Safety and feasibility of rivaroxaban in deferred workup of patients with suspected deep vein thrombosis

Abstract

Guidelines suggest using empiric low-molecular-weight heparin if the diagnostic workup of deep vein thrombosis (DVT) is expected to be delayed. The role of direct oral anticoagulants for deferred compression ultrasound imaging (CUS) in patients with suspected DVT remains unexplored. The main objective of the study was to assess the safety of deferring CUS with therapeutic doses of rivaroxaban. We prospectively included consecutive outpatients referred to the Emergency Department at Østfold Hospital, Norway, with suspected first or recurrent lower-extremity DVT between February 2015 and November 2018. Patients were discharged with rivaroxaban 15 mg twice daily while awaiting CUS within 24 hours if D-dimer level was ≥0.5 mg/L fibrinogen-equivalent units. The primary outcome was the rate of major bleeding incidents from study inclusion until DVT was confirmed and anticoagulation therapy continued, or otherwise up to 48 hours following administration of the last tablet of rivaroxaban. The secondary outcome was the rate of progressive DVT symptoms or symptoms or signs of pulmonary embolism between hospital discharge until venous thromboembolism was diagnosed. Six hundred twenty-four of 1653 patients referred with suspected DVT were included (37.7%; 95% confidence interval [CI], 35.4-40.1). DVT was diagnosed in 119 patients (19.1%; 95% CI, 16.1-22.3). There were no major bleeding incidents, yielding an observed major bleeding rate of 0% (1-sided 95% CI <0.4). No patients experienced major complications in the interval that CUS was deferred (0%; 95% CI, 0.0-0.6). Deferring CUS for up to 24 hours in patients with suspected DVT with therapeutic doses of rivaroxaban is a safe strategy. This trial was registered at www.clinicaltrials.gov as #NCT02486445.

Keywords: COAGULATION/venous thromboembolism prophylaxis; and treatment; diagnosis.

Conflict of interest statement

Conflict-of-interest disclosure: S.G.F. and C.T.J. received grants from Bayer, the South-Eastern Norway Regional Health Authority, and the Østfold Hospital Trust to the conduct of the study (no personal fees). A.E.A.D. received grants and personal fees from Pfizer AS and personal fees from Bristol-Myers Squibb and Novartis Norway AS outside the submitted work. F.A.K. received research grants from Bayer, Bristol-Myers Squibb, Boehringer-Ingelheim, Daiichi-Sankyo, MSD and Actelion, the Dutch Heart foundation, and the Dutch Thrombosis association outside the submitted work. W.G. received grants from Bayer, the South-Eastern Norway Regional Health Authority, and Østfold Hospital Trust for the conduct of this study; received grants from Bayer, Bristol-Myers Squibb, and Novartis outside the submitted work; and participated on advisory boards for Amgen and Novartis. The remaining authors declare no competing financial interests.

© 2020 by The American Society of Hematology.

Figures

Graphical abstract

Figure 1.

Study design.

Figure 2.

Eligibility and inclusion of patients.

Figure 3.

Origin and number of bleeding events.