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. 2022 Jul 27;12(8):1128.
doi: 10.3390/life12081128.

Rivaroxaban Monotherapy in Patients with Pulmonary Embolism: Off-Label vs. Labeled Therapy

Affiliations

Rivaroxaban Monotherapy in Patients with Pulmonary Embolism: Off-Label vs. Labeled Therapy

Pierpaolo Di Micco et al. Life (Basel). .

Abstract

Background: The use of rivaroxaban in clinical practice often deviates from manufacturer prescribing information. No studies have demonstrated an association between this practice and improved outcomes. Methods: We used the RIETE registry to assess the clinical characteristics of patients with pulmonary embolism (PE) who received off-label rivaroxaban, and to compare their 3-month outcomes with those receiving the labeled therapy. The patients were classified into four subgroups: (1) labeled therapy; (2) delayed start; (3) low doses and (4) both conditions. Results: From May 2013 to May 2022, 2490 patients with PE received rivaroxaban: labeled therapy—1485 (58.6%); delayed start—808 (32.5%); low doses—143 (5.7%); both conditions—54 (2.2%). Patients with a delayed start were more likely to present with syncope, hypotension, raised troponin levels and more severe abnormalities on the echocardiogram than those on labeled therapy. Patients receiving low doses were most likely to have cancer, recent bleeding, anemia, thrombocytopenia or renal insufficiency. During the first 3 months, 3 patients developed PE recurrence, 4 had deep-vein thrombosis, 11 had major bleeding and 16 died. The rates of major bleeding (11 vs. 0; p < 0.001) or death (15 vs. 1; OR: 22.5; 95% CI: 2.97−170.5) were higher in patients receiving off-label rivaroxaban than in those on labeled therapy, with no differences in VTE recurrence (OR: 1.11; 95% CI: 0.25−6.57). Conclusions: In patients with severe PE, the start of rivaroxaban administration was often delayed. In those at increased risk for bleeding, it was often prescribed at low doses. Both subgroups had a worse outcome than those on labeled rivaroxaban.

Keywords: DOACs; RIETE; oral anticoagulants; rivaroxaban; venpus thromboembolism.

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Conflict of interest statement

The authors declare no conflict of interest.

References

    1. Goldhaber S.Z., Visani L., De Rosa M. Acute pulmonary embolism: Clinical outcomes in the International Cooperative Pulmonary Embolism Registry. Lancet. 1999;353:24–27. doi: 10.1016/S0140-6736(98)07534-5. - DOI - PubMed
    1. Ortel T.L., Neumann I., Ageno W., Beyth R., Clark N.P., Cuker A., Hutten B.A., Jaff M.R., Manja V., Zhang Y., et al. American Society of Hematology 2020 guidelines for the management of venous thromboembolism: Treatment of deep vein thrombosis and pulmonary embolism. Blood Adv. 2020;4:4693–4738. doi: 10.1182/bloodadvances.2020001830. - DOI - PMC - PubMed
    1. EINSTEIN-PE Investigators Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N. Engl. J. Med. 2012;366:1287–1297. doi: 10.1056/NEJMoa1113572. - DOI - PubMed
    1. Hussein A.A., Alvarez P., Reed G., Heresi G.A. Off-label use and inappropriate dosing of direct oral anticoagulants in cardiopulmonary disease. Chest. 2022;161:1360–1369. doi: 10.1016/j.chest.2022.01.033. - DOI - PubMed
    1. Aguilar F., Lo K.B., Quintero E.E., Torres R.J., Hung W.A., Albano J.C., Alviz I., Rodriguez C., Garcia M.J., Slipczuk L., et al. Off-label direct oral anticoagulants dosing in atrial fibrillation and venous thromboembolism is associated with higher mortality. Expert Rev. Cardiovasc. Ther. 2021;19:1119–1126. doi: 10.1080/14779072.2021.2013816. - DOI - PubMed