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Meta-Analysis
. 2018 Jun 1;6(6):CD006468.
doi: 10.1002/14651858.CD006468.pub6.

Anticoagulation for people with cancer and central venous catheters

Lara A Kahale  1 , Ibrahim G Tsolakian, Maram B Hakoum, Charbel F Matar, Maddalena Barba, Victor Ed Yosuico, Irene Terrenato, Francesca Sperati, Holger Schünemann, Elie A Akl
Affiliations
Meta-Analysis

Anticoagulation for people with cancer and central venous catheters

Lara A Kahale et al. Cochrane Database Syst Rev. .

Abstract

Background: Central venous catheter (CVC) placement increases the risk of thrombosis in people with cancer. Thrombosis often necessitates the removal of the CVC, resulting in treatment delays and thrombosis-related morbidity and mortality. This is an update of the Cochrane Review published in 2014.

Objectives: To evaluate the efficacy and safety of anticoagulation for thromboprophylaxis in people with cancer with a CVC.

Search methods: We conducted a comprehensive literature search in May 2018 that included a major electronic search of Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), and Embase (Ovid); handsearching of conference proceedings; checking of references of included studies; searching for ongoing studies; and using the 'related citation' feature in PubMed. This update of the systematic review was based on the findings of a literature search conducted on 14 May 2018.

Selection criteria: Randomized controlled trials (RCTs) assessing the benefits and harms of unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), vitamin K antagonists (VKA), or fondaparinux or comparing the effects of two of these anticoagulants in people with cancer and a CVC.

Data collection and analysis: Using a standardized form, we extracted data and assessed risk of bias. Outcomes included all-cause mortality, symptomatic catheter-related venous thromboembolism (VTE), pulmonary embolism (PE), major bleeding, minor bleeding, catheter-related infection, thrombocytopenia, and health-related quality of life (HRQoL). We assessed the certainty of evidence for each outcome using the GRADE approach (Balshem 2011).

Main results: Thirteen RCTs (23 papers) fulfilled the inclusion criteria. These trials enrolled 3420 participants. Seven RCTs compared LMWH to no LMWH (six in adults and one in children), six RCTs compared VKA to no VKA (five in adults and one in children), and three RCTs compared LMWH to VKA in adults.LMWH versus no LMWHSix RCTs (1537 participants) compared LMWH to no LMWH in adults. The meta-analyses showed that LMWH probably decreased the incidence of symptomatic catheter-related VTE up to three months of follow-up compared to no LMWH (risk ratio (RR) 0.43, 95% confidence interval (CI) 0.22 to 0.81; risk difference (RD) 38 fewer per 1000, 95% CI 13 fewer to 52 fewer; moderate-certainty evidence). However, the analysis did not confirm or exclude a beneficial or detrimental effect of LMWH on mortality at three months of follow-up (RR 0.82, 95% CI 0.53 to 1.26; RD 14 fewer per 1000, 95% CI 36 fewer to 20 more; low-certainty evidence), major bleeding (RR 1.49, 95% CI 0.06 to 36.28; RD 0 more per 1000, 95% CI 1 fewer to 35 more; very low-certainty evidence), minor bleeding (RR 1.35, 95% CI 0.62 to 2.92; RD 14 more per 1000, 95% CI 16 fewer to 79 more; low-certainty evidence), and thrombocytopenia (RR 1.03, 95% CI 0.80 to 1.33; RD 5 more per 1000, 95% CI 35 fewer to 58 more; low-certainty evidence).VKA versus no VKAFive RCTs (1599 participants) compared low-dose VKA to no VKA in adults. The meta-analyses did not confirm or exclude a beneficial or detrimental effect of low-dose VKA compared to no VKA on mortality (RR 0.99, 95% CI 0.64 to 1.55; RD 1 fewer per 1000, 95% CI 34 fewer to 52 more; low-certainty evidence), symptomatic catheter-related VTE (RR 0.61, 95% CI 0.23 to 1.64; RD 31 fewer per 1000, 95% CI 62 fewer to 51 more; low-certainty evidence), major bleeding (RR 7.14, 95% CI 0.88 to 57.78; RD 12 more per 1000, 95% CI 0 fewer to 110 more; low-certainty evidence), minor bleeding (RR 0.69, 95% CI 0.38 to 1.26; RD 15 fewer per 1000, 95% CI 30 fewer to 13 more; low-certainty evidence), premature catheter removal (RR 0.82, 95% CI 0.30 to 2.24; RD 29 fewer per 1000, 95% CI 114 fewer to 202 more; low-certainty evidence), and catheter-related infection (RR 1.17, 95% CI 0.74 to 1.85; RD 71 more per 1000, 95% CI 109 fewer to 356; low-certainty evidence).LMWH versus VKAThree RCTs (641 participants) compared LMWH to VKA in adults. The available evidence did not confirm or exclude a beneficial or detrimental effect of LMWH relative to VKA on mortality (RR 0.94, 95% CI 0.56 to 1.59; RD 6 fewer per 1000, 95% CI 41 fewer to 56 more; low-certainty evidence), symptomatic catheter-related VTE (RR 1.83, 95% CI 0.44 to 7.61; RD 15 more per 1000, 95% CI 10 fewer to 122 more; very low-certainty evidence), PE (RR 1.70, 95% CI 0.74 to 3.92; RD 35 more per 1000, 95% CI 13 fewer to 144 more; low-certainty evidence), major bleeding (RR 3.11, 95% CI 0.13 to 73.11; RD 2 more per 1000, 95% CI 1 fewer to 72 more; very low-certainty evidence), or minor bleeding (RR 0.95, 95% CI 0.20 to 4.61; RD 1 fewer per 1000, 95% CI 21 fewer to 95 more; very low-certainty evidence). The meta-analyses showed that LMWH probably increased the risk of thrombocytopenia compared to VKA at three months of follow-up (RR 1.69, 95% CI 1.20 to 2.39; RD 149 more per 1000, 95% CI 43 fewer to 300 more; moderate-certainty evidence).

Authors' conclusions: The evidence was not conclusive for the effect of LMWH on mortality, the effect of VKA on mortality and catheter-related VTE, and the effect of LMWH compared to VKA on mortality and catheter-related VTE. We found moderate-certainty evidence that LMWH reduces catheter-related VTE compared to no LMWH. People with cancer with CVCs considering anticoagulation should balance the possible benefit of reduced thromboembolic complications with the possible harms and burden of anticoagulants.

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Conflict of interest statement

LAK: declares no conflicts of interests. IGT: declares no conflicts of interests. MBH: declares no conflicts of interests. CM: declares no conflicts of interests. MB: declares no conflicts of interests. VY: declares no conflicts of interests. IT: declares no conflicts of interests. FS: declares no conflicts of interests. HJS: panel member of the ASH VTE in cancer patients, Vice‐Chair of the ASH VTE guidelines and played various leadership roles from 1999 until 2014 with ACCP VTE guidelines. EAA: served on the executive committee the ACCP Antithrombotic Therapy Guidelines published in 2016.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgments about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgments about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Low‐molecular‐weight heparin (LMWH) versus no LMWH, Outcome 1 All‐cause mortality (up to 3 months).
1.2
1.2. Analysis
Comparison 1 Low‐molecular‐weight heparin (LMWH) versus no LMWH, Outcome 2 Symptomatic catheter‐related thrombosis (up to 3 months).
1.3
1.3. Analysis
Comparison 1 Low‐molecular‐weight heparin (LMWH) versus no LMWH, Outcome 3 Asymptomatic catheter‐related thrombosis (up to 3 months).
1.4
1.4. Analysis
Comparison 1 Low‐molecular‐weight heparin (LMWH) versus no LMWH, Outcome 4 Major bleeding (up to 3 months).
1.5
1.5. Analysis
Comparison 1 Low‐molecular‐weight heparin (LMWH) versus no LMWH, Outcome 5 Minor bleeding (up to 3 months).
1.6
1.6. Analysis
Comparison 1 Low‐molecular‐weight heparin (LMWH) versus no LMWH, Outcome 6 Catheter‐related infection (up to 3 months).
1.7
1.7. Analysis
Comparison 1 Low‐molecular‐weight heparin (LMWH) versus no LMWH, Outcome 7 Thrombocytopenia (up to 3 months).
2.1
2.1. Analysis
Comparison 2 Vitamin K antagonist (VKA) versus no VKA, Outcome 1 All‐cause mortality (up to 3 months).
2.2
2.2. Analysis
Comparison 2 Vitamin K antagonist (VKA) versus no VKA, Outcome 2 Symptomatic catheter‐related thrombosis (up to 3 months).
2.3
2.3. Analysis
Comparison 2 Vitamin K antagonist (VKA) versus no VKA, Outcome 3 Asymptomatic catheter‐related thrombosis.
2.4
2.4. Analysis
Comparison 2 Vitamin K antagonist (VKA) versus no VKA, Outcome 4 Major bleeding (up to 3 months).
2.5
2.5. Analysis
Comparison 2 Vitamin K antagonist (VKA) versus no VKA, Outcome 5 Minor bleeding (up to 3 months).
2.6
2.6. Analysis
Comparison 2 Vitamin K antagonist (VKA) versus no VKA, Outcome 6 Catheter‐related infection.
2.7
2.7. Analysis
Comparison 2 Vitamin K antagonist (VKA) versus no VKA, Outcome 7 Premature central venous catheter removal.
3.1
3.1. Analysis
Comparison 3 Low‐molecular‐weight heparin (LMWH) versus vitamin K antagonist (VKA), Outcome 1 All‐cause mortality (up to 3 months).
3.2
3.2. Analysis
Comparison 3 Low‐molecular‐weight heparin (LMWH) versus vitamin K antagonist (VKA), Outcome 2 Symptomatic catheter‐related thrombosis (up to 3 months).
3.3
3.3. Analysis
Comparison 3 Low‐molecular‐weight heparin (LMWH) versus vitamin K antagonist (VKA), Outcome 3 Asymptomatic catheter‐related thrombosis.
3.4
3.4. Analysis
Comparison 3 Low‐molecular‐weight heparin (LMWH) versus vitamin K antagonist (VKA), Outcome 4 Pulmonary embolism (up to 3 months).
3.5
3.5. Analysis
Comparison 3 Low‐molecular‐weight heparin (LMWH) versus vitamin K antagonist (VKA), Outcome 5 Major bleeding (up to 3 months).
3.6
3.6. Analysis
Comparison 3 Low‐molecular‐weight heparin (LMWH) versus vitamin K antagonist (VKA), Outcome 6 Minor bleeding (up to 3 months).
3.7
3.7. Analysis
Comparison 3 Low‐molecular‐weight heparin (LMWH) versus vitamin K antagonist (VKA), Outcome 7 Thrombocytopenia (up to 3 months).
See this image and copyright information in PMC

Update of

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Abdelkefi 2004 {published data only}
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Akl 2011a
    1. Akl EA, Vasireddi SR, Gunukula S, Yosuico VE, Barba M, Sperati F, et al. Anticoagulation for patients with cancer and central venous catheters. Cochrane Database of Systematic Reviews 2011, Issue 2. [DOI: 10.1002/14651858.CD006468.pub3] - DOI - PubMed
Akl 2011b
    1. Akl EA, Vasireddi SR, Gunukula S, Yosuico VE, Barba M, Sperati F, et al. Anticoagulation for patients with cancer and central venous catheters. Cochrane Database of Systematic Reviews 2011, Issue 4. [DOI: 10.1002/14651858.CD006468.pub4] - DOI - PubMed
Akl 2014
    1. Akl EA, Ramly EP, Kahale LA, Yosuico VE, Barba M, Sperati F, et al. Anticoagulation for people with cancer and central venous catheters. Cochrane Database of Systematic Reviews 2014, Issue 10. [DOI: 10.1002/14651858.CD006468.pub5] - DOI - PubMed

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