Warfarin transition appears tolerable in patients with cancer-associated thrombosis

ORLANDO, Fla. — Switching to warfarin compared with remaining on low–molecular-weight heparin did not appear associated with increased recurrent venous thromboembolism, major bleeding or total bleeding among patients with cancer-associated thrombosis, according to study results presented at the ASH Annual Meeting and Exposition.

Perspective from Annemarie Fogerty, MD

Further, warfarin acted as an acceptable alternative anticoagulant in patients who could not tolerate long-term treatment with low–molecular-weight heparin (LMWH).

“LMWH is considered to be the anticoagulation of choice for the treatment of cancer-associated thrombosis,” Chatree Chai-Adisaksopha, MD, clinical fellow at McMaster University in Hamilton, Ontario, said during a press conference. “This is based on the results of the CLOT trial, which found that dalteparin [Fragmin, Pfizer] significantly reduced the risk for recurrent VTE compared with warfarin. However, the data regarding the choice of anticoagulation after 6 months of treatment remains unclear.”

Chai-Adisaksopha and colleagues accessed the RIETE registry to identify 1,502 consecutive patients with cancer-associated thrombosis who completed 6 months of LMWH. They divided patients into two groups: those who continued to receive LMWH (n = 763) after 6 months and those who switched to warfarin (n = 739).

Incidence of recurrent VTE, major bleeding and total bleeding served as the primary endpoints.

The median follow-up was 11 months (interquartile range, 7.4-18,1).

The researchers did not observe any significant differences in terms of recurrent VTE (HR = 0.7; 95% CI, 0.46-1.07). Recurrent VTE occurred in 55 patients (7.2%) who continued to receive LMWH and 44 patients (6%) who switched to warfarin.

Both groups had similar instances of major bleeding (2.6% vs. 2.7%; HR = 1.05; 95% CI, 0.79-1.55) and total bleeding (6.7% vs. 7%; HR = 0.92; 95% CI, 0.62-1.37).

“Switching to warfarin does not increase the risk for VTE or major bleeding after 6 months on anticoagulation treatment,” Chai-Adisaksopha said. “However, our study may have some confounding factors, and these results need to be confirmed by a prospective study.” – by Cameron Kelsall

Reference:

Chai-Adisaksopha C, et al. Abstract 430. Presented at: ASH Annual Meeting and Exposition; Dec. 5-8, 2015; Orlando, Fla.

Disclosure: One study researcher reports consultant roles and advisory committee memberships with Bayer, Boehringer Ingelheim, Daiichi Sankyo and Sanofi.

Perspective

Annemarie Fogerty, MD

The CLOT trial established low–molecular-weight heparin (LMWH) as the standard of care in patients, and this paper doesn’t change that in the upfront setting, because patients are not transitioning to warfarin until after 6 months. What it does is identify a population of people who, after 6 months, are sick of shots and can be candidates for a warfarin transition. The primary problem with warfarin — even in the earlier trials — was the difficulty maintaining a therapeutic international normalized ratio in patients who were actively being treated with chemotherapy, and with issues of nausea and vomiting in patients having difficulty taking a drug and throwing up after. If you are removed from those first 6 months, when the therapy is often most intense, then warfarin will be successful due to a higher likelihood of maintaining a therapeutic INR.

Annemarie Fogerty, MD

Massachusetts General Hospital

Disclosures: Fogerty reports no relevant financial disclosures.