Preventing VTE in cancer patients undergoing major surgery
Download
Report
Transcript Preventing VTE in cancer patients undergoing major surgery
Cancer og trombose
Tromboseprofylakse
Morten Schnack Rasmussen
Overlæge
Kirurgisk Gastroenterologisk K
Bispebjerg Hospital
Disposition
Primær profylakse
Kemoterapi og anti-hormonel behandling
Central Vene Katetre
Stråle behandling
Postoperative venøs tromboemboliske komplikationer
Sekundær profylakse
Øger LMWH overlevelsen hos cancer patienter?
Concurrent VTE and cancer
increases the risk of death
Probability of death within 183 days of initial hospital admission
Probability of death
1.00
DVT/PE and
malignant disease
0.80
0.60
0.40
Malignant
disease alone
0.20
0.00
0
40
80
120
Number of days
180
Levitan et al Medicine 1999
Kemoterapi og anti-hormonel behandling
Incidence of VTE in malignancy:
Breast cancer
17.6%
9.6%
1.6%
0.9%
0.2%
0.1%
0.2%
Prevention (1) Node –ve (2) Node +ve (3) Advanced (4)
1:Fischer et al J Natl Cancer Inst 1997;89:1673; 2:Fischer et al New Eng J Med 1989; 320: 479; 3: Pritchard
J Clin Oncol 1996: 14; 4:Goodnough et al Cancer; 1984: 54
LAVDOSIS Warfarin BEHANDLING ved C. MAMMAE
5
4.5
• 6 week 1mg Warfarin dagligt.
• INR 1.3–1.9
• Median behandlingstid 181 dage
4
3.5
Thrombosis (%)
• 311 kvinder, stage 3 and 4
mamma cancer. Kemoterapi.
4.4 %
3
2.5
p=0.03
2
1.5
0.7%
1
0.5
0
Placebo
Warfarin
85% VTE reduction
Levine M et al. Lancet 1994;886:886–9
Kemo terapi og VTE komplikationer
Mangler evidensbaserede rekommandationer
Ingen fra ACCP
Kun et enkelt randomiseret studie med peroral AK
behandling.
Central venøse katetre og venøse
tromboemboliske komplikationer
Central Venous Catheter
VTE complications
Author
VTE
Diagnosis
control
n/N
treatment
n/N
P
value
15/40
4/42
< 0.001
LMWH
8/13
1/16
0.002
Symp
LMWH
3.7%
3.4%
n.s
Symp
Warfarin
5/125
6/130
n.s
Bern et al. 1992
Veno
Warfarin
Monreal et al.
1996
Reitchard et al
2002
Couban et al
2002
Veno
LMWH=low-molecular-weight heparin
Stråle behandling og
venøse tromboemboliske komplikationer
VTE og strålebehandling
Author
VTE
control
Strålebehandling
P
value
Holm et al. 1996
Rectum cancer
3.6%
7.5%
0.001
Goldberg et al.
1994
Rectum cancer
3.0%
13.0%
<0.001
Silvani et al 2003
Malignt Glioma
19.0%
Postoperative venøs
tromboemboliske komplikationer
The ENOXACAN II study design
Surgery
Randomization
Phlebography
control
prophylaxis
Day 30
Prophylaxis
6-10 days
Bergqvist et al. N Engl J Med 2002;346:975-80
Incidence of venous thromboembolic events:
The ENOXACAN II study
p = 0.02
Placebo
Enoxaparin
Percentage of patients
14
12
12
10
8
6
ns
4.8
ns
4
1.8
2
0.6
0.6
0
All VTE
Proximal DVT
Bergqvist et al. N Engl J Med 2002;346:975-80
PE
FAME study design
7 days
R
Dalteparin
(5,000 IU sc od)
+ TED
21 days
Dalteparin (5,000 IU sc od)
No further prophylaxis
Major abdominal
surgery
TED: graduated compression stockings
Bilateral venography
(assessor-blinded)
Incidence of all VTE 28 days after major
abdominal surgery
p = 0.01
18
RRR: 55% (95% CI: 15% - 76%)
16.2%
NNT: 12 (7 – 44)
Incidence of all VTE (%)
16
14
12
10
8
7.3%
Prolonged TP (28 day) with
dalteparin
6
4
Short-term TP (7 day) with
dalteparin
2
0
n=165
n=178
Incidence of proximal DVT 28 days after major
abdominal surgery
10
Incidence of proximal DVT (%)
RRR: 77% (95% CI: 22% – 93%)
p = 0.009
NNT: 17 (10 – 59)
8.0%
8
6
4
2
Prolonged TP (28 day)
with dalteparin
1.8%
Short-term TP (7 day)
with dalteparin
0
n=165
n=175
Conclusions
Cancer patients undergoing surgery: High risk
patients
TP: LMWH in combination with TED.
In selected high risk patients, including
those operated for cancer, we suggest
post hospital discharge prophylaxis with
LMWH
The 7th ACCP Guidelines. Chest 2004; 126 (3 suppl): 410S
Anti-koagulations behandling
hos cancer patienter
Øget risiko for recidiv og blødning
Cumulative incidence of recurrence in
cancer patients
30
Cumulative proportion
of recurrent VTE (%)
Hazard ratio 3.2
20
Cancer
10
No cancer
Cumulative incidence of clinically
important bleeding in cancer patients
0
6
1
160
631
2
3
129
602
4
5
6
92
161
7
8
9
73
120
10
11
12
64
115
Time (months)
Cancer
No cancer
Prandoni P et al. Blood 2002;100:3484-3488
30
6
Hazard ratio 2.2
Cumulative proportion
with major bleeding (%)
0
181
661
20
Cancer
10
No cancer
0
0
181
661
8
1
170
636
2
3
141
615
4
5
6
102
170
7
8
9
81
127
10
11
12
68
124
Time (months)
Cancer
No cancer
Prandoni P et al. Blood 2002;100:3484-3488
8
AK-behandling: Effekt, risiko
VTE recidiv
Blødning *
* : Fatal, hjerne, retroperitoneum. ≥ 2 transfusioner, fald i Hb ≥ 2 mmol/L
Hutten BA, et al. J Clin Oncol 2000; 18: 3078-83
Lavmolekylært heparin ved VTE
•
•
•
•
•
•
•
Veldokumenteret til behandling og profylakse af VTE
Bedre end UFH
Pålidelig biotilgængelighed og kinetik, få interaktioner
Vægtbaseret dosering. Ingen monitorering
Bedre effekt, færre blødninger
Sikkert i langtidsbehandling (HIT, osteoporose)
Selvadministration, behandling i hjemmet
Long-term treatment of cancer patients with
VTE: LMWH versus warfarin
Outcome
3 months
Warfarin
n=71 (%)
LMWH*
n=67 (%)
Major bleed
VTE
Total
12 (16.9)
3 (4.2)
15 (21.1)
5 (7.5)
2 (3.0)
7 (10.5)†
*Enoxaparin 1.5 mg/kg; †P=0.09
Meyer G et al. Arch Intern Med. 2002;162:1729–35.
LITE trial
Event
Tinzaparin (n=369)
OAC (n=368)
Recurrent VTE (%)
Major bleeding (%)
4.9
3.3
5.7
4.6
Subgruppe-analyse:
Cancer
Recurrent VTE (%)
n=80
6.3
n=87
11.5 *
*P=0.03
LITE trial: Hull et al. ASH 2002
14
14
CLOT in cancer
Dalteparin
• Acute VTE
• 5-7 days
• Dalteparin
R
• 200 IU/kg
Oral
anticoagulant
Lee A et al. N Engl J Med 2003;349:146-153
CLOT trial
Treatment
group
Initial treatment
(5-7 days)
Long-term therapy
(180 days)
OAC
Dalteparin 200 IU/kg
sc once-daily
Warfarin or acenocoumarol
(target INR 2.5)
LMWH
Dalteparin 200 IU/kg
sc once-daily
Day 30: dalteparin 200 IU/kg
Day 31 to 180: 75-80% of full dose
Probability of recurrent VTE (%)
Recurrent VTE
25
Risk reduction=52%
p=0.0017
20
15
OAC
10
Dalteparin
5
0
0
30
60
90
120
150
180
Days post-randomisation
210
Recidiv af VTE
8,0%
15,8%
Absolut risikoreduktion
7,8%
1 event sparet pr. 13 behandlede (NNT 13)
CLOT-studiet
Treatment
Outcomes
Results
Recurrent VTE
Long-term LMWH
Bleeding
Quality of life
”For patients with DVT and cancer, we recommend
LMWH for the first 3 to 6 months of long-term
anticoagulant therapy (Grade 1A)”.
”For these patients, we recommend anticoagulant
therapy indefinitely or until the cancer is resolved
(Grade 1C)”.
The 7th ACCP Guidelines. Chest 2004; 126 (3 suppl): 410S
No increase
LMWH AND SURVIVAL
FAMOUS
385 patients with solid
tumour malignancy
R
Dalteparin
5000 units once daily
for up to 1 year
Placebo
Up to 1 year
SCLC study
84 patients with
Small cell lung
cancer (SCLC)
R
Chemotherapy (cyclophosphamide,
epirubicin, vincristine)
18 weeks
MALT
302 patients with
solid tumor
malignancy
Chemotherapy plus
dalteparin 5000 IU od
18 weeks
R
Nadroparin
2 weeks therapeutic dose
4 weeks 1/2 therapeutic dose
Placebo
6 weeks
LMWH and Survival Data
Survival (months)
Median (95% CI)
Year
LMWH
Overall population
Good prognosis
population
FAMOUS
2002
Dalteparin
D 10.80
P 9.14
43.5
24.3
CLOT
2003
Dalteparin
D 62%*
OAC 61%* (HR 1.0)
80%*
64%* (HR 0.5)
SCLC study
2003
Dalteparin
D 13.0
P 8.0
16.0
10.0
MALT
2003
Nadroparin
N 8.0
P 6.6 (HR 0.75)
15.4
9.4 (HR 0.64)
*% surviving at 1 year
D = dalteparin; N = nadroparin;
OAC = oral anticoagulant; P = placebo; HR = hazard ratio