A Systematic Review and Meta-Analysis of Proportions of Thrombosis and Bleeding in Patients Receiving Venous Thromboembolism (VTE) Prophylaxis After Orthopedic Surgery (OS). An Update.
Authors: Lazo-Langner Alejandro , Hawell Jeff , Kovacs Michael J. , Wells Philip S , Scarvelis Dimitrios , Forgie Melissa Anne , Rodger Marc 
Published: October 2019

Abstract
Abstract 3125
Poster Board III-62
VTE is the most frequent complication of OS and it can be prevented through anticoagulant prophylaxis. Numerous studies have evaluated different agents for this purpose and there are new agents currently under development or recently approved for this indication. We conducted a systematic review of randomized controlled trials (RCT) evaluating administration of anticoagulants for VTE prophylaxis in OS and performed a MA of proportions to estimate the overall incidence of major VTE (proximal VTE, pulmonary embolism (PE), or death from PE), total VTE (proximal and distal VTE, PE or death from PE), symptomatic VTE and major bleeding episodes (as defined by the International Society on Thrombosis and Hemostasis). We included RCT comparing currently approved anticoagulants (head-to-head or placebo-controlled) for VTE prophylaxis in OS (hip and knee arthroplasty and hip fracture surgery) using systematic evaluation of VTE (ultrasound or venography, pulmonary angiography, CT pulmonary angiography, or ventilation perfusion scan). Heterogeneity of proportions was evaluated using a chi2 test and pooled estimates of proportions were obtained using either a fixed or a random effects model in which the weights were estimated as proposed by Laird and Mosteller. We retrieved 74 studies including180 research arms and enrolling 71,012 patients. The total number of events and evaluable patients, percentage of events and 95% CI, and number of study arms included are shown in the table. We found differences in the percentage of VTE and bleeding events associated with the use of different anticoagulants for VTE prophylaxis after OS. Due to the nature of the analysis no effect measure can be estimated. These estimates might help to design future studies.
Major VTE Total VTE Symptomatic VTE Major Bleeding Cases / Evaluable Pts. (N) Percentage (95% CI) Study arms (N) Cases / Evaluable Pts. (N) Percentage (95% CI) Study arms (N) Cases / Evaluable Pts. (N) Percentage (95% CI) Study arms (N) Cases / Evaluable Pts. (N) Percentage (95% CI) Study arms (N) All patients LMWH 993/23692 5.96 (5.81, 6.11) 72 4068/22610 20.29 (20.04, 20.55) 80 193/19431 1.32 (1.27, 1.37) 35 476/28725 1.98 (1.93, 2.02) 70 UFH 234/2407 13.39 (12.86, 13.93) 14 596/2537 22.54 (22, 23.08) 17 11/339 3.24 (3.06, 3.43) 4 70/2849 2.75 (2.61, 2.89) 16 Warfarin 269/5677 6.28 (6.09, 6.46) 12 1317/4203 31.05 (30.44, 31.66) 12 71/4146 1.95 (1.83, 2.08) 6 96/6751 1.78 (1.69, 1.87) 12 Fonda 96/3673 3.81 (3.53, 4.09) 7 223/3477 6.82 (6.57, 7.07) 6 69/6398 1.06 (1.01, 1.1) 8 121/6576 1.63 (1.55, 1.71) 9 Riva 50/5025 2.02 (1.86, 2.19) 8 242/4595 13.05 (12.16, 13.94) 8 29/6252 0.46 (0.45, 0.48) 6 31/6643 0.63 (0.59, 0.68) 8 Dabi 149/4091 3.64 (3.59, 3.69) 6 834/4051 22.96 (21.91, 24.01) 6 26/3664 0.71 (0.67, 0.75) 4 67/5419 1.21 (1.17, 1.26) 6 Placebo 193/710 24.26 (23.17, 25.34) 10 379/816 49.35 (48.08, 50.62) 11 19/198 12.02 (10.32, 13.72) 3 12/753 1.59 (1.5, 1.68) 7 Total 1984/45275 129 7659/42289 140 418/40428 66 873/57716 128 Total Hip Arthroplasty LMWH 653/15978 6 (5.85, 6.16) 50 1817/14480 15.58 (15.35, 15.82) 55 81/11552 0.7 (0.69, 0.72) 19 306/18010 1.97 (1.92, 2.02) 45 UFH 187/1739 14.3 (13.64, 14.96) 11 354/1836 20.13 (19.46, 20.8) 13 11/246 4.47 (4.21, 4.73) 3 52/1451 3.2 (3.01, 3.39) 11 Warfarin 77/2758 4.28 (4.08, 4.48) 6 265/1273 20.82 (20.59, 21.04) 6 32/1833 1.75 (1.69, 1.81) 2 47/2856 2.23 (2.09, 2.37) 5 Fonda 28/1799 2.96 (2.58, 3.33) 3 85/1695 5.01 (4.91, 5.12) 2 15/2255 0.67 (0.63, 0.7) 2 69/2349 2.94 (2.87, 3.01) 3 Riva 25/2938 2.21 (1.95, 2.46) 5 73/2749 9.72 (8.92, 10.53) 5 10/3468 0.29 (0.27, 0.31) 3 14/3795 0.49 (0.44, 0.54) 5 Dabi 72/1803 3.99 (3.88, 4.11) 2 124/1766 7.02 (6.77, 7.27) 2 21/2293 0.92 (0.91, 0.93) 2 38/2309 1.65 (1.58, 1.72) 2 Placebo 105/414 26.01 (24.76, 27.27) 7 174/418 45.43 (43.74, 47.13) 7 4/147 2.72 (2.46, 2.98) 2 3/388 0.77 (0.69, 0.86) 5 Total 1147/27429 84 2892/24217 90 174/21794 33 529/31158 76 Total Knee Arthroplasty LMWH 277/6916 4.45 (4.34, 4.55) 25 2062/7326 30.72 (30.37, 31.07) 32 83/4902 1.69 (1.66, 1.73) 11 89/7808 1.14 (1.12, 1.16) 26 UFH 42/638 6.58 (6.39, 6.78) 3 226/638 35.42 (35.05, 35.79) 3 0/93 NE 1 3/318 0.94 (0.84, 1.05) 2 Warfarin 192/2919 8.1 (7.88, 8.32) 9 1052/2930 39.36 (38.69, 40.02) 9 39/2056 1.9 (1.84, 1.96) 3 28/3407 0.82 (0.79, 0.85) 8 Fonda 23/452 9.3 (7.93, 10.67) 2 45/361 12.47 (12.12, 12.81) 1 3/517 0.58 (0.51, 0.65) 1 12/601 2 (1.88, 2.11) 2 Riva 25/2087 1.2 (1.15, 1.24) 3 169/1846 18.55 (16.47, 20.63) 3 19/2784 0.68 (0.65, 0.71) 3 17/2848 0.6 (0.57, 0.63) 3 Dabi 77/2288 3.37 (3.32, 3.41) 4 710/2285 30.98 (30.42, 31.55) 4 5/1371 0.36 (0.32, 0.41) 2 29/3110 0.93 (0.89, 0.98) 4 Placebo 88/296 27.12 (24.54, 29.7) 4 205/398 55.19 (53.53, 56.84) 5 15/51 29.41 (28.16, 30.66) 1 9/365 2.47 (2.31, 2.62) 4 Total 724/15596 50 4469/15784 57 164/11774 22 187/18457 49 LMWH Low molecular weight heparin, UFH unfractionated heparin, Riva Rivaroxaban, Dabi Dabigatran etexilate

Disclosures
Lazo-Langner: Boehringer Ingelheim: Honoraria. Rodger:Bayer: Research Funding; Leo Pharma: Research Funding; Pfizer: Research Funding; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees; Biomerieux: Research Funding; GTC Therapeutics: Research Funding.