Prophylactic warfarin is not associated with a reduction in catheter-related or other thromboses in cancer patients, and thus new treatments are needed. These are the conclusions of authors of an Article published in this week's edition of The Lancet, written by Annie Young, Cancer Research UK Trials Unit, Institute for Cancer Studies, University of Birmingham, UK, and colleagues. This trial (the WARP study) was funded by both Cancer Research UK and the Medical Research Council, UK.
Venous thromboembolism (VTE) is a well known complication of cancer and is related to the production of a range of pro-clotting factors by tumours, certain chemotherapies and hormone therapies, and the use of central venous catheters (CVCs). Around 50% of patients with cancer have VTE, but it remains an underdiagnosed and undertreated condition. The use of CVCs to deliver infusional chemotherapy has increased enormously in the past decade, as has recognition of catheter-related thrombosis as a source of considerable complications. The use of warfarin with CVCs to prevent VTE is controversial because previous studies have produced mixed results and there is as yet no clear evidence of its efficacy. The authors assessed whether warfarin reduces catheter-related thrombosis compared with no warfarin, and whether any success of warfarin treatment is dose-dependent.
This randomised trial, at 68 centres in the UK, studied 1590 patients aged at least 16 years with cancer who were receiving chemotherapy through CVCs. Patients were randomised to no warfarin, fixed-dose warfarin 1 mg per day, or dose-adjusted warfarin per day. However, if the clinicians were certain of the indication of warfarin, they could randomise between 1mg wafarin and dose adjusted warfarin. The researchers found that any warfarin did not reduce the level of catheter-related thromboses compared with no warfarin (6% vs 6%) However dose-adjusted warfarin did reduce catheter-related thromboses versus fixed-dose warfarin (3% vs 7%), although major bleeding events were highest in the dose-adjusted warfarin group (16) versus the fixed-dose warfarin group (7). The combination of thrombosis and bleeding event data showed no clear benefit in any group, including no survival benefit.
The authors conclude: "The rate of symptomatic catheter-related thromboses reported in clinical trials has fallen substantially over the past decade. The improvements in catheter technology, placement, and aftercare are contributing to this reduction. When any benefit of thromboprophylaxis was balanced against the risk of major bleeding, the combined outcome showed no advantage with the use of any dose of warfarin. These findings only add to the assertion that the time has come to move on from warfarin for thromboprophylaxis in patients with cancer...We should consider newer treatments."
In an accompanying Comment, Dr Paolo Prandoni, Thromboembolism Unit, University of Padua, Italy says that while there is no evidence for the benefit of warfarin an effort should be made to identify those patients at highest risk of VTE and therefore who may benefit from thromboprophylaxis.
Annie Young, Cancer Research UK Trials Unit, Institute for Cancer Studies, University of Birmingham, UK T) +44 (0) 771 204 8853 E) a.young@bham.ac.uk
Dr Paolo Prandoni, Thromboembolism Unit, University of Padua, Italy T) +39 049 8212656 E) paoloprandoni@tin.it
For full Article and Comment: http://press.thelancet.com/warpfinal.pdf
Journal
The Lancet