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In patients with cancer-associated VTE who received anticoagulant therapy for a minimum of 3 months, case-fatality of recurrent VTE is higher than case-fatality of major bleeding

Question

In people who have cancer-associated VTE who are treated for a minimum of 3 months with anticoagulant therapy, what is the incidence and case-fatality of recurrent VTE versus incidence and case-fatality of major bleeding?

The research

A summary of 29 studies (randomized controlled 14, prospective cohort 15) published up to Jan 2019.

Who? The studies included 8,000 people who had active cancer with confirmed PE and/or DVT treated with anticoagulation for at least 3 months (4,786 patient-years of follow-up; range 3-36 months). 

What? The studies compared incidence and case-fatality of recurrent VTE with incidence and case-fatality of major bleeding.

Recurrent VTE

vs

Major Bleeding

Incidence (number of recurrent VTE per 100 patient-years)

Case-fatality (proportion of total recurrent VTE resulting in death)

Recurrent VTE were objectively confirmed with conventional imaging



Incidence (number of major bleeds per 100 patient-years)

Case-fatality (proportion of total major bleeds resulting in death)

Definition of major bleeding varied across the studies


What the researchers found

The quality of the studies varied from low to high.

Incidence of recurrent VTE was 23.7 per 100 patient-years and incidence of major bleeding was 13.1 per 100 patient-years.

Case-fatality of recurrent VTE was 14.8% and case-fatality of major bleeding was 8.9%.


The bottom line

In people with cancer-associated VTE who received anticoagulant therapy for a minimum of 3 months, recurrent VTE is both more common and more likely to be fatal than major bleeding.

Summary of findings

Recurrent VTE vs major bleeding in patients with cancer-associated VTE who received a minimum of 3 months of anticoagulant therapy

Outcomes

Recurrent VTE

Major Bleeding

Number of studies and quality of the evidence

Rate


(95% CI)

23.7

per 100 pt-yrs

(20.1 to 27.8)

13.1

per 100 pt-yrs

(10.3 to 16.7)


29 studies of low-high quality

Case-fatality

(95% CI)

14.8%

(6.6 to 30.1%)

8.9%

(3.5 to 21.1%)

29 studies of low-high quality


This Evidence Summary is based on the following article:

Abdulla A, Davis WM, Ratnaweera N, et al. A Meta-Analysis of Case Fatality Rates of Recurrent Venous Thromboembolism and Major Bleeding in Patients with Cancer. Thromb Haemost. 2020 Apr;120(4):702-713. doi: 10.1055/s-0040-1708481. Epub 2020 Apr 14. PubMed

Higher rate of case-fatality from recurrent VTE than major bleeding in patients with cancer-associated VTE  

VTE is the second leading cause of death in people with cancer. Decisions about duration of treatment for VTE depend on weighing the risk of recurrent VTE against the risk of anticoagulant-associated major bleeding. This meta-analysis by Abdulla et al shows that in patients with cancer-associated VTE treated with anticoagulation for at least 3 months, the case-fatality of recurrent VTE is two-fold higher than the case-fatality of major bleeding.

There are limitations of this meta-analysis that should be considered. The reviewed studies were heterogenous with respect to outcome (PE only (4/29), DVT only (4/29), both (21/29)), definition of active cancer, and definition of VTE- or bleeding-associated death. Variation in anticoagulation type across the studies makes the pooled incidence rates more difficult to interpret. For instance,13 studies (45%) had a VKA arm, which is not currently considered first-line treatment for cancer-associated VTE due to a higher recurrence rate than with LMWH. Lastly, the incidence of bleeding was not reported according to cancer-specific site, which is one of the key factors that influences bleeding risk. 

The bottom-line

In general, this meta-analysis supports anticoagulation for patients with cancer-associated VTE, given that the case-fatality for recurrent VTE is higher than for major bleeding. However, the risk of bleeding should be assessed on an individual basis.


Published: Wednesday, July 29, 2020