| Dabigatran | atrial fibrillation, in all type of patients | vs warfarin standard dose | Gastrointestinal major bleeding by 30% adverse event thrombo-embolic event (cerebral or systemic) by 22% suggested Lifethreatening major bleeding by 25% suggested Major bleeding by 13% suggested Haemmorhagic stroke by 71% suggested Cardiovascular death by 12% suggested stroke (fatal and non fatal) by 22% suggested All cause death by 10% suggested Fatal stroke by 19% suggested Non fatal stroke by 25% suggested | | Endpoint | TE [95% CI] | p val | I2 | n | k | |
|---|
| systemic thrombo-embolic complication | 0.82 [0.47 1.42] | p=1.00 | 0 | 24135 | 2 | RE-LY (150mg), RE-LY (110mg), | | thrombo-embolic event (cerebral or systemic) | 0.78 [0.68 0.91] | p=0.04 | 0 | 24135 | 2 | RE-LY (150mg), RE-LY (110mg), | | TE event or ischemic stroke or systemic embolism | 0.92 [0.75 1.12] | p=1.00 | 0 | 12037 | 1 | RE-LY (110mg), | | ischemic stroke | 0.94 [0.79 1.11] | p=1.00 | 0 | 24135 | 2 | RE-LY (150mg), RE-LY (110mg), | | Lifethreatening major bleeding | 0.75 [0.65 0.87] | p=0.04 | 0 | 24135 | 2 | RE-LY (150mg), RE-LY (110mg), | | Non-lifethreatening major bleeding | 1.02 [0.88 1.16] | p=1.00 | 0 | 24135 | 2 | RE-LY (150mg), RE-LY (110mg), | | Gastrointestinal major bleeding | 1.30 [1.10 1.55] | p=0.04 | 0 | 24135 | 2 | RE-LY (150mg), RE-LY (110mg), | | major or clinically relevant non-major bleeding | no data | | hypertransaminasemia | no data | | Major bleeding | 0.87 [0.78 0.96] | p=0.04 | 0 | 24135 | 2 | RE-LY (150mg), RE-LY (110mg), | | Haemmorhagic stroke | 0.29 [0.19 0.44] | p=0.04 | 0 | 24135 | 2 | RE-LY (150mg), RE-LY (110mg), | | Fatal bleeding | 0.82 [0.67 1.00] | p=1.00 | 0 | 12098 | 1 | RE-LY (150mg), | | Cardiovascular death | 0.88 [0.78 0.98] | p=0.04 | 0 | 24135 | 2 | RE-LY (150mg), RE-LY (110mg), | | stroke (fatal and non fatal) | 0.78 [0.66 0.91] | p=0.04 | 0 | 24135 | 2 | RE-LY (150mg), RE-LY (110mg), | | Coronary event | 1.29 [0.99 1.69] | p=1.00 | 0 | 18113 | 1 | RE-LY (150mg), | | All cause death | 0.90 [0.82 0.98] | p=0.04 | 0 | 24135 | 2 | RE-LY (150mg), RE-LY (110mg), | | Fatal stroke | 0.81 [0.67 0.98] | p=0.04 | 0 | 24135 | 2 | RE-LY (150mg), RE-LY (110mg), | | Non fatal stroke | 0.75 [0.58 0.97] | p=0.04 | 0 | 24135 | 2 | RE-LY (150mg), RE-LY (110mg), |
| Trial | Studied treatment | Control | Patients |
|---|
| PETRO (150mg), 2007 | dabigatran
150 mg twice daily (alone or combined with 81- or 325-mg aspirin) | warfarin administered to achieve an international normalized ratio of 2 to 3 for | patients
with AF at high risk for thromboembolic events | | RE-LY (150mg), 2009 | dabigatran 150 mg twice a day | warfarin adjusted-dose to a 2.0 to 3.0 INR | Patients With Non-Valvular Atrial Fibrillation | | RE-LY (110mg), 2009 | dabigatran 110 mg twice a day
| warfarin adjusted dose to a 2-3 INR | Patients With Non-Valvular Atrial Fibrillation
|
| |
| Dabigatran | | vs enoxaparin | Symptomatic deep-vein thrombosis by 635% suggested | | Endpoint | TE [95% CI] | p val | I2 | n | k | |
|---|
| Symptomatic deep-vein thrombosis | 7.35 [1.67 32.30] | p=0.04 | 0 | 4577 | 2 | RE-NOVATE (220mg), RE-NOVATE (150mg), | | major VTE (fatal and non fatal DVT,PE) | 0.94 [0.67 1.32] | p=1.00 | 0 | 3631 | 2 | RE-NOVATE (220mg), RE-NOVATE (150mg), | | Deep vein thrombosis | no data | | total VTE and all-cause mortality | 1.09 [0.84 1.41] | p=1.00 | 0 | 3548 | 2 | RE-NOVATE (220mg), RE-NOVATE (150mg), | | asymptomatic DVT | 0.94 [0.71 1.24] | p=1.00 | 0 | 3542 | 2 | RE-NOVATE (220mg), RE-NOVATE (150mg), | | non-fatal pulmonary embolism | 1.06 [0.32 3.57] | p=1.00 | 0 | 4075 | 2 | RE-NOVATE (220mg), RE-NOVATE (150mg), | | distal DVT | 1.21 [0.82 1.80] | p=1.00 | 0 | 3533 | 2 | RE-NOVATE (220mg), RE-NOVATE (150mg), | | proximal DVT | 0.74 [0.50 1.09] | p=1.00 | 0 | 3618 | 2 | RE-NOVATE (220mg), RE-NOVATE (150mg), | | Symptomatic venous thromboembolism (DVT, PE) | no data | | myocardial infarction (fatal and non fatal) | no data | | All cause death | 3.43 [0.32 36.51] | p=1.00 | 0 | 4588 | 2 | RE-NOVATE (220mg), RE-NOVATE (150mg), | | Major bleeding | 1.06 [0.66 1.68] | p=1.00 | 0 | 4617 | 2 | RE-NOVATE (220mg), RE-NOVATE (150mg), | | any bleedings | no data | | Coronary event | 0.74 [0.33 1.68] | p=1.00 | 0 | 5476 | 2 | RE-NOVATE (150mg), RE-NOVATE 2, | | major or clinically relevant non-major bleeding | no data |
| Trial | Studied treatment | Control | Patients |
|---|
| RE-NOVATE (220mg), 2007 | dabigatran etexilate 220 mg q.d. for 28-35 days | Enoxaparin 40 mg q.d. for 23-35 days | Total hip replacement | | RE-NOVATE (150mg), 2007 | dabigatran etexilate 150 mg q.d. 28-35 days
| Enoxaparin 40 mg q.d. for 28-25 days | Total hip replacement
| | RE-NOVATE 2, 0 | dabigatran 220mg once daily for 28-35 Days | enoxaparin 40mg subcutaneous once daily for 28-35 Days | patients undergoing total hip-replacement surgery |
| |
| Dabigatran | | vs enoxaparin (europe regimen) | Symptomatic deep-vein thrombosis by 73% suggested | | Endpoint | TE [95% CI] | p val | I2 | n | k | |
|---|
| Symptomatic deep-vein thrombosis | 0.27 [0.09 0.82] | p=0.04 | 0 | 2398 | 2 | RE-MODEL (220mg), RE-MODEL (150mg), | | major VTE (fatal and non fatal DVT,PE) | 0.91 [0.56 1.47] | p=1.00 | 0 | 2055 | 2 | RE-MODEL (220mg), RE-MODEL (150mg), | | Deep vein thrombosis | no data | | total VTE and all-cause mortality | 1.02 [0.85 1.22] | p=1.00 | 0 | 2053 | 2 | RE-MODEL (220mg), RE-MODEL (150mg), | | asymptomatic DVT | 1.05 [0.88 1.26] | p=1.00 | 0 | 2053 | 2 | RE-MODEL (220mg), RE-MODEL (150mg), | | non-fatal pulmonary embolism | 2.92 [0.12 71.85] | p=1.00 | 0 | 1038 | 1 | RE-MODEL (150mg), | | distal DVT | 1.05 [0.87 1.25] | p=1.00 | 0 | 2052 | 2 | RE-MODEL (220mg), RE-MODEL (150mg), | | proximal DVT | 0.93 [0.57 1.53] | p=1.00 | 0 | 2051 | 2 | RE-MODEL (220mg), RE-MODEL (150mg), | | Symptomatic venous thromboembolism (DVT, PE) | no data | | myocardial infarction (fatal and non fatal) | no data | | All cause death | 1.00 [0.14 7.11] | p=1.00 | 0 | 2741 | 2 | RE-MODEL (220mg), RE-MODEL (150mg), | | Major bleeding | 1.06 [0.55 2.03] | p=1.00 | 0 | 2770 | 2 | RE-MODEL (220mg), RE-MODEL (150mg), | | any bleedings | no data | | Coronary event | 1.26 [0.39 4.02] | p=1.00 | 0 | 2076 | 1 | RE-MODEL (220mg), | | major or clinically relevant non-major bleeding | 1.17 [0.87 1.56] | p=1.00 | 0 | 2770 | 2 | RE-MODEL (220mg), RE-MODEL (150mg), |
| Trial | Studied treatment | Control | Patients |
|---|
| RE-MODEL (220mg), 2007 | dabigatran etexilate 220 mg q.d. 6-10 days
| Enoxaparin 40 mg q.d. for 6-10 days | patients undergoing total knee replacement | | RE-MODEL (150mg), 2007 | dabigatran etexilate 150 mg q.d. for 6-10 days | Enoxaparin 40 mg q.d. for 6-10 days | Total knee replacement |
| |
| Dabigatran | | vs enoxaparin (US regimen) | total VTE and all-cause mortality by 28% suggested distal DVT by 26% suggested Major bleeding by 58% suggested | | Endpoint | TE [95% CI] | p val | I2 | n | k | |
|---|
| Symptomatic deep-vein thrombosis | no data | | major VTE (fatal and non fatal DVT,PE) | 1.43 [0.89 2.31] | p=1.00 | 0 | 2610 | 2 | RE-MOBILIZE (220mg), RE-MOBILIZE (150mg), | | Deep vein thrombosis | no data | | total VTE and all-cause mortality | 1.28 [1.08 1.52] | p=0.04 | 0 | 2539 | 2 | RE-MOBILIZE (220mg), RE-MOBILIZE (150mg), | | asymptomatic DVT | no data | | non-fatal pulmonary embolism | 0.09 [0.00 1.63] | p=1.00 | 0 | 1292 | 1 | RE-MOBILIZE (150mg), | | distal DVT | 1.26 [1.06 1.51] | p=0.04 | 0 | 2539 | 2 | RE-MOBILIZE (220mg), RE-MOBILIZE (150mg), | | proximal DVT | 1.49 [0.66 3.38] | p=1.00 | 0 | 1247 | 1 | RE-MOBILIZE (220mg), | | Symptomatic venous thromboembolism (DVT, PE) | no data | | myocardial infarction (fatal and non fatal) | no data | | All cause death | 3.00 [0.12 73.66] | p=1.00 | 0 | 1753 | 1 | RE-MOBILIZE (150mg), | | Major bleeding | 0.42 [0.20 0.88] | p=0.04 | 0 | 3464 | 2 | RE-MOBILIZE (220mg), RE-MOBILIZE (150mg), | | any bleedings | no data | | Coronary event | 1.05 [0.47 2.33] | p=1.00 | 0 | 2586 | 1 | RE-MOBILIZE (220mg), | | major or clinically relevant non-major bleeding | 0.84 [0.58 1.21] | p=1.00 | 0 | 3464 | 2 | RE-MOBILIZE (220mg), RE-MOBILIZE (150mg), |
| Trial | Studied treatment | Control | Patients |
|---|
| RE-MOBILIZE (220mg), 2008 | dabigatran etexilate 220 mg for 12-15 days
| Enoxaparin 30mg SC BID after surgery for 12-15 days | Total knee replacement
| | RE-MOBILIZE (150mg), 2008 | dabigatran etexilate 150 mg q.d. for 12-15 days
| enoxaparin 30 mg SC BID after surgery for 12-15 days
| Total knee replacement
|
| |
| Ximelagatran | atrial fibrillation, in all type of patients | vs warfarin standard dose | hypertransaminasemia by 681% adverse event Major bleeding by 27% suggested | | Endpoint | TE [95% CI] | p val | I2 | n | k | |
|---|
| systemic thrombo-embolic complication | 2.47 [0.70 8.67] | p=1.00 | 0 | 7583 | 3 | SPORTIF II (ximelagatran vs warfarin standard dose), SPORTIF III, SPORTIF V, | | thrombo-embolic event (cerebral or systemic) | 0.98 [0.73 1.32] | p=1.00 | 0 | 7329 | 2 | SPORTIF III, SPORTIF V, | | TE event or ischemic stroke or systemic embolism | 0.94 [0.68 1.29] | p=1.00 | 0 | 7329 | 2 | SPORTIF III, SPORTIF V, | | ischemic stroke | 0.94 [0.69 1.29] | p=1.00 | 0 | 7583 | 3 | SPORTIF II (ximelagatran vs warfarin standard dose), SPORTIF III, SPORTIF V, | | Lifethreatening major bleeding | no data | | Non-lifethreatening major bleeding | no data | | Gastrointestinal major bleeding | no data | | major or clinically relevant non-major bleeding | no data | | hypertransaminasemia | 7.81 [4.54 13.42] | p=0.04 | 0 | 3922 | 1 | SPORTIF V, | | Major bleeding | 0.73 [0.55 0.95] | p=0.04 | 0 | 7583 | 3 | SPORTIF II (ximelagatran vs warfarin standard dose), SPORTIF III, SPORTIF V, | | Haemmorhagic stroke | 0.54 [0.20 1.43] | p=1.00 | 0 | 7583 | 3 | SPORTIF II (ximelagatran vs warfarin standard dose), SPORTIF III, SPORTIF V, | | Fatal bleeding | no data | | Cardiovascular death | 1.21 [0.76 1.93] | p=1.00 | 0 | 3407 | 1 | SPORTIF III, | | stroke (fatal and non fatal) | 0.91 [0.67 1.23] | p=1.00 | 0 | 7583 | 3 | SPORTIF II (ximelagatran vs warfarin standard dose), SPORTIF III, SPORTIF V, | | Coronary event | 0.99 [0.66 1.49] | p=1.00 | 0 | 7329 | 2 | SPORTIF III, SPORTIF V, | | All cause death | 0.96 [0.79 1.18] | p=1.00 | 0 | 7583 | 3 | SPORTIF II (ximelagatran vs warfarin standard dose), SPORTIF III, SPORTIF V, | | Fatal stroke | 1.51 [0.73 3.13] | p=1.00 | 0 | 7583 | 3 | SPORTIF II (ximelagatran vs warfarin standard dose), SPORTIF III, SPORTIF V, | | Non fatal stroke | no data |
| Trial | Studied treatment | Control | Patients |
|---|
| SPORTIF II (ximelagatran vs warfarin standard dose), 2002 | ximelegatran 20,40,60 mg twice daily | warfarin standard dose(target INR 2-3) | Medium to high risk patients with chronic non valvular atrial fibrillation. | | SPORTIF III, 2003 | ximelagatran 36 mg twice daily | warfarin standard dose (target INR 2-3) | One or more stroke risk factor in addition to AF.High risk patients with non valvular atrial fibrillation. | | SPORTIF V, 2005 | ximelegatran 36 mg twice daily | warfarin standard dose(target INR 2-3) | One or more stroke risk factor in addition to atrial fibrillation.High risk patients with non valvular atrial fibrillation.
|
| |
| Ximelagatran | thrombosis prevention, in orthopedic surgery | vs Dalteparin | Venous thromboembolism by 45% suggested | | Endpoint | TE [95% CI] | p val | I2 | n | k | |
|---|
| Acute coronary syndrome | no data | | Venous thromboembolism | 0.55 [0.37 0.82] | p=0.04 | 0 | 646 | 2 | METHRO I, METHRO II, | | Major bleeding | 1.95 [0.88 4.33] | p=1.00 | 0 | 827 | 2 | METHRO I, METHRO II, |
| Trial | Studied treatment | Control | Patients |
|---|
| METHRO I, 2002 | Melagatran 1–4 mg s.c. immediately before surgery, melagatran at 20.00 hours, then ximelagatran 6–24 mg orally b.d. for 6–9 days | Dalteparin 5000 IU o.d., started evening before surgery for 6–9 days | adults undergoing hip or knee replacement | | METHRO II, 2002 | Melagatran 1–3 mg s.c. immediately before surgery,melagatran same day, then ximelagatran 8–24 mg orally b.d. for 7–10 days | Dalteparin 5000 IU o.d., started evening before surgery for 7–10 days | undergoing hip or knee replacement |
| |
| Ximelagatran | | vs Enoxaparin | all NS | | Endpoint | TE [95% CI] | p val | I2 | n | k | |
|---|
| Acute coronary syndrome | no data | | Venous thromboembolism | 0.98 [0.87 1.11] | p=1.00 | 0 | 6342 | 4 | Phase II (Heit), Platinum (Colwell), METHRO III, EXPRESS, | | Major bleeding | 1.46 [1.00 2.14] | p=1.00 | 0 | 7621 | 4 | Phase II (Heit), Platinum (Colwell), METHRO III, EXPRESS, |
| Trial | Studied treatment | Control | Patients |
|---|
| Phase II (Heit), 2001 | Ximelagatran 8, 12, 18 or 24 mgorally b.d., at least 12 h after surgery for 6–12 days | Enoxaparin 30 mg s.c. b.d.,starting at least 12 h after surgery for 6–12 days | adults (age>18 years and weight at least 40 kg) undergoing knee replacements | | Platinum (Colwell), 2003 | Ximelagatran 24 mg orally b.d., starting at least 12 h after surgery for 7–12 days | Enoxaparin 30 mg s.c. b.d.,starting at least 12 h after surgery for 7–12 days | adults undergoing hip replacement | | METHRO III, 2002 | Melagatran 3 mg s.c. 4–12h after surgery, then ximelagatran24 mg orally b.d. for 7–10 days | Enoxaparin 40 mg s.c. o.d. 12 h before surgery for 7–10 days | hip or knee replacement | | EXPRESS, 2003 | Melagatran 2 mg s.c. up to 30 min before surgery, then melagatran 3 mg at least 8 hafter surgery, then ximelagatran 24 mg orally b.d. for 8–11 days | Enoxaparin 40 mg s.c. o.d.,starting 12 h before surgery for 8–11 days | hip or knee replacement |
| |
