Oral rivaroxaban versus subcutaneous low molecular weight heparin treatment for venous thromboembolism in patients with upper gastrointestinal, hepatobiliary and pancreatic cancer

Background

Although low molecular weight heparin (LMWH) is preferred treatment of cancer-related venous thromboembolism (VTE), rivaroxaban is increasingly used owing to its convenience. We aimed to compare the LMWH and rivaroxaban maintenance therapy for VTE in patients with upper gastrointestinal (GI), hepatobiliary and pancreatic (HBP) cancer.

Methods

From JAN 2004 to DEC 2014, a totla of 777 and 217 patients with upper GI or HBP cancer were prescribed LMWH and rivaroxaban, respectively. With exclusion of patients who had resectable disease, received treatment less than 14 days unless discontinued due to bleeding and took anticoagulation not for therapeutic purpose, 111 and 78 patients were analyzed, respectively.

Results

Most baseline characteristics were similar between the two groups (rivaroxaban vs. LMWH), except age ≥65 (57.1% vs. 29.7%, p = 0.001) and ECOG ≥2 (6.4% vs. 19.8%, p = 0.009). The recurrent or aggravated VTEs during anticoagulation were observed at 4 (5.1%) in the rivaroxaban group and 1 (0.9%) in the LMWH group (HR 4.41, 95% CI 0.48-40.13, p = 0.188). Regarding the safety, the rivaroxaban group had significantly higher incidences of total events of bleeding (37.2% vs. 18.0%; HR 2.06, 95% CI 1.17-3.65, p = 0.013) and clinical relevant bleeding (29.5% vs. 13.5%; HR 2.16, 95% CI 1.13-4.14, p = 0.021). Major bleeding events also tended to occur more frequently in the rivaroxaban group (16.7% vs. 7.2%; HR 2.29, 95% CI 0.95-5.53, p = 0.066). In multivariate analysis, treatment with rivaroxaban was significantly associated with total bleeding (HR 2.34, 95% CI 1.30-4.23, p = 0.005) and clinical relevant bleeding (HR 2.16, 95% CI 1.13-4.14, p = 0.021) after adjusting for possible confounding factors, such as age ≥65, sex, presence of a GI mucosa lesion, poor performance status, lower BMI (

Conclusions

Rivaroxaban had similar efficacy to LMWH for the treatment of cancer-associated VTE, but was associated with a higher rate of total bleeding and clinical relevant bleeding in patients with upper GI and HBP cancer. Further studies are needed to validate our findings.

Clinical trial identification

Legal entity responsible for the study

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Funding

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Disclosure

Y-K. Kang: received research grant from Bayer, Novartis, Roche, Sanofi. All other authors have declared no conflicts of interest.