Tags

Type your tag names separated by a space and hit enter

Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy.
Cochrane Database Syst Rev. 2016 12 01; 12:CD008500.CD

Abstract

BACKGROUND

Venous thromboembolism (VTE) often complicates the clinical course of cancer. The risk is further increased by chemotherapy, but the trade-off between safety and efficacy of primary thromboprophylaxis in cancer patients treated with chemotherapy is uncertain. This is the second update of a review first published in February 2012.

OBJECTIVES

To assess the efficacy and safety of primary thromboprophylaxis for VTE in ambulatory cancer patients receiving chemotherapy compared with placebo or no thromboprophylaxis.

SEARCH METHODS

For this update the Cochrane Vascular Information Specialist searched the Cochrane Vascular Group Specialised Register (June 2016). In addition, the Information Specialist searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 5). Clinical trials registries were searched up to June 2016.

SELECTION CRITERIA

Randomised controlled trials comparing any oral or parenteral anticoagulant or mechanical intervention to no thromboprophylaxis or placebo, or comparing two different anticoagulants.

DATA COLLECTION AND ANALYSIS

We extracted data on methodological quality, participant characteristics, interventions, and outcomes including symptomatic VTE and major bleeding as the primary effectiveness and safety outcomes, respectively.

MAIN RESULTS

We identified five additional randomised controlled trials (2491 participants) in the updated search, considering in this update 26 trials with a total of 12,352 participants, all evaluating pharmacological interventions and performed mainly in people with locally advanced or metastatic cancer. The quality of the evidence ranged from high to very low across the different outcomes and comparisons. The main limiting factors were imprecision and risk of bias. One large trial of 3212 participants found a 64% (risk ratio (RR) 0.36, 95% confidence interval (CI) 0.22 to 0.60) reduction of symptomatic VTE with the ultra-low molecular weight heparin (uLMWH) semuloparin relative to placebo, with no apparent difference in major bleeding (RR 1.05, 95% CI 0.55 to 2.00). When compared with no thromboprophylaxis, LMWH significantly reduced the incidence of symptomatic VTE (RR 0.54, 95% CI 0.38 to 0.75; no heterogeneity, Tau2 = 0.00%) with a non-statistically significant 44% higher risk of major bleeding events (RR 1.44, 95% CI 0.98 to 2.11). In participants with multiple myeloma, LMWH was associated with a significant reduction in symptomatic VTE compared with the vitamin K antagonist warfarin (RR 0.33, 95% CI 0.14 to 0.83), while the difference between LMWH and aspirin was not statistically significant (RR 0.51, 95% CI 0.22 to 1.17). Major bleeding was observed in none of the participants treated with LMWH or warfarin and in less than 1% of those treated with aspirin. Only one study evaluated unfractionated heparin against no thromboprophylaxis but did not report on VTE or major bleeding. When compared with placebo, warfarin was associated with a non-statistically significant reduction of symptomatic VTE (RR 0.15, 95% CI 0.02 to 1.20). Antithrombin, evaluated in one study involving paediatric patients, had no significant effect on VTE or on major bleeding when compared with no antithrombin. The direct oral factor Xa inhibitor apixaban was evaluated in a phase II dose-finding study that suggested a low rate of major bleeding (2.1% versus 3.4%) and symptomatic VTE (1.1% versus 13.8%) in comparison with placebo.

AUTHORS' CONCLUSIONS

In this second update, we confirmed that primary thromboprophylaxis with LMWH significantly reduced the incidence of symptomatic VTE in ambulatory cancer patients treated with chemotherapy. In addition, the uLMWH semuloparin, which is not commercially available, significantly reduced the incidence of symptomatic VTE. The risk of major bleeding associated with LMWH, while not reaching statistical significance, suggest caution and mandate additional studies to determine the risk-to-benefit ratio of LMWH in this setting. Despite the encouraging results of this review, routine prophylaxis in ambulatory cancer patients cannot be recommended before safety issues are adequately addressed. We need additional studies investigating targeted primary prophylaxis in people with specific types or stages of cancer associated with a higher risk of VTE.

Authors+Show Affiliations

Department of Medical, Oral and Biotechnological Sciences, University "G. D'Annunzio" of Chieti-Pescara, via dei Vestini 31, Chieti, Italy, 66013. Department of Vascular Medicine, Academic Medical Center, Amsterdam, Netherlands.Department of Medical, Oral and Biotechnological Sciences, University "G. D'Annunzio" of Chieti-Pescara, via dei Vestini 31, Chieti, Italy, 66013.Internal Medicine Unit, "University G. D'Annunzio" Foundation, Chieti, Italy.Internal Medicine Unit, "University G. D'Annunzio" Foundation, Chieti, Italy.Department of Medical, Oral and Biotechnological Sciences, University "G. D'Annunzio" of Chieti-Pescara, via dei Vestini 31, Chieti, Italy, 66013.Centre for Systematic Reviews, Fondazione "Università G. D'Annunzio", Via dei Vestini 31, Chieti, Chieti, Italy, 66100. CTU Bern, University of Bern, Bern, Bern, Switzerland, 3012.

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Review
Systematic Review

Language

eng

PubMed ID

27906452

Citation

Di Nisio, Marcello, et al. "Primary Prophylaxis for Venous Thromboembolism in Ambulatory Cancer Patients Receiving Chemotherapy." The Cochrane Database of Systematic Reviews, vol. 12, 2016, p. CD008500.
Di Nisio M, Porreca E, Candeloro M, et al. Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Cochrane Database Syst Rev. 2016;12:CD008500.
Di Nisio, M., Porreca, E., Candeloro, M., De Tursi, M., Russi, I., & Rutjes, A. W. (2016). Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy. The Cochrane Database of Systematic Reviews, 12, CD008500. https://doi.org/10.1002/14651858.CD008500.pub4
Di Nisio M, et al. Primary Prophylaxis for Venous Thromboembolism in Ambulatory Cancer Patients Receiving Chemotherapy. Cochrane Database Syst Rev. 2016 12 1;12:CD008500. PubMed PMID: 27906452.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy. AU - Di Nisio,Marcello, AU - Porreca,Ettore, AU - Candeloro,Matteo, AU - De Tursi,Michele, AU - Russi,Ilaria, AU - Rutjes,Anne Ws, Y1 - 2016/12/01/ PY - 2016/12/3/pubmed PY - 2017/1/31/medline PY - 2016/12/2/entrez SP - CD008500 EP - CD008500 JF - The Cochrane database of systematic reviews JO - Cochrane Database Syst Rev VL - 12 N2 - BACKGROUND: Venous thromboembolism (VTE) often complicates the clinical course of cancer. The risk is further increased by chemotherapy, but the trade-off between safety and efficacy of primary thromboprophylaxis in cancer patients treated with chemotherapy is uncertain. This is the second update of a review first published in February 2012. OBJECTIVES: To assess the efficacy and safety of primary thromboprophylaxis for VTE in ambulatory cancer patients receiving chemotherapy compared with placebo or no thromboprophylaxis. SEARCH METHODS: For this update the Cochrane Vascular Information Specialist searched the Cochrane Vascular Group Specialised Register (June 2016). In addition, the Information Specialist searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 5). Clinical trials registries were searched up to June 2016. SELECTION CRITERIA: Randomised controlled trials comparing any oral or parenteral anticoagulant or mechanical intervention to no thromboprophylaxis or placebo, or comparing two different anticoagulants. DATA COLLECTION AND ANALYSIS: We extracted data on methodological quality, participant characteristics, interventions, and outcomes including symptomatic VTE and major bleeding as the primary effectiveness and safety outcomes, respectively. MAIN RESULTS: We identified five additional randomised controlled trials (2491 participants) in the updated search, considering in this update 26 trials with a total of 12,352 participants, all evaluating pharmacological interventions and performed mainly in people with locally advanced or metastatic cancer. The quality of the evidence ranged from high to very low across the different outcomes and comparisons. The main limiting factors were imprecision and risk of bias. One large trial of 3212 participants found a 64% (risk ratio (RR) 0.36, 95% confidence interval (CI) 0.22 to 0.60) reduction of symptomatic VTE with the ultra-low molecular weight heparin (uLMWH) semuloparin relative to placebo, with no apparent difference in major bleeding (RR 1.05, 95% CI 0.55 to 2.00). When compared with no thromboprophylaxis, LMWH significantly reduced the incidence of symptomatic VTE (RR 0.54, 95% CI 0.38 to 0.75; no heterogeneity, Tau2 = 0.00%) with a non-statistically significant 44% higher risk of major bleeding events (RR 1.44, 95% CI 0.98 to 2.11). In participants with multiple myeloma, LMWH was associated with a significant reduction in symptomatic VTE compared with the vitamin K antagonist warfarin (RR 0.33, 95% CI 0.14 to 0.83), while the difference between LMWH and aspirin was not statistically significant (RR 0.51, 95% CI 0.22 to 1.17). Major bleeding was observed in none of the participants treated with LMWH or warfarin and in less than 1% of those treated with aspirin. Only one study evaluated unfractionated heparin against no thromboprophylaxis but did not report on VTE or major bleeding. When compared with placebo, warfarin was associated with a non-statistically significant reduction of symptomatic VTE (RR 0.15, 95% CI 0.02 to 1.20). Antithrombin, evaluated in one study involving paediatric patients, had no significant effect on VTE or on major bleeding when compared with no antithrombin. The direct oral factor Xa inhibitor apixaban was evaluated in a phase II dose-finding study that suggested a low rate of major bleeding (2.1% versus 3.4%) and symptomatic VTE (1.1% versus 13.8%) in comparison with placebo. AUTHORS' CONCLUSIONS: In this second update, we confirmed that primary thromboprophylaxis with LMWH significantly reduced the incidence of symptomatic VTE in ambulatory cancer patients treated with chemotherapy. In addition, the uLMWH semuloparin, which is not commercially available, significantly reduced the incidence of symptomatic VTE. The risk of major bleeding associated with LMWH, while not reaching statistical significance, suggest caution and mandate additional studies to determine the risk-to-benefit ratio of LMWH in this setting. Despite the encouraging results of this review, routine prophylaxis in ambulatory cancer patients cannot be recommended before safety issues are adequately addressed. We need additional studies investigating targeted primary prophylaxis in people with specific types or stages of cancer associated with a higher risk of VTE. SN - 1469-493X UR - https://www.unboundmedicine.com/medline/citation/27906452/Primary_prophylaxis_for_venous_thromboembolism_in_ambulatory_cancer_patients_receiving_chemotherapy_ L2 - https://doi.org/10.1002/14651858.CD008500.pub4 DB - PRIME DP - Unbound Medicine ER -