Table 1.
Rates of recurrent VTE and bleeding reported in clinical studies of novel oral anticoagulants
| Study | Patients, N | Treatment duration | Rate of VTE recurrence |
Rate of bleeding |
||
|---|---|---|---|---|---|---|
| Major bleeding | All bleeding | Major/CRNM bleeding | ||||
| Schulman 2009 RE-COVER [21] |
2564 |
6 months |
Dabigatran 2.4% LMWH + VKA 2.1% Difference 0.4% (95% CI −0.8%, 1.5%); p < 0.001, non-inferiorHR 1.10 (95% CI 0.65, 1.84) |
a Dabigatran 1.6% LMWH + VKA 1.9% HR 0.82 (95% CI 0.45, 1.48) |
Dabigatran 16.1%LMWH + VKA 21.9% HR 0.71 (95% CI 0.59, 0.85) |
b Dabigatran 5.6% LMWH + VKA 8.8% HR 0.63 (95% CI 0.47, 0.84); p = 0.002 |
| Schulman 2011 RE-COVER II [22] |
2568 |
6 months |
Dabigatran 2.4% LMWH + VKA 2.2% Difference 0.2% (95% CI −1.0%, 1.5%); p < 0.0001, non-inferiorHR 1.08 (95% CI 0.64, 1.80) |
a Dabigatran 1.2% LMWH + VKA 1.7% HR 0.69 (95% CI 0.36, 1.32) |
Dabigatran 15.6% LMWH + VKA 22.1% HR 0.67 (95% CI 0.56, 0.81) |
|
| EINSTEIN Investigators 2010 EINSTEIN-DVT [18] |
3451 |
3, 6 or 12 months |
Rivaroxaban 2.1% LMWH + VKA 3.0% p < 0.001, non-inferiorHR 0.68 (95% CI 0.44, 1.04) |
c Rivaroxaban 0.8% LMWH + VKA 1.2% HR 0.65 (95% CI 0.33, 1.30); p = 0.21 |
|
d Rivaroxaban 8.1% LMWH + VKA 8.1% HR 0.97 (95% CI 0.76, 1.22); p = 0.77 |
| EINSTEIN-PE Investigators 2012 EINSTEIN-PE [19] | 4832 | 3, 6 or 12 months | Rivaroxaban 2.1% LMWH + VKA 1.8% p = 0.003, non-inferiorHR 1.12 (95% CI 0.75, 1.68) | c Rivaroxaban 1.1% LMWH + VKA 2.2% HR 0.49 (95% CI 0.31, 0.79); p = 0.003 | d Rivaroxaban 10.3% LMWH + VKA 11.4% HR 0.90 (95% CI 0.76, 1.07); p = 0.23 | |
CRNM, clinically relevant non-major; HR, hazard ratio; LMWH, low molecular weight heparin; VKA, vitamin K antagonist.
a: Bleeding defined as major if clinically overt and if it was associated with a fall in the haemoglobin level of at least 20 g/L, resulted in the need for transfusion of 2 or more units of red cells, involved a critical site or was fatal.
b: Clinically relevant non-major bleeding was defined as bleeding not meeting the criteria for major bleeding but associated with spontaneous skin haematoma of at least 25 cm2, spontaneous nose bleed of more than 5 minutes’ duration, macroscopic haematuria (spontaneous or, if associated with intervention, lasting more than 24 hours), spontaneous rectal bleeding (more than spotting on toilet paper), gingival bleeding for more than 5 minutes, bleeding leading to hospitalisation and/or requiring surgical treatment, bleeding leading to a transfusion of less than 2 units of whole blood or red cells, or any other bleeding considered clinically relevant by the investigator.
c: Bleeding was defined as major if it was clinically overt and associated with a fall in the haemoglobin level of 20 g/L or more, or if it led to transfusion of two or more units of red cells, or if it was retroperitoneal, intracranial, occurred in a critical site or contributed to death.
d: Clinically relevant non-major bleeding was defined as overt bleeding not meeting the criteria for major bleeding but associated with medical intervention, unscheduled contact with a physician, interruption or discontinuation of study treatment, or associated with any other discomfort such as pain or impairment of activities of daily life.