Oral anticoagulation for prolonging survival in patients with cancer

Elie A. Akl, G. Kamath, S. Y. Kim, V. Yosuico, M. Barba, I. Terrenato, F. Sperati, H. J. Schünemann

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Background: A number of basic research and clinical studies have led to the hypothesis that oral anticoagulants may improve the survival of patients with cancer through an antitumour effect in addition to their antithrombotic effect. Objectives: To evaluate the effectiveness and safety of oral anticoagulation (including vitamin K antagonists and ximelagatran) as an intervention to improve survival of patients with cancer. Search strategy: A comprehensive search for studies of anticoagulation in cancer patients including (1) a January 2007 electronic search of the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, ISI the Web of Science; (2) hand search of the American Society of Clinical Oncology (starting with its first volume, 1982) and of the American Society of Hematology (starting with its 2003 issue); (3) checking of references of included studies; and (4) use of "related article" feature in PubMed. Selection criteria: Randomized clinical trials (RCTs) comparing vitamin K antagonist or ximelagatran to no intervention or placebo in cancer patients without clinical evidence of venous thromboembolism. Data collection and analysis: Using a standardized data form we extracted data on methodological quality, participants, interventions and outcome of interest that included all cause mortality, symptomatic deep venous thrombosis, symptomatic pulmonary embolism, major bleeding and minor bleeding. Main results: Of 3986 identified citations five RCTs fulfilled the inclusion criteria. Warfarin was the oral anticoagulant in all of these RCTs and it was compared to either placebo or no intervention. The overall methodological quality of these RCTs was acceptable. The effect of warfarin on reduction in mortality was not statistically significant at six months (Relative risk (RR) = 0.96; 95% CI 0.80 to 1.16), at one year (RR = 0.95; 95% CI 0.86 to 1.05) at 2 years (RR = 0.97; 95% CI 0.87 to 1.08) or at five years (RR 0.91; 95% CI 0.83 to 1.01). In the subgroup of patients with small cell lung cancer (SCLC), warfarin reduced mortality at six months (RR = 0.69; 95% CI 0.50 to 0.96) but not at one year (RR = 0.88; 95% CI 0.77 to 1.01). This six month mortality benefit was statistically significant in the subgroup of extensive SCLC (RR = 0.65; 95% CI 0.45 to 0.93) but not in the subgroup of limited SCLC (RR = 0.68; 95% CI 0.36 to 1.28). One study assessed the effect of warfarin on venous thromboembolism and showed a RR reduction of 85% (p = 0.031). Warfarin increased both major bleeding (RR = 4.24; 95% CI 1.85 to 9.68) and minor bleeding (RR = 3.34; 95% CI 1.66 to 6.74). Warfarin increased the risk of major bleeding (RR 5.46; 95% CI 3.04 to 9.81) and minor bleeding (RR 4.01; 95% CI 1.30 to 12.42) also in patients with SCLC. There was no evidence for a significant reduction in mortality in any other cancer subtype. Authors' conclusions: Existing evidence does not suggest a mortality benefit from oral anticoagulation in patients with cancer in general. In patients with SCLC, the evidence suggests a potential mortality benefit at six months from warfarin particularly when the disease is extensive. The decision for a patient with extensive SCLC to start warfarin for mortality benefit should balance that benefit with the downsides of increased bleeding risk in light of patient values for these outcomes.

Original languageEnglish
Article numberCD006466
JournalThe Cochrane database of systematic reviews
Issue number2
DOIs
Publication statusPublished - 2007

Fingerprint

Survival
Warfarin
Small Cell Lung Carcinoma
Neoplasms
Hemorrhage
Mortality
Randomized Controlled Trials
Vitamin K
Venous Thromboembolism
Anticoagulants
Placebos
Risk Reduction Behavior
Pulmonary Embolism
PubMed
MEDLINE
Venous Thrombosis
Patient Selection
Databases
Safety
Research

Keywords

  • Administration, oral
  • Anticoagulants [*administration & dosage; adverse effects]
  • Carcinoma, small cell [mortality]
  • Hemorrhage [chemically induced]
  • Lung neoplasms [mortality]
  • Neoplasms [*mortality]
  • Randomized controlled trials as topic

ASJC Scopus subject areas

  • Medicine(all)
  • Pharmacology (medical)

Cite this

Akl, E. A., Kamath, G., Kim, S. Y., Yosuico, V., Barba, M., Terrenato, I., ... Schünemann, H. J. (2007). Oral anticoagulation for prolonging survival in patients with cancer. The Cochrane database of systematic reviews, (2), [CD006466]. https://doi.org/10.1002/14651858.CD006466

Oral anticoagulation for prolonging survival in patients with cancer. / Akl, Elie A.; Kamath, G.; Kim, S. Y.; Yosuico, V.; Barba, M.; Terrenato, I.; Sperati, F.; Schünemann, H. J.

In: The Cochrane database of systematic reviews, No. 2, CD006466, 2007.

Research output: Contribution to journalArticle

Akl, EA, Kamath, G, Kim, SY, Yosuico, V, Barba, M, Terrenato, I, Sperati, F & Schünemann, HJ 2007, 'Oral anticoagulation for prolonging survival in patients with cancer', The Cochrane database of systematic reviews, no. 2, CD006466. https://doi.org/10.1002/14651858.CD006466
Akl, Elie A. ; Kamath, G. ; Kim, S. Y. ; Yosuico, V. ; Barba, M. ; Terrenato, I. ; Sperati, F. ; Schünemann, H. J. / Oral anticoagulation for prolonging survival in patients with cancer. In: The Cochrane database of systematic reviews. 2007 ; No. 2.
@article{65a4aee8fc8a468181e535f7532b2240,
title = "Oral anticoagulation for prolonging survival in patients with cancer",
abstract = "Background: A number of basic research and clinical studies have led to the hypothesis that oral anticoagulants may improve the survival of patients with cancer through an antitumour effect in addition to their antithrombotic effect. Objectives: To evaluate the effectiveness and safety of oral anticoagulation (including vitamin K antagonists and ximelagatran) as an intervention to improve survival of patients with cancer. Search strategy: A comprehensive search for studies of anticoagulation in cancer patients including (1) a January 2007 electronic search of the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, ISI the Web of Science; (2) hand search of the American Society of Clinical Oncology (starting with its first volume, 1982) and of the American Society of Hematology (starting with its 2003 issue); (3) checking of references of included studies; and (4) use of {"}related article{"} feature in PubMed. Selection criteria: Randomized clinical trials (RCTs) comparing vitamin K antagonist or ximelagatran to no intervention or placebo in cancer patients without clinical evidence of venous thromboembolism. Data collection and analysis: Using a standardized data form we extracted data on methodological quality, participants, interventions and outcome of interest that included all cause mortality, symptomatic deep venous thrombosis, symptomatic pulmonary embolism, major bleeding and minor bleeding. Main results: Of 3986 identified citations five RCTs fulfilled the inclusion criteria. Warfarin was the oral anticoagulant in all of these RCTs and it was compared to either placebo or no intervention. The overall methodological quality of these RCTs was acceptable. The effect of warfarin on reduction in mortality was not statistically significant at six months (Relative risk (RR) = 0.96; 95{\%} CI 0.80 to 1.16), at one year (RR = 0.95; 95{\%} CI 0.86 to 1.05) at 2 years (RR = 0.97; 95{\%} CI 0.87 to 1.08) or at five years (RR 0.91; 95{\%} CI 0.83 to 1.01). In the subgroup of patients with small cell lung cancer (SCLC), warfarin reduced mortality at six months (RR = 0.69; 95{\%} CI 0.50 to 0.96) but not at one year (RR = 0.88; 95{\%} CI 0.77 to 1.01). This six month mortality benefit was statistically significant in the subgroup of extensive SCLC (RR = 0.65; 95{\%} CI 0.45 to 0.93) but not in the subgroup of limited SCLC (RR = 0.68; 95{\%} CI 0.36 to 1.28). One study assessed the effect of warfarin on venous thromboembolism and showed a RR reduction of 85{\%} (p = 0.031). Warfarin increased both major bleeding (RR = 4.24; 95{\%} CI 1.85 to 9.68) and minor bleeding (RR = 3.34; 95{\%} CI 1.66 to 6.74). Warfarin increased the risk of major bleeding (RR 5.46; 95{\%} CI 3.04 to 9.81) and minor bleeding (RR 4.01; 95{\%} CI 1.30 to 12.42) also in patients with SCLC. There was no evidence for a significant reduction in mortality in any other cancer subtype. Authors' conclusions: Existing evidence does not suggest a mortality benefit from oral anticoagulation in patients with cancer in general. In patients with SCLC, the evidence suggests a potential mortality benefit at six months from warfarin particularly when the disease is extensive. The decision for a patient with extensive SCLC to start warfarin for mortality benefit should balance that benefit with the downsides of increased bleeding risk in light of patient values for these outcomes.",
keywords = "Administration, oral, Anticoagulants [*administration & dosage; adverse effects], Carcinoma, small cell [mortality], Hemorrhage [chemically induced], Lung neoplasms [mortality], Neoplasms [*mortality], Randomized controlled trials as topic",
author = "Akl, {Elie A.} and G. Kamath and Kim, {S. Y.} and V. Yosuico and M. Barba and I. Terrenato and F. Sperati and Sch{\"u}nemann, {H. J.}",
year = "2007",
doi = "10.1002/14651858.CD006466",
language = "English",
journal = "Cochrane Database of Systematic Reviews",
issn = "1361-6137",
publisher = "John Wiley and Sons Ltd",
number = "2",

}

TY - JOUR

T1 - Oral anticoagulation for prolonging survival in patients with cancer

AU - Akl, Elie A.

AU - Kamath, G.

AU - Kim, S. Y.

AU - Yosuico, V.

AU - Barba, M.

AU - Terrenato, I.

AU - Sperati, F.

AU - Schünemann, H. J.

PY - 2007

Y1 - 2007

N2 - Background: A number of basic research and clinical studies have led to the hypothesis that oral anticoagulants may improve the survival of patients with cancer through an antitumour effect in addition to their antithrombotic effect. Objectives: To evaluate the effectiveness and safety of oral anticoagulation (including vitamin K antagonists and ximelagatran) as an intervention to improve survival of patients with cancer. Search strategy: A comprehensive search for studies of anticoagulation in cancer patients including (1) a January 2007 electronic search of the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, ISI the Web of Science; (2) hand search of the American Society of Clinical Oncology (starting with its first volume, 1982) and of the American Society of Hematology (starting with its 2003 issue); (3) checking of references of included studies; and (4) use of "related article" feature in PubMed. Selection criteria: Randomized clinical trials (RCTs) comparing vitamin K antagonist or ximelagatran to no intervention or placebo in cancer patients without clinical evidence of venous thromboembolism. Data collection and analysis: Using a standardized data form we extracted data on methodological quality, participants, interventions and outcome of interest that included all cause mortality, symptomatic deep venous thrombosis, symptomatic pulmonary embolism, major bleeding and minor bleeding. Main results: Of 3986 identified citations five RCTs fulfilled the inclusion criteria. Warfarin was the oral anticoagulant in all of these RCTs and it was compared to either placebo or no intervention. The overall methodological quality of these RCTs was acceptable. The effect of warfarin on reduction in mortality was not statistically significant at six months (Relative risk (RR) = 0.96; 95% CI 0.80 to 1.16), at one year (RR = 0.95; 95% CI 0.86 to 1.05) at 2 years (RR = 0.97; 95% CI 0.87 to 1.08) or at five years (RR 0.91; 95% CI 0.83 to 1.01). In the subgroup of patients with small cell lung cancer (SCLC), warfarin reduced mortality at six months (RR = 0.69; 95% CI 0.50 to 0.96) but not at one year (RR = 0.88; 95% CI 0.77 to 1.01). This six month mortality benefit was statistically significant in the subgroup of extensive SCLC (RR = 0.65; 95% CI 0.45 to 0.93) but not in the subgroup of limited SCLC (RR = 0.68; 95% CI 0.36 to 1.28). One study assessed the effect of warfarin on venous thromboembolism and showed a RR reduction of 85% (p = 0.031). Warfarin increased both major bleeding (RR = 4.24; 95% CI 1.85 to 9.68) and minor bleeding (RR = 3.34; 95% CI 1.66 to 6.74). Warfarin increased the risk of major bleeding (RR 5.46; 95% CI 3.04 to 9.81) and minor bleeding (RR 4.01; 95% CI 1.30 to 12.42) also in patients with SCLC. There was no evidence for a significant reduction in mortality in any other cancer subtype. Authors' conclusions: Existing evidence does not suggest a mortality benefit from oral anticoagulation in patients with cancer in general. In patients with SCLC, the evidence suggests a potential mortality benefit at six months from warfarin particularly when the disease is extensive. The decision for a patient with extensive SCLC to start warfarin for mortality benefit should balance that benefit with the downsides of increased bleeding risk in light of patient values for these outcomes.

AB - Background: A number of basic research and clinical studies have led to the hypothesis that oral anticoagulants may improve the survival of patients with cancer through an antitumour effect in addition to their antithrombotic effect. Objectives: To evaluate the effectiveness and safety of oral anticoagulation (including vitamin K antagonists and ximelagatran) as an intervention to improve survival of patients with cancer. Search strategy: A comprehensive search for studies of anticoagulation in cancer patients including (1) a January 2007 electronic search of the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, ISI the Web of Science; (2) hand search of the American Society of Clinical Oncology (starting with its first volume, 1982) and of the American Society of Hematology (starting with its 2003 issue); (3) checking of references of included studies; and (4) use of "related article" feature in PubMed. Selection criteria: Randomized clinical trials (RCTs) comparing vitamin K antagonist or ximelagatran to no intervention or placebo in cancer patients without clinical evidence of venous thromboembolism. Data collection and analysis: Using a standardized data form we extracted data on methodological quality, participants, interventions and outcome of interest that included all cause mortality, symptomatic deep venous thrombosis, symptomatic pulmonary embolism, major bleeding and minor bleeding. Main results: Of 3986 identified citations five RCTs fulfilled the inclusion criteria. Warfarin was the oral anticoagulant in all of these RCTs and it was compared to either placebo or no intervention. The overall methodological quality of these RCTs was acceptable. The effect of warfarin on reduction in mortality was not statistically significant at six months (Relative risk (RR) = 0.96; 95% CI 0.80 to 1.16), at one year (RR = 0.95; 95% CI 0.86 to 1.05) at 2 years (RR = 0.97; 95% CI 0.87 to 1.08) or at five years (RR 0.91; 95% CI 0.83 to 1.01). In the subgroup of patients with small cell lung cancer (SCLC), warfarin reduced mortality at six months (RR = 0.69; 95% CI 0.50 to 0.96) but not at one year (RR = 0.88; 95% CI 0.77 to 1.01). This six month mortality benefit was statistically significant in the subgroup of extensive SCLC (RR = 0.65; 95% CI 0.45 to 0.93) but not in the subgroup of limited SCLC (RR = 0.68; 95% CI 0.36 to 1.28). One study assessed the effect of warfarin on venous thromboembolism and showed a RR reduction of 85% (p = 0.031). Warfarin increased both major bleeding (RR = 4.24; 95% CI 1.85 to 9.68) and minor bleeding (RR = 3.34; 95% CI 1.66 to 6.74). Warfarin increased the risk of major bleeding (RR 5.46; 95% CI 3.04 to 9.81) and minor bleeding (RR 4.01; 95% CI 1.30 to 12.42) also in patients with SCLC. There was no evidence for a significant reduction in mortality in any other cancer subtype. Authors' conclusions: Existing evidence does not suggest a mortality benefit from oral anticoagulation in patients with cancer in general. In patients with SCLC, the evidence suggests a potential mortality benefit at six months from warfarin particularly when the disease is extensive. The decision for a patient with extensive SCLC to start warfarin for mortality benefit should balance that benefit with the downsides of increased bleeding risk in light of patient values for these outcomes.

KW - Administration, oral

KW - Anticoagulants [administration & dosage; adverse effects]

KW - Carcinoma, small cell [mortality]

KW - Hemorrhage [chemically induced]

KW - Lung neoplasms [mortality]

KW - Neoplasms [mortality]

KW - Randomized controlled trials as topic

UR - http://www.scopus.com/inward/record.url?scp=42949084376&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=42949084376&partnerID=8YFLogxK

U2 - 10.1002/14651858.CD006466

DO - 10.1002/14651858.CD006466

M3 - Article

AN - SCOPUS:42949084376

JO - Cochrane Database of Systematic Reviews

JF - Cochrane Database of Systematic Reviews

SN - 1361-6137

IS - 2

M1 - CD006466

ER -