Anticoagulation may improve survival in patients with cancer through a speculated
anti‐tumour effect, in addition to the antithrombotic effect, although may increase
the risk of bleeding. To evaluate the efficacy and safety of parenteral anticoagulants
in ambulatory patients with cancer who, typically, are undergoing chemotherapy, hormonal
therapy, immunotherapy or radiotherapy, but otherwise have no standard therapeutic
or prophylactic indication for anticoagulation. A comprehensive search included (1)
a major electronic search (February 2016) of the following databases: Cochrane Central
Register of Controlled Trials (CENTRAL) (2016, Issue 1), MEDLINE (1946 to February
2016; accessed via OVID) and Embase (1980 to February 2016; accessed via OVID); (2)
handsearching of conference proceedings; (3) checking of references of included studies;
(4) use of the 'related citation' feature in PubMed and (5) a search for ongoing studies
in trial registries. As part of the living systematic review approach, we are running
searches continually and we will incorporate new evidence rapidly after it is identified.
This update of the systematic review is based on the findings of a literature search
conducted on 14 August 2017. Randomized controlled trials (RCTs) assessing the benefits
and harms of parenteral anticoagulation in ambulatory patients with cancer. Typically,
these patients are undergoing chemotherapy, hormonal therapy, immunotherapy or radiotherapy,
but otherwise have no standard therapeutic or prophylactic indication for anticoagulation.
Using a standardized form we extracted data in duplicate on study design, participants,
interventions outcomes of interest, and risk of bias. Outcomes of interested included
all‐cause mortality, symptomatic venous thromboembolism (VTE), symptomatic deep vein
thrombosis (DVT), pulmonary embolism (PE), major bleeding, minor bleeding, and quality
of life. We assessed the certainty of evidence for each outcome using the GRADE approach
( GRADE handbook ). Of 6947 identified citations, 19 RCTs fulfilled the eligibility
criteria. These trials enrolled 9650 participants. Trial registries' searches identified
nine registered but unpublished trials, two of which were labeled as 'ongoing trials'.
In all included RCTs, the intervention consisted of heparin (either unfractionated
heparin or low molecular weight heparin). Overall, heparin appears to have no effect
on mortality at 12 months (risk ratio (RR) 0.98; 95% confidence interval (CI) 0.93
to 1.03; risk difference (RD) 10 fewer per 1000; 95% CI 35 fewer to 15 more; moderate
certainty of evidence) and mortality at 24 months (RR 0.99; 95% CI 0.96 to 1.01; RD
8 fewer per 1000; 95% CI 31 fewer to 8 more; moderate certainty of evidence). Heparin
therapy reduces the risk of symptomatic VTE (RR 0.56; 95% CI 0.47 to 0.68; RD 30 fewer
per 1000; 95% CI 36 fewer to 22 fewer; high certainty of evidence), while it increases
in the risks of major bleeding (RR 1.30; 95% 0.94 to 1.79; RD 4 more per 1000; 95%
CI 1 fewer to 11 more; moderate certainty of evidence) and minor bleeding (RR 1.70;
95% 1.13 to 2.55; RD 17 more per 1000; 95% CI 3 more to 37 more; high certainty of
evidence). Results failed to confirm or to exclude a beneficial or detrimental effect
of heparin on thrombocytopenia (RR 0.69; 95% CI 0.37 to 1.27; RD 33 fewer per 1000;
95% CI 66 fewer to 28 more; moderate certainty of evidence); quality of life (moderate
certainty of evidence). Heparin appears to have no effect on mortality at 12 months
and 24 months. It reduces symptomatic VTE and likely increases major and minor bleeding.
Future research should further investigate the survival benefit of different types
of anticoagulants in patients with different types and stages of cancer. The decision
for a patient with cancer to start heparin therapy should balance the benefits and
downsides, and should integrate the patient's values and preferences. Editorial note:This
is a living systematic review. Living systematic reviews offer a new approach to review
updating in which the review is continually updated, incorporating relevant new evidence,
as it becomes available. Please refer to the Cochrane Database of Systematic Reviews
for the current status of this review. Injectable blood thinners (anticoagulants)
in patients with cancer Background
Research evidence suggests that blood thinners may improve the survival of patients
with cancer, by preventing life‐threatening blood clots and might also have a direct
anticancer effect. However, blood thinners can also increase the risk of bleeding,
which can be serious and reduce survival. It is therefore important to understand
the pros and cons of treatment to allow patients and their doctors to be aware of
the balance of risks and benefits. Study characteristics
We searched the scientific literature for studies of anticoagulants in people with
cancer. The evidence is current to 14 August 2017. We included 19 eligible trials.
Key results
We selected 19 trials including 9650 participants with cancer. Most trials included
participants with various types of cancer, especially small cell lung cancer, non‐small
cell lung cancer, and pancreatic cancer. All studies were conducted in the outpatient
setting. The results suggest that the effect of injectable blood thinners on survival
is uncertain, but if anything of small size. Also the results suggest that injectable
blood thinners reduce the risk of blood clots by about half and possibly increase
the risk of major bleeding and minor bleeding by 4 more per 1000 and 17 more per 1000,
respectively. The effect on quality of life is uncertain. Certainty of evidence
We judged the certainty of evidence to be high for symptomatic VTE and minor bleeding,
and moderate for mortality, major bleeding and quality of life. Editorial note: This
is a living systematic review. Living systematic reviews offer a new approach to review
updating in which the review is continually updated, incorporating relevant new evidence,
as it becomes available. Please refer to the Cochrane Database of Systematic Reviews
for the current status of this review.