Author Contributions

Conceptualization, O.A.A. (Omar A. Alshaya), G.B.K., M.S.A.Y., A.H.Q. and O.A.A. (Omar A. Almohammed); Data curation, O.A.A. (Omar A. Alshaya), G.B.K., M.S.A.Y., A.H.Q., S.A. (Sara Althewaibi), L.F., S.A. (Shaden Alshehri), F.A., M.A., L.A., L.M.A. and O.A.A. (Omar A. Almohammed); Formal analysis, O.A.A. (Omar A. Almohammed); Funding acquisition, G.B.K.; Investigation, S.A. (Sara Althewaibi), L.F., S.A. (Shaden Alshehri), F.A., M.A., L.A. and L.M.A.; Methodology, O.A.A. (Omar A. Alshaya), G.B.K., M.S.A.Y., A.H.Q., S.A. (Sara Althewaibi), L.F., S.A. (Shaden Alshehri), F.A., M.A., L.A., L.M.A. and O.A.A. (Omar A. Almohammed); Project administration, O.A.A. (Omar A. Alshaya), G.B.K., A.H.Q. and O.A.A. (Omar A. Almohammed); Resources, O.A.A. (Omar A. Alshaya), G.B.K., M.S.A.Y., A.H.Q., S.A. (Sara Althewaibi), L.F., S.A. (Shaden Alshehri), F.A., M.A., L.A., L.M.A. and O.A.A. (Omar A. Almohammed); Software, O.A.A. (Omar A. Almohammed); Supervision, O.A.A. (Omar A. Alshaya), G.B.K., M.S.A.Y., A.H.Q., S.A. (Sara Althewaibi), L.F., S.A. (Shaden Alshehri), F.A., M.A., L.A., L.M.A. and O.A.A. (Omar A. Almohammed); Validation, O.A.A. (Omar A. Alshaya), G.B.K., M.S.A.Y., A.H.Q., S.A. (Sara Althewaibi), L.F., S.A. (Shaden Alshehri), F.A., M.A., L.A., L.M.A. and O.A.A. (Omar A. Almohammed); Visualization, O.A.A. (Omar A. Alshaya), G.B.K., M.S.A.Y., A.H.Q., S.A. (Sara Althewaibi), L.F., S.A. (Shaden Alshehri), F.A., M.A., L.A., L.M.A. and O.A.A. (Omar A. Almohammed); Writing—riginal draft, O.A.A. (Omar A. Alshaya), G.B.K., M.S.A.Y., A.H.Q., S.A. (Sara Althewaibi), L.F., S.A. (Shaden Alshehri), F.A., M.A., L.A., L.M.A. and O.A.A. (Omar A. Almohammed); Writing—review & editing, O.A.A. (Omar A. Alshaya), G.B.K., M.S.A.Y., A.H.Q., S.A. (Sara Althewaibi), L.F., S.A. (Shaden Alshehri), F.A., M.A., L.A., L.M.A. and O.A.A. (Omar A. Almohammed). All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2022R78), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board of KSUMC (ref. no. E-21-6295), KAAUH (ref. No. 22-0139), and KAMC (ref. no. NRC21R/400/09).

Informed Consent Statement

Patient consent was waived by the Institutional Review Board of KSUMC, KAAUH, and KAMC given the retrospective nature of this cohort study.

Data Availability Statement

All data are presented in this article.

Conflicts of Interest

The authors declare no conflict of interest.

Figure 1. Flow diagram of included and excluded patients in the study. Abbreviations: VTE: venous thromboembolism; APIX: apixaban; RIVA: rivaroxaban.

Figure 1. Flow diagram of included and excluded patients in the study. Abbreviations: VTE: venous thromboembolism; APIX: apixaban; RIVA: rivaroxaban.

Table 1. Patient demographics, clinical characteristics, and risk factors for VTE recurrence.

Table 1. Patient demographics, clinical characteristics, and risk factors for VTE recurrence.

Patient CharacteristicsOverallLead-in Groupp-ValueMixedRecommendedOverall number of patients36872296  Age in years, mean (SD)53.1 ± 19.655.2 ± 19.252.6 ± 19.70.316 BMI (kg/m2), mean (SD)30.8 ± 7.029.3 ± 7.131.1 ± 6.90.054 Hospital length of Stay (days)6.1 ± 13.312.2 ± 25.34.6 ± 7.4<0.0001 Gender 0.355   Male131 (35.6)29 (40.3)102 (34.5)    Female237 (64.4)43 (59.7)194 (65.5) Pre-existing conditions  Atrial fibrillation8 (2.2)3 (4.2)5 (1.7)0.192 Coronary artery disease19 (5.2)6 (8.3)13 (4.4)0.229 Hypertension137 (37.2)33 (45.8)104 (35.1)0.092 Valvular disease3 (0.8)1 (1.4)2 (0.7)0.481 Stroke33 (9.0)5 (6.9)28 (9.5)0.503 Transient ischemic attack3 (0.8)0 (0.0)3 (1.0)1.000 Diabetes mellitus124 (33.7)27 (37.5)97 (32.8)0.446 Chronic kidney disease18 (4.9)3 (4.2)15 (5.1)1.000 Active smoking28 (7.6)5 (6.9)23 (7.8)0.323 Thrombophilia13 (3.5)3 (4.2)10 (3.4)0.419 Active cancer12 (3.3)5 (6.9)7 (2.4)0.061  On chemotherapy (among patients with cancer)5 (41.7)2 (40.0)3 (42.9)1.000 History of MB (within 12 months)22 (6.0)8 (11.1)14 (4.7)0.058 History of CRNMB (within 12 months)11 (3.0)1 (1.4)10 (3.4)0.698 History of any bleeding (within 12 months)8 (2.2)2 (2.8)6 (2.0)0.651Concomitant antithrombotic medications  Aspirin54 (14.7)9 (12.5)45 (15.2)0.547 P2Y12 Inhibitors10 (2.7)3 (4.2)7 (2.4)0.623Risk Factors for VTE recurrence  History of previous VTE39 (10.6)4 (5.6)35 (11.8)0.119  Type of historical VTE 0.0006   DVT27 (69.2)0 (0.0)27 (0.8)---   PE9 (23.1)4 (100)5 (14.3)0.638   DVT plus PE3 (7.7)0 (0.0)3 (8.6)   Time of historical VTE 0.258   Within 3 months3 (7.7)0 (0.0)3 (8.6)    Within 12 months2 (5.1)0 (0.0)2 (5.7)    Within >12 months32 (82.1)3 (75.0)29 (82.9)  Use of oral contraceptive or ERT43 (11.7)5 (6.9)38 (12.8)0.148 Obesity (BMI ≥ 30)181 (49.2)31 (43.1)150 (50.7)0.349 Immobility83 (22.6)18 (25.0)65 (22.0)0.515 Major general surgery (within one year)41 (11.1)11 (15.3)30 (10.1)0.254  Time of major surgery 0.550   Within 3 months30 (73.2)7 (63.6)23 (76.7)    Within 3–6 months3 (7.3)2 (18.2)1 (3.3)    Within 6–12 months3 (7.3)1 (9.1)2 (6.7)    Within >12 months4 (9.8)1 (9.1)3 (10.0)  Orthopedic surgery (within one year)29 (7.9)8 (11.1)21 (7.1)0.282  Time of orthopedic surgery 0.622   Within 3 months25 (86.2)8 (100.0)17 (81.0)    Within 12 months2 (6.9)0 (0.0)2 (9.5)    Within >12 months1 (3.4)0 (0.0)2 (9.5)

Table 2. Laboratory values at the lead-in dose initiation.

Table 2. Laboratory values at the lead-in dose initiation.

Laboratory ValuesOverallLead-in Groupp-ValueMixedRecommendedScr at lead-in dose initiation (mg/dL)0.8 ± 0.30.71 ± 0.20.77 ± 0.30.120eGFR at lead-in dose initiation (mL/min/1.73 m2)102.7 ± 46.8115.4 ± 65.799.6 ± 40.50.009CrCl at lead-in dose initiation (ml/min)103.2 ± 50.0109.7 ± 68.3101.7 ± 44.50.223Hgb level before lead-in dose initiation (g/dL)12.5 ± 2.111.7 ± 2.212.7 ± 2.0<0.001

Table 3. Type and etiology of the new VTE event and the risk of bleeding.

Table 3. Type and etiology of the new VTE event and the risk of bleeding.

Patient CharacteristicsOverallLead-in Groupp-ValueMixedRecommendedOverall number of patients36872296 Type of current VTE event <0.001 DVT151 (41.0)10 (13.9)141 (47.6)0.601  Proximal109 (72.2)8 (80.0)101 (71.6)   Distal14 (9.3)0 (0.0)14 (9.9)   Mixed21 (13.9)2 (20.0)19 (13.5)   Unspecified7 (4.6)0 (0.0)7 (5.0)  PE188 (51.1)54 (75.0)134 (45.3)0.086  Segmental68 (36.2)16 (29.6)52 (38.8)   Subsegmental28 (14.9)5 (9.3)23 (17.2)   Mixed58 (30.9)18 (33.3)40 (29.9)   Unspecified34 (18.1)15 (27.8)19 (14.2)  DVT plus PE29 (7.9)8 (11.1)21 (7.1)   DVT type 0.562   Proximal12 (41.4)3 (37.5)9 (42.9)    Distal6 (20.7)1 (12.5)5 (23.8)    Mixed5 (17.2)1 (12.5)4 (19.0)    Unspecified6 (20.7)3 (37.5)3 (14.3)   PE type 0.468   Segmental11 (37.9)3 (37.5)8 (38.1)    Subsegmental2 (6.9)1 (12.5)1 (4.8)    Mixed9 (31.1)1 (12.5)8 (38.1)    Unspecified7 (24.1)3 (37.5)4 (19.0) VTE Etiology 0.694 Provoked203 (55.2)37 (51.4)166 (56.1)  Unprovoked81 (22.0)16 (22.2)65 (22.0)  Not reported84 (22.8)19 (26.4)65 (22.0) Bleeding Risk a 0.297 High risk11 (3.0) 4 (5.6)7 (2.4)  Intermediate risk283 (76.9) 52 (72.2)231 (78.0)  Low risk74 (20.1) 16 (22.2)58 (19.6)

Table 4. Recommended vs. mixed-lead-in dosing for VTE treatment.

Table 4. Recommended vs. mixed-lead-in dosing for VTE treatment.

Patient StatusOverallApixabanRivaroxabanOverall number of patients368176192Recommended-lead-in dosing group296149147 Type of parenteral anticoagulant used   LMWH (enoxaparin)168 (56.8)68 (45.6)100 (68.0)  UFH29 (9.8)22 (14.8)7 (4.8)  Fondaparinux1 (0.3)1 (0.7)0 (0.00)  None98 (33.1)58 (38.9)40 (27.2) Duration for the received lead-in dose of DOAC (days) 7.0 ± 0.021.0 ± 0.0 Duration for the received parenteral anticoagulant (days) 1.3 ± 0.41.2 ± 0.4 Duration for the received parenteral anticoagulant and DOAC (days) 8.3 ± 0.422.2 ± 0.4Mixed-lead-in dosing group722745 Type of parenteral anticoagulant used   LMWH (enoxaparin)61 (84.7)21 (77.8)40 (88.9)  UFH11 (15.3)6 (22.2)5 (11.1) Duration of the received lead-in dose of DOAC (days) 4.0 ± 1.115.0 ± 3.1 Duration of the received parenteral anticoagulant (days) 2.2 ± 1.45.6 ± 3.1 Duration of the received parenteral anticoagulant and DOAC (days) 6.2 ± 0.820.7 ± 0.8

Table 5. Outcomes during hospitalization and up to 90 days after the VTE event.

Table 5. Outcomes during hospitalization and up to 90 days after the VTE event.

Patient CharacteristicOverallLead-in Groupp-ValueMixedRecommendedOverall number of patients36872296 rVTE event  During hospitalization2 (0.5)0 (0.0)2 (0.7)1.000 Within 30 days a2 (0.5)0 (0.0)2 (0.7)1.000 Cumulative within 90 days b3 (0.8)1 (1.4)2 (0.7)0.481 Patients with at least one rVTE within 90 days c5 (1.4)1 (1.4)4 (1.4)1.000MB event  During hospitalization18 (4.9)7 (9.7)11 (3.7)0.060 Within 30 days4 (1.1)0 (0.0)4 (1.4)1.000 Cumulative within 90 days6 (1.6)1 (1.4)5 (1.7)1.000 Patients with at least one MB within 90 days21 (5.7)7 (9.7)14 (4.7)0.150CRNMB event  During hospitalization12 (3.3)3 (4.2)9 (3.0)0.890 Within 30 days27 (7.3)4 (5.6)23 (7.8)0.518 Cumulative within 90 days27 (7.3)4 (5.6)23 (7.8)0.518 Patients with at least one CRNMB within 90 days36 (9.8)7 (9.7)29 (9.8)0.984Rehospitalization d  Within 30 days7 (1.9) 0 (0.0)7 (2.4)0.353 Cumulative within 90 days15 (4.1)2 (2.8)13 (4.4)0.745Death during hospitalization0 (0.0)0 (0.0)0 (0.0)---