Transcript Overall efficacy of Pentasaccharide versus enoxaparin

March 1, 2002
Medical College of Virginia
Venous Thromboembolism in
Rehabilitation Medicine:
“the Last Frontier”
Dr. Bill Geerts
Sunnybrook & Women’s College HSC
University of Toronto
OBJECTIVES
1. Risks of venous thromboembolism in various
patient groups who undergo rehabilitation.
2. Current thromboprophylaxis recommendations
for each of these groups in acute care.
3. Published studies of VTE in rehabilitation settings.
4. Thromboprophylaxis strategies in rehabilitation.
5. Current treatment of acute VTE.
Risk of DVT in Hospitalized Patients
Patient group
Medical patients
Major gyne/urol/gen surgery
Neurosurgery
Stroke
Critical care patients
Hip/knee surgery
Major trauma
Spinal cord injury
Rehabilitation
DVT prevalence
10-20 %
15-40 %
15-40 %
20-50 %
15-80 %
40-60 %
40-80 %
60-80 %
low-high
6th American College of Chest Physicians
Consensus Conference
on Antithrombotic Therapy
Prevention of Venous
Thromboembolism
Chest January 2001 Supplement
Mechanical Prophylaxis
• Graduated compression
stockings
• Intermittent pneumatic
compression
• Venous foot pump
Mechanical Prophylaxis
ADVANTAGES
• no bleeding
• efficacious in moderate
risk patients
DISADVANTAGES
Mechanical Prophylaxis
ADVANTAGES
DISADVANTAGES
• no bleeding
• efficacious in moderate
risk patients
• limited efficacy data
• no data related to
routine use
• cumbersome
• poor compliance
• may  mobilization
• no long-term use data
• no mortality data
• cost
Pharmacologic Prophylaxis
• Low dose heparin
• Adjusted-dose heparin
• Low molecular weight heparin
• Danaparoid
• Hirudin
• Pentasaccharide
• Oral thrombin inhibitors: ximelagatran
• Warfarin
Pharmacologic Prophylaxis
ADVANTAGES
DISADVANTAGES
• proven efficacy
(RRR 60-80%)
• broad spectrum of pts
• N > 100,000
• multiple agents
• ease of use
• high compliance
• no monitoring (except OAC)
• demonstrated cost-effectiveness
• mortality reduction
Pharmacologic Prophylaxis
ADVANTAGES
DISADVANTAGES
• proven efficacy
• bleeding - GS 0.1%
(RRR 60-80%)
- ortho 1%
• broad spectrum of pts
• cost (low  high)
• N > 100,000
• multiple agents
• ease of use
• high compliance
• no monitoring (except OAC)
• demonstrated cost-effectiveness
• mortality reduction
Orthopedic
Surgery
Hip arthroplasty
Knee arthroplasty
Hip fracture surgery
HIP ARTHROPLASTY - PROPHYLAXIS
• prospective trials with mandatory venography
No. of
No. of
Regimen
Trials Patients
Control/placebo
12
626
Grad comp stockings 4
290
Aspirin
6
473
Low dose heparin
11
1016
Warfarin
13
1828
Int pneum compress
7
423
LMW heparin
30
6216
Hirudin
3
1172
DVT
54 %
42 %
40 %
30 %
22 %
20 %
16 %
16 %
ACCP CONSENSUS GUIDELINES - CHEST (2001)
Risk
Red’n
--23 %
26 %
45 %
59 %
63 %
70 %
70 %
Elective hip replacement
Recommended:
 LMWH started 12 hr before surgery,
12-24 hr after surgery, or 4-6 hr after
surgery at half the usual high dose
or
 Warfarin (INR 2-3)
Alternative:
 adjusted-dose heparin to aPTT > ULN
Not recommended: aspirin, LDH, IPC alone
6th ACCP Consensus Conference on Antithrombotic Therapy
1A
1A
2A
KNEE ARTHROPLASTY - PROPHYLAXIS
• prospective trials with mandatory venography
Regimen
No. of
No. of
Risk
Trials Patients DVT Red’n
Placebo
6
199
64 %
---
Aspirin
6
443
56 %
13 %
Warfarin
9
1294
47 %
27 %
Low dose heparin
2
236
43 %
33 %
LMW heparin
13
1740
31 %
52 %
Int pneum compress
4
110
28 %
56 %
ACCP CONSENSUS GUIDELINES - CHEST (2001)
Elective knee replacement
Recommended:
 LMWH
or
 Warfarin (INR 2-3)
1A
Alternative:
 optimal use of IPC
1B
Not recommended: aspirin, LDH
1C+
6th ACCP Consensus Conference on Antithrombotic Therapy
1A
HIP FRACTURE - PROPHYLAXIS
• prospective trials with mandatory venography
No. of
Studies
No. of
Patients
DVT
Risk
Red’n
Control/placebo
9
381
48 %
---
Aspirin
3
171
34 %
29 %
Low dose heparin
2
59
27 %
44 %
LMW heparin
5
437
27 %
44 %
Warfarin
5
239
24 %
48 %
Regimen
ACCP CONSENSUS GUIDELINES - CHEST (2001)
Hip fracture surgery
Recommended:
 LMWH
or
 Warfarin (INR 2-3)
1B
Alternative:
 Low dose heparin
2B
Not recommended: aspirin
2A
6th ACCP Consensus Conference on Antithrombotic Therapy
1B
NEED FOR POST-DISCHARGE PROPHYLAXIS
placebo
THR
LMWH
R
(or warfarin)
LMWH
discharge
day 6-14
In-hosp
In-hosp + 3-4 weeks post-discharge
venogram
day 30-35
In-hospital vs Post-discharge LMWH After THR
Author, year
Bergqvist, 1996
Patients
223
DVT
Proximal DVT
Placebo LMWH
37 % 18 %
Placebo LMWH
24 % 7 %
Planes, 1996
173
19 %
7%
8%
6%
Dahl, 1997
218
32 %
19 %
13 %
9%
Spiro, 1997
435
23 %
8%
13 %
3%
Lassen, 1998
215
12 %
4%
5%
1%
Hull, 2000*
533
37 %
20 %
9%
3%
1797
27 %
14 %
12 %
4%
COMBINED
* In-hospital prophylaxis with warfarin.
6th ACCP Consensus Conference on Antithrombotic Therapy
Extended Duration Prophylaxis:
Symptomatic VTE
Eikelboom - Lancet (2001)
Trauma
MAJOR TRAUMA PATIENTS ARE
THE HIGHEST RISK GROUP
FOR THROMBOSIS
Sunnybrook VTE in Trauma Study - 1
• ISS > 9; no prophylaxis given
• Prospective; routine bilateral venography
• N = 443; mean age 39; ISS 27
DVT
PROX DVT
All patients
58 %
16 %
Major injuries:
Face/ chest / abdomen
50 %
15 %
Head
54 %
20 %
Spine
62 %
27 %
L.E. Ortho
69 %
24 %
Geerts - NEJM (1994)
Major Trauma
Recommended:
 Prophylaxis should be used if possible
 LMWH as soon as considered safe
1A
With high bleeding risk:
 initial mechanical prophylaxis (IPC, 1C
ES) until LMWH safe
High TE risk + suboptimal prophylaxis:
 consider screen with DUS
IVC Filter:
 not for prophylaxis
6th ACCP Consensus Conference on Antithrombotic Therapy
1C
1C
Spinal Cord
Injury
ACUTE SPINAL CORD INJURY: LDH + EPC vs LMWH
• Randomized trial in 27 acute spinal cord units
• C2-T12 SCI ASIA A, B, or C (motor nonfunctional)
Acute Phase
Heparin + IPC
5000 U Q8H
R
Rehab Phase
No VTE
Heparin 5000 U Q8H
VTE
Enoxaparin
30 mg Q12H
Enoxaparin 40 mg once daily
No VTE
2 weeks
bilateral venography
+ DUS
8 weeks
DUS
SCI Multicenter Trial:
Rehabilitation Phase (Weeks 2-8)
• Patients who completed Acute Phase without VTE
• Routine DUS at start of Rehab Phase + 6 weeks later
Heparin
5000 Q8H
Enoxaparin
40 mg QD
No.
60
59
New VTE
22%
8%
DVT
18%
7%
PE
3%*
2%
Major bleeding
1
0
* 1 fatal
Acute Spinal Cord Injury
Recommended:
 LMWH
1B
If anticoagulants C/I early after injury:
 IPC and ES  LMWH
2B
Possible alternative:
 IPC/ES + LMWH/LDH
2B
Not recommended:
 LDH, ES, IPC alone
1C
Rehabilitation phase:
 continue LMWH or warfarin (INR2-3)
1C
6th ACCP Consensus Conference on Antithrombotic Therapy
Stroke
Ischemic Stroke
Recommended:
 LDH, LWMH, danaparoid
1A
If anticoagulants contraindicated:
 ES or IPC
1C+
6th ACCP Consensus Conference on Antithrombotic Therapy
Studies of
VTE in
Rehabilitation
VTE IN REHABILITATION: PROBLEMS
1. Scanty, poor quality data - ??? risk
2. Huge patient variability: underlying conditions, time
in acute care, pre-rehab prophylaxis, duration of rehab
3. Some patients have DVT on admission
4. Symptoms/signs: nonspecific, reduced communication
5. Risk often prolonged
6. Often no diagnostic testing on site
7. ? Higher threshold for Dx  larger thrombi/emboli
8. Resource utilization: transportation, diagnostic tests,
two hosp beds, interrupts/prolongs rehab, drug costs
GENERAL REHABILITATION
Author,
year
Prophylaxis
prior to Method
of Dx
rehab
Halvorsen,
1985a
Katz,
1995
NS
70 %
(various)
FgLS 
veno
When
screened No.
NS
150
IPG  on adm 301
DUS (< 6 mos)
Prox
DVT DVT
18% NS
---
1%
STROKE REHABILITATION
Author, yr
Prophylaxis
prior to Method When
of Dx screened No.
rehab
Prox
DVT DVT
Cope, 73
NS
veno
on adm
42
40 %
NS
Miyamoto, 80
NS
FgLS
10-14 d 141
28 %
NS
21%
IPG
45 d
98
---
33 %
NS
DUS
21 d
123
18 %
NS
Oczkowski, 92
35 %
IPG
81 d
93
---
12 %
Pambianco, 95
NS
DUS
14 %
NS
some
DUS
13 %
NS
Sioson, 88
Desmukh, 91
Harvey, 96
on adm 421
25 d
105
TRAUMATIC BRAIN INJURY
REHABILITATION
Prophylaxis
Author,
Prox
prior to Method When
year
of Dx screened No. DVT DVT
rehab
Cifu,
All
DUS
On adm 82 18% 14 %
1996
(LDH or
(4-29 d)
IPC)
Meythaler, none
DUS
On adm 116 NS
8%
1996
(< 4 mos)
SPINAL CORD INJURY REHAB
Prophylaxis
prior to Method When
Author,
rehab
year
of Dx screened No.
Jarrell,
LDH
FgLS
NS
209
1983
+ IPG
Yelnik,
91%
veno on adm 127
1991
(45 d)
all
veno
80 d
87
Gunduz,
none
veno
27 d
30
1993
Prox
DVT DVT
65 % NS
23 %
NS
14 % NS
53 % 28 %
VTE in Rehabilitation
The best strategy is
optimal prophylaxis
in the acute care setting
PROPHYLAXIS OPTIONS IN REHAB
1. Mobilization
2. Physiotherapy
3. Low dose heparin
4. Low molecular weight heparins
5. Warfarin
PREVENTING VTE in REHAB:
PRINCIPLES
• Appropriate prophylaxis MUST start in acute care
• Written policy (care pathway)
• Simple, universal
• Routine prophylaxis for high risk patients (SCI,
hip and knee surgery, orthopedic trauma)
• No prophylaxis (or individual decision) for lower
risk patients (stroke, head injury, amputation, burn)
• No routine screening for DVT
Strategies to facilitate effective, safe,
efficient, and cost-effective
thromboprophylaxis in rehab settings
• Written, “approved” and used protocols
• Pharmacy involvement
• Point of care INR testing
• Greater use of LMWH if LOS < 2 weeks
• “Education” of referring centers
REHAB PROPHYLAXIS SUMMARY
Patient Group
Method
Spinal cord injury Warfarin
(INR 2-3)
LE orthop trauma Warfarin
(INR 2-3)
• LMWH
THR
• Warfarin
TKR
(INR 2-3)
Hip fracture
Others
Duration
Until discharge
Until discharge
2-4 wks postop
(~ til discharge)
• None
• Individualize
? Post-rehab Prophylaxis
Almost never
Treatment of
VTE in
Rehabilitation
Treatment of Venous Thromboembolism:
S/C Low Molecular Weight Heparin
is Preferred over IV Heparin
1. At least as efficacious
2. Safer:  bleeding
 HIT
3. Reduced all-cause mortality
4. Cheaper
5. No lab monitoring
6. Most can be treated as out-patients
Treatment of DVT/PE
LMWH S/C
Oral Anticoagulation (INR 2.0 - 3.0)
5-7 d
3 mos-indefinite
• Subcutaneous LMWH:
dalteparin (Fragmin) 100 U/kg BID or 200 U/kg QD
enoxaparin (Lovenox) 1 mg/kg BID or 1.5 mg/kg QD
nadroparin (Fraxiparine) 86 U/kg BID
tinzaparin (Innohep) 175 U/kg QD
• No lab monitoring or dosage adjustment
INDICATIONS FOR PROLONGED LMWH THERAPY
1.
2.
3.
4.
5.
6.
Pregnancy
Uncontrolled malignancy
High risk of bleeding
Warfarin failure
Major chemotherapy
INR monitoring difficult
- poor venous access
- geographic inaccessibility
- unstable values
7. Need for recurrent invasive procedures
8. PATIENT PREFERENCE
Indications for an IVC Filter
Recent PROXIMAL DVT PLUS:
1. Absolute C/I to full anticoagulation
2. Untreatable, major bleeding on anticoag
NOT for: PE without proximal DVT
Minor bleeding
Minor/moderate surgery
Primary prophylaxis
“Recurrent” VTE/failure of Rx
Vitamin K: Routes & Doses
IM  NEVER
SC  RARELY (only if NPO)
IV  1 mg for MINOR bleeding
10 mg for MAJOR bleeding
PO  ROUTE OF CHOICE
INR < 9 1 mg
INR > 9 2.5-5 mg
FFP  Only if major bleeding, surgery
imminent
Duration of Anticoagulation
1. RISK FACTOR RESOLUTION
2. NUMBER OF EPISODES OF VTE
3. THROMBOEMBOLISM RESOLUTION
4. BLEEDING RISK
5. PATIENT PREFERENCE
 INDIVIDUALIZE
Discussion
Questions
6th ACCP Consensus Conference on Antithrombotic Therapy
Chest Supplement January 2001
Prevention of Venous
Thromboembolism
Bill Geerts, chair
John Heit
Patrick Clagett
Graham Pineo
Cliff Colwell
Fred Anderson
Brownell Wheeler
ACCP CONSENSUS
CONFERENCES ON
ANTITHROMBOTIC
THERAPY
Chest 1986, 1989, 1992,
1995, 1998, 2001, 2003
Pulmonary Embolism in UK Hospitals
• 0.9 % of pts admitted to hospital DIE from PE
• < 1/2 of high risk pts had any prophylaxis
• 400 deaths/yr could be saved by prophylaxis
• £ 33-82 million/yr COST SAVINGS with more
appropriate use of prophylaxis
Office of Health Economics (1996)
Making Health Care Safer: A Critical
Analysis of Patient Safety Practices
• UCSF-Stanford Evidence-Based Practice Center report for
Agency for Healthcare Research and Quality, US DOHHR
• systematic review of practices to improve patient safety
• rank practices according to strength of evidence supporting
more widespread implementation
No. 1 = “Appropriate use of prophylaxis to prevent venous
thromboembolism in patients at risk”
Shojania (2001)
Rationale for Prophylaxis
• high incidence of VTE
• associated mortality and morbidity
• cost of diagnosis and treatment
• treatment-related complications
OPPORTUNITY TO:
1. Improve patient outcomes, AND
2. Reduce costs
VTE Prevalence after THR or TKR Surgery,
or Surgery for Hip Fracture
Deep Vein Thrombosis* Pulmonary Embolism
Procedure
Total, %
Proximal, %Total, %
Fatal, %
THR
45-57
23-36
0.7-30
0.1-0.4
TKR
40-84
9-20
1.8-7
0.2-0.7
Hip fracture surgery
36-60
17-36
4.3-24
3.6-12.9
* DVT rates among control/placebo groups in RCTs using routine venography
6th ACCP Consensus Conference on Antithrombotic Therapy
HIP ARTHROPLASTY
1000 patients undergoing THA
Without Prophylaxis:
500 develop DVT
166 have symptomatic DVT
100 develop symptomatic nonfatal PE
20 die due to PE
Paiement - Am J Surg (1991)
DVT after THR
• 289 patients prophylaxed with GCS + SCD
• Ipsilateral duplex ultrasound 5 days postop
Proximal DVT
Overall
Anesthetic - general
- regional
Age > 75
< 75
Age > 75 + GA
6%
11 %
4%
16 %
3%
26 %
Woolson - JBJS (1996)
Warfarin vs Dalteparin in THR
• 580 patients; bilateral contrast venography
Warfarin
INR 2.5
Patients
DVT
Proximal DVT
Major bleeding
Op site bleeding
Transfused - OR day
-D1-8
190
26 %
8%
1%
1%
65 %
44 %
Dalteparin
5000 U daily
192
15 %
5%
2%
4%
69 %
68 %
P
0.006
NS
NS
0.03
NS
0.004
Francis - JBJS (1997)
Prevention of DVT After THR Surgery*
Total DVT
Proximal DVT
No. of Combined
Prophylaxis Regimen Trials Enrollment Prevalence RRRPrevalence RRR
Control/placebo
12
626
54 %
Elastic stockings
4
290
42 %
23 % 26 %
4%
Aspirin
6
473
40 %
26 % 11 %
57 %
11
1016
30 %
45 % 19 %
27 %
Adjusted-dose warfarin13
1828
22 %
59 %
5%
80 %
Low dose heparin
---
27 %
--
IPC
7
423
20 %
63 % 14 %
48 %
LMWH
30
6216
16 %
70 %
6%
78 %
3
1172
16 %
70 %
4%
85 %
Adjusted-dose heparin 4
293
14 %
74 % 10 %
62 %
Recombinant hirudin
* Pooled DVT rates using routine contrast venography.
6th ACCP Consensus Conference on Antithrombotic Therapy
Prevention of DVT After TKR Surgery*
Total DVT
Proximal DVT
No. of Combined
Prophylaxis RegimenTrials Enrollment Prevalence RRRPrevalence RRR
Control/placebo
6
199
64 %
---
15 %
--
Elastic stockings
2
145
61 %
6 % 17 %
--
Aspirin
6
443
56 %
13 %
9%
42 %
Warfarin
9
1294
47 %
27 % 10 %
35 %
Low dose heparin
2
236
43 %
33 % 11 %
25 %
Venous foot pump
4
172
41 %
37 %
2%
85 %
LMWH
13
1740
31 %
52 %
6%
63 %
Int. Pneum. Compr.
4
110
28 %
56 %
7%
52 %
* Pooled DVT rates using routine contrast venography.
6th ACCP Consensus Conference on Antithrombotic Therapy
Prevention of DVT After Surgery for Hip Fracture*
No. of Combined
Prophylaxis Regimen Trials Enrollment
Control/placebo
9
381
Relative Risk
DVT (95 % CI) Reduction
-48 % (43-53)
Aspirin
3
171
34 %
(27-42)
29 %
Low dose heparin
2
59
27 %
(16-40)
44 %
LMWH/heparinoid
5
437
27 %
(23-31)
44 %
Warfarin
5
239
24 %
(19-30)
48 %
* Pooled total DVT rates in RCTs using routine contrast venography.
6th ACCP Consensus Conference on Antithrombotic Therapy
This concept has been challenged by 4
prospective studies based on symptomatic VTE
after in-hospital prophylaxis for THR or TKR
Procedure
n
Therapy
Duration,
d
Sympt
DVT
Fatal PE
Robinson
THR
249
W
9.8
1.2%
0
1997
TKR
257
W
9.8
0.6%
0
Leclerc
THR
1142
LM
9.0
4.3%
0
1998
TKR
842
LM
9.0
3.9%
0.4%
Colwell
THR
1516
LM
7.5
3.6%
0.1%
1999
THR
1494
W
7.0
3.7%
0.1%
Heit 2000
THR
588
LM
7.3
2.0%
0
W, warfarin; LM, low molecular weight heparin
ACCP - Chest (2001)
Extended Duration Prophylaxis:
Venography
Eikelboom - Lancet (2001)
Risk reduction of clinical VTE
Study
Expt
n/N
Ctrl
n/N
Bergqvist
2/191
Dahl
Weight
%
Peto OR
(95% CI Fixed)
10/131
19.7
0.26 (0.08, 0.79)
4/117
6/110
16.6
0.62 (0.17, 2.18)
Helt
7/607
10/588
26.6
0.66 (0.26, 1.78)
Hull
4/291
9/133
10.2
0.58 (0.12, 2.91)
Lassen
2/140
9/141
8.5
0.57 (0.11,6.92)
Planes
3/90
7/88
16.9
0.49 (0.12, 1.52)
22/1370
39/1192
100.0
0.50 (0.30, 0.83)
Total (95% CI)
Peto OR
(95% CI Fixed)
.1
1
.2
Favours treatment
5
10
Favours control
Cohen - Thromb Haemost (2001)
Orthopedic Surgery - Other Issues
Duration of Prophylaxis:
 Uncertain, but at least 7-10 days
1A
 Extended, out-of-hospital LMWH may reduce
1A
clinically-important VTE and is recommended
at least for high-risk patients
Pre-discharge Screening:
 Routine DUS not recommended
6th ACCP Consensus Conference on Antithrombotic Therapy
1A
Symptomatic VTE After In-hospital Prophylaxis
Author, year Operation
Robinson, 1997 THR
Leclerc, 1998
Colwell, 1999
Heit, 2000
Duration of Sympt.
No. Prophylaxis Prophylaxis VTE, (%)
9.8 d
6 (1.2)
506 warfarin
Fatal PE,
(%)
0
TKR
518
warfarin
9.8 d
3 (0.6)
THR
1,142
LMWH
9.0 d
49 (4.3)
0
TKR
842
LMWH
9.0 d
33 (3.9)
3 (0.4)
THR
1,516
LMWH
7.5 d
55 (3.6)
2 (0.1)
THR
1,495
warfarin
7.0 d
56 (3.7)
2 (0.1)
588
LMWH
7.3 d
11 (1.9)
3 (0.5)
THR/TKR
6th Consensus Conference on Antithrombotic Therapy
1 (0.2)
Clinical Outcomes After THA
• Patients: elective, unilateral, primary THA
• Design: 156 centers, unblinded RCT
• Interventions: enoxaparin 30 mg BID postop
warfarin INR 2-3 pre- or postop
}
in hospital
(x = 7.3 d)
Warfarin* Enoxaparin
No.
1495
1516
Symptomatic VTE (OR ---> 3 mos) 3.7 %
3.6 %
In-hospital
1.1 %
0.3 % p=0.008
Discharge ---> 3 mos
2.6 %
3.4 %
Fatal PE
2
2
Bleeding - all
7.4 %
10.0 % p=0.01
- major
0.5 %
1.2 % p=0.06
* only 35 % had INR >2 by day 7
Colwell - JBJS (1999)
• Extended duration of prophylaxis for
30 – 42 days reduced symptomatic VTE:
1.3 % vs 3.3 %, OR: 0.38,
95% CI: 0.24 – 0.61, NNT = 50
• Asymptomatic venographic DVT also
significantly reduced:
9.6 % vs 19.6 %, OR: 0.49,
95% CI: 0.36 – 0.63, NNT = 10
• Major bleeding: similar in extended
prophylaxis as in placebo and untreated
groups
• Routine use of extended-duration
prophylaxis will prevent 20 sympt.
VTE/1000 elective THR or TKR
• Assuming 5% case-fatality rate, this is
equivalent to preventing 1 additional
death for every 1000 patients
• Outpatient costs is  US $24 – 28
Eikelboom - Lancet (2001)
Conclusions
• There is good evidence that prolonged
prophylaxis reduces asymptomatic DVT
• Also good evidence that prolonged prophylaxis
reduces symptomatic VTE
• Unable to identify the patients at risk for late
VTE
• A 2 % rate for (preventable) symptomatic VTE
is excessive in view of the high frequency of
major orthopedic surgery
Duration of Prophylaxis after
Major Orthopedic Surgery
Optimal duration after THR/TKR uncertain
Recommendations:
 at least 7-10 days
1A
 extended out-of-hospital prophylaxis 2A
may reduce clinically important VTE
and is recommended at least for highrisk patients
6th ACCP Consensus Conference on Antithrombotic Therapy
Incidence of DVT in Trauma Patients (No Prophylaxis)
LE
No . Fracture DVT
Prox
DVT
Author, yr
Patients
Freeark, 1967
Injuries  bedrest > 3 weeks
42
33 %
29 %
NS
Hjelmstedt, 1968
Tibial fractures
76 100 %
45 %
8%
Nylander, 1972
Tibial fractures
14 100 %
57 %
NS
Kudsk, 1989
Multisystem trauma, bedrest > 10 d 38
55 %
63 %
32 %
Geerts, 1994
Major trauma, ISS > 9
349
52 %
58 %
18 %
Abelseth, 1996
Isolated LE # Rx’d surgically
102 100 %
28 %
4%
6th ACCP Consensus Conference on Antithrombotic Therapy
Randomized Studies of DVT Prevention after Acute SCI
Regimen
Author, yr
Low-dose heparin
Green, 1988 IPG
Green, 1990 IPG, DUS
Geerts, 1996 Venography
IPC
Green, 1982
FgLS/IPG
6/15 (40)
Adjusted-dose heparin
Green, 1988
IPG
2/29 ( 7)
LMWH
Green, 1990 IPG, DUS
Geerts, 1996 Venography
Combinations
Green, 1982
(IPC, ASA, dipyridamole)
Endpoints
FgLS/IPG
DVT, No. (%)
9/29 (31)
5/19 (26)
10/15 (67)
0/16 ( 0)
4/8 (50)
3/12 (25)
6th ACCP Consensus Conference on Antithrombotic Therapy
DVT in Patients with Acute SCI - No Prophylaxis
No. of
Author, year
Endpoint
Patients
Brach, 1977
FgLS/IPG
10
90 %
NS
Rossi, 1980
FgLS
18
72 %
17 %
Myllynen, 1985
FgLS
9
100 %
NS
Merli, 1988
FgLS/IPG
8
48 %
NS
Petaja, 1989
FgLS
9
67 %
NS
Geerts, 1994
Venography
26
81 %
35 %
DVT
Proximal DVT
6th ACCP Consensus Conference on Antithrombotic Therapy
SCI Multicenter Trial:
Acute Treatment Phase (Weeks 0-2)
• Routine venography and DUS day 14 + 3; blinded interpretation
Heparin 5000 Q8H
+ IPC
No. rand/completed
Enoxaparin
30 mg BID
246/48
230/58
VTE
63%
66%
DVT
46%
60%
7%
9%
PE
10%
3%
Major VTE (pDVT+PE)
16%
12%
5%
3%
Proximal DVT
Major bleeding
RISK OF SYMPTOMATIC VTE AFTER SCI
A. age-matched controls
B. no prophylaxis
C. prophylaxis
RISK
B
1
2
3 4 5
weeks
6
1
years
C
A
2
Cost-effectiveness of Prophylaxis
• 1000 patients undergoing THA
Strategy
Fatal PE
Charges (US $)
20.0
$ 774,000
Warfarin
4.0
394,000
Warfarin + duplex scan
0.3
616,000
Warfarin X 12 wks
0.15
595,000
Observation only
Paiement - Am J Surg (1991)
VTE in Stroke
• Prospective studies
• No prophylaxis
• Routine screening for DVT (17/18 used FgLS)
Studies
Patients
DVT
Prox DVT
PE
Fatal PE
18
749
49 %
11 % (17/152)
6 % (10/174)
4 % (12/270)
Prevention of DVT in Ischemic Stroke
Trials Patients DVT
RRR
---
Control
8
346
55 %
Low dose heparin
5
364
24 %
56 %
LMWH
3
158
23 %
58 %
Danaparoid
4
203
10 %
82 %
Geerts (6th ACCP) - Chest (2001)
Risk Factors for VTE in Stroke
YES
NO
UNKNOWN
Degree of paralysis
Age
Level of consciousness
Improvement in weakness
Previous VTE
Varicose veins
Obesity
DVT Treatment: UFH or LMWH?
• meta-analysis of RCTs
• adjusted UFH vs fixed-dose S/C LMWH
• 11 studies, 3674 patients
UFH
LMWH
RRR
P
NNT
5.4 %
4.6 %
15 %
> 0.2
114
All cause mortality 6.8 %
5.0 %
27 %
0.02
61
Major bleeding
1.1 %
42 %
0.47
164
Recurrent VTE
1.9 %
Gould - AIM (1999)