Edoxaban | atrial fibrillation, in all type of patients | vs warfarin standard dose | Gastrointestinal major bleeding by 23% adverse event Lifethreatening major bleeding by 49% suggested major or clinically relevant non-major bleeding by 14% suggested Major bleeding by 20% suggested Haemmorhagic stroke by 53% suggested Fatal bleeding by 45% suggested Cardiovascular death by 14% suggested | Endpoint | TE [95% CI] | p val | I2 | n | k | |
---|
systemic thrombo-embolic complication | 0.65 [0.34 1.24] | p=1.00 | 0 | 14071 | 1 | ENGAGE-AF TIMI 48 High dose, | thrombo-embolic event (cerebral or systemic) | 0.87 [0.73 1.04] | p=1.00 | 0 | 14071 | 1 | ENGAGE-AF TIMI 48 High dose, | TE event or ischemic stroke or systemic embolism | no data | ischemic stroke | 1.00 [0.84 1.20] | p=1.00 | 0 | 14071 | 1 | ENGAGE-AF TIMI 48 High dose, | Lifethreatening major bleeding | 0.51 [0.38 0.69] | p=0.04 | 0 | 14071 | 1 | ENGAGE-AF TIMI 48 High dose, | Non-lifethreatening major bleeding | no data | Gastrointestinal major bleeding | 1.23 [1.01 1.49] | p=0.04 | 0 | 14071 | 1 | ENGAGE-AF TIMI 48 High dose, | major or clinically relevant non-major bleeding | 0.86 [0.80 0.92] | p=0.04 | 0 | 14071 | 1 | ENGAGE-AF TIMI 48 High dose, | hypertransaminasemia | no data | Major bleeding | 0.80 [0.71 0.91] | p=0.04 | 0 | 14071 | 1 | ENGAGE-AF TIMI 48 High dose, | Haemmorhagic stroke | 0.47 [0.35 0.64] | p=0.04 | 0 | 14071 | 1 | ENGAGE-AF TIMI 48 High dose, | Fatal bleeding | 0.55 [0.36 0.84] | p=0.04 | 0 | 14071 | 1 | ENGAGE-AF TIMI 48 High dose, | Cardiovascular death | 0.86 [0.77 0.97] | p=0.04 | 0 | 14071 | 1 | ENGAGE-AF TIMI 48 High dose, | stroke (fatal and non fatal) | 0.88 [0.75 1.03] | p=1.00 | 0 | 14071 | 1 | ENGAGE-AF TIMI 48 High dose, | Coronary event | no data | All cause death | 0.92 [0.83 1.01] | p=1.00 | 0 | 14071 | 1 | ENGAGE-AF TIMI 48 High dose, | Fatal stroke | 0.92 [0.68 1.25] | p=1.00 | 0 | 14071 | 1 | ENGAGE-AF TIMI 48 High dose, | Non fatal stroke | no data |
Trial | Studied treatment | Control | Patients |
---|
Weitz (edoxaban phase 2), 0 | Four Fixed Dose Regimens of edoxaban (DU-176b) | warfarin | Subjects With Non- Valvular Atrial Fibrillation | ENGAGE-AF TIMI 48 High dose, 2013 | edoxaban 60mg once daily | warfarin (INR 2-3) | AF patients (CHADS2 >=2) | phase 2 edoxaban, 0 | edoxaban (DU-176b) | warfarin | male and female subjects aged 18 to 80 years, inclusive, with non-valvular AF and a CHADS2 Score of at least 1 |
| |
Edoxaban | | vs enoxaparin (short duration) | major VTE (fatal and non fatal DVT,PE) by 66% suggested asymptomatic DVT by 62% suggested distal DVT by 64% suggested | Endpoint | TE [95% CI] | p val | I2 | n | k | |
---|
Symptomatic deep-vein thrombosis | 0.97 [0.02 49.21] | p=1.00 | 0 | 503 | 1 | STARS J-V, | major VTE (fatal and non fatal DVT,PE) | 0.34 [0.13 0.89] | p=0.04 | 0 | 503 | 1 | STARS J-V, | Deep vein thrombosis | no data | total VTE and all-cause mortality | no data | asymptomatic DVT | 0.38 [0.16 0.92] | p=0.04 | 0 | 503 | 1 | STARS J-V, | non-fatal pulmonary embolism | no data | distal DVT | 0.36 [0.14 0.95] | p=0.04 | 0 | 503 | 1 | STARS J-V, | proximal DVT | 0.49 [0.04 5.40] | p=1.00 | 0 | 503 | 1 | STARS J-V, | Symptomatic venous thromboembolism (DVT, PE) | no data | myocardial infarction (fatal and non fatal) | no data | All cause death | no data | Major bleeding | no data | any bleedings | no data | Coronary event | no data | major or clinically relevant non-major bleeding | no data |
Trial | Studied treatment | Control | Patients |
---|
STARS J-V, 0 | edoxaban 30 mg once daily for 11 to 14 days | subcutaneous enoxaparin 2,000 IU, equivalent to 20 mg, twice daily (BID) for 11 to 14 days | total hip arthroplasty |
| |
Dabigatran | acute coronary syndrome, in all type of patients | vs placebo | all NS | Endpoint | TE [95% CI] | p val | I2 | n | k | |
---|
Acute coronary syndrome | no data |
Trial | Studied treatment | Control | Patients |
---|
REDEEM, 2009 | dabigatran 4 dosages (50mg twice daily, 75mg twice daily, 110mg twice daily, 150mg twice daily) | placebo | patients with recent acute coronary syndromes (ST- or non-ST-elevation myocardical infarction) |
| |
Apixaban | acute coronary syndrome, in all type of patients | vs placebo | major or minor bleeding by 174% adverse event any bleedings by 121% adverse event major or clinically relevant non-major bleeding by 139% adverse event Major bleeding by 153% adverse event | Endpoint | TE [95% CI] | p val | I2 | n | k | |
---|
cardiac event (fatal and non fatal ) | 0.95 [0.81 1.10] | p=1.00 | 0 | 7392 | 1 | APPRAISE 2, | cardiovascular events | 0.93 [0.80 1.08] | p=1.00 | 0 | 8923 | 3 | APPRAISE-1 (10mg od), APPRAISE-1 (2.5 mg bid), APPRAISE 2, | Cardiovascular death | 0.96 [0.73 1.26] | p=1.00 | 0 | 7392 | 1 | APPRAISE 2, | myocardial infarction (fatal and non fatal) | 0.93 [0.76 1.15] | p=1.00 | 0 | 7392 | 1 | APPRAISE 2, | ischemic stroke | 0.67 [0.40 1.14] | p=1.00 | 0 | 7392 | 1 | APPRAISE 2, | All cause death | 1.08 [0.86 1.36] | p=1.00 | 0 | 7392 | 1 | APPRAISE 2, | stent thrombosis | 0.73 [0.47 1.12] | p=1.00 | 0 | 7392 | 1 | APPRAISE 2, | major or minor bleeding | 2.74 [1.78 4.19] | p=0.04 | 0 | 7315 | 1 | APPRAISE 2, | any bleedings | 2.21 [1.91 2.55] | p=0.04 | 0 | 7315 | 1 | APPRAISE 2, | major or clinically relevant non-major bleeding | 2.39 [1.82 3.14] | p=0.04 | 0 | 8846 | 3 | APPRAISE-1 (10mg od), APPRAISE-1 (2.5 mg bid), APPRAISE 2, | Major bleeding | 2.53 [1.47 4.38] | p=0.04 | 0 | 7315 | 1 | APPRAISE 2, | Fatal bleeding | 10.91 [0.60 197.33] | p=1.00 | 0 | 7315 | 1 | APPRAISE 2, |
Trial | Studied treatment | Control | Patients |
---|
APPRAISE-1 (10mg od), 2009 | apixaban 10 mg once daily | placebo | patients with a recent ST-elevation or non–ST-elevation
acute coronary syndrome(<7 days) | APPRAISE-1 (2.5 mg bid), 2009 | Apixaban 2.5mg twice daily
| placebo
| patients with a recent ST-elevation or non–ST-elevation
acute coronary syndrome(<7 days)
| APPRAISE 2, 2011 | apixaban 5mg twice daily | placebo | patients with a recent acute coronary syndrome and at least two
additional risk factors for recurrent ischemic events |
| |
Apixaban | atrial fibrillation, in all type of patients | vs warfarin standard dose | thrombo-embolic event (cerebral or systemic) by 20% fully demonstrated Major bleeding by 30% fully demonstrated All cause death by 11% fully demonstrated major or clinically relevant non-major bleeding by 30% suggested Haemmorhagic stroke by 49% suggested stroke (fatal and non fatal) by 21% suggested | Endpoint | TE [95% CI] | p val | I2 | n | k | |
---|
systemic thrombo-embolic complication | 0.88 [0.44 1.76] | p=1.00 | 0 | 18201 | 1 | ARISTOTLE, | thrombo-embolic event (cerebral or systemic) | 0.80 [0.66 0.96] | p=0.04 | 0 | 18201 | 1 | ARISTOTLE, | TE event or ischemic stroke or systemic embolism | no data | ischemic stroke | 0.92 [0.74 1.14] | p=1.00 | 0 | 18201 | 1 | ARISTOTLE, | Lifethreatening major bleeding | no data | Non-lifethreatening major bleeding | no data | Gastrointestinal major bleeding | 0.88 [0.67 1.14] | p=1.00 | 0 | 18201 | 1 | ARISTOTLE, | major or clinically relevant non-major bleeding | 0.70 [0.63 0.78] | p=0.04 | 0 | 18201 | 1 | ARISTOTLE, | hypertransaminasemia | no data | Major bleeding | 0.70 [0.61 0.81] | p=0.04 | 0 | 18201 | 1 | ARISTOTLE, | Haemmorhagic stroke | 0.51 [0.35 0.75] | p=0.04 | 0 | 18201 | 1 | ARISTOTLE, | Fatal bleeding | no data | Cardiovascular death | no data | stroke (fatal and non fatal) | 0.79 [0.66 0.96] | p=0.04 | 0 | 18201 | 1 | ARISTOTLE, | Coronary event | 0.88 [0.66 1.17] | p=1.00 | 0 | 18140 | 1 | ARISTOTLE, | All cause death | 0.89 [0.81 0.98] | p=0.04 | 0 | 18201 | 1 | ARISTOTLE, | Fatal stroke | no data | Non fatal stroke | no data |
Trial | Studied treatment | Control | Patients |
---|
ARISTOTLE, 2011 | apixaban 5mg twice daily
| warfarin adjusted for an INR between 2 and 3
| subjects with atrial fibrillation and risk factors for stroke
| phase 2 apixaban, 0 | apixaban 5 or 2.5 mg twice daily | warfarin | patient with non valvular AF |
| |
Apixaban | | vs aspirin | thrombo-embolic event (cerebral or systemic) by 54% suggested ischemic stroke by 63% suggested stroke (fatal and non fatal) by 54% suggested | Endpoint | TE [95% CI] | p val | I2 | n | k | |
---|
systemic thrombo-embolic complication | no data | thrombo-embolic event (cerebral or systemic) | 0.46 [0.33 0.64] | p=0.04 | 0 | 5599 | 1 | AVERROES, | TE event or ischemic stroke or systemic embolism | no data | ischemic stroke | 0.37 [0.25 0.55] | p=0.04 | 0 | 5599 | 1 | AVERROES, | Lifethreatening major bleeding | no data | Non-lifethreatening major bleeding | no data | Gastrointestinal major bleeding | 0.85 [0.39 1.85] | p=1.00 | 0 | 5599 | 1 | AVERROES, | major or clinically relevant non-major bleeding | no data | hypertransaminasemia | no data | Major bleeding | 1.14 [0.74 1.75] | p=1.00 | 0 | 5599 | 1 | AVERROES, | Haemmorhagic stroke | 0.66 [0.24 1.86] | p=1.00 | 0 | 5599 | 1 | AVERROES, | Fatal bleeding | 0.84 [0.26 2.72] | p=1.00 | 0 | 5599 | 1 | AVERROES, | Cardiovascular death | 0.86 [0.64 1.16] | p=1.00 | 0 | 5599 | 1 | AVERROES, | stroke (fatal and non fatal) | 0.46 [0.33 0.65] | p=0.04 | 0 | 5599 | 1 | AVERROES, | Coronary event | 0.85 [0.49 1.47] | p=1.00 | 0 | 5599 | 1 | AVERROES, | All cause death | 0.79 [0.62 1.01] | p=1.00 | 0 | 5599 | 1 | AVERROES, | Fatal stroke | no data | Non fatal stroke | no data |
Trial | Studied treatment | Control | Patients |
---|
AVERROES, 2011 | apixaban 5 mg (or 2.5 mg) twice daily | aspirin 81-324 md daily | patients with atrial fibrillation who have failed or are unsuitable for vitamin K antagonist treatment |
| |
Apixaban | | vs enoxaparin | major VTE (fatal and non fatal DVT,PE) by 60% suggested Deep vein thrombosis by 68% suggested total VTE and all-cause mortality by 64% suggested asymptomatic DVT by 67% suggested proximal DVT by 65% suggested | Endpoint | TE [95% CI] | p val | I2 | n | k | |
---|
Symptomatic deep-vein thrombosis | 0.20 [0.02 1.71] | p=1.00 | 0 | 5407 | 1 | ADVANCE 3, | major VTE (fatal and non fatal DVT,PE) | 0.40 [0.17 0.94] | p=0.04 | 0 | 4394 | 1 | ADVANCE 3, | Deep vein thrombosis | 0.32 [0.20 0.52] | p=0.04 | 0 | 3855 | 1 | ADVANCE 3, | total VTE and all-cause mortality | 0.36 [0.23 0.56] | p=0.04 | 0 | 3866 | 1 | ADVANCE 3, | asymptomatic DVT | 0.33 [0.20 0.55] | p=0.04 | 0 | 5407 | 1 | ADVANCE 3, | non-fatal pulmonary embolism | 0.40 [0.08 2.06] | p=1.00 | 0 | 5407 | 1 | ADVANCE 3, | distal DVT | no data | proximal DVT | 0.35 [0.15 0.83] | p=0.04 | 0 | 4386 | 1 | ADVANCE 3, | Symptomatic venous thromboembolism (DVT, PE) | 0.40 [0.04 4.00] | p=1.00 | 0 | 5407 | 1 | ADVANCE 3, | myocardial infarction (fatal and non fatal) | 2.24 [0.69 7.29] | p=1.00 | 0 | 5407 | 1 | ADVANCE 3, | All cause death | 2.99 [0.31 28.76] | p=1.00 | 0 | 5407 | 1 | ADVANCE 3, | Major bleeding | 1.22 [0.65 2.27] | p=1.00 | 0 | 5332 | 1 | ADVANCE 3, | any bleedings | no data | Coronary event | 1.66 [0.40 6.94] | p=1.00 | 0 | 5332 | 1 | ADVANCE 3, | major or clinically relevant non-major bleeding | 0.96 [0.75 1.23] | p=1.00 | 0 | 5332 | 1 | ADVANCE 3, |
Trial | Studied treatment | Control | Patients |
---|
ADVANCE 3, 2010 | apixaban 2.5mg twice daily for 35 days | enoxaparin 40mg once daily for 35 days | patients undergoing elective total hip replacement surgery |
| |
Apixaban | | vs enoxaparin (europe regimen) | major VTE (fatal and non fatal DVT,PE) by 50% suggested Deep vein thrombosis by 40% suggested total VTE and all-cause mortality by 38% suggested proximal DVT by 65% suggested | Endpoint | TE [95% CI] | p val | I2 | n | k | |
---|
Symptomatic deep-vein thrombosis | 0.43 [0.11 1.66] | p=1.00 | 0 | 3057 | 1 | ADVANCE 2, | major VTE (fatal and non fatal DVT,PE) | 0.50 [0.26 0.98] | p=0.04 | 0 | 2394 | 1 | ADVANCE 2, | Deep vein thrombosis | 0.60 [0.48 0.75] | p=0.04 | 0 | 1968 | 1 | ADVANCE 2, | total VTE and all-cause mortality | 0.62 [0.49 0.78] | p=0.04 | 0 | 1973 | 1 | ADVANCE 2, | asymptomatic DVT | no data | non-fatal pulmonary embolism | no data | distal DVT | no data | proximal DVT | 0.35 [0.16 0.75] | p=0.04 | 0 | 2391 | 1 | ADVANCE 2, | Symptomatic venous thromboembolism (DVT, PE) | 1.00 [0.35 2.86] | p=1.00 | 0 | 3057 | 1 | ADVANCE 2, | myocardial infarction (fatal and non fatal) | 1.00 [0.06 16.01] | p=1.00 | 0 | 3057 | 1 | ADVANCE 2, | All cause death | 5.00 [0.24 104.31] | p=1.00 | 0 | 3057 | 1 | ADVANCE 2, | Major bleeding | 0.65 [0.28 1.50] | p=1.00 | 0 | 3009 | 1 | ADVANCE 2, | any bleedings | no data | Coronary event | 1.00 [0.06 16.08] | p=1.00 | 0 | 3009 | 1 | ADVANCE 2, | major or clinically relevant non-major bleeding | 0.74 [0.51 1.06] | p=1.00 | 0 | 3009 | 1 | ADVANCE 2, |
Trial | Studied treatment | Control | Patients |
---|
ADVANCE 2, 2010 | apixaban 2.5mg twice daily during 12 days | enoxaparin 40mg once daily 12 days | patients undergoing elective unilateral or bilateral total knee replacement |
| |
Apixaban | | vs enoxaparin (US regimen) | major or clinically relevant non-major bleeding by 33% suggested | Endpoint | TE [95% CI] | p val | I2 | n | k | |
---|
Symptomatic deep-vein thrombosis | 0.98 [0.06 15.90] | p=1.00 | 0 | 220 | 1 | APROPOS 2.5mg, | major VTE (fatal and non fatal DVT,PE) | 0.58 [0.25 1.33] | p=1.00 | 0 | 220 | 1 | APROPOS 2.5mg, | Deep vein thrombosis | 0.95 [0.70 1.29] | p=1.00 | 0 | 2264 | 1 | ADVANCE-1, | total VTE and all-cause mortality | 0.99 [0.74 1.31] | p=1.00 | 0 | 2507 | 2 | APROPOS 2.5mg, ADVANCE-1, | asymptomatic DVT | 0.63 [0.26 1.53] | p=1.00 | 0 | 220 | 1 | APROPOS 2.5mg, | non-fatal pulmonary embolism | no data | distal DVT | no data | proximal DVT | 0.70 [0.31 1.60] | p=1.00 | 0 | 2681 | 2 | APROPOS 2.5mg, ADVANCE-1, | Symptomatic venous thromboembolism (DVT, PE) | 1.46 [0.72 2.96] | p=1.00 | 0 | 3195 | 1 | ADVANCE-1, | myocardial infarction (fatal and non fatal) | 0.40 [0.08 2.06] | p=1.00 | 0 | 3195 | 1 | ADVANCE-1, | All cause death | 1.24 [0.30 5.19] | p=1.00 | 0 | 3415 | 2 | APROPOS 2.5mg, ADVANCE-1, | Major bleeding | 0.51 [0.25 1.04] | p=1.00 | 0 | 3487 | 2 | APROPOS 2.5mg, ADVANCE-1, | any bleedings | 0.73 [0.25 2.14] | p=1.00 | 0 | 303 | 1 | APROPOS 2.5mg, | Coronary event | 0.50 [0.05 5.50] | p=1.00 | 0 | 3183 | 1 | ADVANCE-1, | major or clinically relevant non-major bleeding | 0.67 [0.46 0.99] | p=0.04 | 0 | 3184 | 1 | ADVANCE-1, |
Trial | Studied treatment | Control | Patients |
---|
APROPOS 2.5mg, 2007 | apixaban 2.5mg BID for 12 days | enoxaparin 30mg twice daily for 12 days | patients undergoing elective total knee replacement surgery | ADVANCE-1, 2008 | apixaban 2.5 mg orally twice daily for 10 to 14 days | enoxaparin 30mg subcutaneously every 12 hours for 10-14 days | patients undergoing knee-replacement surgery |
| |
Otamixaban | acute coronary syndrome, in all type of patients | vs unfractionated heparin | all NS | Endpoint | TE [95% CI] | p val | I2 | n | k | |
---|
cardiac event (fatal and non fatal ) | no data | cardiovascular events | no data | Cardiovascular death | no data | myocardial infarction (fatal and non fatal) | no data | ischemic stroke | no data | All cause death | no data | stent thrombosis | no data | major or minor bleeding | no data | any bleedings | no data | major or clinically relevant non-major bleeding | no data | Major bleeding | no data | Fatal bleeding | no data |
Trial | Studied treatment | Control | Patients |
---|
SEPIA-ACS1 TIMI 42, 2009 | otamixaban 5 doses (0·08 mg/kg bolus followed by 0.035, 0.070, 0.105, 0.140, 0.175 mg/kg/h) | Heparin+eptifibatide | patients with non-ST-elevation
acute coronary syndromes |
| |
Rivaroxaban | acute coronary syndrome, in all type of patients | vs placebo | major or minor bleeding by 75% adverse event any bleedings by 100% adverse event major or clinically relevant non-major bleeding by 106% adverse event Major bleeding by 304% adverse event cardiovascular events by 37% suggested Cardiovascular death by 49% suggested myocardial infarction (fatal and non fatal) by 33% suggested All cause death by 48% suggested | Endpoint | TE [95% CI] | p val | I2 | n | k | |
---|
cardiac event (fatal and non fatal ) | 0.60 [0.29 1.25] | p=1.00 | 0 | 1151 | 1 | ATLAS ACS-TIMI 46 (2.5mg), | cardiovascular events | 0.63 [0.57 0.70] | p=0.04 | 0 | 22757 | 4 | ATLAS ACS 2 - TIMI 51 (2.5mg), ATLAS ACS 2 - TIMI 51 (5mg), ATLAS ACS-TIMI 46 (5mg), ATLAS ACS-TIMI 46 (2.5mg), | Cardiovascular death | 0.51 [0.43 0.61] | p=0.04 | 0 | 20455 | 2 | ATLAS ACS 2 - TIMI 51 (2.5mg), ATLAS ACS 2 - TIMI 51 (5mg), | myocardial infarction (fatal and non fatal) | 0.67 [0.59 0.77] | p=0.04 | 0 | 20455 | 2 | ATLAS ACS 2 - TIMI 51 (2.5mg), ATLAS ACS 2 - TIMI 51 (5mg), | ischemic stroke | no data | All cause death | 0.52 [0.44 0.62] | p=0.04 | 0 | 20455 | 2 | ATLAS ACS 2 - TIMI 51 (2.5mg), ATLAS ACS 2 - TIMI 51 (5mg), | stent thrombosis | no data | major or minor bleeding | 1.75 [1.50 2.03] | p=0.04 | 0 | 10240 | 1 | ATLAS ACS 2 - TIMI 51 (2.5mg), | any bleedings | 2.00 [1.80 2.22] | p=0.04 | 0 | 20475 | 2 | ATLAS ACS 2 - TIMI 51 (2.5mg), ATLAS ACS 2 - TIMI 51 (5mg), | major or clinically relevant non-major bleeding | 2.06 [1.86 2.28] | p=0.04 | 0 | 22777 | 4 | ATLAS ACS 2 - TIMI 51 (2.5mg), ATLAS ACS 2 - TIMI 51 (5mg), ATLAS ACS-TIMI 46 (5mg), ATLAS ACS-TIMI 46 (2.5mg), | Major bleeding | 4.04 [2.85 5.73] | p=0.04 | 0 | 24134 | 4 | ATLAS ACS 2 - TIMI 51 (2.5mg), ATLAS ACS 2 - TIMI 51 (5mg), ATLAS ACS-TIMI 46 (5mg), ATLAS ACS-TIMI 46 (2.5mg), | Fatal bleeding | 1.17 [0.61 2.23] | p=1.00 | 0 | 20475 | 2 | ATLAS ACS 2 - TIMI 51 (2.5mg), ATLAS ACS 2 - TIMI 51 (5mg), |
Trial | Studied treatment | Control | Patients |
---|
ATLAS ACS 2 - TIMI 51 (2.5mg), 2011 | rivaroxaban 2.5 mg twice daily in addition to standard care | placebo | patients with a recent ACS | ATLAS ACS 2 - TIMI 51 (5mg), 2011 | rivaroxaban 5 mg twice daily in addition to standard care
| placebo
| patients with a recent ACS
| ATLAS ACS-TIMI 46 (5mg), 2009 | rivaroxaban 5 mg twice daily
| placebo
| recent ACS patients treated with aspirin alone (n=761) or aspirin plus clopidogrel (n=2730)
| ATLAS ACS-TIMI 46 (2.5mg), 2009 | rivaroxaban 2.5 mg twice daily
| placebo
| recent ACS patients treated with aspirin alone (n=761) or aspirin plus clopidogrel (n=2730)
|
| |
Rivaroxaban | atrial fibrillation, in all type of patients | vs warfarin standard dose | Gastrointestinal major bleeding by 46% adverse event Lifethreatening major bleeding by 31% suggested Haemmorhagic stroke by 42% suggested Fatal bleeding by 50% suggested | Endpoint | TE [95% CI] | p val | I2 | n | k | |
---|
systemic thrombo-embolic complication | 0.74 [0.42 1.31] | p=1.00 | 0 | 14264 | 1 | ROCKET-AF, | thrombo-embolic event (cerebral or systemic) | 0.88 [0.75 1.04] | p=1.00 | 0 | 14171 | 1 | ROCKET-AF, | TE event or ischemic stroke or systemic embolism | no data | ischemic stroke | 0.99 [0.82 1.20] | p=1.00 | 0 | 14143 | 1 | ROCKET-AF, | Lifethreatening major bleeding | 0.69 [0.52 0.90] | p=0.04 | 0 | 14236 | 1 | ROCKET-AF, | Non-lifethreatening major bleeding | no data | Gastrointestinal major bleeding | 1.46 [1.18 1.79] | p=0.04 | 0 | 14236 | 1 | ROCKET-AF, | major or clinically relevant non-major bleeding | 1.03 [0.96 1.11] | p=1.00 | 0 | 14236 | 1 | ROCKET-AF, | hypertransaminasemia | no data | Major bleeding | 1.04 [0.90 1.20] | p=1.00 | 0 | 14236 | 1 | ROCKET-AF, | Haemmorhagic stroke | 0.58 [0.38 0.89] | p=0.04 | 0 | 14143 | 1 | ROCKET-AF, | Fatal bleeding | 0.50 [0.31 0.80] | p=0.04 | 0 | 14236 | 1 | ROCKET-AF, | Cardiovascular death | 0.94 [0.81 1.09] | p=1.00 | 0 | 14143 | 1 | ROCKET-AF, | stroke (fatal and non fatal) | 0.84 [0.68 1.02] | p=1.00 | 0 | 14143 | 1 | ROCKET-AF, | Coronary event | 0.80 [0.62 1.05] | p=1.00 | 0 | 14236 | 1 | ROCKET-AF, | All cause death | 0.92 [0.82 1.03] | p=1.00 | 0 | 14143 | 1 | ROCKET-AF, | Fatal stroke | 0.70 [0.48 1.02] | p=1.00 | 0 | 14143 | 1 | ROCKET-AF, | Non fatal stroke | no data |
Trial | Studied treatment | Control | Patients |
---|
ROCKET-AF, 2010 | Rivaroxaban 20mg p.o. once daily | Warfarin p.o. once daily titrated to a target INR of 2.5 (range 2.0 to 3.0, inclusive) | Subjects With Non-Valvular Atrial Fibrillation |
| |
Rivaroxaban | cardiovascular prevention, in secondary prevention | vs aspirin | Cardiovascular death by 7700% suggested stroke (fatal and non fatal) by 5700% suggested ischemic stroke by 5000% suggested All cause death by 8100% suggested Fatal stroke by 7700% suggested | Endpoint | TE [95% CI] | p val | I2 | n | k | |
---|
Cardiovascular death | 78.00 [63.69 95.53] | p=0.04 | 0 | 18278 | 1 | COMPASS (rivaroxaban + aspirin), | stroke (fatal and non fatal) | 58.00 [44.13 76.23] | p=0.04 | 0 | 18278 | 1 | COMPASS (rivaroxaban + aspirin), | Coronary event | no data | ischemic stroke | 51.00 [38.12 68.22] | p=0.04 | 0 | 18278 | 1 | COMPASS (rivaroxaban + aspirin), | Coronary death | no data | Non fatal MI | no data | All cause death | 82.00 [70.52 95.35] | p=0.04 | 0 | 18278 | 1 | COMPASS (rivaroxaban + aspirin), | Fatal stroke | 78.00 [63.69 95.53] | p=0.04 | 0 | 18278 | 1 | COMPASS (rivaroxaban + aspirin), | Haemmorhagic stroke | no data |
Trial | Studied treatment | Control | Patients |
---|
COMPASS (rivaroxaban alone), 2017 | Rivaroxaban 2.5 mg twice daily alone | aspirin 100 mg once daily | Patients With Coronary or Peripheral Artery Disease | COMPASS (rivaroxaban + aspirin), 2017 | rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily) | aspirin 100 mg once daily
| Patients With Coronary or Peripheral Artery Disease
|
| |
Rivaroxaban | thrombosis prevention, in all type of patients | vs enoxaparin | major VTE (fatal and non fatal DVT,PE) by 88% suggested Deep vein thrombosis by 77% suggested total VTE and all-cause mortality by 70% suggested proximal DVT by 97% suggested | Endpoint | TE [95% CI] | p val | I2 | n | k | |
---|
Symptomatic deep-vein thrombosis | no data | major VTE (fatal and non fatal DVT,PE) | 0.12 [0.04 0.34] | p=0.04 | 0 | 3364 | 1 | RECORD 1, | Deep vein thrombosis | 0.23 [0.12 0.43] | p=0.04 | 0 | 4433 | 1 | RECORD 1, | total VTE and all-cause mortality | 0.30 [0.18 0.52] | p=0.04 | 0 | 3153 | 1 | RECORD 1, | asymptomatic DVT | no data | non-fatal pulmonary embolism | 3.91 [0.44 35.00] | p=1.00 | 0 | 3153 | 1 | RECORD 1, | distal DVT | 0.49 [0.24 1.01] | p=1.00 | 0 | 3153 | 1 | RECORD 1, | proximal DVT | 0.03 [0.00 0.23] | p=0.04 | 0 | 3153 | 1 | RECORD 1, | Symptomatic venous thromboembolism (DVT, PE) | 0.55 [0.20 1.49] | p=1.00 | 0 | 4399 | 1 | RECORD 1, | myocardial infarction (fatal and non fatal) | no data | All cause death | 0.98 [0.24 3.91] | p=1.00 | 0 | 3153 | 1 | RECORD 1, | Major bleeding | 3.02 [0.61 14.98] | p=1.00 | 0 | 4433 | 1 | RECORD 1, | any bleedings | no data | Coronary event | 0.49 [0.12 1.96] | p=1.00 | 0 | 3153 | 1 | RECORD 1, | major or clinically relevant non-major bleeding | no data |
Trial | Studied treatment | Control | Patients |
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RECORD 1, 2008 | rivaroxaban 10mg once daily for 35 days | enoxaparin 40mg subcutaneous once daily for 31-39 days | patients undergoing total hip arthroplasty |
| |
Rivaroxaban | | vs enoxaparin (europe regimen) | major VTE (fatal and non fatal DVT,PE) by 62% suggested Deep vein thrombosis by 47% suggested total VTE and all-cause mortality by 49% suggested distal DVT by 47% suggested Symptomatic venous thromboembolism (DVT, PE) by 66% suggested | Endpoint | TE [95% CI] | p val | I2 | n | k | |
---|
Symptomatic deep-vein thrombosis | no data | major VTE (fatal and non fatal DVT,PE) | 0.38 [0.18 0.83] | p=0.04 | 0 | 1833 | 1 | RECORD 3, | Deep vein thrombosis | 0.53 [0.39 0.70] | p=0.04 | 0 | 1702 | 1 | RECORD 3, | total VTE and all-cause mortality | 0.51 [0.38 0.68] | p=0.04 | 0 | 1702 | 1 | RECORD 3, | asymptomatic DVT | no data | non-fatal pulmonary embolism | 0.21 [0.01 4.45] | p=1.00 | 0 | 1702 | 1 | RECORD 3, | distal DVT | 0.53 [0.39 0.72] | p=0.04 | 0 | 1702 | 1 | RECORD 3, | proximal DVT | 0.48 [0.22 1.06] | p=1.00 | 0 | 1702 | 1 | RECORD 3, | Symptomatic venous thromboembolism (DVT, PE) | 0.34 [0.15 0.75] | p=0.04 | 0 | 2418 | 1 | RECORD 3, | myocardial infarction (fatal and non fatal) | 0.51 [0.05 5.62] | p=1.00 | 0 | 2531 | 1 | RECORD 3, | All cause death | 0.08 [0.00 1.39] | p=1.00 | 0 | 2418 | 1 | RECORD 3, | Major bleeding | 1.19 [0.40 3.55] | p=1.00 | 0 | 2531 | 1 | RECORD 3, | any bleedings | no data | Coronary event | 0.51 [0.05 5.61] | p=1.00 | 0 | 2459 | 1 | RECORD 3, | major or clinically relevant non-major bleeding | no data |
Trial | Studied treatment | Control | Patients |
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RECORD 3, 2008 | rivaroxaban 10 mg once daily for 10- 14 days | enoxaparin 40 mg subcutaneous once daily for 10-14 days | patients undergoing total knee arthroplasty |
| |
Rivaroxaban | | vs enoxaparin (short duration) | major VTE (fatal and non fatal DVT,PE) by 88% suggested Deep vein thrombosis by 74% suggested total VTE and all-cause mortality by 73% suggested distal DVT by 66% suggested proximal DVT by 81% suggested Symptomatic venous thromboembolism (DVT, PE) by 80% suggested | Endpoint | TE [95% CI] | p val | I2 | n | k | |
---|
Symptomatic deep-vein thrombosis | no data | major VTE (fatal and non fatal DVT,PE) | 0.12 [0.05 0.29] | p=0.04 | 0 | 1923 | 1 | RECORD 2, | Deep vein thrombosis | 0.26 [0.17 0.42] | p=0.04 | 0 | 1953 | 2 | ODIXa-HIP 10mg, RECORD 2, | total VTE and all-cause mortality | 0.27 [0.17 0.41] | p=0.04 | 0 | 1953 | 2 | ODIXa-HIP 10mg, RECORD 2, | asymptomatic DVT | no data | non-fatal pulmonary embolism | 0.34 [0.05 2.34] | p=1.00 | 0 | 1953 | 2 | ODIXa-HIP 10mg, RECORD 2, | distal DVT | 0.34 [0.20 0.60] | p=0.04 | 0 | 1953 | 2 | ODIXa-HIP 10mg, RECORD 2, | proximal DVT | 0.19 [0.09 0.43] | p=0.04 | 0 | 1953 | 2 | ODIXa-HIP 10mg, RECORD 2, | Symptomatic venous thromboembolism (DVT, PE) | 0.20 [0.06 0.69] | p=0.04 | 0 | 2419 | 1 | RECORD 2, | myocardial infarction (fatal and non fatal) | no data | All cause death | 0.34 [0.07 1.67] | p=1.00 | 0 | 1733 | 1 | RECORD 2, | Major bleeding | 1.00 [0.06 16.02] | p=1.00 | 0 | 2457 | 1 | RECORD 2, | any bleedings | no data | Coronary event | 1.33 [0.30 5.97] | p=1.00 | 0 | 2457 | 1 | RECORD 2, | major or clinically relevant non-major bleeding | 1.20 [0.91 1.58] | p=1.00 | 0 | 2457 | 1 | RECORD 2, |
Trial | Studied treatment | Control | Patients |
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ODIXa-HIP 10mg, 2006 | rivaroxaban 10mg daily for 5–9 days | once-daily subcutaneous enoxaparin dose of 40 mg for 5–9 days | patients undergoing elective total hip replacement | RECORD 2, 2008 | extended thromboprophylaxis with rivaroxaban 10mg once daily for 31-39 days | enoxaparin 40mg subcutaneous once daily for 10-14 days | patients undergoing elective total hip replacement |
| |
Rivaroxaban | | vs enoxaparin (US regimen) | total VTE and all-cause mortality by 31% suggested proximal DVT by 77% suggested | Endpoint | TE [95% CI] | p val | I2 | n | k | |
---|
Symptomatic deep-vein thrombosis | 0.60 [0.22 1.65] | p=1.00 | 0 | 1924 | 1 | RECORD 4, | major VTE (fatal and non fatal DVT,PE) | 0.59 [0.29 1.17] | p=1.00 | 0 | 2234 | 1 | RECORD 4, | Deep vein thrombosis | no data | total VTE and all-cause mortality | 0.69 [0.50 0.95] | p=0.04 | 0 | 1924 | 1 | RECORD 4, | asymptomatic DVT | 0.72 [0.50 1.03] | p=1.00 | 0 | 1924 | 1 | RECORD 4, | non-fatal pulmonary embolism | 0.49 [0.15 1.64] | p=1.00 | 0 | 3034 | 1 | RECORD 4, | distal DVT | 0.82 [0.56 1.20] | p=1.00 | 0 | 1924 | 1 | RECORD 4, | proximal DVT | 0.23 [0.07 0.81] | p=0.04 | 0 | 1924 | 1 | RECORD 4, | Symptomatic venous thromboembolism (DVT, PE) | 0.60 [0.28 1.28] | p=1.00 | 0 | 3034 | 1 | RECORD 4, | myocardial infarction (fatal and non fatal) | 0.20 [0.02 1.69] | p=1.00 | 0 | 3148 | 1 | RECORD 4, | All cause death | 0.66 [0.11 3.95] | p=1.00 | 0 | 3034 | 1 | RECORD 4, | Major bleeding | 1.80 [0.61 5.33] | p=1.00 | 0 | 3240 | 2 | ODIXa-KNEE, RECORD 4, | any bleedings | no data | Coronary event | 0.33 [0.03 3.17] | p=1.00 | 0 | 3034 | 1 | RECORD 4, | major or clinically relevant non-major bleeding | 1.34 [0.85 2.09] | p=1.00 | 0 | 3034 | 1 | RECORD 4, |
Trial | Studied treatment | Control | Patients |
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ODIXa-KNEE, 2005 | BAY 59-7939 5mg b.i.d. for 5–9 days | enoxaparin 30 mg b.i.d. for 5–9 days | patients undergoing elective total knee replacement | RECORD 4, 2009 | rivaroxaban 10mg once daily for 10 to 14 days | enoxaparin 30 mg twice daily by subcutaneous injection for 10-14 days | patients who had undergone total-knee-replacement surgery |
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Ximelagatran | acute coronary syndrome, in all type of patients | vs placebo | all NS | Endpoint | TE [95% CI] | p val | I2 | n | k | |
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cardiac event (fatal and non fatal ) | no data | cardiovascular events | no data | Cardiovascular death | no data | myocardial infarction (fatal and non fatal) | no data | ischemic stroke | no data | All cause death | no data | stent thrombosis | no data | major or minor bleeding | no data | any bleedings | no data | major or clinically relevant non-major bleeding | no data | Major bleeding | no data | Fatal bleeding | no data |
Trial | Studied treatment | Control | Patients |
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ESTEEM, 2003 | oral ximelagatran at doses of
24 mg, 36 mg, 48 mg, or 60 mg twice daily | placebo | patients who had had recent ST-elevation or non-STelevation
myocardial infarction |
| |
Ximelagatran | venous thrombosis, in all type of patients | vs discontinuation | VTE by 76% suggested | Endpoint | TE [95% CI] | p val | I2 | n | k | |
---|
recurrent DVT | no data | VTE | 0.24 [0.14 0.41] | p=0.04 | 0 | 1223 | 1 | THRIVE III, | fatal pulmonary embolism | no data | non-fatal pulmonary embolism | no data | Major bleeding | 1.20 [0.36 3.95] | p=1.00 | 0 | 1223 | 1 | THRIVE III, | any bleedings | 1.21 [0.91 1.60] | p=1.00 | 0 | 1223 | 1 | THRIVE III, | Fatal bleeding | no data | All cause death | 0.86 [0.29 2.56] | p=1.00 | 0 | 1223 | 1 | THRIVE III, |
Trial | Studied treatment | Control | Patients |
---|
THRIVE III, 2003 | ximelagatran 24 mg twice daily for 18 months | placebo for 18 months | patients with venous thromboembolism who had undergone six months of anticoagulant therapy |
| |