Efficacy and Safety of VTE Prophylaxis with Oral Rivaroxaban Compared to Fondaparinux or Low-Molecular Weight Heparin In a Large Cohort of Consecutive Patients Undergoing Major Orthopaedic Surgery

Abstract

Abstract 210Efficacy and safety of VTE prophylaxis with oral rivaroxaban compared to fondaparinux or low-molecular weight heparin in a large cohort of consecutive patients undergoing major orthopaedic surgery. Aim:Patients undergoing major orthopaedic surgery (MOS) have a high risk of postoperative venous thromboembolism (VTE). Several types of pharmacological thromboprophylaxis are approved for this indication. In phase III VTE prevention trials in MOS, the new oral facor Xa inhibitor rivaroxaban proved superior efficacy over LMWH in preventing VTE without increasing bleeding complications. However, study populations consist of selected patients screened for strict exclusion criteria before randomisation. Little is known about efficacy and safety of rivaroxaban prophylaxis in large unselected cohorts of patients undergoing MOS in daily practice. Method:We retrospectively evaluated 5346 consecutive patients undergoing MOS at our centre between January 2005 and June 2011 for the rate of VTE events, bleeding complications and surgical revisions by review of patient charts, complication and transfusion databases and autopsy reports. All events were analyzed according to the type of thromboprophylaxis used. Results:Of the 5346 patients, 1055 patients received thromboprophylaxis with rivaroxaban (R; hospital standard since 2010), 1683 patients received LMWH (hospital standard 2005–2007), 2069 received fondaparinux (F; hospital standard 2007–2009) and 539 patients received other prophylaxis. Symptomatic VTE event rates for patients receiving R, F or LMWH were 2.5%, 5.5% and 3.9%, respectively (table 1). R was significantly more effective to prevent symptomatic VTE compared to F or LMWH, mostly due to significantly lower rates of distal VTE.Table 1:Efficacy and safety of VTE thromboprophylaxis with Low molecular weight heparin (LMWH), Fondaparinux (F) and Rivaroxaban (R).endpointLMWH n = 1683 % (n)Fondaparinux n = 1994 % (n)Rivaroxaban n = 1055 % (n)p-value LMWH vs. Rp-value F vs. RPrimary efficacy endpoint% major VTE (n)1.43 (24)1.74 (36)1.04 (11)0.4850.162Secondary efficacy endpoints% all VTE (n)3.92 (66)5.51 (114)2.46 (26)0.049<0.0005% proximal DVT (n)1.19 (20)1.35 (28)0.85 (9)0.4490.294% PE (n)0.48 (8)0.48 (10)0.19 (2)0.3340.359% distal VTE (n)2.44 (41)3.87 (80)1.42 (15)0.072<0.0005% any death (n)0.24 (4)0.10 (2)0.38 (4)0.4940.188Primary Safety endpoint% severe bleeding14.91 (251)11.12 (230)7.39 (78)<0.00050.001 % transfusion > 2 RBC concentrates (n)14.02 (236)10.58 (219)7.11 (75)<0.00050.001 % surgical revisions due to bleeding complications1.66 (28)1.06 (22)0.38 (4)0.00020.059 % bleeding into critical site0.18 (3)0.05 (1)0.09 (1)0.99990.999Secondary Safety endpoints% any surgical revision (n)4.69 (79)1.79 (37)1.14 (12)<0.00050.222% transfusion of any RBC concentrates (n)42.96 (723)39.15 (810)27.96 (295)<0.0005<0.0005% transfusion 1–2 RBC concentrates (n)28.94 (487)28.56 (591)20.85 (220)<0.0005<0.0005% transfusions plasma concentrates (n)1.54 (26)0.77 (16)0.09 (1)<0.00050.017% transfusions platelet concentrates (n)8.56 (144)6.19 (128)5.12 (54)0.0010.258Length of hospital stay (days) (95%-CI)11.6 (11.2–12.0)9.3 (9.1–9.5)8.3 (8.1–8.5)<0.0005<0.0005Length of hospital stay (days) Median (25th and 75th percentile)9.0 (8.0–11.0)9.0 (8.0–9.0)8.0 (7.0–9.0)<0.0005<0.0005Overall, the safety of VTE prophylaxis with R was superior over F or LMWH with significantly lower rates of surgical revisions (1.1%, 1.8% and 4.7%, respectively) and lower rates of severe bleeding complications (7.4%, 11.1% and 14.9%, respectively, which also was statistically significant. Conclusion:VTE prophylaxis with rivaroxaban is superior over prophylaxis with fondaparinux or LMWH with regard to the prevention of symptomatic VTE complications. Furthermore, rivaroxaban prophylaxis was also safer with regard to severe bleeding complications and surgical complications compared to fondaparinux or LMWH, which is in contrast to the results of large phase III trials and the current opinion, that superior efficacy of prophylaxis has the downside of higher bleeding complications. We conclude that real world patients undergoing MOS are different from study populations and may especially benefit from rivaroxaban prophylaxis with regard to both efficacy and safety. Disclosures:Beyer-Westendorf:Bayer Healthcare: Research Funding, Speakers Bureau.