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Rivaroxaban in comparison with low molecular weight heparin for the treatment of cancer-associated thrombosis: a systematic review and meta-analysis

Abstract

Background. Apixaban, edoxaban, and rivaroxaban are now recommended over low-molecular-weight heparins (LMWH) for long-term treatment of cancer-associated thrombosis (CAT).

Objective. Our study was aimed at comparing efficacy, safety and effect of rivaroxaban and LMWH on all-cause mortality in patients with cancer-associated thrombosis.

Methods. A systematic literature search was performed through the Medline and Cochrane libraries according to the previously developed in compliance with the PRISMA guidelines protocol (CRD42022310908). Randomized controlled trials comparing full-therapeutic dose of rivaroxaban with full-therapeutic and/or the intermediate dose of LMWH in patients with verified CAT were included. The main outcomes were: VTE recurrence, major bleeding, and all-cause mortality. Individual study events were converted into rates per patient-years of follow-up and combined using a pooled proportion meta-analysis with a random-effect model or fixed effect model according to the heterogeneity. The final results are reported as per 100 patient-years.

Results. The systematic search was performed in March 2022 and revealed 715 records. Of these, 16 full-text papers were screened for eligibility and two RCTs (SELECT-D and CASTA DIVA) combining the data on 564 patients were included into the analysis. The pooled event rate of VTE recurrence in those who received rivaroxaban and dalteparin was estimated as 10.0 and 19.6 per 100 patient-years, respectively. The pooled event rate for major bleeding and all-cause mortality amounted to 10.0 vs. 7.3 and 55.8 vs. 62.0 per 100 patient-years for those treated with rivaroxaban vs. dalteparin, respectively. The odds ratio (OR) for VTE recurrence was in favor of rivaroxaban (OR 0.45; 95% CI 0.22–0.96; p=0.04; I²=0.0%), with no differences in the risk of major bleeding (OR 1.12; 95% CI 0.23–5.53; p=0.136; I²=44.5%) and all-cause mortality (OR 0.77; 95% CI 0.45–1.31; p=0.330; I²=0.0%) observed.

Conclusion. In patients with cancer-associated thrombosis, the use of rivaroxaban in comparison with LMWH is associated with a reduced risk of VTE recurrence without an increase in the risk of major bleeding and does not affect all-cause mortality.

Keywords:venous thrombosis; pulmonary embolism; venous thromboembolism; malignancy; rivaroxaban

Funding. The study had no financial support.

Conflict of interest. Lobastov K.V. and Schastlivtsev I.V. received payments from Bayer AG for lectures, Pyatskaya A.V. and Navasardyan A.R. at the moment of writing the article were employed at Bayer AG, Kovalchuk A.V. has no conflicts of interest to declare.

Authors’ contribution. Study conception and design – Lobastov K.V., Pyatskaya A.V.; data collection and handling – Pyatskaya A.V., Kovalchuk A.V., Schastlivtsev I.V., Navasardyan A.R.; statistical processing – Lobastov K.V.; draft manuscript preparation – Lobastov K.V.; manuscript revision – Lobastov K.V., Schastlivtsev I.V., Pyatskaya A.V., Navasardyan A.R.

For citation: Lobastov K.V., Schastlivtsev I.V., Kovalchuk A.V., Pyatskaya A.V., Navasardyan A.R. Rivaroxaban in comparison with low molecular weight heparin for the treatment of cancer-associated thrombosis: a systematic review and meta-analysis. Angiology and Vascular Surgery. 2022; 28 (4): 126–34. DOI: https://doi.org/10.33029/1027-6661-2022-28-4-126-134 (in Russian)

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Akchurin Renat Suleymanovich

Doctor of Medical Sciences, Professor, Academician of the Russian Academy of Sciences, Deputy General Director for Surgery, Head of the Department of Cardiovascular Surgery, National Medical Research Center for Cardiology named after Academician E.I. Chazov, President of the Russian Society of Angiologists and Vascular Surgeons

In accordance with the decision of the Presidium of the Russian Society of Angiologists and Vascular Surgeons, the journal "Angiology and Vascular Surgery" will be named after Academician A.V. Pokrovsky starting from No. 2/2022.