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1.1. Bibliographic strategy results
1.2. Data extraction
1.3. Data analysis
1.4. Discussion
1.5. Recommendations – Initial treatment (first 5 to 10 days) of established VTE
HTA Questions |
Studies included |
HTA 1: UFH followed by VKA |
8 retrospective studies [MOORE1981] [CLARKEPEARSON 1983] [KRAUTH1987] [CALLIGARO1991] [CHAN1992] [DEBOURDEAU1996] [HARRINGTON1997] [ELTING2004] 5 prospective studies [BONA2000] [HUTTEN2000] PALARETTI2000] [PRANDONI2002] [VUCIC2002] 2 control arms of randomized studies [HULL2006] [VANDOORMAAL2009] |
HTA 2: LMWH followed by VKA |
5 control arms of randomized studies [MEYER2002] [LEE2003] [DEITCHER2006] [ROMERA2009] [VANDOORMAAL2009] |
HTA 3: LMWH vs. UFH |
8 meta-analyses not specific to cancer patients (5-22% cancer) [LENSING1995] [SIRAGUSA1996] [HETTIARATCHI1998] [GOULD1999] [DOLOVITCH2000[J1] ] [ROCHA2000] [QUILAN2004] [MISMETTI2005] 2 cancer specific meta-analyses [AKL2008] [AKL2011] |
HTA 4: Fondaparinux |
Analysis of the subgroup of cancer patients included in 2 randomized controlled trials [VANDOORMAAL2009] |
HTA 5: Thrombolytics |
1 retrospective study of cancer patients included in a prospective trial [MIKKOLA 1997] |
HTA 6: Vena cava filters |
14 retrospective studies [COHEN1991] [CALLIGARO1991] [COHEN1992] [LEVIN1993] [HUBBARD1994] [SCHIFF1994] [SCHWARZ1996] [GREENFIELD1997] [IHNAT1998] [SCHLEICH2001] [JARRETT2002] [WALLACE2004] [ZERATI2005] [SCHUNN2006] |
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1.3. Data analysis

Conclusion
Treatment of VTE in cancer patients with UFH followed by VKA is associated with a high rate of relapse and bleeding.

Conclusion
Treatment of VTE in cancer patients with LMWH followed by VKA is associated with a high rate of relapse and bleeding.
Using indirect comparison, the rate of major bleeding and relapse of VTE in cancer patients treated with LMWH and VKA:
· appears lower than the rate with UFH + VKA,
· is increased in “cancer patients” compared to “non-cancer patients”.

Conclusion
There is little evidence to demonstrate the superiority of LMWH over UFH in the initial treatment of VTE in cancer patients. LMWH could be superior in reducing the rate of mortality and the incidence of recurrent VTE at 3 months as compared to UFH in the initial treatment of VTE in cancer patients.

Conclusion
There are insufficient data to adequately compare the efficacy and safety of fondaparinux, UFH and LMWH for the initial treatment of thrombosis in cancer patients.

Conclusion
Due to lack of data, the indications of thrombolytics cannot be specified in cancer patients.

Conclusion
Since vena cava filters were inserted in cancer patients included in the studies for different
reasons, evidence is lacking to recommend their use in the case of VTE recurrence. Cancer is neither a specific indication nor a special contraindication to vena cava filter placement.
Initial treatment is defined as the first ten days of anticoagulation. There is little evidence to demonstrate the superiority of LMWH over UFH in the initial treatment of VTE in cancer patients. In this setting, LMWH could be superior in reducing the rate of mortality and the incidence of recurrent VTE at 3 months as compared to UFH. Overall, in the general population, the results favor the use of short-term LMWH vs. UFH. Given that no RCTs have evaluated the optimal initial therapy in cancer patients, but that no study reported a difference between cancer and non-cancer patients, the experts considered that this conclusion may be applied to the cancer population, although the meta-analyses did not show any substantial differences in the subgroup of patients with cancer.
The balance between desirable and undesirable effects favors the use of LMWH (lower risk
of heparin-induced thrombocytopenia) which are more convenient to use (once or twice a day vs. continuous perfusion or three times a day).
Analysis of cancer patients included in the studies performed in the general population shows that UFH and fondaparinux can be used during the first ten days of treatment.
Although the data were insufficient to conclude on the indications of thrombolytic drugs
in cancer patients with VTE, they suggest that the use of fibrinolytics is possible in these
patients and that cancer in general is not a contraindication to thrombolytic therapy, with
the exception of patients with brain metastases or with a high bleeding risk because of the
unfavorable balance between desirable and undesirable effects.
Studies on vena cava filters are not specific for patients with cancer. Since cancer patients have a high risk of recurrent VTE and bleeding, the benefit of these devices should be further analyzed. Furthermore, because the quality of the evidence is very low and the balance between desirable and undesirable effects cannot be determined, the experts consider that temporary or retrievable (optional) vena cava filters may prove to be particularly valuable in cancer patients, especially when anticoagulation is contraindicated. However, further studies are necessary.
1.5. Recommendations – Initial treatment (first 5 to 10 days) of
established VTE
R1. LMWH is recommended for the initial treatment of established VTE in cancer patients.
Quality of evidence |
Moderate |
Balance between desirable and undesirable effects |
Favorable |
Values and preferences |
Easier to use than UFH |
Costs (resource allocation) |
Not considered |
Level of recommendation |
Strong |
R2. Fondaparinux and UFH can be used equally for the initial treatment of established VTE in cancer patients
Quality of evidence |
Low |
Balance between desirable and undesirable effects |
Favorable |
Values and preferences |
Fondaparinux easier to use than UFH |
Costs (resource allocation) |
Not considered |
Level of recommendation |
Weak |
R3. Thrombolysis in cancer patients with established VTE may only be considered on a case-by-case basis, with specific attention to contraindications, especially bleeding risk (brain metastasis)
Quality of evidence |
Very low |
Balance between desirable and undesirable effects |
Thrombolytic therapy is associated with a high bleeding risk |
Values and preferences |
An expert opinion is recommended before using thrombolytics |
Costs (resource allocation) |
Not considered |
Level of recommendation |
Best practice |
R4. In the initial treatment of VTE, vena cava filters may be considered in the case of contraindication to anticoagulation or in the case of PE recurrence under optimal anticoagulation. Periodic reassessment of contraindications to anticoagulation is recommended and anticoagulation should be resumed when safe. Vena cava filtesr are not recommended for primary VTE prophylaxis in cancer patients
Quality of evidence |
Very low |
Balance between desirable and undesirable effects |
Unknown |
Values and preferences |
Not considered |
Costs (resource allocation) |
Not considered |
Level of recommendation |
Best practice |