Chapter 1. Initial treatment of established VTE

Menu
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

 


 


1.1. Bibliographic strategy results

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]


 [J1]dolovich – corrigé partout

Menu


1.2. Data extraction

Data extraction.* Cliquez pour le pdf

 

1.3. Data analysis

rq1

Q 1: UFH followed by VKA

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

Q 2: LMWH followed by VKA

Q 2: LMWH followed by VKA

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”.

Q 3: LMWH vs. UFH

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.

 

Q 4: Fondaparinux

Q 4: Fondaparinux

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.

Q 5: Thrombolytics

Q 5: Thrombolytics

 

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

 

Q 6: Vena cava filters

Q 6: Vena cava filters

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.

Menu


 

1.4. Discussion

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.

Menu


 

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

Menu