Researching Venous Thromboembolism in
vulnerable adult populations
Professor DA FitzmauriceDepartment of Primary Care & General Practice
University of Birmingham
Conclusions 1• Risk factors for venous thromboembolism (VTE) are
common and widespread (and not just in hospital)• VTE is a common disease
• VTE is a major cause of death
• The majority of VTE-associated deaths are sudden PE or following undiagnosed and untreated VTE
• Therefore VTE must be managed by prevention
Conclusions 2• Many of these events and deaths are
preventable with available effective prophylaxis
• We know this is true for hospital in-patients, lack of research outside medical/surgical environments
VTE
• Comprises DVT and PE
• 3rd leading cause of cardiovascular mortality• 25-60,000 deaths per year in UK• 900,000 across Europe• 50% may be due to hospital stay • 1/20 lifetime incidence
THE SIZE OF THE VTE PROBLEM
• An estimated 60,000 deaths due to VTE in the UK• 2/3 due to hospital admission of which 25,000 are preventable
• Hospital acquired VTE causes more deaths than hospital -
acquired infection (MRSA & C difficile, peaked at 10,000)
• Autopsy data suggests reported incidences are markedly
underestimated. Baglin J Clin Path 1997; 50: 609-10
• Registered deaths in England in 2007 -19,000- but
underdiagnosed…(House of Commons Question summer 2009)
Hospital Preventive Strategies
"Making Health Care Safer: a Critical Analysis..."
A systematic review ranked 79 safety interventions
• Based on the strength of evidence
• The highest ranked safety practice was the "appropriate use of prophylaxis to prevent VTE.."
• Based on overwhelming evidence that thromboprophylaxis reduces adverse patient outcomes and decreasing overall costs
Shojania KG. Agency for Healthcare Research and Quality 2001; 20 July. Available at www.ahrq.gov/clinic/ptsafety.
VTE prevention in
SURGICAL patients
Heparin Reduces Total Mortality, Fatal PE and does not Increase Major Bleeding1
1. Collins R, et al. N Engl J Med 1988;318:1162–73
(1.7%) 109
7
191 (3.0%)
6
210223
PE Fatalbleeds
‘Other’ deaths
0
50
100
150
200
250
H C H C H C
Heparin n = 6366 Control n = 6426
Num
ber o
f sub
ject
s af
fect
ed
Non-fatal events
Fatal events
55 (0.9%)
(0.3%) 19
Total mortality
RRR 21%, p <0.02
VTE prevention in
MEDICAL patients
Anticoagulant prophylaxis to prevent symptomatic
VTE in hospitalized medical patients
RR [CI] Absolute risk reduction (%)
NNTB
Any PE 0.43 0.26 – 0.71 0.29 345
Fatal PE 0.38 0.21 – 0.69 0.25 400
Symptomatic DVT 0.47 0.22 – 1.00
Major bleeding 1.32 0.73 – 2.37
All cause mortality 0.97 0.79 – 1.19
Dentali F et al. Ann Intern Med. 2007; 146:278-288
• meta-analysis of 9 randomized trials comparing anticoagulant prophylaxis (UFH, LMWH, fondaparinux) with no treatment in hospitalized medical patients, n = 19,958
VTE prevention in
PRACTICE
ALIVE
DEAD
Coils of fresh thrombo-emboli straddled the pulmonary bifurcation and occluded branches of pulmonary arteries
Fresh thrombi in deep veins of both calves
Enlarged LV and evidence of hypertensive heart disease
Post mortem
Overview
• The problem
• Risk factors
• Prophylaxis in medical patients
• Therapeutic options
• New studies
Public / Media perception - travel
Travelling in cramped conditions
Other media perceptions: Game-
related / Office Workers?
VTE Hospital Trends
1. Alikhan R et al. J Clin Pathol 2004;57(12)1254-1257.2. Cohen AT, et al. Haemostasis. 1996;26:65-71.
71% reduction in fatal PE
Fata
l P
E (
%)
Surgical patients1,2
2.1%
0.6%
0
2
4
1966 2000
18% reduction in fatal PE
Medical patients1,2
Fata
l P
E (
%)
3.3%4.0%
0
2
4
1966 2000
Autopsy-detected Fatal PE inSurgical and Medical patients (21,515): 1966–2000
• Incidence of fatal PE
• Studies from Scandinavia, USA and UK
• 59% to 83%Nielsen et al. Acta Med Scand 1981;209:351-5Hauch et al. Acta Chir Scand 1990;156:747-9
Sperry et al. Hum Pathol 1990;21:159-65Cohen et al. Haemostasis 1996;26:65-71
Autopsy Proven Fatal PE
% in Medical Patients
60% of admissions
75% of PE deaths
Medical Inpatients
10% of consensus statements
Cohen et al. Haemostasis 1996;26:65-71
Epidemiology of VTE
• Mortality
Hypothesised Cause of Death of Jesus
Cause of Death Author’s background
Cardiac Rupture Cardiologist
Heart Failure General Physician
Hypovolaemic shock Forensic Pathologist
Syncope Surgeon
Acidosis Physician
Asphyxia Surgeon
Arrhythmia + Asphyxia Pathologist
Pulmonary Embolism Haematologist
Voluntary Surrender Life Physician
Didn’t actually Die Doctor of Theology
Clinical Suspicion of PE
Author Major
PE (n)
Autopsy
(n)
Death
(n)
SuspectedPE
Goldhaber
1973–1977
54 1,455 2,372 30%
Rubinstein
1980–1984
44 1,276 3,517 32%
Morgenthaler
1985–1989
92 2,427 5,358 32%
Pineda
1991–1996
67 778 6,023 45%
Pineda LA et al. Chest 2001;120:791–5
Overview
• The problem
• Risk factors
• Prophylaxis in medical patients
• New studies
Attributable Risk for DVT/PE
Risk factor AR (95% CI)
Hospitalization with surgery 23.8 (20.3–27.3)
Hospitalization without surgery 21.5 (17.3–25.6)
Malignant neoplasm 18.0 (13.4–22.6)
Congestive heart failure 9.5 (3.3–15.8)
Neurological disease with extremity paresis 6.9 (3.5–10.2)
Heit et al. Arch Intern Med 2002;162:1245-859 % Medical
Overview
• The problem
• Risk factors
• Prophylaxis in medical patients
• New studies
• Therapeutic options
Here is Darla being kissed by Chuck Ford, Senior Director of Clinical Operations for the Emergency Department of the IU Burn Center at Wishar
Heparins work
No trials of mechanical compression in general medical
patientsPassive Active
MEDENOX1 63% Placebo
Enoxaparin
PREVENT2 49% Placebo
Dalteparin
ARTEMIS3 47% Placebo
Fondaparinux
14.9*
5.5
Study RRR Thromboprophylaxis Patients with VTE (%)
5.0*
2.8
10.5†
5.6
*VTE at day 14; †VTE at day 15.1Samama MM, Cohen AT et al. N Engl J Med. 1999;341:793-800.
2Leizorovicz A, Cohen AT et al. Circulation. 2004;110:874-9.3Cohen AT, Davidson B et al. BMJ 2006.
p < 0.001
p = 0.0015
p = 0.029
RRR = relative risk reduction
Medical thromboprophylaxis – consistent response
Major bleeding
MEDENOX 1. 1% 1.7%
PREVENT 0.2% 0.5%
ARTEMIS 0.2% 0.2%
Overview
• The problem
• Risk factors
• Prophylaxis in medical patients
• New studies
– based on ACCP recommendations
ACCP
American College of Chest Physicians recommendations
Are the gold standard
Are not just American but are written by experts from all over the globe
New Studies
VITAE – Epidemiology
PREVAIL Study – Stroke
ENDORSE study – Survey
EXCLAIM study – Medical
The Burden – VITAE Study
0
10000
20000
30000
40000
50000
60000
70000
VTE Breast cancer Road trafficaccidents
AIDS
VTE is a serious and preventable problem
(UK)More people die from VTE than the combined figure who die
from breast cancer, road traffic accidents and AIDS1-5
Num
ber
of d
eath
s pe
r ye
ar
1. House of Commons Health Committee Report. Second Session 2004-2005.2. Cohen AT,.VITAE, Thrombosis and Haemostasis 20073. Cancer Research UK Mortality Cancer Stats 2005. Available at www.cancerresearchuk.org4. Department of Transport, Road Casualties Great Britain, Main results 2006. Available at www.dft.gov.uk5. National Office of Statistics (NAO). HIV and AIDS. Available at www.statistics.gov.uk
VTE is a serious medical problem
VTE causes 60,000 deaths each year in the UK.;
37 times greater than the annual deaths from MRSA1,2
0
10000
20000
30000
40000
50000
60000
70000
VTE MRSA
Num
ber
of d
eath
s pe
r ye
ar
1. Cohen AT et al T&H 2007 2. National Office of Statistics (NAO). MRSA. Deaths Available at www.statistics.gov.uk
Total VTE events and mortality per year
extrapolated to 25 EU countries
*Cohen AT et al VITAE study, Thrombosis and Haemostasis Oct 2007.**Eurostat statistics on health and safety 2001. Available from: http://epp.eurostat.cec.eu.int.
Deaths due to VTE 543,454*
Exceed combined deaths due to– AIDS 5,860**
– breast cancer 86,831**
– prostate cancer 63,636**
– transport accidents 53,599**
Design and hospital characteristics
• Multinational, cross-sectional survey
• Hospitals randomly selected from authoritative national lists of all acute care hospitals
• Hospitals with greater than 50 beds for
– Acute medical illnesses
– Elective major surgery
All hospital wards were included in this
survey except• Psychiatric
• Pediatric
• Palliative care
• Maternity/obstetrics
• Neonatal
• Burn units
• Eye, ear, nose and throat units
• Dermatological/ophthalmologic wards
• Rehabilitation units/wards
• Emergency units
• Long-term care units
Objectives
• Primary
– To identify patients at risk for venous thromboembolism (VTE) hospitalized in representative hospitals throughout the world
– To determine the proportion of patients who receive effective VTE prophylaxis
• Secondary
– To define the above globally by acute illness (in medical and surgical populations)
32 countries -- 358 hospital32 countries -- 358 hospital
First pt in August 2006 - Last pt in January 2007Median of 8 days to enroll patients/hospital
Patients in medical & surgical wards
( N =68,183)
55%
45%
Surgical(N =30,827)
Medical(N =37,356)
Patients at risk for VTE and receiving ACCP
recommended prophylaxisPrimary objectives
52% at risk for VTE
50% received ACCPrecommended Px
Overall
( N= 68,163 )
42% at risk for VTE
48% received ACCPrecommended Px
Medical( n = 37,356 )
Secondary objectives
64% at risk for VTE
59% received ACCPrecommended Px
Surgical( n = 30,827 )
Cohen AT, Tapson VF, Bergmann J-F et al, Lancet 2008; 371:387-394
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 1011121314151617181920212223242526272829303132
Pe
rce
nt
Patients at risk for VTE by country
Mean=52%
N= 68,183
52% at risk for VTE
Alger
ia
Austra
lia
Bangl
ades
h
Brazil
Bulga
ria
Colom
bia
Czech
Rep
Egyp
t
Fran
ce
Germ
any
Greec
e
Hunga
ryIn
dia
Ireland
Kuwai
t
Mex
ico
Pakist
an
Poland
Portu
gal
Roman
ia
Russia
Saud
i Ara
bia
Slov
akia
Spain
Switz
erland
Thailand
Tuni
sia
Turk
eyUAE UK
USA
Venez
uela
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 1011121314151617181920212223242526272829303132
Pe
rce
nt
ACCP recommended prophylaxis
by country in patients at risk for VTE
Alger
ia
Austra
lia
Bangl
ades
h
Brazil
Bulga
ria
Colom
bia
Czech
Rep
Egyp
t
Fran
ce
Germ
any
Greec
e
Hunga
ryIn
dia
Ireland
Kuwai
t
Mex
ico
Pakist
an
Poland
Portu
gal
Roman
ia
Russia
Saud
i Ara
bia
Slov
akia
Spain
Switz
erland
Thailand
Tuni
sia
Turk
eyUAE UK
USA
Venez
uela
50% received VTE prophylaxis
Conclusions - ENDORSE
• First global view of VTE risk and prophylaxis practices
• Unprecedented scope: 32 Countries, 358 Hospitals, 68,183 Patients
• Risk for VTE is common (52%)– 64% of surgical patients– 42% of medical patients
• Prophylaxis is underutilized (50%)– Surgical patients: Omitted in 41%– Medically ill population: Omitted in 60%
Cohen AT, Tapson VF, Bergmann J-F et al, Lancet 2008; 371:387-394
These data reinforce the rationale to
• Urgently implement hospital-wide strategies
• Systematically assess patient risk for VTE
• Provide appropriate prophylaxis to prevent VTE
Cohen AT, Tapson VF, Bergmann J-F et al, Lancet 2008; 371:387-394
Thromboprophylaxis political momentum
NHS Operating Framework inclusion 2010/11
2004 2005 2006 2007 2008 2009 2010
Consistent investment and a coherent strategy leads to Department of
Health taking ownership for VTE prevention
Government documents on VTE prevention
March 2005 July 2005 April 2007 April 2007
The role of Primary Care
• Ensuring implementation of extended thromboprophylaxis
• Education of patients
• Risk Assessment?
• Commissioning of services?
Research?
• Residential homes
• Nursing homes
• Hospices
• Acutely unwell in own home
Issues
• Perception of importance
• “A good way to go”
• Measuring incidence/prevalence
• Use of chemical agents in the community
Proposed study
• Nursing home
• 1000 residents from 60 homes
• Baseline assessment of VTE risk taken, co-morbidity, medication, functional ability and VTE prevention strategies and then followed up 3 monthly for 1 year.
• Case records will be checked for any change in risk status from baseline.
Proposed study
• Outcomes: number of VTE events, associated hospital admissions, deaths and costs in relation to risk assessment and preventive strategies.
• Develop a pragmatic risk assessment tool for NH residents, building on the DH risk assessment tool for hospital in-patients
Conclusions 1• Risk factors for venous thromboembolism (VTE) are
common and widespread (and not just in hospital)• VTE is a common disease
• VTE is a major cause of death
• The majority of VTE-associated deaths are sudden PE or following undiagnosed and untreated VTE
• Therefore VTE must be managed by prevention
Conclusions 2• Many of these events and deaths are
preventable with available effective prophylaxis
• We know this is true for hospital in-patients, lack of research outside medical/surgical environments
Co-operation and balance are the keys to success
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