Transcript ArtWheeler-PreventionOfDVTPE

Prevention of DVT & PE
Arthur P. Wheeler, M.D.
Associate Professor of Medicine
Director MICU, Co-chair P&T
Division of Allergy, Pulmonary and Critical Care Medicine
Vanderbilt Medical Center
Disclosures:
Consultant: Sanofi-Aventis, Astra-Zeneca, Eli-Lilly, Pfizer, Boehringer-Ingleheim
Research support: NIH-NHLBI, Takeda, Novo-nordisc
Stockholder: Cumberland pharmaceuticals
Copyright A.P. Wheeler 2007
Thromboembolism epidemiology
5 million DVT’s
900,000
PE’s
290,000 fatalities
Heit J. Blood. 2005;106:910.
Thromboembolism is a disease of
hospitalized patients
1000
71% received no prophylaxis
in prior 30 days
100
50% in nursing homes or
<90 days post-discharge
Cases / 10,000
person years
10
1
Hospitalized
Heit Mayo Clin Proc 2001; 76:1102
Goldhaber Am J Cardiol 2004; 93:259
Community
Virchow’s triad
Advancing age
Immobilization
Stroke - cord injury
Anesthesia
Heart or lung failure
Hyperviscosity
Surgery
Prior DVT
Venous access
Trauma
Sepsis
Vasculitis
Hypercoagulable State
Cancer
Estrogen
Family history
Sepsis
HIT
Protein C, S or AT III deficiency
Activated protein C resistance
(Leiden)
Hyperhomocystenemia
Antiphospholipid antibody
Prothrombin 20210 mutation
DVT Incidence absent prophylaxis
Cord Injury
Nicolaides 1997
Stroke
Nicolaides 1997
MICU
Hirsch 1995
General Surgery
Gallus 1994
Acute MI
Handley 1972
General Medical
Mismetti 2000
0
Geerts WH. Chest. 2008;133:381S-453S
20
40
60
80
100
LMWH prophylaxis in medical
patients: study design
Treatment
Follow-up
Placebo
Respiratory failure
CHF
Infections
Enoxaparin 20 mg QD
Day -3
Enoxaparin 40 mg QD
Day 1
Day 6-14
Randomization
n=1102
Bilateral
Venography
Samama NEJM 1999;341:793.
Day 83-110
LMWH prophylaxis in medical
patients: thrombosis to day 14
P=0.0002
Placebo
20
Enoxaparin 20 mg
Enoxaparin 40 mg
15
P=0.0370
10
5
NS
0
All VTE
Samama NEJM 1999;341:793
Proximal DVT
PE
Risk stratification in surgery
Calf DVT
%
Proximal
DVT %
Clinical
PE %
Fatal PE
%
<2
0.4
0.2
.002
Moderate
10-20
2-4
1-2
.1-.4
High
20-40
4-8
2-4
04-1
Very High
40-80
10-20
4-10
0.2-5
Low
Geerts WH. Chest. 2008;133:381S-453S
Medical prophylaxis: placebo
controlled trials
Nadro
3800-5700 U qd
p=0.05
30
25
20
Percent
15
VTE
placebo
heparin
5000 UFH
q12
p=NS
Enox
40 mg qd
p<0.001
5000 UFH
q12
p=NS
Nadro
7500 U qd
p=NS
Enox
60 mg qd
p=0.04
10
5
0
Halkin 1982 Gardlund
1996
n=1358
n=11,693
Dahan
1986
n=270
Samama
1999
Caulin
1989
n=1102
n=2474
Fraisse
2000
n=223
Prophylaxis LMWH vs. UFH:
lower risk groups
UFH
LMWH
10
8
Percent
VTE
Nadro 1500 QD
5000 UFH q12
p=NS
Enox 40mg QD
5000 UFH q8
p=NS
Enox 20mg QD
5000 UFH q12
p=NS
Nadro 3600 QD
5000 UFH q8
p=0.01
Lechler 1995
Bergman 1996
Harenberg 1996
n=442
n=1968
6
4
2
0
Harenberg 1990
n=166
n=959
Meta-analysis
UFH Prophylaxis: q 12h vs q 8h
-20.5
Effect Size
Weight
q 12h
Cade (1982)
Zawilska (1989)
Gardlund (1996)
Bergmann (1996)
Cade (1982)
Subtotal
3.6 (1.2, 8.3)
5.7 (.7, 20.5)
2.7 (2.3, 3.3)
0.9 (0.1, 3.2)
3.1 (0.6, 9.1)
2.34 (1.3, 3.3)
5.7
1.0
21.8
14.7
4.4
q 8h
Harenberg (1990)
Gallus (1973)
Pitney (1980)
Lechler (1996)
Harenberg (1996)
Belch (1981)
Kleber (2003)
Subtotal
4.1 (1.9, 17.9)
2.5 (0.06, 13.7)
2.7 (0.7, 14.9)
1.8 (0.7, 3.9)
0.6 (.2, 1.4)
5.0 (0.6, 17.9)
2.0 (0.5, 5.0)
0.86 (0.3, 1.4)
1.4
1.9
1.6
14.4
21.2
1.2
10.6
0
Per 1000 patient days
-20.5
King CS. Chest. 2007;131:507-516.
VTE Prophylaxis: LMWH vs UFH
Meta-analysis of 36 trials of LMWH or UFH
DVT Study
Risk Ratio
(95% CI)
0.70 (0.16-3.03)
0.29 (0.10-0.81)
0.74 (0.38-1.43)
0.94 (0.39-2.26)
Harenberg et al, 1990
Turpie et al, 1992
Dumas et al, 1994
Bergmann and Neuhart et al,
1996
Harenberg et al, 1996
Lechler et al, 1996
Hillborn et al, 2002
Kleber et al, 2003
Diener et al, 2006
Overall (95% CI)
2.89 (0.30-27.71)
0.25 (0.03-2.23)
0.55 (0.31-0.98)
0.77 (0.43-1.38)
0.76 (0.43-1.38)
0.68 (0.52-0.88)
-1
1
10
Risk Ratio
LMWH Better
LMWH Worse
Wein L. Arch Intern Med. 2007;167:1476-1486.
Weight, %
3.4
11.2
14.4
8.1
0.8
3.3
20.5
19.4
18.9
DVT prophylaxis:
Important, not perfect
LMWH / FPX
$ 16
Use in cancer, CHF or respiratory failure or
reduced mobility & 1 other risk factor: 1A
$ 2-13
UFH tid
ICD
$ 150
Use in high bleeding risk 1C or
as adjunct to anticoagulants 2A
$ 100
Stockings
$1
ASA
0
“Should not be used”: 1A
10
20
30
40
50
60
DVT Relative Risk Reduction
Geerts WH. Chest. 2008;133:381S-453S.
70
80
VTE Prophylaxis for Patients
Recommended to Receive it
47
Prophylaxis Rates (%)
50
45
40
35
40
US
Non-US
33
30
25
20
22
21
N=15,156
14
15
9
10
5
7
0.2
3
3
1
0
Total
LMWH
Tapson V. Chest 2007;132:936
UFH
IPC
Stockings
ASA
Physician response to prompts &
overall prophylaxis rate
50%
40%
*
Total Prophylaxis Rate
30%
20%
10%
0%
Control
Neutral
Conner Chest 118: 162S, 2000
Educational
Risk
Prophylaxis following consistent
reminders
Computerized prophylaxis prompts
35
Control
Prompted
30
25
Percent
20
15
Δ 41 %
10
5
0
Prophylaxis rates
VTE indicence
63% had risk score >4
Kucher N NEJM 2005; 352:969
Electronic Alerts to Prevent VTE
Freedom From DVT
or PE (%)
100
98
96
Intervention group
94
92
Control group
90
P<.001
0
0
No. at Risk
Intervention group
Control group
1255
1251
Kucher N. N Engl J Med. 2005;352:969-977.
30
Days
977
976
60
90
900
893
853
839
National initiatives
• Leapfrog: A preventable cause of death in US hospitals
• ACCP: Grade 1A for pharmacological DVT prophylaxis in
patients with VTE risk factors.
• SCIP: Prophylaxis ordered on admission, given +/-24 hr
from surgery.
• AHRQ: 1 of 8 “major patient safety concerns “ “Appropriate
VTE prophylaxis in patients at risk.”
• NQF/JCAH: “Evaluate each patient upon admission, and
regularly thereafter, for the risk of developing DVT/VTE.”
• CMS: 2009 “Never event”, VTE within 30 days nonreimbursed
Venous thromboembolism
5-30%?
90%
~50%
~50%
~10%
63-70% of fatal PE’s
unsuspected during life
Stein Chest 1995; 110:978
Sandler J R Soc Med 1989; 82:203
Quality of Life after VTE
• Post-thrombotic syndrome
develops in 25-40% of
DVTs.
• DVT recurs in ~30% after
anticoagulation stopped
• Permanent disability for 15
million Americans
90 day costs to care for DVT
15,000
$12,166
$12,146
12,500
$11,558
10,000
7,500
5,000
2,500
0
UFH
(n=104)
Enoxaparin QD
(n=112)
de Lissovoy G Arch Intern Med. 2000;160:3160
Enoxaparin q12h
(n=123)
Conclusions
•
•
•
•
•
DVT is common and > 50% preventable.
Prophylaxis is underused.
DVT results in a 30-50% incidence of PE.
Long-term leg vein sequella are common.
DVT and PE are expensive to treat.