Patient Management Strategies and Long-Term Outcomes in Isolated Distal Deep-Vein Thrombosis versus Proximal Deep-Vein Thrombosis: Findings from XALIA

Walter Ageno, Lorenzo G Mantovani, Sylvia Haas, Reinhold Kreutz, Danja Monje, Jonas Schneider, Jörg-Peter Bugge, Martin Gebel, Alexander G G Turpie, Walter Ageno, Lorenzo G Mantovani, Sylvia Haas, Reinhold Kreutz, Danja Monje, Jonas Schneider, Jörg-Peter Bugge, Martin Gebel, Alexander G G Turpie

Abstract

Background Overall, 30 to 50% of lower-limb deep-vein thrombosis (DVT) cases are isolated distal DVT (IDDVT). The recurrent venous thromboembolism (VTE) risk is unclear, leaving uncertainty over optimal IDDVT treatment. We present data on patients with IDDVT and proximal DVT (PDVT) from the prospective, noninterventional XALIA study of rivaroxaban for acute and extended VTE treatment. Methods Patients aged ≥18 years scheduled to receive ≥3 months' anticoagulation with rivaroxaban or standard anticoagulation were eligible, with follow-up for ≥12 months. We describe baseline characteristics, management strategies, and incidence proportions of VTE recurrence, major bleeding, and all-cause mortality in patients with IDDVT or PDVT, with or without distal vein involvement. Findings Overall, 1,004 patients with IDDVT and 3,098 with PDVT were enrolled; 641 (63.8%) and 1,683 (54.3%) received rivaroxaban, respectively. Patients with IDDVT were younger and had lower incidences of renal impairment, cancer, and unprovoked VTE than those with PDVT. On-treatment recurrence incidences for IDDVT versus PDVT were 1.0 versus 2.4% (adjusted hazard ratio [HR]: 0.56; 95% confidence interval [CI]: 0.29-1.08), and incidences posttreatment cessation were 1.1 versus 2.1% (adjusted HR: 0.65; 95% CI: 0.32-1.35), respectively. On-treatment major bleeding incidences were 0.9 versus 1.4% and mortality was 0.8 versus 2.2%, respectively. Median treatment duration in patients with IDDVT was shorter than in those with PDVT (102 vs. 192 days, respectively). Interpretation Patients with IDDVT had fewer comorbidities and were more frequently treated with rivaroxaban than those with PDVT. On-treatment and posttreatment recurrences were less frequent in patients with IDDVT. Trial registration number: NCT01619007.

Keywords: deep-vein thrombosis; rivaroxaban; routine clinical practice; venous thromboembolism.

Conflict of interest statement

Conflicts of Interest W.A. has received speaker's honoraria from, and participated in scientific advisory boards for, Aspen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, CSL Behring, Daiichi Sankyo, Portola, and Stago, and has received research support from Bayer. L.G.M. has received consultancy fees from Bayer and Daiichi Sankyo, and research support from Boehringer Ingelheim, Janssen-Cilag Ltd, and Pfizer Inc. S.H. has received consultancy fees from Aspen, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Pfizer Inc., and Sanofi SA. R.K. has received consultancy fees from Bayer, Berlin-Chemie Menarini, Daiichi Sankyo, Lundbeck Ltd and Servier Laboratories Ltd, and speaker's honoraria from Bayer, Bristol-Myers Squibb, and Daiichi Sankyo. D.M., J.S., J.-P.B. and M.G. are employees of Bayer AG. A.G.G.T. has received speaker's honoraria and consultancy fees from, and participated in scientific advisory boards for, Bayer and Janssen Research & Development, LLC.

Figures

Fig. 1
Fig. 1
Patient flow through the study. Abbreviations: IDDVT, isolated distal deep-vein thrombosis; PDVT, proximal deep-vein thrombosis; VKA, vitamin K antagonist; VTE, venous thromboembolism.
Fig. 2
Fig. 2
Unadjusted treatment-emergent outcomes in patients with (A) IDDVT or (B) PDVT in the safety analysis set treated with rivaroxaban or standard anticoagulation. Abbreviations: IDDVT, isolated distal deep-vein thrombosis; PDVT, proximal deep-vein thrombosis; VTE, venous thromboembolism.

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