Table 2.
Primary outcomes – subgroup and sensitivity analyses
| Anticoagulation regimen | Maternal mortality |
Thromboembolism |
Livebirth rate |
Foetal adverse events |
||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Studies | Events | Estimate (%) | I2 (%) | Studies | Events | Estimate (%) | I2 (%) | Studies | Events | Estimate (%) | I2 (%) | Studies | Events | Estimate (%) | I2 (%) | |
| VKA (INR target 2.5–3.5) | 11 | 7/581 | 0.9 (0.1, 1.6) | 0 | 11 | 22/581 | 2.7 (1.4, 4.0) | 0 | 10 | 369/531 | 64.5 (48.8, 80.2) | 95 | 11 | 14/410 | 2.6 (0.5, 4.6) | 36 |
| VKA (INR target 1.5–2.5) | 9 | 3/391 | 0.8 (0, 1.7) | 0 | 9 | 13/391 | 2.4 (0.9, 4.0) | 0 | 7 | 242/309 | 84.0 (73.1, 94.8) | 89 | 9 | 19/321 | 4.2 (1.7, 6.6)† | 18 |
| VKA (Stratified INR target) | 6 | 3/298 | 1.2 (0, 2.4) | 0 | 6 | 5/298 | 1.6 (1.2, 4.3) | 0 | 5 | 208/288 | 72.6 (59.3, 85.9) | 87 | 6 | 13/223 | 4.2 (0.5, 7.8) | 47 |
| VKA regardless of INR target | 30 | 14/1373 | 0.9 (0.4, 1.4) | 0 | 30 | 40/1373 | 2.1 (1.3, 2.8) | 0 | 26 | 879/1224 | 71.5 (64.2, 78.8) | 92 | 30 | 49/1014 | 3.5 (2.1, 4.9) | 38 |
| VKA until delivery | 6 | 0/240 | 1.0 (0, 2.3) | 0 | 6 | 3/240 | 1.6 (1.2, 4.3) | 0 | 5 | 141/200 | 70.8 (50.0, 91.5) | 96 | 6 | 9/180 | 4.3 (1.4, 7.3) | 0 |
| Studies reporting newer valves only | 6 | 5/261 | 2.3 (0.5, 4.1) | 0 | 6 | 8/261 | 2.5 (0.6, 4.4) | 0 | 6 | 156/261 | 65.8 (43.2, 88.4) | 96 | 6 | 8/156 | 3.4 (0.4, 6.5) | 13 |
| Excluding studies with high risk of bias | 9 | 1/350 | 1.1 (0.1, 2.2) | 0 | 9 | 1/350 | 1.2 (0.1, 2.3) | 0 | 9 | 242/333 | 72.9 (59.5, 86.2) | 94 | 9 | 11/249 | 3.3 (1.1, 5.5) | 0 |
| High-income countries | 10 | 0/228 | 2.7 (0.2, 5.2) | 0 | 10 | 3/228 | 1.3 (0, 2.3) | 0 | 9 | 130/217 | 60.6 (41.4, 79.8) | 92 | 10 | 9/142 | 3.9 (0.9, 7.0) | 0 |
| Middle-income countries | 20 | 14/1145 | 0.9 (0.3, 1.4) | 0 | 20 | 37/1145 | 2.4 (1.5, 3.2) | 0 | 17 | 749/1007 | 76.1 (68.3, 83.8) | 91 | 20 | 40/872 | 3.3 (1.8, 4.9) | 47 |
| LMWH alone | 10 | 1/132 | 2.9 (0.2, 5.7) | 0 | 9 | 13/127 | 8.7 (3.9, 13.4) | 0 | 7 | 68/74 | 92.0 (86.1, 98.0) | 0 | 8 | 1/103 | 3.6 (0.1, 7.0) | 0 |
| LMWH studies reporting newer valves | 5 | 1/63 | 4.2 (0, 8.9) | 0 | 4 | 5/58 | 6.9 (0.5, 13.3) | 0 | 4 | 43.48 | 91.4 (83.8, 99.0) | 0 | 4 | 0/43 | NA | 0 |
| UFH alone | 4 | 2/64 | 3.4 (0, 7.7) | 0 | 3 | 7/52 | 11.2 (2.8, 19.6) | 0 | 3 | 33/51 | 69.5 (37.8, 100) | 87 | 3 | 2/35 | 4.3 (0, 100) | 6 |
| UFH studies reporting newer valves | 1 | 0/24 | NA | 0 | 1 | 2/24 | 8.3 (0, 19.4) | 0 | 1 | 9/23 | 39.0 (19.0 – 59.0) | 0 | 0 | – | – | – |
| Excluding studies with high risk of bias | 8 | 1/101 | 3.5 (0, 6.9) | 0 | 7 | 7/96 | 7.1 (2.1, 12.1) | 0 | 7 | 66/85 | 84.1 (70.6, 97.6) | 78 | 6 | 0/57 | NA | 0 |
| High-income countries | 10 | 1/151 | 2.7 (0.2, 5.2) | 0 | 8 | 16/139 | 9.0 (0.4, 13.7) | 0 | 7 | 73/95 | 82.4 (68.9, 95.9) | 77 | 8 | 3/110 | 3.6 (0.3, 7.0) | 0 |
| Middle-income countries | 4 | 2/45 | 5.6 (0, 12.0) | 0 | 3 | 4/40 | 10.3 (1.0, 19.5) | 0 | 3 | 28/30 | 5.6 (0, 12.0) | 0 | 3 | 0/28 | NA | 0 |
| Sequential treatment | 20 | 11/530 | 2.0 (0.8, 3.1) | 0 | 20 | 44/530 | 5.8 (3.8, 7.7) | 29 | 18 | 381/475 | 79.9 (74.3, 85.6) | 61 | 19 | 5/431 | 1.4 (0.3, 2.5) | 0 |
| Sequential with LMWH | 4 | 1/33 | 6.8 (1.4, 15.1) | 0 | 4 | 3/33 | 8.3 (0, 17.5) | 0 | 4 | 28/32 | 89.5 (77.7, 100) | 30 | 4 | 0/28 | NA | 0 |
| Sequential with UFH | 15 | 10/454 | 2.0 (0.7, 3.3) | 0 | 15 | 38/454 | 6.1 (3.6, 8.5) | 0 | 13 | 310/402 | 72.4 (63.6, 81.2) | 80 | 14 | 5/363 | 1.4 (0.2, 2.5) | 0 |
| Studies reporting newer valves only | 4 | 2/86 | 3.4 (0, 7.2) | 0 | 4 | 13/86 | 14.4 (7.0, 21.7) | 0 | 4 | 66/85 | 78.4 (68.3, 88.5) | 14 | 4 | 1/69 | 2.7 (0, 6.3) | 0 |
| Excluding studies with high risk of bias | 7 | 4/133 | 2.4 (0, 4.9) | 0 | 7 | 14/133 | 9.7 (4.7, 14.7) | 0 | 6 | 68/103 | 65.4 (47.6, 83.1) | 74 | 6 | 2/88 | 2.2 (0, 5.1) | 0 |
| High-income countries | 8 | 1/124 | 2.8 (0, 5.6) | 0 | 8 | 8/124 | 4.7 (1.1, 8.4) | 0 | 8 | 76/123 | 65.9 (50.2, 81.7) | 77 | 8 | 3/106 | 3.8 (0.3, 72) | 0 |
| Middle-income countries | 12 | 10/406 | 1.8 (0.5, 3.1) | 0 | 12 | 36/406 | 6.9 (4.1, 9.8) | 22 | 10 | 295/352 | 84.0 (78.2, 89.7) | 54 | 11 | 2/325 | 1.2 (0, 2.3) | 0 |
VKA, Vitamin-K antagonists; INR, international normalized ratio; LMWH, low molecular weight heparin; UFH, unfractionated heparin; NA, not applicable.