CARDIO `016

J.C. WAUTRECHT
Service de Pathologie Vasculaire , Hôpital ERASME
Université Libre de Bruxelles
CARDIO ‘016
THE HOTEL BRUSSELS
21 MAI 2016
LIGUE
CARDIOLOGIQUE
BELGE
ASBL
VEINES
§  Traitement de la TVP
§  Traitement de l’IVC MI
§  Bas de compression
31/05/16
2
VEINES
§  Traitement de la TVP
§  Traitement de l’IVC MI
§  Bas de compression
31/05/16
3
risk factor identifıed (idiopathic), and in 10%–20% there is
no acquired or genetic risk identifıed, signifying the effect of
still unknown genetic and/or acquired risk factors.12,13,18
Known acquired risks include chronic disease, cancer,
obesity, antiphospholipid antibodies, and advanced
Morbidity and Mortality
age.6,9,11,19 –21 Other acquired risks can be thought of as
Venous thromboembolism is often fatal. Depending on
transient states, which include surgery, trauma, immobicase ascertainment and the use of autopsy data, studies
lization, infection, and hospitalization.6,8,19 –21 Women
estimate that 10%–30% of all patients suffer mortality
also have increased risk during pregnancy and the postS496
/ Am J Prev
Med
2010;38(4S):S495–S501
within 30 days; the Beckman
majorityetofaldeaths
occur
among
those
partum period and while taking hormonal contraceptives
11,22–25
withincidence
PE, as anofestimated
present
Table 1. Estimated
venous 20%–25% of all PE cases
hormone
replacement
therapy.
Hospitalizaclots, which also and
decreases
quality
of life and places
them
6,8 –10
asbysudden
death.
Other serious complications
of
thromboembolism
age, race,
and gender
tionfor
is an
especially
important
risk factor as it provides a
at an increased risk
adverse
bleeding
episodes.
DVT and PE include increased risks of recurrent thromunique period in which multiple risk factors may be
Characteristics boembolismAnnual
incidence
per 1000
and chronic
morbidity
(e.g., venous
insuffı- Burden
Economic
Race/ethnicity ciency, pulmonary hypertension). Following a standard
is complex
and presents
in
Table 2. Identified
risk factors
for venous
course of anticoagulant
therapy, about oneVenous
third ofthromboembolism
all
White
1.173
thromboembolism
both
inpatient
and
outpatient
settings,
and
although
many
VTE patients experience
a recurrence within 10 years of the
Black
0.776–1.415
casesthe
have
to hospitalization, about two
initial event, with the highest risk occurring within
fırstbeen attributed
Genetic
Acquired
Transient acquired
7
6,14
thirds ofOne
cases occur in outpatients.16 Although data are
Asian
0.29 at risk throughout their lives.
year, yet they remain
history
Advanced
ageanalysis
Pregnancy
lacking
on the exactFamily
cost attributed
to VTE,
a recent
third to one half
of7lower-extremity DVT patients
develop
Hispanic
0.61
Factor
V Leiden
Oral contraceptives
of healthcare
estimated
that the Antiphospholipid
total annual healthpost-thrombotic syndrome and chronic venous
insuffı- claims
Age (years)
antibodies
care
cost
for
VTE
ranges
from
$7594
to
$16,644
per
paciency, lifelong conditions
characterized by pain, swelling,
!15
!0.53,8
tient.17 With estimates
of 300,000 – 600,000
Prothrombin
Cancerincident cases
Hormone therapy
skin necrosis, and
ulceration.6,15
G20210A
3
per
year,
this
cost
equates
to
a
total
annual
cost
of
$2
billion
15–44
1.49has been reported to be adversely afQuality of life
$10 billion
VTE.
Protein to
C deficiency
Chronic disease Hospitalization
9
fected
up
to
4
months
after DVT, and fortothose
with attributable
45–79
1.92
post-thrombotic syndrome,
quality
of
life
actually
deProtein S deficiency Obesity
Surgery
!80
5–63,4,8,9
Etiology
and Risk Factors
clines further during this period, with changes
similar to
Antithrombin
—
Trauma
Gender
those seen in individuals with chronic heart,
or of VTEdeficiency
Thelung,
etiology
is not fully understood. It is a multi15
arthritic disease.
patients
factorial
conditionSickle
involving
genetic —
and both constant
Male
1.33 In addition, subsets of VTE
cell trait
Immobilization
require
long-term
additional
and
transient
acquired
risk
factors
(Table
2). A threshold
3 anticoagulation to prevent
Female
1.1
seems to exist, as the presence of one risk factor does not
Overall
1–23–5
always result in disease status; however, an interactive
www.ajpm-online.net
effect of multiple triggers and events can lead to clot
formation. Yet, in about 50% of cases there is no acquired
risk factor identifıed (idiopathic), and in 10%–20% there is
and PE, the limitations of administrative databases, and
no acquired or genetic risk identifıed, signifying the effect of
the regional and racial specifıcity of community-based
12,13
still unknown genetic and/or acquired risk factors.12,13,18
studies, VTE may be vastly under-reported.
Known acquired risks include chronic disease, cancer,
obesity, antiphospholipid antibodies, and advanced
Morbidity and Mortality
age.6,9,11,19 –21 Other acquired risks can be thought of as
Venous thromboembolism is often fatal. Depending on
transient states, which include surgery, trauma, immobicase ascertainment and the use of autopsy data, studies
lization, infection, and hospitalization.6,8,19 –21 Women
31/05/16
estimate that 10%–30% of all patients suffer mortality
also have increased risk during pregnancy and the postwithin 30 days; the majority of deaths occur among those
partum period and while taking hormonal contraceptives
and PE, the limitations of administrative databases, and
the regional and racial specifıcity of community-based
studies, VTE may be vastly under-reported.12,13
VTE : quelques données…
MG Beckman et al. Am J Prev Med 2010;38:S495-­‐S501 4
CONCEPT ACTUEL DE L ’ANTICOAGULATION SI TVP/EP
§  Traitement initial (anticoagulation rapide)
§  HBPM puis AOD (Dabigatran, Edoxaban)
§  AODs seuls (Rivaroxaban, Apixaban)
§  Traitement prolongé (extended treatment)
§  Minimum 3 mois
§  Traitement au long cours (long term treatment)
§  Au-delà de 3 à 12 mois
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5
INCIDENCE CUMULÉE DE RÉCIDIVES DE VTE APRÈS
ARRÊT DES ANTICOAGULANTS
FU moyen de 50 mois de 1626 pa3ents consécu3fs avec EP ou TVP proximale P Prandoni et al.Haematologica 2007;92:199-­‐205 31/05/16
6
TAUX CUMULÉ DE RÉCIDIVES DE VTE (TVP/EP) APRÈS ARRÊT
DES ANTICOAGULANTS
TVP prox n= 259 TVP dist isolées n= 490 OPTIMEV. Galanaud JP et al. J Thromb Haem 2014;12:436-­‐443 31/05/16
7
ACUTE AND EXTENDED (LONG-TERM) TREATMENT OF
VTE
Dabigatran LMWH > 150 mg bid 150 mg bid Edoxaban LMWH > 60 or 30 mg od (vs warfarin) (vs placebo) (vs placebo) Rivaroxaban 15 mg bid 21 days > 20 mg od 20 mg od Apixaban 10 mg bid 7 days > 5 mg bid 5 or 2.5 mg bid 31/05/16
Adapted from P Fontana et al. Eur Heart J 2014;35:1836-­‐1843 8
TRAITEMENT DE LA TVP/EP AVEC LES AODS (NOACS)
§  Apixaban (Eliquis®)
§ 
§ 
§ 
§ 
Aigu : 2 x 10 mg /j (comp à 5 mg) pendant 7 jours
Entretien : 2 X 5 mg/j 6 mois et si plus longtemps : 2 x 2,5 mg/j
Précautions si Clearance créat 15-29 ml/min
CI si Clearance créat < 15 ml/min
§  Dabigatran (Pradaxa®)
§  Aigu : HBPM min 5 j puis 150 mg 2x/j
§  Entretien : 2 x 150 mg/j
§  Adaptation à 2 x 110 mg/j si ≥ 80 ans et/ou vérapamil et/ou risque
hémorragique individuel accru
§  CI si Clearance créat < 30 ml/min
31/05/16
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TRAITEMENT DE LA TVP/EP AVEC LES AODS (NOACS)
§  Edoxaban (Lixiana®) : prévu septembre 2016
§  Aigu : HBPM min 5 j puis 60 mg/j
§  Entretien : 60 mg/j
§  Adaptation à 30 mg/j si Clearance créat 30-59 ml/min et/ou ≤ 60
kg
§  Rivaroxaban (Xarelto®)
§ 
§ 
§ 
§ 
31/05/16
Aigu : 2 x 15 mg/j pendant 21 jours
Entretien : 20 mg/j
Prudence si Clearance créat 15-29 ml/min
CI si clearance créat< 15 ml/min
10
ELIQUIS®
TVP ET EP
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XARELTO® TVP
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XARELTO EP
(glissé(e)s).pdf
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13
PRADAXA TVP
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PRADAXA EP
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LONG COURS : POSSIBILITE DE DIMINUER DOSES ?
EINSTEIN CHOICE STUDY : CRITÈRES D’ INCLUSION
§  Patients ayant reçu un traitement anticoagulant
de 6 à 12 mois (± 1 mois) et n’ayant pas
interrompu leur traitement pendant plus d’une
semaine
16
EINSTEIN CHOICE STUDY
§  Etude multicentrique, en double-aveugle, en
double insu, randomisée, guidée par les
événements et contrôlée par comparateur actif
§  Randomisation : système réponse vocale
automatique (IVRS) ou réponse web interactif
(IWR)
§  Traitement pendant 12 mois
§  10 mg Rivaroxaban OU
§  20 mg Rivaroxaban OU
§  100 mg ASA
31 mai 2016
17
VEINES
§  Traitement de la TVP
§  Traitement de l’IVC MI
§  Bas de compression
31/05/16
18
SUMMARY OF THE 2014 GUIDELINE RECOMMENDATIONS
FOR THE USE OF VENO-ACTIVE DRUGS
Indication Relief of symptoms associated with
CVD (CEAP C0s to C6s) and those
with venous edema (CEAP C3) Veno-active drug MPFF Nonmicronized diosmins or
synthetic diosmins Rutosides Red-vine-leaf extracts Calcium dobesilate Horse chestnut seed extract Ruscus extracts Gingko biloba Other veno-active drugs Healing of primary venous ulcer
(CEAP C6), as an adjunct to
comprehensive and local therapy MPFF Recommendation
for use Strong Weak Weak Weak Weak Weak Weak Weak
Weak Quality of evidence Grade Moderate Poor Moderate Moderate Moderate Moderate Moderate Poor
Poor 1B 2C 2B 2B 2B 2B 2B 2C
2C Strong Moderate 1B CEAP : clinical, etiological, anatomical, and pathophysiological classi7ication
MPFF : micronized puri7ied 7lavonoid fraction
Int Angiol 2014;33:126-­‐139 31/05/16
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VEINES
§  Traitement de la TVP
§  Traitement de l’IVC MI
§  Bas de compression
31/05/16
20
31/05/16
21
POST THROMBOTIC SYNDROME (PTS)
§  PTS develops in 20 to 50 % of patients with DVT, even
when appropriate anticoagulant therapy is prescribed.
§  PTS is the single most frequent complication of DVT.
§  PTS is burdensome and potentially debilitating to patients.
§  PTS has been shown to have significant, adverse effects
on quality of life and productivity, and is costly as
measured by health resource utilization, directs costs, and
indirect costs.
SR Kahn, Blood 2009;114:4624-­‐4631 31/05/16
22
POST THROMBOTIC SYNDROME (PTS)
§  « Syndrome » because various symptoms and
clinical signs – PTS is a clinical diagnosis
SR Kahn, Blood 2009;114:4624-­‐4631 31/05/16
23
POST THROMBOTIC SYNDROME (PTS)
31/05/16
SR Kahn, Blood 2009;114:4624-­‐4631 24
POST THROMBOTIC SYNDROME (PTS)
§  Risk factors
§  Higher BMI
§  No relationship between age, sex or thrombophilia and the
development of PTS
§  No clear greater risk for proximal over distal DVT
§  Strong association when ipsilateral recurrent DVT
§  Role of venous reflux due to valvular incompetence and venous
hypertension due to thrombotic occlusion
§  Persistent D-dimer level could be a predictor of PTS
W Ageno et al. Thromb Haemost 2003;89:305-­‐309 L Spieza et al. J Thromb Haemost 2010;8:211-­‐213 J Latella et al. J Thromb Haemost 2010;8:2169-­‐2175 31/05/16
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PREVENTION OF POST THROMBOTIC SYNDROME (PTS)
WALKING
§  Several small studies and meta-analyses have
shown that early ambulation does not increase
the risk of recurrent or fatal PE
N Aissaoui et al. Int J Cardiol 2009;137;37-­‐41 §  The risk of PE during more aggressive forms of
exercise, physical therapy, or rehabilitation is
unknown
31/05/16
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PREVENTION OF POST THROMBOTIC SYNDROME (PTS)
COMPRESSION STOCKINGS
§  Evidence supporting the use of GCS for the prevention of PTS is
conflicting.
§  3 small randomized trials of patients with acute proximal DVT that used
the Villalta criteria for PTS suggested that GCS that apply an ankle
pressure of 30 to 40 mm Hg started within 2 weeks and continued for 2
years reduced the risk of PTS by 50 %
§  Compliance was up to 90 %
DPM Brandjes et al. Lancet 1997;349:759-­‐762;JS Ginsberg et al. Arch Intern Med 2001;161:2105-­‐2109; P Prandoni et al. Ann Intern Med 2004;141:249-­‐256 §  A recent randomized placebo-controlled trial of 806 patients with a
proximal DVT using the less stringent Ginsberg criteria reported no
difference in the rate of PTS with GCS (14 vs 13 %). A similar lack of
benefit was reported when the more rigorous Villalta criteria were applied.
§  Compliance was lower than in the 3 other studies : only 55.6 % of patients
used GCS for 3 or more days a week after 2 years.
RS Kahn et al. Lancet 2014;383:880-­‐888 31/05/16
27
PTS AND GCS : META-ANALYSIS
31/05/16
AL Skervin et al., Eur J Vasc Endovasc Surg 2016 h\p://dx.doi.org/10.1016/j.ejvs.2016.02.022 28
TAKE HOME MESSAGE FOR THE DOCTOR
PREVENTION OF PTS TODAY : COMPRESSION OR NOT ?
§  The role of compression stockings following DVT remains uncertain,
with further evidence needed
§  It is presently reasonable to prescribe below-knee GCS with 30 to 40
mm Hg pressure to patients who have residual leg pain or swelling
after proximal or distal DVT if they have benefit and if they are able to
tolerate them.
§  GCS should be started after initiation of anticoagulant therapy, within
2 weeks of the diagnosis, during the day and for at least 2 years.
§  A multicentre randomised trial comparing usual care (ECS for 2 years)
with individualised care based on Villalta scores is in progress
(ClinicalTrials.gov, NCT01429714). This future study will hopefully
give additional information on some open questions: is there any
benefit of treatment with GCS, which patients benefit most, and what
is the optimum treatment duration?
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TAKE HOME MESSAGE FOR THE PATIENT ABOUT
COMPRESSION STOCKINGS
31/05/16
SR Vazquez,SR Kahn. Circula`on 2010;121:e217-­‐e219 30