Apixaban, Dalteprin Shown to Have Same Bleeding Risk in Patients With Cancer

Results of a study comparing apixaban (Eliquis) with low-molecular-weight heparin as a treatment prevent recurrent blood clots in cancer patients may assuage some of the concern about the bleeding risk associated with direct-acting oral anticoagulants (DOACs).

The findings from open-label noninferiority Caravaggio trial show that apixaban is noninferior to dalteparin, a low-molecular-weight heparin formulation, as far as preventing venous thromboembolism (VTE) and, importantly that the occurrence of major bleeding was similar: 3.8% in the apixaban group vs. 4.0% in the dalteparin group (hazard ratio [HR], 0.82; 95% CI, 0.40—1.69; P = .60).

There are some caveats. Giancarlo Agnelli, MD, and his co-investigators noted that the study was designed to discover differences in recurrent VTE and that the study sample was not large enough to make definite conclusions about bleeding. Also, in a secondary outcome, more patients in the apixaban group had bleeding that the investigators classified as nonmajor but still “clinically relevant” than patients in the dalteprin group (9.0% vs. 6.0%, HR, 1.42; 95% CI 0.88—2.30).

The researchers reported their findings today at the 2020 American College of Cardiology / World Congress of Cardiology meeting that is being conducted virtually because of coronavirus disease 2019. The results were published simultaneously in the New England Journal of Medicine.¹

In an accompanying editorial in the Journal,² Agnes Y. Y. Lee, MD, of the University of British Columbia notes that the Caravaggio results cast apaxiban’s bleeding risk in a favorable light relative to other DOACS, edoxaban (Savaysa) and rivaroxaban (Xarelto). But she cautions against concluding that one of the DOACs is better than the other without evidence from a head-to-head comparison. Lee also say that low-molecular-weight heparin is preferred over DOACs in patients for whom drug-to-drug interactions are a concern and in those who have had upper GI surgery because the DOACs are absorbed in the stomach and the upper part of the small intestine.

Venous thromboembolism is a common and potentially deadly problem for patients with cancer. It occurs both as deep-vein thrombosis and pulmonary embolism. Subcutaneous injections of low-molecular weight heparin have been the standard treatment, but the DOACs, as oral drugs, would be more convenient. Trials comparing the approaches have shown that they are comparable as far as preventing venous thromboembolism but bleeding risk as a drawback of the DOACs. The American Society of Clinical Oncology published guidelines in August 2019 warn about an increased risk major bleeding risk with DOACs, particularly in gastrointestinal and possible genitourinary malignancies.

The Carvaggio study was funded by from Bristol-Myers Squibb-Pfizer Alliance; Bristol-Myers Squibb markets Eliquis and Pfizer markets dalteparin as Fragmin. Agnelli and his colleagues say the alliance had no role in the design or analysis of their study and no role in manuscript that was published in NEJM.

Adults with cancer from 9 European countries, Israel, and the United States were enrolled in Caravaggio. The study subjects were either newly diagnosed with symptomatic venous thromboembolism or had the condition discovered incidentally on an imaging test. Half (585 patients) were randomized to take apixaban for 6 months (10 mg twice daily for the first 7 days, 5 mg twice daily thereafter) and other half, to dalteparin injections (200 IU per kilogram of body weight once daily for a month, 150 IU per kilogram once daily thereafter). For intention-to-treat reasons the numbers were winnowed down so for the analysis there were 576 patients in the apixaban group and 579 in the dalteparin group.

During the 6 months of treatment, 32 of the 576 (5.6%) patients assigned to apixaban had recurrent venous thromboembolism compared with 46 of 579 (7.9%) in the dalteparin group.

References

1. Agnelli G, Becattini C, Meyer G, et al, for the Carvaggio Investigators. Apixaban for the treatment of venous thromboembolism associated with cancer [published online March 29, 2020]. N Engl J Med. doi:10.1056/NEJMoa1915103.
2. Lee AYY. Anticoagulant therapy for venous thromboembolism in cancer [published online March 29, 2020]. N Engl J Med. doi: 10.1056/NEJMe2004220.