Background
Methods
Search strategy
Eligibility
Quality assessment
Data and statistical analysis
Results
Search results
Characteristics of included studies
1st author (year) | Treatments | Details of treatment (dose and routes of Administration) | number of patients | Procedure (n) | Age mean ± SD years | Sex, Males (%) | BMI, kg/m2 | Follow-up time (days) |
---|---|---|---|---|---|---|---|---|
I. LMWH vs. placebo (saline) | ||||||||
Fuji (2008) [10] | Enoxaparin | 20 mg sc qd for 14d | 81 | THR | 63.3 ± 10.4 | 10 (12.3) | 23.5 ± 3.4 | 90 |
40 mg sc qd for 14d | 80 | 60.6 ± 9.9 | 6 (7.5) | 23.5 ± 3.7 | ||||
20 mg sc bid for 14d | 90 | 63.0 ± 9.3 | 15 (16.7) | 23.7 ± 3.6 | ||||
Placebo | Saline bid for 14d | 86 | 62.0 ± 10.3 | 11 (12.8) | 24.0 ± 3.4 | |||
Enoxaparin | 20 mg sc qd for 14d | 78 | TKR | 68.8 ± 9.0 | 15 (19.2) | 25.7 ± 4.5 | 90 | |
40 mg sc qd for 14d | 74 | 70.0 ± 9.4 | 11 (14.9) | 25.3 ± 4.0 | ||||
20 mg sc bid for 14d | 84 | 68.3 ± 8.7 | 5 (6) | 24.0 ± 4.0 | ||||
Placebo | Saline bid for 14d | 79 | 68.7 ± 9.5 | 15 (19) | 25.4 ± 3.7 | |||
Bergqvist (1996) [20] | Enoxaparin | 40 mg (0.4 ml) sc qd | 131 | THR | median = 70 (range: 44–87) | 56 (42.7) | median = 25.8 (range:18.6–37.9) | n/a |
Placebo | 0.4 ml saline qd | 131 | median = 70 (range: 44–87) | 57 (43.5) | median = 26.8 (range: 19.2–49.1) | |||
Planes (1996) [21] | Enoxaparin | 40 mg sc qd for 2d | 90 | THR | 70 ± 9·1 | 47 (52.2) | 25·55 ± 3·19 | 21 |
Placebo | Saline qd | 89 | 68 ± 8·2 | 55 (61.8) | 25·85 ± 3·49 | |||
II. LMWH vs. inhibitor of factor Xa | ||||||||
Kim (2016) [1] | Enoxaparin | 40 mg sc qd for 14d | 184 | THR | 43.9 ± 9.4 | 114 (62.0) | 25.4 ± 3.8 | N/A |
Rivaroxaban | 10 mg qd for 14d | 184 | 44.4 ± 8.6 | 99 (53.8) | 24.8 ± 3.1 | |||
Placebo | 1 ml saline or placebo tablet qd | 185 | 43.4 ± 9.9 | 109 (58.9) | 24.3 ± 3.4 | |||
Zou (2014) [3] | Enoxaparin | 4000 anti-Xa IU (0.4 ml) qd for 14d | 112 | TKR | mean = 65.7 (range:54–80) | 20 (17.85) | mean = 27.0 (range:20.3–37.0) | 28 |
Rivaroxaban | 10 mg qd for 14d | 102 | mean = 63.5 (range:50–82) | 32 (31.37) | mean = 27.5 (range:18.0–39.5) | |||
Aspirin | 100 mg qd for 14d | 110 | mean = 62.7 (range:47–79) | 28 (25.45) | mean = 27.8 (range:17.8–40.0) | |||
Kakkar (2008) [RECORD 2] [11] | enoxaparin | 40 mg sc qd for 10–14 d (with placebo tablet for 31–39d) | 1229 | THR | 61.6 ± 13.7 | 578 (47) | 27.1 ± 5.2 | n/a |
Rivaroxaban | 10 mg qd 31–39 d (with placebo injection for 10–14 d) | 1228 | 61.4 ± 13.2 | 561 (45.7) | 26.8 ± 4.8 | |||
Eriksson (2008) [RECORD 1] [12] | Enoxaparin | 40 mg sc qd for 35d (range, 31-39d) (with placebo tablet) | 2224 | THR | median = 63.3 (range:18–93) | 982 (44.2) | median = 27.9 (range:15.2–50.2) | 30–42 |
Rivaroxaban | 10 mg qd for 35d (range, 31-39d) (with placebo injection) | 2209 | median = 63.1 (range:18–91) | 989 (44.8) | median = 27.8 (range:16.2–53.4) | |||
Lassen (2008) [RECORD 3] [13] | Enoxaparin | 40 mg sc qd for 10-14d | 1239 | TKR | median = 67.6 (range:30–90) | 419 (33.7) | median = 29.8 (range:16.0–54.3) | 30–35 |
Rivaroxaban | 10 mg qd for 10-14d | 1220 | median = 67.6 (range:28–91) | 363 (29.8) | median = 29.5 (range:16.3–51.1) | |||
Turpie (2009) [RECORD 4] [8] | Enoxaparin | 30 mg sc bid for 10-14d | 1508 | TKR | 64.7 ± 9.7 | 541(35.9) | 30.7 ± 6.0 | 30–35 |
Rivaroxaban | 10 mg qd for 10-14d | 1526 | 64.4 ± 9.7 | 519 (34.0) | 30.9 ± 6.2 | |||
Lassen (2009) [ADVANCE-1] [9] | Enoxaparin | 30 mg sc bid for 10-14d (with placebo tablet) | 1596 | TKR | mean = 65.7 (range: 33–89) | 610 (38.2) | mean = 31.1 (range:17.7–57.6) | 60 |
Apixaban | 2.5 mg bid for 10-14d (with placebo tablet) | 1599 | mean = 65.9 (range:26–93) | 602 (37.6) | mean = 31.2 (range:18.1–57.7) | |||
Lassen (2010a) [ADVANCE-2] [5] | Enoxaparin | 40 mg sc qd for 10-14d (with placebo tablet) | 1529 | TKR | median = 67 (IQR:60–73) | 402 (26) | median = 29.3 (IQR:26.1–32.7) | 60 |
Apixaban | 2.5 mg bid for 10-14d (with placebo tablet) | 1528 | median = 67 (IQR:59–73) | 439 (29) | median = 29.1 (IQR:25.8–32.4) | |||
Lassen (2010b) [ADVANCE-3] [6] | Enoxaparin | 40 mg sc qd for 32-38d (with placebo tablet) | 2699 | THR | mean = 60.6 (range: 19–93) | 1248 (46.2) | mean = 28.1 (range:12.5–48.7) | 65 ± 5 |
Apixaban | 2.5 mg bid for 32-38d (with placebo tablet) | 2708 | mean = 60.9 (range: 19–92) | 1278 (47.2) | mean = 28.2 (range:15.4–58.5) | |||
Eriksson (2014) [2] | enoxaparin | 40 mg sc qd, for 35 d | 314/393(ITT) | 61.1 ± 11.79 | 166 (42.2) | 28.4 ± 4.66 | 12 | |
Darexaban | 15 mg bid for 35 d | 374/269 (ITT) | THR | 60.4 ± 10.95 | 188 (50.3) | 28.4 ± 4.97 | ||
30 mg qd for 35 d | 383/293 (ITT) | 59.5 ± 11.73 | 191 (49.9) | 28.8 ± 5.14 | ||||
30 mg bid for 35 d | 296/387 (ITT) | 59.8 ± 12.13 | 204 (52.7) | 28.5 ± 5.22 | ||||
60 mg qd for 35 d | 274/385 (ITT) | 59.5 ± 11.82 | 182 (47.3) | 28.9 ± 5.00 | ||||
III. LMWH vs. direct thrombin inhibitor | ||||||||
Heit (2001) [19] | LMWH | Enoxaparin: 30 mg sc bid for 6-12d | 125 | TKR | 68 ± 10 | 48 (38) | 31.8 ± 7.0 | n/a |
Ximelagatran | Ximelagatran | 475 | ||||||
8 mg for 6-12d | 85 | 65 ± 10 | 34 (40) | 32.6 ± 5.7 | ||||
12 mg for 6-12d | 134 | 67 ± 11 | 56 (42) | 30.9 ± 6.0 | ||||
18 mg for 6-12d | 126 | 68 ± 10 | 45 (36) | 30.9 ± 6.0 | ||||
24 mg for 6-12d | 130 | 67 ± 11 | 46 (35) | 31.4 ± 5.7 | ||||
Eriksson (2003); METHRO III study [18] | Enoxaparin | 40 mg sc qd started 12 h before surgery for 8-10d | 1389 | THR (957) TKR (432) | mean = 65.8 (range: 26–93) | 549 (40) | n/a | |
Ximelagatran | 24 mg bid for 8-10d beginning the next day of surgery for 8-10d | 1399 | THR (966) TKR (433) | mean = 66.4 (range:25–93) | 515 (37) | |||
Colwell (2003) [17] | Enoxaparin | 30 mg sc bid for 7-12d | 910 | THR | 64.0 ± 13.1 (n = 775) | 377 (48.6) | 28.3 ± 5.3 | n/a |
Ximelagatran | 24 mg bid for 7-12d | 906 | 64.5 ± 12.8 (n = 782) | 372 (47.6) | 28.4 ± 5.3 | |||
Eriksson (2003); EXPRESS study [16] | Enoxaparin | 40 mg sc qd started 12 h before surgery for 8-10d | 1387 (ITT) | THR (942) TKR (445) | median = 67 (range:20–89) | 542 (39.1) | n/a | |
Ximelagatran | 24 mg bid for 8-10d beginning the next day of surgery for 8-10d | 1377 (ITT) | THR (914) TKR (463) | median = 67 (range:24–88) | 509 (37.0) | |||
RE-MOBILIZE (2009) [7] | Enoxaparin | 30 mg sc bid for 12-15d | 868 | TKR | 66.3 ± 9.6 | 4364 (1.9) | n/a | |
Dabigatran Etexilate | 220 mg qd for 12-15d | 857 | 66.2 ± 9.5 | 371 (43.3) | ||||
150 mg qd for 12-15d | 871 | 65.9 ± 9.5 | 364 (41.8) | |||||
Eriksson (2007) a [RE-MODEL] [14] | Enoxaparin | 40 mg sc qd for 6-10d | 694 | TKR | 68 ± 9 | 216 (31) | 6–10 | |
Dabigatran etexilate | 220 mg qd for 6-10d | 679 | 67 ± 9 | 238 (35) | ||||
150 mg qd for 6-10d | 703 | 68 ± 9 | 252 (36) | |||||
Eriksson (2007) b [RE-NOVATE; Patients from Europe, Australia, and South Africa] [15] | Enoxaparin | 40 mg sc qd for 28-35d | 1154 | THR | 64 ± 11 | 503 (44) | 28–35 | |
Dabigatran etexilate | 220 mg qd for 28-35d | 1146 | 65 ± 10 | 510 (44) | ||||
150 mg qd for 28-35d | 1163 | 63 ± 11 | 496 (43) | |||||
Eriksson (2011) [RE-NOVATE II; Patients from North America] [4] | Enoxaparin | 40 mg sc qd for 28-35d (with placebo tablet for 28-35d) | 1003 | THR | 62 ± 11 | 501 (50) | 27.8 ± 4.8 | 28–35 |
Dabigatran etexilate | 220 mg qd for 28-35d (with placebo injection for 28-35d) | 1010 | 62 ± 12 | 541 (53.6) | 27.8 ± 4.8 |
1st author (year) | Treatments | number of patients | Procedure | Efficacyb | Safetyb | ||||
---|---|---|---|---|---|---|---|---|---|
Death during follow-up | Major VTE (DVT + PE)a | DVT | PE | Major bleeding | Minor or non-major bleeding | ||||
I. LMWH vs. placebo (saline) | |||||||||
Fuji (2008) [29] | Enoxaparin | 251 | THR | 66/251 | 66/251 | 0/251 | 6/306 | 12/306 | |
20 mg qd | 81 | 21/81 | 21/81 | – | 1/100 | 1/100 | |||
40 mg qd | 80 | 27/80 | 27/80 | – | 2/102 | 7/102 | |||
20 mg bid | 90 | 18/90 | 18/90 | – | 3/104 | 4/104 | |||
Placebo | 86 | 36/86 | 36/86 | 0/86 | 0/101 | 2/101 | |||
Enoxaparin | 236 | TKR | 86/236 | 84/236 | 2/236 | 4/275 | 21/275 | ||
20 mg qd | 78 | 35/78 | 34/78 | 1/78 | 0/89 | 5/89 | |||
40 mg qd | 74 | 26/74 | 25/74 | 1/74 | 1/91 | 6/91 | |||
20 mg bid | 84 | 25/84 | 25/84 | 0/84 | 3/95 | 10/95 | |||
Placebo | 79 | 48/79 | 48/79 | 0/79 | 4/89 | 4/89 | |||
Bergqvist (1996) [38] | Enoxaparin, 40 mg | 131 | THR | 0 | 21/117 | 21/117 | 0/117 | ||
Placebo | 131 | THR | 0 | 45/116 | 45/116 | 0/116 | |||
Planes (1996) [39] | Enoxaparin, 40 mg | 90 | THR | 0 | 6/85 | ||||
Placebo | 89 | THR | 0 | 17/88 | |||||
Kim (2016) [20] | Enoxaparin | 184 | THR | 0 | 11/184 | 11/184 | 0/184 | ||
Rivaroxaban | 184 | 0 | 11/184 | 10/184 | 1/184 | ||||
Placebo | 185 | 0 | 13/185 | 12/185 | 1/185 | ||||
Zou (2014) [22] | LMWH | 112 | TKA | 14/112 | |||||
Rivaroxaban | 102 | 3/102 | |||||||
Aspirin | 110 | 18/110 | |||||||
Kakkar (2008) [RECORD 2] [30] | enoxaparin | 1229 | 6/869 | 75/869 | 71/869 | 4/869 | 1/1229 | ||
Rivaroxaban | 1228 | THR | 2/864 | 15/864 | 14/864 | 1/864 | 1/1228 | ||
Eriksson (2008) [RECORD 1] [31] | Enoxaparin | 2224 | THR | 0/1558 | 33/1678 | 53/1558 | 1/1558 | 2/2224 | 129/2224 |
Rivaroxaban | 2209 | 1/1598 | 4/1686 | 12/1598 | 4/1598 | 6/2209 | 128/2209 | ||
Lassen (2008) [RECORD 3] [32] | Enoxaparin | 1239 | TKR | 4/1217 | 24/925 | 160/878 | 4/878 | 6/1239 | 54/1239 |
Rivaroxaban | 1220 | 0/1201 | 9/908 | 79/824 | 0/824 | 7/1220 | 53/1220 | ||
Turpie (2009) [RECORD 4] [27] | Enoxaparin | 1564 | TKR | 3/1508 | 22/1112 | 86/959 | 8/1508 | 4/1508 | 138/1508 |
Rivaroxaban | 1584 | 4/1526 | 13/1122 | 61/965 | 4/1526 | 10/1526 | 155/1526 | ||
Lassen (2009) [ADVANCE-1] [28] | Enoxaparin | 1596 | THR | 3/1554 | 20/1216 | 92/1122 | 7/1596 | 22/1588 | 47/1588 |
Apixaban | 1599 | 0/1562 | 26/1269 | 89/1142 | 16/1599 | 11/1596 | 35/1596 | ||
Lassen (2010a) [ADVANCE-2] [24] | Enoxaparin | 1529 | TKR | 1/1469 | 26/1199 | 248/997 | 0/1529 | 14/1508 | 58/1508 |
Apixaban | 1528 | 1/1458 | 13/1195 | 142/971 | 4/1528 | 9/1501 | 44/1501 | ||
Lassen (2010b) [ADVANCE-3] [25] | Enoxaparin | 2699 | TKR | 1/2577 | 25/2195 | 68/1911 | 5/2699 | 18/2659 | 120/2659 |
Apixaban | 2708 | 2/2598 | 10/2199 | 22/1944 | 3/2708 | 22/2673 | 109/2673 | ||
Eriksson (2014) [21] | enoxaparin | 393 | THA | 0/393 | 48/314 (ITT) | 6/314 | 1/314 | 8/393 (2.0) | 20/393 (5.0) |
Darexaban | 1529 | 1/1529 | 150/1132 (ITT) | 9/1132 | 4/1132 | 25/1529 (1.6) | 61/1529 (4.0) | ||
15 mg bid | 374 | 42/269 (ITT) | 3/269 | 2/269 | 5/374 | ||||
30 mg qd | 383 | 39/293 (ITT) | 1/293 | 1/293 | 4/383 | ||||
30 mg bid | 387 | 33/296 (ITT) | 2/296 | 1/296 | 9/387 | ||||
60 mg qd | 385 | 36/274 (ITT) | 3/274 | 0/274 | 7/385 | ||||
II. LMWH vs. direct thrombin inhibitor | |||||||||
Heit (2001) [10] | Enoxaparin | 125 | TKR | 0/125 | 23/97 | 23/97 | 0/97 | 1/125 | |
Ximelagatran | 475 | TKR | 1/475 | 77/447 | 74/447 | 3/447 | |||
8 mg | 85 | 17/63 | 17/63 | 0/63 | 0/85 | ||||
12 mg | 134 | 20/202 | 20/202 | 0/202 | 0/134 | ||||
18 mg | 126 | 25/87 | 23/87 | 2/87 | 2/126 | ||||
24 mg | 130 | 15/95 | 14/95 | 1/95 | 0/130 | ||||
Eriksson (2003b) [37] | Enoxaparin | 957 | THR | 0/957c | 45/823 | 10/942 | 61/942 | ||
Ximelagatran, 24 mg | 966 | 4/966c | 14/773 | 37/915 | 87/915 | ||||
Enoxaparin | 432 | TKR | 29/355 | 6/445 | 36/445 | ||||
Ximelagatran, 24 mg | 433 | 12/365 | 9/463 | 39/463 | |||||
Colwell (2003) [36] | Enoxaparin | 910 | 36/775 | 36/775 | 0/775 | 8/910 | |||
Ximelagatran, 24 mg | 906 | THR | 62/782 | 62/782 | 0/782 | 7/906 | |||
Eriksson (2003a) [35] | Enoxaparin | 942 (ITT) | THR | 0/942c | 146/801 | 142/801 | 4/801 | 10/942 | |
Ximelagatran, 24 mg | 914 (ITT) | 5/914c | 99/765 | 97/765 | 2/765 | 37/915 | |||
Enoxaparin | 445 (ITT) | TKR | 169/383 | 167/383 | 2/383 | 6/445 | |||
Ximelagatran, 24 mg | 463 (ITT) | 132/376 | 131/376 | 1/376 | 9/463 | ||||
Ginsberg (2009) [RE-MOBILIZE] [26] | Enoxaparin | 868 | TKR | 0 | 163/868 | 158/868 | 5/868 | 12 (1.4) | |
Dabigatran Etexilate | 1728 | 2 | 405/1728 | 399/1728 | 6/1728 | ||||
220 mg | 857 | 1 | 187/857 | 6/857 | 5 (0.6) | ||||
150 mg | 871 | 1 | 218/871 | 0/871 | 5 (0.6) | ||||
Eriksson (2007a) [RE-MODEL] [33] | Enoxaparin | 694 | TKR | 1/685 (0.1) | 1/685 | 9/694 (1.3) | 69 (9.9) | ||
Dabigatran Etexilate | 1382 | 2/763 | 1/1382 | ||||||
220 mg | 679 | 1/675 (0.1) | 0/675 | 10/679 (1.5) | 60 (8.8) | ||||
150 mg | 703 | 1/696 (0.1) | 1/696 | 9/703 (1.3) | 59 (8.4) | ||||
Eriksson (2007b) [RE-NOVATE; Europe, Australia, and South Africa] [34] | Enoxaparin | 1154 | THR | 0/1142 | 36/917 | Asymptomatic: 56/894 Symptomatic: 1/1142 | 3/1142 | 18 | 74 |
Dabigatran etexilate | 2309 | 6/2293 | 66/1797 | Asymptomatic: 56/894 Symptomatic: 1/1142 | 6/2293 | 38 | 142 | ||
220 mg | 1146 | THR | 3/1137 | 28/909 | Asymptomatic: 40/874 Symptomatic: 6/1137 | 5/1137 | 23 | 70 | |
150 mg | 1163 | 3/1156 | 38/888 | Asymptomatic: 63/871 Symptomatic: 9/1156 | 1/1156 | 15 | 72 | ||
11Eriksson (2011), 220 mg [RE-NOVATE II; North America] [23] | Enoxaparin | 1.003 | THR | 1/951 | 4/951 | 67/783 | 2/992 | 9/1003 | 54/1003 |
Dabigatran etexilate | 1010 | 0/942 | 2/942 | 60/791 | 1/1001 | 14/1010 | 61/1010 |
Meta-analysis
Venous thromboembolism
Deep vein thrombosis
Pulmonary embolism
Major bleeding
Sensitivity analysis
Quality assessment
Discussion
Conclusions
Key messages
-
In comparison with patients without prophylaxis, low molecular weight heparin (LMWH) effectively reduces venous thromboembolism (VTE) and deep vein thrombosis (DVT) after total hip replacement (TKR).
-
Compared to factor Xa inhibitors, LMWH may have higher incidence of VTE and DVT but similar rates of pulmonary embolism and major bleeding in THR or TKR subjects.
-
In comparison with direct thrombin inhibitors, LMWH have similar incidence of VTE, DVT and pulmonary embolism but lower incidence of major bleeding in THR or TKR subjects.