(adopted and updated from Bauersachs, Thrombosis Research, 2012):
AF=atrial fibrillation, VTE=venous thromboembolism, ACS=acute coronary syndrome
| Indication | Rivaroxaban (Xarelto) |
Apixaban (Eliquis) |
Dabigatran (Pradaxa) |
Edoxaban (Lixiana) |
| VTE prevention hip/knee repl. surgery | Record1 Record2 Record3 Record4 |
Advance-1 Advance-2 Advance-3 |
Re-Novate Re-Novate II Re-Model Re-Mobilize |
Stars J-V |
| VTE prevention medical ill patients | Magellan | Adopt | ||
| VTE prevention in cancer (chemotherapy) | Cassini | Avert(internal) | ||
| Acute VTE treatment/secondary prevention | Einstein DVT(Di Bisceglie and Hoofnagle 1990)* Einstein EXT(Di Bisceglie and Hoofnagle 1990)* Einstein PE(22449293) |
Amplify Amplify-Ext(23216615) |
Re-Cover(19966341) Re-Cover II Re-Medy Re-Sonate |
Hokusai-VTE(23991658) |
| Acute VTE in cancer | Select-D pilot(internal) | Adam VTE (internal) | Hokusai-VTE Cancer(internal) | |
| Stroke prevention in AF | Rocket AF | Averroes Aristotle(20211292)(23036896) |
Re-Ly Rely-Able |
Engage AF-Timi 48(20694273) |
| Secondary prevention in ACS | Atlas ACS TIMI 51 | Appraise-2 | ||
| VTE in Cancer |
Select-D Pilot Trial (02583191) |
Hokusai VTE Cancer (2073682) |
| Einstein-DVT 2010 | Einstein-PE 2012 | Einstein-Ext 2010 | Amplify 2013 |
Amplify-Ext 2012 | Re-Cover 2009 | Re-Cover-II (Abstract ASH 2011) | Re-Medy 2013 |
Re-Sonate 2013 |
Hokusai-VTE (2013) | ||
| Identifier | NCT00440193 | NCT00439777 | NCT00439725 | NCT00643201 | NCT00633893 | NCT00291330 | NCT00680186 | NCT00329238 | NCT00558259 | NCT00986154 | |
| Indications | Acute proximal DVT | Acute symptomatic PE | Extended treatement proximal DVT or PE | Acute VTE | Extended treatment in acute proximal DVT or PE | Acute symptomatic proximal DVT or PE | Acute symptomatic proximal DVT or PE | Extended treatement in VTE | Extended treatment in proximal DVT or PE | Acute symptomatic proximal DVT or PE | |
| Drug | Rivaroxaban | Rivaroxaban | Rivaroxaban | Apixaban | Apixaban | Dabigatran | Dabigatran | Dabigatran | Dabigatran | Edoxaban | |
| Comparator | Warfarin | Warfarin | Placebo | Warfarin | Placebo | Warfarin | Warfarin | Warfarin | Placebo | Warfarin | |
| Design | Randomized Open label |
Randomized Open label |
Randomized Double blind | Randomized Double blind | Randomized Double blind | Randomized Double blind | Randomized Double blind | Randomized Double blind | Randomized Double blind | Randomized Double blind | |
| Duration | 3,6, or 12 mo | 3,6, or 12 mo | (6,12) + 6 or 12 mo | 6 mo | (6,12) + 12 mo | 6 mo | 6 mo | (3-12) + 6-36 mo | (6-18) + 6 | 3,6, or 12 mo | |
| Initial LMWH | No | No | – | No | – | Yes | Yes | – | – | Yes | |
| Long-term treatment | od | od | od | bid | bid | bid | bid | bid | bid | od | |
| N | 3449 | 4832 | 1196 | 5395 | 2486 | 2564 | 2568 | 2856 | 1343 | 8240 | |
| Age | 56.1 | 57.7 | 58.3 | 56.9 | 56.7 | 54.7 | 54.9 | 54.5 | 55.8 | 55.8 | |
| Exclusion | CrCl mL/min | <30 | <30 | <30 | <25 | <25 | <30 | severe renal impairment | <=30 | <30 | <30 |
| Liver disease | excl. | excl. | excl. | excl. | excl. | excl. | excl. | excl. | excl. | excl. | |
| active cancer | (excl. life exp.<3mo) | (excl. life exp.<3mo) | (excl. life exp.<3mo) | excl. if LMWH planned | if indefinite anticoagulation (short life exp.) | (excl. life exp.<6mo) | (patients unsuited?) | excluded | if longterm anticoagulation, (life exp. <3 mo) | ||
| chronic NSAIDs | discuraged | discuraged | discuraged | caution | caution | excl. | |||||
| Aspirin 100mg / Clopidogrel 75mg | allowed | allowed | allowed | low dose single drug allowed | low dose single drug allowed | aspirin <=100mg allowed | restricted (Aspirin if > 100mg) | restricted (Aspirin if > 100mg) | asprin <=100mg allowed | ||
| Coagulation disorder | excl. | ||||||||||
| Population | Unprovoked | 62.0% | 64.5% | 73.7% | 89.8% | 91.7% | 65.7% | ||||
| Proximal DVT | 100% | 62.0% | 65.5% | 65.4% | 68.9% | 65.1% | 64.9% | 59.7% | |||
| Distal DVT | – | – | – | – | – | – | – | – | – | – | |
| PE | – | 100% | 38.0% | 34.0% | 34.6% | 31.0% | 36.8% | 33.0% | 40.3% | ||
| Previous VTE | 19.3% | 19.5% | 16.1% | 16.2% | 12.7% | 25.6% | 1.5% | 0.1% | 18.4% | ||
| Active Cancer | 6.0% | 4.6% | 4.5% | 2.7% | 1.7% | 4.8% | 4.1% | 0.2% | 2.6% | ||
| Outcomes (HR) | Recurrent VTE | 0.68 (0.44-1.04) | 1.12 (0.75-1.68) | 0.18 (0.09-0.39) ARR -5.8% |
0.84 (0.60-1.18) | 2.5mg: 0.19(0.11-0.33) ARR -7.1% 5mg: 0.20(0.11-0.34) ARR -7.1% |
1.10 (0.65-1.84) | 1.08 (0.64-1.80) | 1.44 (0.78-2.64) | 0.08 (0.02-0.25) ARR -5.2% |
0.82 (0.60–1.14) (on treatment) |
| Major bleeding | 0.65 (0.33-1.03) | 0.49 (0.31-0.79) ARR -1.1% |
0.31 (0.17-0.55) ARR -1.2% |
2.5mg: 0.49(0.09-2.64) 5mg: 0.25(0.03-2.24) |
0.82 (0.45-1.48) | 0.69 (0.36-1.32) | 0.52 (0.27-1.02) | not estimable [preliminary results 3.89 (0.18-86.1)] |
0.84 (0.59–1.21) | ||
| Minor bleeding | 5.0% vs. 4.1% | ||||||||||
| Clinically relevant bleeding | 0.97 (0.76-1.22) | 0.90 (0.76-1.07) | 5.19 (2.3-11.7) ARI +4.8% |
0.44 (0.36-0.55) ARR -5.4% |
2.5mg: 1.20(0.69-2.10) 5mg: 1.62(0.96-2.73) |
0.63 (0.47-0.84) ARR -2.2% |
0.54 (0.41-0.71 | 2.92 (1.52-5.60) ARI +3.5% |
0.81 (0.71–0.94) ARR -1.8% |
||
| Any bleeding | 0.67 (0.56-0.81) | 0.71 (0.61-0.83) ARR -6.8% |
1.82 (1.23-2.68) | 0.82 (0.75–0.90) ARR -3.9% |
|||||||
| Total deaths | 0.67 (0.44-1.02) | 1.13 (0.77-1.65) | 0.49 (0.04-5.43) | 0.79 (0.53-1.19) | 0.98 (0.53-1.79) | 0.90 (0.47-1.72) | unclear [preliminary results: 0.49 (0.02-14.5)] |
1.05 (0.82-1.35) | |||