
outlined to residents and physicians of each geriatric ward during a Myeloproliferative 10 (1.4) 14 (1.9) 12 (1.5) 11 (1.4)
disease
lecture. These guidelines were summarized on posters and pocket Varicose veins 61 (8.6) 23 (3.2) 65 (8.3) 35 (4.5)
cards, which were given to physicians at the end of the educational Impaired mobility 499 (70.7) 460 (63.9) 533 (68.4) 539 (68.8)
intervention and displayed in all staff rooms and physician offices. The (ECOG-PS 3-4)
main objective was to evaluate the efficacy of a multifaceted Acute medical events
Congestive heart 52 (7.4) 43 (6.0) 39 (5.0) 47 (6.0)
intervention for VTE prevention practice in geriatric settings.
failure
Myocardial infarction 7 (1.0) 13 (1.8) 6 (0.8) 4 (0.5)
Statistical Analysis Respiratory failure 37 (5.2) 41 (5.7) 18 (2.3) 36 (4.6)
Stroke 9 (1.3) 15 (2.1) 10 (1.3) 10 (1.3)
At a 2-sided type 1 error level of 5%, we needed 12 geriatric Others* 80 (11.3) 84 (11.7) 94 (12.1) 91 (14.4)
Type of unit/ward
departments with a total of 1300 patients (650 per arm) to have 80% Acute care, N ¼ 235 53 (7.5) 182 (25.3) 41 (5.3) 232 (29.6)
power to detect an absolute 10% difference between intervention and Post-acute care, 364 (51.6) 208 (28.9) 460 (59.1) 227 (29.0)
control groups in the rate of adequate thromboprophylaxis in the N ¼ 572
postintervention period, assuming an intraclass correlation coefficient Long-term care, 289 (40.9) 330 (45.8) 278 (35.7) 325 (41.5)
N ¼ 619
of 0.01 to account for clustering by geriatric ward. The effect of the
intervention on the rate of adequate practice was assessed by a mixed IQR, interquartile range; ECOG-PS, Eastern Cooperative Oncology Group Perfor-
logistic regression model to account for the clustering of patients mance Status, grades 3-4.
Results are n (%) unless otherwise stated.
within geriatric wards. Changes in adequacy rates between baseline *Pulmonary infection (n ¼ 204), sepsis (n ¼ 56), urogenital infection (n ¼ 33),
(preintervention) and postintervention periods were compared digestive infection (n ¼ 23), acute infectious rheumatologic and rheumatic disorders
between the 2 groups by calculating the odds ratio (OR) with 95% (n ¼ 13), skin infection (n ¼ 13), other severe inflammatory disorders (n ¼ 7)
500 J.P. Rwabihama et al. / JAMDA 19 (2018) 497e503
Preintervention characteristics were globally similar among patients
from the 2 groups: median age [interquartile range] 85 [79;90] and 84
[78;89] years for the control and intervention groups, a prevalence of
VTE risk factors unrelated to mobility ranging from 0.8% [hormone
replacement therapy (intervention group)] to 23.4% [chronic heart
failure (control group)], and rates of acute medical events ranging
from 1.3% [stroke (control group)] to 11.7% [others (intervention
group)]. We found marginal to notable differences between the
groups for sex (62.2% vs 67.5%), impaired mobility (70.7% vs 63.9%),
and ward (acute care 7.5% vs 25.3%; post-acute care 51.6% vs 28.9%), for
which adjustments were made in subsequent multivariable analyses.
The preintervention rates of adequate thromboprophylaxis were
79.9% and 78.9% in the control and intervention groups, respectively.
Adequacy rates significantly improved in the postintervention period
for the intervention group, overall (þ4.5% from 78.9% to 83.4%;
P ¼ .027) and in post-acute care wards (þ11.9% from 75.4% to
86.3%; P ¼ .004) and long-term care wards (þ4.7% from 87.0% to
91.7%; P ¼ .050), with no significant trend observed in the control
group (Figure 1).
Results from unadjusted and multivariable analyses of the primary
endpoint are in Table 2. The difference between the intervention and
control groups in crude change in adequacy rate from baseline
was þ2.6% in favor of the intervention group, with no statistically
significant intervention effect found on mixed logistic modeling
(crude OR 1.12 [95% confidence interval 0.76;1.64]; adjusted OR
[aOR] ¼ 1.20 [0.81;1.76], P ¼ .366). The intervention group showed an
overall improvement in adequacy of 4.5%. After stratifying by care
unit, intervention effects were more apparent in post-acute and
long-term care wards but were not statistically significant (aOR ¼ 1.44
[0.78;2.66], P ¼ .241; and OR 1.44 [0.68;3.06], P ¼ .345).
Table 3 shows the rates of inadequate, underuse, and overuse of
thromboprophylaxis, globally and by selection for potential predictive
factors of inadequacy (left panel), along with the results from
univariable and multivariable analysis to identify independent
predictors of inadequate practices (right panel). For the overall
18.9% inadequacy rate, 11.1% was attributable to underuse and
7.9% to overuse. Multivariable analysis identified several factors
independently associated with risk of inadequate practices, including
factors associated with overuse (ie, active cancer, acute care ward),
Fig. 1. Adequate thromboprophylaxis practice rates by randomized groups, study period, and care unit.
underuse (cardiac decompensation, myocardial infarction, respiratory
failure, other acute medical event), or both (varicose veins, impaired
mobility).
Discussion
This cluster-randomized trial did not demonstrate efficacy of a
multifaceted intervention for improving thromboprophylaxis
practices in a geriatric setting, despite a significant positive evolution
in the intervention group. Results varied among care wards, with
significant changes in adequacy rates in long-term and post-acute care
wards but no improvement in acute care wards. Several factors
relating to characteristics of patients and medical events were
identified as independent predictors of thromboprophylaxis
inadequacy.
Several explanations might explain our negative result. First, our
intervention, based on educational lectures, posters, and pocket cards,
may be insufficient. A meta-analysis of strategies21 to improve
VTE prophylaxis found that education, alerts, and multifaceted
interventions could increase the prescription of appropriate
prophylaxis, but multifaceted interventions, which included
reminders, audit, and feedback had the largest effect. Second, different
barriers to guideline implementation were identified: lack of
awareness, lack of conviction in the approach, and lack of time.27e29
Some negative attitudes such as disbelief that the intervention will
have the desired outcome may also explain the results.30 Finally, our
preintervention thromboprophylaxis adequacy rate (about 80%) was
higher than those recorded in previous studies, thus, leaving little
room for improvement. Kahn et al,14 with a multinational
cross-sectional survey in acute hospital care settings, found that the
use of recommended VTE prophylaxis varied from 3% to 70% between
countries,14 whereas Garasto et al20 recently reported an overall
adequacy rate of 67.5% for LMWH prescription, with 7.3% and 25.2%
under/over-prescription rates, respectively. The lower frequency of
thromboprophylaxis inadequacy we found might at least partially be
explained by the large diffusion and low cost of DVT prevention
practices with LMWH in France.31
Nevertheless, we found some evidence of improvement of
thromboprophylaxis practice in the intervention group, especially in
P=.027 P=.004 P=.050
 J.P. Rwabihama et al. / JAMDA 19 (2018) 497e503 501

Table 2
Primary Outcome Analysis: Global and Stratified by Care Sector Results

Change from Preintervention in Adequate Practice Rates Effect of Intervention

Control Intervention InterventioneControl OR [95% CI] aOR [95% CI]* Adjusted

Group Group Difference P Value*

Global þ1.9 þ4.5 þ2.6 1.12 [0.76;1.64] 1.20 [0.81;1.76] .366

Stratified by care unit
Acute care þ0.1 þ0.6 þ0.5 0.94 [0.32;2.76] 1.06 [0.35;3.21] .911
Post-acute care þ3.6 þ11.9 þ8.3 1.40 [0.76;2.57] 1.44 [0.78;2.66] .241
Long-term care þ1.7 þ4.7 þ3.0 1.42 [0.67;3.00] 1.44 [0.68;3.06] .345

aOR, adjusted OR; CI, confidence interval.

*aOR and corresponding P value for interaction between group (intervention vs control) and period (postintervention vs preintervention), adjusted for age, sex, mobility
and care sector

post-acute and long-term care wards. This finding is somewhat
consistent with a previous multicenter study32 finding improved VTE
risk assessment and prophylaxis practices for long-term care residents
after a simple educational intervention based on clinical practice
guidelines. The reasons for variations between geriatric care settings
in our study may be related to differences in the characteristics of the
patients. Indeed, in acute care settings, VTE is a frequent and
potentially lethal disease and the increased risk of VTE associated with
acute medical conditions that have an inflammatory component, such
as respiratory/cardiac disease, acute infection, or cancer, is well
recognized. In the study of Oger et al,33 the prevalence of
asymptomatic deep-vein thrombosis on admission in an acute care
ward reached 17.8% among patients older than 80 years. Age
75 years is an independent risk factor of VTE in medically ill
patients,34,35 and the presence of only 1 additional “acute medical
condition” is required to consider thromboprophylaxis for these
patients. Therefore, and as we showed, the risk in geriatric acute care
wards is, above all, prophylaxis overuse. Conversely, VTE prevalence is
assumed to be lower36 in long-stay units for older people with high
chronic dependency but without acute medical conditions, and the
prevention of venous thromboembolic disease is less often discussed.
Then, in long-term care wards, as we also demonstrated, the risk is
prophylaxis underuse.37,38 Relatedly, we found slightly higher rates of
thromboprophylaxis underuse in post-acute care units. Post-acute
care patients constitute a specific population that requires
rehabilitation services to ensure the transition between the short-stay
hospital ward and home.39 In addition to older age, these patients also
have functional disabilities and mobility impairments for which some

Table 3
Factors Associated With Inadequate Thromboprophylaxis Practice: Overall Inadequacy, Underuse and Overuse Rates, and Univariable and Multivariable Analyses (N ¼ 2989)

Inadequacy Underuse Overuse Univariable Analysis Multivariable Analysis

N (%) N (%) N (%) OR (95% CI) P Value aOR (95% CI) P Value

Overall 565 (18.9%) 330 (11.1%) 235 (7.9%) - -

Demographics and general characteristics
Age, y
<80 127 (15.5%) 71 (8.7%) 56 (6.8%) 1 (ref) .001 -
[80‒85] 118 (17.4%) 63 (9.3%) 55 (8.1%) 1.15 (0.87;1.51)
85 320 (21.6%) 196 (13.2%) 124 (8.4%) 1.51 (1.20;1.89)
Creatinine clearance (mL/min)
60 178 (16.7%) 93 (8.7%) 85 (8.0%) 1 (ref) .018 -
<60 386 (20.2%) 236 (12.4%) 150 (7.9%) 1.27 (1.04;1.54)
Sex, women 376 (19.4%) 219 (11.3%) 157 (8.1%) 1.08 (0.89;1.31) .437 -
Signs of dehydration 159 (23.0%) 110 (15.9%) 49 (7.1%) 1.30 (1.06;1.61) .012 -
VTE risk factors
Chronic heart failure 147 (23.4%) 112 (17.9%) 35 (5.6%) 1.42 (1.15;1.75) .001 -
Chronic respiratory failure 66 (30.7%) 54 (25.1%) 12 (5.6%) 2.02 (1.49;2.74) <.001 -
Active cancer 87 (30.7%) 24 (8.5%) 63 (22.3%) 2.06 (1.57;2.70) <.001 2.14 (1.57;2.94) <.001
Hormone replacement therapy 12 (44.4%) 2 (7.4%) 10 (37.0%) 3.47 (1.62;7.46) .001 -
VTE history 41 (21.4%) 17 (8.9%) 24 (12.5%) 1.17 (0.82;1.68) .381 -
Myeloproliferative disease 14 (29.8%) 8 (17.0%) 6 (12.8%) 1.83 (0.98;3.45) .060 -
Varicose veins 51 (27.7%) 23 (12.5%) 28 (15.2%) 1.70 (1.22;2.38) .002 1.89 (1.27;2.82) .002
Impaired mobility (ECOG-PS 3-4) 437 (21.6%) 241 (11.9%) 196 (9.7%) 1.77 (1.43;2.20) <.001 1.43 (1.12;1.82) .004
Acute medical events
Congestive heart failure 96 (53.6%) 91 (50.8%) 5 (2.8%) 5.75 (4.22;7.84) <.001 4.66 (3.29;6.61) <.001
Myocardial infarction 17 (56.7%) 17 (56.7%) 0 (0.0%) 5.73 (2.77;11.88) <.001 8.27 (3.71;18.44 <.001
Respiratory failure 68 (52.7%) 62 (48.1%) 6 (4.7%) 5.28 (3.69;7.56) <.001 3.33 (2.19;5.07) <.001
Stroke 13 (31.0%) 12 (28.6%) 1 (2.4%) 1.94 (1.00;3.76) .049 -
Others 200 (57.8%) 182 (52.6%) 18 (5.2%) 8.12 (6.38;10.34) <.001 7.53 (5.81;9.75) <.001
Care unit and study period
Unit
Acute care 152 (30.3%) 55 (11.0%) 97 (19.4%) 1 (ref) <.001 1 (ref) <.001
Post-acute care 283 (22.5%) 174 (13.8%) 109 (8.7%) 0.67 (0.53;0.84) 0.83 (0.64;1.08)
Long-term care 130 (10.6%) 101 (8.3%) 29 (2.4%) 0.27 (0.21;0.36) 0.41 (0.30;0.56)
Period
Preintervention 293 (20.6%) 187 (13.2%) 106 (7.5%) 1 (ref) .027 -
Postintervention 272 (17.4%) 143 (9.2%) 129 (8.3%) 0.81 (0.68;0.98)

aOR, adjusted OR; CI, confidence interval; ECOG-PS, Eastern Cooperative Oncology Group Performance Status.
Bolded results are statistically significant at the P < .05 level.
502 J.P. Rwabihama et al. / JAMDA 19 (2018) 497e503
evidence exists regarding a possible association with VTE,40 but whose
assessment remains challenging because of to the lack of a
standardized and operational definition.41 Altogether, a possible
explanation for the lack of improvement in acute care settings in our
study may lie in the design of our intervention, whose motivational
components may have had more success in incentivizing professionals
to increase their prophylaxis practices rather than to limit overuse, an
effect that translated favorably in post-acute care and long-stay units
mostly characterized by underuse, but with mixed results in acute
care wards.
Active cancer was found independently associated with
thromboprophylaxis inadequacy, mostly by overuse. Hospitalized
patients with cancer are at increased risk of VTE. Current clinical
international practice guidelines all recommend the usual
prophylactic doses of LMWH for patients with cancer requiring
hospitalization for acute medical illness in the absence of bleeding or
other contraindications to anticoagulation therapy.42 However, the
risk/benefit ratio of thromboprophylaxis in patients with cancer who
are hospitalized with a medical illness has never been formally
assessed.43 Consistent with other studies,14,17,44,45 congestive heart
failure, myocardial infarction, and respiratory failure were found
independently associated with thromboprophylaxis underuse.
The main strengths of our study include the cluster-randomized
design and the large sample size, which provided sufficient
statistical power to check for a time effect and avoid contamination
bias. Our study is also the first, to our knowledge, to compare the
efficacy of a multifaceted intervention on VTE prevention practice in
different geriatric settings, which allowed for assessing potential
variability in intervention effect. The study also has some limitations.
First, we focused on antithrombotic treatment and did not assess
mechanical thromboprophylaxis, or contraindications of thrombo-
prophylaxis, such as history of bleeding or induced thrombopenia.
Second, despite specific randomization procedures to limit imbalance
in the groups, we found some differences in the number of patients
and patient characteristics between the 2 groups, an observation
probably relating to the relatively low number of randomized wards.
Finally, our study was performed in French teaching hospitals, and
generalizability to other countries and/or settings is cautioned.
Conclusions
This prospective, controlled, cluster-randomized, multifaceted,
interventional trial, aiming to implement current recommendations for
thromboprophylaxis for older patients in different hospital settings,
failed to demonstrate improvement in prophylaxis adequacy. The
intervention seemed to improve practice in post-acute and long-term
care but not in acute care wards. The trend was for prophylaxis
overuse in acute care wards and underuse in post-acute and long-term
care wards. New strategies are required to address thromboprophylaxis
in older patients, including those accounting for the specificity of care
and based on computerized reminders and alerts.
Acknowledgments
We thank Laura Smales for language editing the manuscript.
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