4. 入院患者におけるDVTの予防
! Meta-Analysis (Ann Intern Med 2007;146:278-88)
– 9個のRCT, Exposure; UFH, LMWH
Outcome Exposure vs Placebo RR NNT
肺塞栓全体 0.20% vs 0.49% 0.46[0.26-0.71] 345
致命的肺塞栓 0.14% vs 0.39% 0.38[0.21-0.69] 400
症候性DVT 0.38% vs 0.81% 0.47[0.22-1.00] 233
全死亡Risk 4.3% vs 4.5% 0.97[0.77-1.21] 有意差無し
Major Bleeding 0.58% vs 0.44% 1.32[0.73-2.37] 有意差無し
内科疾患の入院患者(Stroke含む)でも,
VTE予防効果は認められるが, NNTはかなり高い.
出血リスクは上昇しない.
5. Study Design Exposure Control Outcome 頻度 NNT
PREVENT RCT, DB, Dalteparin Placebo 症候性DVT 0.28% vs 0.63% 286
N=3706, 21D 5000IU/d 14D
近位DVT 1.90% vs 4.05% 46.5
PE 0.28% vs 0.34% 1666
VTE全体 2.5% vs 4.79 43.7
Major Bleeding 0.49% vs 0.16% 303
Circulation 2004;110:874-9 Total Bleeding 1.52% vs 0.71% 123
MEDENOX RCT, DB Enoxaparin Placebo 症候性DVT 0.3% vs 0.7% 250
N=1102, 14D 40mg/d 6-14D
追跡 78.6% 近位DVT 4.9% vs 1.7% 31.3
PE 1.0% vs 0 100
VTE 全体 5.5% vs 14.9% 10.6
Major Bleeding 1.70% vs 1.10% 167
NEJM 1999;341:793-800 Total Bleeding 12.60% vs 8.60% 26
ARTEMIS RCT, DB, N=849, Fondaparinux Placebo 症候性DVT 0 vs 0 NA
15D 2.5mg/d 6-14D
症候性PE 0 vs 1.2% NA
VTE 全体 5.6% vs 10.5% 20.4
Major Bleeding 0.20% vs 0.20% 0
BMJ 2006;332:325-9 Total Bleeding 2.60% vs 1.00% 62.5
• 死亡率に関しては有意差は認めない
• 内科的急性期疾患患者におけるVTE自体が無症候性が多く,
症候性, 致死性VTEの合併頻度は低いため, NNTは高い
6. DVT予防; ストッキングについて
Lancet 2009; 373: 1958–65
CLOTS trial 1
– Acute strokeで体動困難な2518名のRCT. Articles
大 部までの弾性ストッキング vs ストッキング以外の治療で比較.
– 7-10日目, 25-30日目にDoppler US施行し, DVT発症を評価.
– 近位部DVT, 死亡率は両者で有意差無し.
ndomised
Thigh-length GCS Avoid GCS Odds ratio
centre or (n=1256) (n=1262) (95% CI)
nnaire to
Primary outcome
nths after
Proximal DVT 126 (10·0%) 133 (10·5%) ··
l status,
Alive and free of primary outcome 974 (77·5%) 1000 (79·2%) ··
arge, and
Dead before any primary outcome 115 (9·2%) 101 (8·0%) ··
lowed up
Missing 41 (3·3%) 28 (2·2%) ··
y postal
Unadjusted (dead and missing excluded) ·· ·· 0·97 (0·75-1·26)
had had a
Adjusted* (dead and missing excluded) ·· ·· 0·98 (0·76-1·27)
econdary
7. econdary
Secondary outcomes by 30 days or later second compression Doppler ultrasound
Dead by 30 days 122 (9·7%) 110 (8·7%) 1·13 (0·86–1·48)
Symptomatic proximal DVT 36 (2·9%) 43 (3·4%) 0·84 (0·53–1·31)
we had Asymptomatic proximal DVT 90 (7·2%) 90 (7·1%) 1·01 (0·74–1·36)
estimated Symptomatic DVT (proximal or distal) 55 (4·4%) 61 (4·8%) 0·90 (0·62–1·31)
vide 90% Any DVT (proximal or distal) 205 (16·3%) 224 (17·7%) 0·90 (0·73–1·11)
ion (from PE confirmed on imaging or autopsy 13 (1·0%) 20 (1·6%) 0·65 (0·32–1·31)
e steering PE on autopsy 1 (0·1%) 1 (0·1%) 1·00 (0·06–16·08)
alysis that Any DVT or PE 213 (17·0%) 232 (18·4%) 0·91 (0·74–1·11)
crease the Skin breaks/ulcers/blisters/skin necrosis 64 (5·1%) 16 (1·3%) 4·18 (2·40–7·27)
t effect of Lower limb ischaemia/amputation 7 (0·6%) 2 (0·2%) 3·53 (0·73–17·03)
orthwhile Primary outcomes within 14 days
ecember, Post-hoc analysis restricting follow-up to 14 days† 87 (6·9%) 95 (7·5%) ··
nue until Unadjusted (dead and missing excluded) ·· ·· 0·95 (0·70–1·28)
period. By Adjusted* (dead and missing excluded) ·· ·· 0·95 (0·70–1·29)
at least
518. The 皮膚障害は弾性ストッキング群で有意に増加する.
Data are number (%) unless otherwise indicated. GCS=graduated compression stockings. DVT=deep vein thrombosis.
PE=pulmonary embolism. *Adjusted for delay from onset to randomisation, stroke severity, and leg strength at
absolute baseline. †Full compliance by 14 days was 79·4% compared with 73·1% by 30 days.
Table 2: Primary and secondary outcomes
f patients
d groups
ns with a author had full access to all the data in the study and had
with odds final responsibility for the decision to submit for Lancet 2009; 373: 1958–65
8. Acute Strokeで体動困難な98名のRCTでも,
– 弾性ストッキングの使用はDVTリスクは有意差無し.
(7/65 vs 7/32, OR0.43[0.14-1.36])
Q J Med 2000;93:359-64
8
12. Chest 2011;140:374-81 We included a total of 16 trials (27,667 patients) in the meta-analysis
[18] , [19] , [20] , [21] , [22] , [23] Thirteen trials reported results
入院患者におけるVTE予防目的のUFH投与 In Figure 1, we present the overall n
bleeding, and 12 reported death.
follow-up of outcomes after initiation of prophylaxis ranged from 6 t
trial characteristics, quality indicators, and event rates. Patients enrol
– 2回/d vs 3回dをガチンコ比較したStudyは無し. in bed confinement due to various causes,
medical illnesses resulting
quality was moderate in most trials, with some high-quality trials. [4]
内科の入院患者でVTEリスクがある患者を対象としたRCTのMeta
– LMWH, UFH bid, tid間で
予防効果に有意差無し.
– UFH bid, tidどちらでも
良いということになる
Figure 1 Overall network of trials evaluating LMWH, UFH, and co
low-molecular-weight heparin; UFH = unfractionated heparin.
DVT RR PE RR 死亡 RR Major bleed RR
LMWH vs Control 0.38[0.24-0.53] 0.47[0.07-1.27] 0.97[0.79-1.19] 1.16[0.40-2.93]
Table 1 -- Characteristics of Trials Evaluating LMWH, UFH, or
UFH bid vs Control 0.28[0.10-0.61] 0.33[0.01-1.35] 0.94[0.71-1.26] 3.81[0.95-26.47]
UFH tid vs Control 0.42[0.23-0.68] 0.54[0.06-4.86] 1.10[0.74-1.69] 3.39[0.69-20.03]
Indication for
UFH bid vs LMWH 0.72[0.28-1.62] 0.72[0.02-4.54] 0.97[0.69-1.37] 3.28[0.72-28.75]
Study/Year No. Prophylaxis Treatm
UFH tid vs LMWH 1.13[0.72-1.72] 1.16[0.24-11.64] 1.14[0.80-1.66] 2.91[0.88-13.69]
Gallus et 26 Heart failure UFH 5,0
UFH tid vs UFH bid 1.56[0.64-4.33] al1.67[0.49-208.9]
[12] /1973 1.17[0.72-1.95] 0.89[0.08-7.05]
units tid
19. 外科患者のDVT予防
C.N. Gutt et al. / The American Jo
外科手術とDVT発症頻度 The American Journal of Surgery 189 (2005) 14–22
Table 1
Type of surgery as a risk factor for DVT
Type of surgery Incidence of DVT
Orthopedic surgery 50%–60%
Oncologic surgery 29%
General surgery 25%
Neurosurgery 22%
Gynecologic surgery 16%
Urologic surgery* 5%
* Data from preponderent prostatectomies and pelvic lymphadenecto-
mies.
26. of ICU LOS Ͻ72 hours. Another five records were excluded chemical thromboprophylaxis had no impact on VTE rates.
for patients with prior diagnosis of VTE during the same Critically ill ICU patients are at risk for developing
重症で凝固障害がある場合のVTE予防は？
hospitalization or missing information. Some records repre-
sented readmissions of patients already included in the study;
coagulation abnormalities. Up to 30% of ICU admissions
demonstrate prolonged INR.5 The causes are multifactorial
only the first ICU admission was examined in these instances. and include infection, systemic inflammatory response syn-
A total of 513 patients met criteria and were included in drome, circulatory shock, and liver failure. Prolonged INR is
the study: 241 patients in group 1ICUのRetrospective study.
Surgical and 272 patients in group associated with worse outcome.5 2011;70: 1398–1400 is the
J Trauma. Thrombocytopenia
2. Baseline patient characteristics and outcomes are displayed most common coagulation abnormality in the ICU with an
Edwards et al. The Journal of TRAUM
in Table 1. The two–groups were similar with respect to all
INR>1.5 or PLT<10万/µLを満たす513名中, incidence ranging from 15% to 60%.9 The presence of
characteristics and outcomes with the exception of higher either abnormality is associated with an increased risk of
抗凝固療法を施行されたのが241名, 施行されなかったのが272名.
platelet counts (116,000 vs. 97,000 per L; p ϭ 0.01) and bleeding. In addition, these patients are perceived to be at
hospital LOS (11.4 days vs. 8.1 days; p Ͻ 0.0001) in group reduced risk for developing VTE and PE or not amendable
1. The difference with 全体でVTEは16.4%. PEは0.8%, 抗凝固(+)群と(-)群で有意差無し.
– respect to platelet count could poten- to chemoprophylaxis.
TABLE 2. to
tially represent clinician hesitancy to prescribe prophylaxisIncidence There have beenPE
of VTE and a few prior studies published evaluat-
thrombocytopenic patients. The difference in LOS is likely a ing chemical thromboprophylaxis in these coagulopathic pa-
result of the study design because patients who received even VTE No VTE
tients. Cook et al.10 determined the incidence of VTE in ICU
one dose of prophylaxis during their ICU admission were
Variable patients with renal insufficiency receiving dalteparin p
Overall Prophylaxis Prophylaxis was
included in the VTE prophylaxis group. The longer a patient considerable at 5.1%. This study noted VTE occurred even
was admitted, the more likely they were to receiveof dose
Incidence a VTE with(16.4%) administration of dalteparin.
84 twice daily 41 (17%) 43 (15.8%) 0.72
Incidence of PE 4 (0.8%) 3 (1.2%) 1 (0.4%) 0.35
TABLE 1. Patient Demographics and Outcomes
Variable Overall (n )715 ؍
Two Prophylaxis (n )142 ؍
VTE
large case-control No VTE Prophylaxis (nbeen published
studies have )272 ؍ p
Age, mean (SD) 625.6 (17.7) 65.8 (18.1)
Male sex 62.2%
incidence of VTE in cirrhotic patients.11,120.8
concerning the61.4% 65.4 (17.4)
62.9%
In
0.78
105.9 (76.6)2006, Northup et al.
11 determined that the incidence of VTE
Platelets, mean (SD) 115.7 (83.8) 97.2 (68.7) 0.01
Trauma patients 8.3% in all cirrhotic 8% patients admitted over an 8-year period was
8.6% 0.87
Postoperative patients 82.6% 83.1% 82.1% 0.81
Cancer patients 26.1% 0.5%. Multivariate analysis showed VTE events were inde-
29.6% 22.9% 0.102
INR, mean (SD) 2.67 (2.69)pendent of INR (2.10) platelet count. In 2008, Gulley et Ͼ0.95
2.58 or 2.76 (3.12) al.12
APACHE, mean (SD)
Hospital LOS, mean (SD)
24.4 (9.5)
9.6 (10.3)
reported a 1.87% incidence of VTE in cirrhotic patients
23.9 (9.9)
11.4 (9.6)
24.8 (9.1)
8.1 (10.7)
0.31
Ͻ0.0001
19.5% compared with19.1% 0.98% in control patients. Senzolo et al. 0.91
13 then
ICU mortality 19.9%
Hospital mortality 25.9% evaluated these studies and all other available literature con-
28.2% 23.9% 0.27
28. phylaxis (Fig. 3). Early prophylaxis was associated with a 5%
J Trauma. 2007;62:557–563.
risk of VTE, whereas a delay beyond 4 days was associated
予防開始時期とVTE発症率
Fig. 3. The proportion of patients with VTE
– 発症 4日以降で予防を開始した群でVTE発症リスクが上昇.in relation to the day of
initiation of pharmacologic prophylaxis. Gray shading represents
<4日での開始群では5%程度だが, >4日での開始ではRR3.0[1.4-6.5]
the 95% confidence intervals.
– 4日以降開始群では, 頭部外傷, 多量輸血施行例が有意に多い.
Volume 62 • Number 3
反対に4日以内開始群では, 下肢外傷例が有意に多い.
– 他に併発症を認めないこともVTE予防が遅れている一因となっている.
28
