| pathology | treatment | patient | Demonstrated benefit and harm | k | | | |
|---|
| acute coronary syndrome | apixaban | not classified | versus placebo or control No demonstrated result for efficacy apixaban inferior to placebo in terms of ISTH major or clinically relevant nonmajor bleeding in APPRAISE-1 (10mg od), 2009 apixaban inferior to placebo in terms of TIMI major or minor bleeding not related to CABG in APPRAISE 2, 2011 apixaban inferior to placebo in terms of major bleeding in APPRAISE 2, 2011 apixaban inferior to placebo in terms of ISTH major or clinically relevant nonmajor bleeding in APPRAISE 2, 2011 apixaban inferior to placebo in terms of any bleeding in APPRAISE 2, 2011 apixaban inferior to placebo in terms of major or minor bleeding in APPRAISE 2, 2011 | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| APPRAISE-1 (10mg od), 2009 | apixaban vs placebo | | ISTH major or clinically relevant nonmajor bleeding 2.45 [1.32; 4.55] | Cardiovascular death, MI, or stroke
0.61 [0.35; 1.06] | | APPRAISE-1 (2.5 mg bid), 2009 | apixaban vs placebo | | | Cardiovascular death, MI, or stroke
0.73 [0.45; 1.18] ISTH major or clinically relevant nonmajor bleeding 1.78 [0.93; 3.41] | | APPRAISE 2, 2011 | apixaban vs placebo | | TIMI major or minor bleeding not related to CABG 2.74 [1.79; 4.17] major bleeding 2.53 [1.47; 4.36] ISTH major or clinically relevant nonmajor bleeding 2.58 [1.83; 3.62] any bleeding 2.21 [1.94; 2.51] major or minor bleeding 2.74 [1.79; 4.17] | net clinical benefit 0.98 [0.84; 1.15] death 1.08 [0.86; 1.35] cardiovascular death 0.96 [0.74; 1.25] fatal bleeding ∞ [NaN; ∞] ischemic stroke 0.67 [0.40; 1.14] MI 0.93 [0.77; 1.14] Cardiovascular death, MI, or stroke
0.99 [0.86; 1.15] death, MI, stroke, recurrent ischaemia 0.95 [0.82; 1.09] Thrombotic complication during PCI 0.73 [0.47; 1.12] |
| Trial | Treatments | Patients | Method |
|---|
| APPRAISE-1 (10mg od), 2009 | apixaban 10 mg once daily (n=318) vs. placebo (n=611) 4 arms: 20mg daily, 10mg twice daily, 10mg daily and 2.5mg twice daily. 10mg twice daily and 20mg once daily were discontinued due to an excess of major and minor bleeding | patients with a recent ST-elevation or non–ST-elevation
acute coronary syndrome(<7 days) | double blind Parallel groups Sample size: 318/611 Primary endpoint: major or clinically relevant nonmajor bleeding FU duration: 6 months dose-finding study | | APPRAISE-1 (2.5 mg bid), 2009 | Apixaban 2.5mg twice daily
(n=-9) vs. placebo
(n=611) 4 arms: 20mg daily, 10mg twice daily, 10mg daily and 2.5mg twice daily. 10mg twice daily and 20mg once daily were discontinued due to an excess of major and minor bleeding
| patients with a recent ST-elevation or non–ST-elevation
acute coronary syndrome(<7 days)
| double blind Sample size: -9/611 Primary endpoint: major or clinically relevant nonmajor bleeding FU duration: 6 months dose-finding study
| | APPRAISE 2, 2011 | apixaban 5mg twice daily (n=3705) vs. placebo (n=3687) | patients with a recent acute coronary syndrome and at least two
additional risk factors for recurrent ischemic events | double blind Parallel groups Sample size: 3705/3687 Primary endpoint: Cv death, MI, ischemic stroke FU duration: 8 months |
|
| acute coronary syndrome | coumadin | not classified | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ASPECT-2 (coumadin+asp vs asp), 2002 | coumadin vs control (on top of aspirin) | all cause death, non-fatal MI, thrombo-embolic stroke 0.56 [0.33; 0.97] | | major bleeding 2.35 [0.61; 9.03] intracranial major bleeding ∞ [NaN; ∞] extracranial major bleeding 2.02 [0.51; 8.00] |
| Trial | Treatments | Patients | Method |
|---|
| ASPECT-2 (coumadin+asp vs asp), 2002 | coumadin(INR mean 2.4) +aspirin (n=333) vs. aspirin (n=336) | UA, AMI | open Sample size: 333/336 Primary endpoint: death, MI or stroke FU duration: 1 year |
|
| acute coronary syndrome | coumadin | not classified | versus antiplatelet drugs No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ASPECT-2 (coumadin vs aspirin), 2002 | coumadin vs aspirin | all cause death 0.28 [0.09; 0.82] | | vascular death 0.34 [0.11; 1.06] MI 0.96 [0.46; 2.01] Revascularization 0.90 [0.58; 1.39] minor bleeding 1.68 [0.92; 3.07] cardiovascular events 0.57 [0.32; 1.00] major bleeding 1.03 [0.21; 5.09] intracranial major bleeding NaN [NaN; NaN] all cause death, non-fatal MI, thrombo-embolic stroke 0.57 [0.32; 1.00] |
| Trial | Treatments | Patients | Method |
|---|
| ASPECT-2 (coumadin vs aspirin), 2002 | coumadin (phenprocoumon or acenocoumarol) target INR 3-4)
(n=325) vs. aspirin 80mg daily
(n=336)
| UA, AMI
| open Parallel groups Sample size: 325/336 Primary endpoint: death, MI or stroke FU duration: 1 year (range 0-26 months)
|
|
| acute coronary syndrome | dabigatran | not classified | versus placebo and control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| REDEEM, 2009 | dabigatran vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| REDEEM, 2009 | dabigatran 4 dosages (50mg twice daily, 75mg twice daily, 110mg twice daily, 150mg twice daily) (n=1501) vs. placebo (n=373) 5 arms: dabigatran 50 mg twice daily (n=372), 75 mg twice daily (n=371), 110 mg twice daily (n=411), 150 mg twice daily (n=351), or placebo (n=373) | patients with recent acute coronary syndromes (ST- or non-ST-elevation myocardical infarction) | double blind Parallel groups Sample size: 1501/373 Primary endpoint: Major and minor bleeding FU duration: 6 months |
|
| acute coronary syndrome | otamixaban | not classified | versus UFH No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| SEPIA-ACS1 TIMI 42, 2009 | otamixaban vs unfractionated heparin | death, MI, recurrent ischaemia, use of Gp2b3a inhibitor 0.58 [0.34; 0.99] | | death, MI 0.56 [0.30; 1.04] TIMI major or minor bleeding not related to CABG 1.26 [0.63; 2.52] Thrombotic complication during PCI 1.44 [0.59; 3.52] |
| Trial | Treatments | Patients | Method |
|---|
| 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) (n=2792) vs. Heparin+eptifibatide (n=449) 6 arms phase 2: otamixaban 5 doses (0·08 mg/kg bolus followed by 0.035, 0.070, 0.105, 0.140, 0.175 mg/kg/h) and unfractionated heparin + eptifi batide | patients with non-ST-elevation
acute coronary syndromes | double blind Parallel groups Sample size: 2792/449 Primary endpoint: death, MI, recurrent ischaemia, use of Gp2b3a FU duration: 7 days dose finding study |
|
| acute coronary syndrome | rivaroxaban | not classified | versus placebo or control No demonstrated result for efficacy rivaroxaban 2.5mg inferior to placebo in terms of major bleeding in ATLAS ACS 2 - TIMI 51 (2.5mg), 2011 rivaroxaban 2.5mg inferior to placebo in terms of ISTH major or clinically relevant nonmajor bleeding in ATLAS ACS 2 - TIMI 51 (2.5mg), 2011 rivaroxaban 2.5mg inferior to placebo in terms of any bleeding in ATLAS ACS 2 - TIMI 51 (2.5mg), 2011 rivaroxaban 2.5mg inferior to placebo in terms of major or minor bleeding in ATLAS ACS 2 - TIMI 51 (2.5mg), 2011 rivaroxaban 5mg inferior to placebo in terms of major bleeding in ATLAS ACS 2 - TIMI 51 (5mg), 2011 rivaroxaban 5mg inferior to placebo in terms of ISTH major or clinically relevant nonmajor bleeding in ATLAS ACS 2 - TIMI 51 (5mg), 2011 rivaroxaban 5mg inferior to placebo in terms of any bleeding in ATLAS ACS 2 - TIMI 51 (5mg), 2011 rivaroxaban 5mg inferior to placebo in terms of major bleeding in ATLAS ACS-TIMI 46 (5mg), 2009 rivaroxaban 5mg inferior to placebo in terms of ISTH major or clinically relevant nonmajor bleeding in ATLAS ACS-TIMI 46 (5mg), 2009 | 4 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ATLAS ACS 2 - TIMI 51 (2.5mg), 2011 | rivaroxaban 2.5mg vs placebo | death 0.67 [0.53; 0.86] cardiovascular death 0.66 [0.51; 0.85] Cardiovascular death, MI, or stroke
0.83 [0.72; 0.96] | major bleeding 3.43 [2.06; 5.71] ISTH major or clinically relevant nonmajor bleeding 1.75 [1.52; 2.01] any bleeding 1.75 [1.52; 2.01] major or minor bleeding 1.75 [1.52; 2.01] | fatal bleeding 0.67 [0.24; 1.88] MI 0.90 [0.74; 1.08] | | ATLAS ACS 2 - TIMI 51 (5mg), 2011 | rivaroxaban 5mg vs placebo | death 0.42 [0.33; 0.53] cardiovascular death 0.42 [0.33; 0.53] MI 0.53 [0.45; 0.63] Cardiovascular death, MI, or stroke
0.50 [0.44; 0.57] | major bleeding 4.33 [2.63; 7.12] ISTH major or clinically relevant nonmajor bleeding 2.27 [1.98; 2.59] any bleeding 2.27 [1.98; 2.59] | fatal bleeding 1.67 [0.73; 3.82] | | ATLAS ACS-TIMI 46 (5mg), 2009 | rivaroxaban 5mg vs placebo | | major bleeding 17.64 [2.34; 132.76] ISTH major or clinically relevant nonmajor bleeding 3.36 [2.21; 5.10] | Cardiovascular death, MI, or stroke
0.63 [0.39; 1.01] | | ATLAS ACS-TIMI 46 (2.5mg), 2009 | rivaroxaban 2.5mg vs placebo | | | major bleeding 3.76 [0.24; 59.88] Cardiovascular death, MI, or stroke
0.52 [0.23; 1.19] death, MI, stroke, recurrent ischaemia 0.60 [0.29; 1.25] ISTH major or clinically relevant nonmajor bleeding 1.71 [0.76; 3.85] |
| Trial | Treatments | Patients | Method |
|---|
| ATLAS ACS 2 - TIMI 51 (2.5mg), 2011 | rivaroxaban 2.5 mg twice daily in addition to standard care (n=5174) vs. placebo (n=5176) 3 arms: rivaroxaban (2.5 mg twice daily or 5 mg twice daily) in addition to standard care and placebo | patients with a recent ACS | double blind Parallel groups Sample size: 5174/5176 Primary endpoint: CV death, MI, stroke FU duration: 13 months | | ATLAS ACS 2 - TIMI 51 (5mg), 2011 | rivaroxaban 5 mg twice daily in addition to standard care
(n=5176) vs. placebo
(n=5176) 3 arms: rivaroxaban (2.5 mg twice daily or 5 mg twice daily) in addition to standard care and placebo
| patients with a recent ACS
| double blind Sample size: 5176/5176 Primary endpoint: CV death, MI, stroke FU duration: 13 months
| | ATLAS ACS-TIMI 46 (5mg), 2009 | rivaroxaban 5 mg twice daily
(n=519) vs. placebo
(n=1160) dose finding study: rivaroxaban 5 mg, 10 mg, or 20 mg once daily, 2.5 mg, 5 mg, or 10 mg twice daily and placebo
| recent ACS patients treated with aspirin alone (n=761) or aspirin plus clopidogrel (n=2730)
| double blind Parallel groups Sample size: 519/1160 Primary endpoint: clinically significant bleeding FU duration: 6 months dose-finding study
| | ATLAS ACS-TIMI 46 (2.5mg), 2009 | rivaroxaban 2.5 mg twice daily
(n=152) vs. placebo
(n=1160) dose finding study: rivaroxaban 5 mg, 10 mg, or 20 mg once daily, 2.5 mg, 5 mg, or 10 mg twice daily and placebo
| recent ACS patients treated with aspirin alone (n=761) or aspirin plus clopidogrel (n=2730)
| double blind Sample size: 152/1160 Primary endpoint: clinically significant bleeding FU duration: 6 months dose-finding study
|
|
| acute coronary syndrome | warfarin | not classified | versus placebo or control No demonstrated result for efficacy warfarin inferior to control (on top of aspirin) in terms of major bleeding in OASIS-2 Warfarin Substudy, 2001 warfarin inferior to control (on top of aspirin) in terms of major bleeding in CHAMP, 2002 warfarin inferior to control (on top of aspirin) in terms of extracranial major bleeding in CHAMP, 2002 warfarin inferior to control (on top of aspirin) in terms of major bleeding in WARIS, 2002 warfarin inferior to control (on top of aspirin) in terms of extracranial major bleeding in WARIS, 2002 warfarin inferior to control (on top of aspirin) in terms of major bleeding in LoWASA, 2004 warfarin inferior to control (on top of aspirin) in terms of extracranial major bleeding in LoWASA, 2004 | 14 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ATACS (pilot study) (warfarin vs control), 1990 | warfarin vs control (on top of aspirin) | | | all cause death NaN [NaN; NaN] MI 0.00 [0.00; NaN] Revascularization 1.59 [0.94; 2.67] minor bleeding 0.86 [0.06; 13.28] major bleeding 0.86 [0.19; 3.99] intracranial major bleeding NaN [NaN; NaN] extracranial major bleeding 0.86 [0.19; 3.99] all cause death, non-fatal MI, thrombo-embolic stroke 0.00 [0.00; NaN] | | ATACS, 1994 | warfarin vs control (on top of aspirin) | | | major bleeding ∞ [NaN; ∞] all cause death, non-fatal MI, thrombo-embolic stroke 0.75 [0.32; 1.80] | | Williams, 1997 | warfarin vs placebo (on top of aspirin) | | | major bleeding ∞ [NaN; ∞] intracranial major bleeding NaN [NaN; NaN] extracranial major bleeding ∞ [NaN; ∞] all cause death, non-fatal MI, thrombo-embolic stroke 0.16 [0.02; 1.25] | | CARS, 1997 | warfarin vs control (on top of aspirin) | | | major bleeding 1.29 [0.94; 1.76] all cause death, non-fatal MI, thrombo-embolic stroke 1.12 [0.99; 1.27] | | OASIS Pilot (phase 1), 1998 | warfarin vs control (on top of aspirin) | | | major bleeding ∞ [NaN; ∞] intracranial major bleeding NaN [NaN; NaN] extracranial major bleeding 2.98 [0.31; 28.34] all cause death, non-fatal MI, thrombo-embolic stroke 2.48 [0.80; 7.75] | | OASIS Pilot (phase 2), 1998 | warfarin vs control (on top of aspirin) | | | major bleeding 2.02 [0.19; 21.92] intracranial major bleeding ∞ [NaN; ∞] extracranial major bleeding 1.01 [0.06; 15.93] all cause death, non-fatal MI, thrombo-embolic stroke 0.39 [0.14; 1.05] | | Huyhn, 2001 | warfarin vs placebo (on top of aspirin) | | | major bleeding ∞ [NaN; ∞] all cause death, non-fatal MI, thrombo-embolic stroke 2.09 [0.20; 22.25] | | OASIS-2 Warfarin Substudy, 2001 | warfarin vs control (on top of aspirin) | | major bleeding 1.98 [1.23; 3.19] | all cause death, non-fatal MI, thrombo-embolic stroke 0.91 [0.73; 1.13] | | APRICOT-2, 2002 | warfarin vs control (on top of aspirin) | | | major bleeding 1.03 [0.15; 7.21] intracranial major bleeding NaN [NaN; NaN] extracranial major bleeding 1.03 [0.15; 7.21] all cause death, non-fatal MI, thrombo-embolic stroke 0.37 [0.12; 1.15] | | CHAMP, 2002 | warfarin vs control (on top of aspirin) | | major bleeding 1.75 [1.24; 2.47] extracranial major bleeding 2.10 [1.41; 3.13] | intracranial major bleeding 0.94 [0.45; 1.94] all cause death, non-fatal MI, thrombo-embolic stroke 1.01 [0.94; 1.10] | | WARIS, 2002 | warfarin vs control (on top of aspirin) | all cause death, non-fatal MI, thrombo-embolic stroke 0.75 [0.63; 0.89] | major bleeding 3.49 [1.60; 7.64] extracranial major bleeding 3.57 [1.55; 8.21] | intracranial major bleeding 3.00 [0.31; 28.75] | | LoWASA, 2004 | warfarin vs control (on top of aspirin) | | major bleeding 2.04 [1.13; 3.69] extracranial major bleeding 2.07 [1.01; 4.23] | intracranial major bleeding 1.98 [0.68; 5.78] all cause death, non-fatal MI, thrombo-embolic stroke 0.97 [0.87; 1.09] | | Zibaeenezhad, 2004 | warfarin vs control (on top of aspirin) | | | major bleeding 2.50 [0.50; 12.46] intracranial major bleeding NaN [NaN; NaN] extracranial major bleeding 2.50 [0.50; 12.46] all cause death, non-fatal MI, thrombo-embolic stroke 0.50 [0.20; 1.26] | | ATACS (pilot study) warfarin vs aspirin, 1990 | warfarin vs aspirin | | | all cause death ∞ [NaN; ∞] MI ∞ [NaN; ∞] Revascularization 1.33 [0.73; 2.43] minor bleeding 0.00 [0.00; NaN] major bleeding NaN [NaN; NaN] |
| Trial | Treatments | Patients | Method |
|---|
| ATACS (pilot study) (warfarin vs control), 1990 | heparin/warfarin target INR 3-4.5 + aspirin (n=37) vs. aspirin alone (n=32) | UA, NSTEMI | open Sample size: 37/32 Primary endpoint: FU duration: 3 months | | ATACS, 1994 | heparin/warfarin (INR median 2.3) + aspirin (n=105) vs. aspirin (n=109) | UA, NSTEMI | open Sample size: 105/109 Primary endpoint: FU duration: 3 months | | Williams, 1997 | warfarin target INR 2–2.5 +aspirin (n=29) vs. placebo +aspirin (n=28) | UA, AMI | double blind Sample size: 29/28 Primary endpoint: quantitative angiography FU duration: 2.5 months | | CARS, 1997 | warfarin (INR mean 1.5) (3 mg warfarin or 1 mg warfarin with 80 mg aspirin) (n=5410) vs. aspirin 160 mg/d (n=3393) | AMI | Sample size: 5410/3393 Primary endpoint: FU duration: 14 months | | OASIS Pilot (phase 1), 1998 | warfarin 3mg/d for 6 months (INR mean 1.5) (n=155) vs. control (n=154) | UA, NSTEMI | open Sample size: 155/154 Primary endpoint: FU duration: 6 months | | OASIS Pilot (phase 2), 1998 | warfarin adjusted dose (INR mean 2.3) for 3 months (n=98) vs. standard treatment (n=99) | UA, NSTEMI | open Sample size: 98/99 Primary endpoint: FU duration: 3 months | | Huyhn, 2001 | warfarin adjusted dose for INR 2–2.5 +aspirin (n=44) vs. placebo +aspirin (n=46) | UA, NSTEMI with prior CABG | double blind Sample size: 44/46 Primary endpoint: FU duration: 1 year | | OASIS-2 Warfarin Substudy, 2001 | warfarin target INR 2–2.5 for 5 months +aspirin (n=1848) vs. control (n=1864) | UA | open Sample size: 1848/1864 Primary endpoint: FU duration: 5 months | | APRICOT-2, 2002 | moderate-intensity coumarin target INR 2-3 (+aspirin) (n=135) vs. aspirin (n=139) | STEMI | Sample size: 135/139 Primary endpoint: FU duration: 3 months | | CHAMP, 2002 | warfarin (INR median 1.8) (n=2522) vs. (n=2537) | AMI | Sample size: 2522/2537 Primary endpoint: FU duration: 2.7 years | | WARIS, 2002 | warfarin (INR 2.2 (mean) (n=1208) vs. (n=1206) | AMI | Sample size: 1208/1206 Primary endpoint: FU duration: 4 years | | LoWASA, 2004 | warfarin (prothrombin complex activity mean 95.5) (n=1659) vs. (n=1641) | AMI | Sample size: 1659/1641 Primary endpoint: FU duration: 5 years | | Zibaeenezhad, 2004 | Warfarin target INR 2–3 (n=70) vs. (n=70) | AMI | Sample size: 70/70 Primary endpoint: FU duration: 1 year | | ATACS (pilot study) warfarin vs aspirin, 1990 | heparin/warfarin target INR 3-4 (n=24) vs. aspirin 325 mg daily (n=32) | UA, NSTEMI | open Sample size: 24/32 Primary endpoint: FU duration: 3 months |
|
| acute coronary syndrome | ximelagatran | not classified | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ESTEEM, 2003 | ximelagatran vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| ESTEEM, 2003 | oral ximelagatran at doses of
24 mg, 36 mg, 48 mg, or 60 mg twice daily (n=1245) vs. placebo (n=638) | patients who had had recent ST-elevation or non-STelevation
myocardial infarction | double-blind Parallel groups Sample size: 1245/638 Primary endpoint: death, MI, severe recurrent ischaemia FU duration: 6 months dose ranging |
|
| acute myocardial infarction | coumadin | not classified | versus placebo or control No demonstrated result for efficacy coumadin inferior to placebo in terms of Major Bleeding in ASPECT, 1994 coumadin inferior to control (on top of aspirin) in terms of Minor Bleeding in ASPECT-2 (coumadin+ASA vs ASA), 2002 | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ASPECT, 1994 | coumadin vs placebo | Thrombotic Stroke 0.60 [0.40; 0.89] myocardial infarction 0.47 [0.38; 0.58] | Major Bleeding 3.85 [2.34; 6.35] | Death 0.90 [0.74; 1.10] | | ASPECT-2 (coumadin+ASA vs ASA), 2002 | coumadin vs control (on top of aspirin) | | Minor Bleeding 3.03 [1.77; 5.20] | Death 0.58 [0.26; 1.31] Revascularization 0.80 [0.51; 1.23] Major Bleeding 2.26 [0.59; 8.67] Thrombotic Stroke 0.00 [0.00; NaN] myocardial infarction 0.69 [0.31; 1.53] |
| Trial | Treatments | Patients | Method |
|---|
| ASPECT, 1994 | nicoumalone or phenprocoumon, target INR 2.8–4.8 (n=1700) vs. placebo (n=1704) | hospital survivors of myocardial infarction | double blind Parallel groups Sample size: 1700/1704 Primary endpoint: FU duration: 37 months (range 6-76) | | ASPECT-2 (coumadin+ASA vs ASA), 2002 | coumadin(INR mean 2.4) +aspirin
(n=298) vs. aspirin
(n=289)
| Acute MI, unstable angina
| open Parallel groups Sample size: 298/289 Primary endpoint: death, MI or stroke FU duration: 1 year
|
|
| acute myocardial infarction | coumadin | not classified | versus antiplatelet drugs No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ASPECT-2 (coumadin alone), 2002 | coumadin vs aspirin | Death 0.28 [0.09; 0.82] | | Revascularization 0.90 [0.58; 1.39] Major Bleeding 1.03 [0.21; 5.09] Minor Bleeding 1.68 [0.92; 3.07] intrcranial major bleeding NaN [NaN; NaN] myocardial infarction 0.96 [0.46; 2.01] all cause death, MI, thrombo-embolic stroke 0.57 [0.32; 1.00] |
| Trial | Treatments | Patients | Method |
|---|
| ASPECT-2 (coumadin alone), 2002 | coumadin (phenprocoumon or acenocoumarol) target INR 3-4 (n=325) vs. aspirin 80mg daily (n=336)
| Acute MI, unstable angina
| open Parallel groups Sample size: 325/336 Primary endpoint: death, MI or stroke FU duration: 1 year (range 0-26 months)
|
|
| acute myocardial infarction | warfarin | not classified | versus placebo or control No demonstrated result for efficacy warfarin inferior to control (on top of aspirin) in terms of Minor Bleeding in Zibaeenezhad, 2004 warfarin inferior to control (on top of aspirin) in terms of Major Bleeding in CHAMP, 2002 warfarin inferior to control (on top of aspirin) in terms of Minor Bleeding in CHAMP, 2002 warfarin inferior to control (on top of aspirin) in terms of Major Bleeding in LoWASA, 2004 warfarin inferior to control (on top of aspirin) in terms of Minor Bleeding in LoWASA, 2004 warfarin inferior to control (on top of aspirin) in terms of cardiovascular event in CARS (warfarin 1mg), 1997 warfarin inferior to control (on top of aspirin) in terms of non fatal MI in CARS (warfarin 1mg), 1997 warfarin inferior to control (on top of aspirin) in terms of Thrombotic Stroke in CARS (warfarin 1mg), 1997 warfarin inferior to control (on top of aspirin) in terms of Major Bleeding in WARIS II (warfarin+ASA), 2002 warfarin inferior to control (on top of aspirin) in terms of Minor Bleeding in WARIS II (warfarin+ASA), 2002 | 9 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| APRICOT-2, 2002 | warfarin vs control (on top of aspirin) | Revascularization 0.33 [0.19; 0.57] myocardial infarction 0.28 [0.08; 0.98] | | Death ∞ [NaN; ∞] Major Bleeding 1.03 [0.15; 7.21] Minor Bleeding 2.57 [0.51; 13.04] | | Williams, 1997 | warfarin vs placebo (on top of aspirin) | myocardial infarction 0.17 [0.03; 1.00] | | Death 0.00 [0.00; NaN] Revascularization 1.11 [0.45; 2.77] Major Bleeding ∞ [NaN; ∞] Minor Bleeding ∞ [NaN; ∞] Thrombotic Stroke NaN [NaN; NaN] | | Zibaeenezhad, 2004 | warfarin vs control (on top of aspirin) | | Minor Bleeding 6.50 [1.52; 27.75] | Death 0.33 [0.07; 1.60] Major Bleeding 2.50 [0.50; 12.46] Thrombotic Stroke NaN [NaN; NaN] myocardial infarction 0.67 [0.20; 2.26] | | WARIS, 1999 | warfarin vs control (on top of aspirin) | | | | | CHAMP, 2002 | warfarin vs control (on top of aspirin) | | Major Bleeding 1.75 [1.24; 2.47] Minor Bleeding 4.56 [3.58; 5.80] | Death 1.02 [0.90; 1.15] Thrombotic Stroke 0.89 [0.66; 1.20] intrcranial major bleeding 0.94 [0.45; 1.94] myocardial infarction 1.02 [0.88; 1.17] | | CARS (warafrin 3mg), 1997 | warfarin vs control (on top of aspirin) | cardiovascular event 0.60 [0.52; 0.70] non fatal MI 0.57 [0.48; 0.69] cardiovascular death 0.69 [0.52; 0.92] Death 0.73 [0.56; 0.94] | | Major Bleeding 1.09 [0.70; 1.70] Thrombotic Stroke 0.93 [0.53; 1.61] | | LoWASA, 2004 | warfarin vs control (on top of aspirin) | Thrombotic Stroke 0.68 [0.48; 0.94] stroke 0.67 [0.50; 0.88] | Major Bleeding 2.23 [1.24; 3.99] Minor Bleeding 2.21 [1.55; 3.14] | cardiovascular event 0.97 [0.87; 1.09] cardiovascular death 0.91 [0.77; 1.07] Death 0.95 [0.83; 1.10] intrcranial major bleeding 1.98 [0.68; 5.78] myocardial infarction 1.04 [0.90; 1.22] | | CARS (warfarin 1mg), 1997 | warfarin vs control (on top of aspirin) | | cardiovascular event 1.29 [1.10; 1.51] non fatal MI 1.31 [1.09; 1.58] Thrombotic Stroke 2.23 [1.27; 3.92] | cardiovascular death 1.07 [0.77; 1.49] Death 1.03 [0.76; 1.41] Major Bleeding 1.45 [0.86; 2.44] | | WARIS II (warfarin+ASA), 2002 | warfarin vs control (on top of aspirin) | cardiovascular event 0.71 [0.59; 0.86] non fatal MI 0.56 [0.42; 0.75] Thrombotic Stroke 0.50 [0.28; 0.91] myocardial infarction 0.56 [0.42; 0.75] all cause death, MI, thrombo-embolic stroke 0.71 [0.59; 0.86] | Major Bleeding 3.32 [1.51; 7.27] Minor Bleeding 3.23 [2.27; 4.61] | Death 0.98 [0.74; 1.30] Revascularization 0.90 [0.79; 1.02] intrcranial major bleeding 2.84 [0.30; 27.32] |
| Trial | Treatments | Patients | Method |
|---|
| APRICOT-2, 2002 | moderate-intensity coumarin target INR 2-3 (+aspirin)
(n=135) vs. aspirin
(n=139)
| Acute MI after thrombolytics
| open Parallel groups Sample size: 135/139 Primary endpoint: reocclusion of the infarct-related artery FU duration: 3 months
| | Williams, 1997 | warfarin target INR 2–2.5 +aspirin
(n=6) vs. placebo +aspirin
(n=5)
| Acute MI, unstable angina
| double blind Parallel groups Sample size: 6/5 Primary endpoint: quantitative angiography FU duration: 2.5 months
| | Zibaeenezhad, 2004 | Warfarin target INR 2–3 +aspirin (n=70) vs. aspirin 100 mg/day (n=70)
| Acute MI
| open Parallel groups Sample size: 70/70 Primary endpoint: FU duration: 1 year
| | WARIS, 1999 | warfarin 2.8–4.8 (n=1208) vs. placebo (n=1206)
| survivors of acute myocardial infarction
| double blind Parallel groups Sample size: 1208/1206 Primary endpoint: FU duration: 37 months
| | CHAMP, 2002 | warfarin target INR 1.5-2.5 + aspirin 81 mg daily (n=2522) vs. aspirin 162 mg/d (n=2537) | AMI (patients enrolled within 14 days of infarction) | open Parallel groups Sample size: 2522/2537 Primary endpoint: all cause mortality FU duration: 2.7 years | | CARS (warafrin 3mg), 1997 | warfarin fixed dose 3mg/d + 80 mg ASA
(n=5410) vs. aspirin 160 mg/d
(n=3393)
| AMI
| double blind Parallel groups Sample size: 5410/3393 Primary endpoint: reinfarction, non-fatal ischaemic stroke, or cardiovascular death FU duration: 14 months
| | LoWASA, 2004 | warfarin fixed dose 1.25mg/d + ASA 75mg/d (n=1659) vs. aspirin alone (n=1641)
| AMI
| open Parallel groups Sample size: 1659/1641 Primary endpoint: Cardiovascular event and CV death FU duration: 5 years
| | CARS (warfarin 1mg), 1997 | warfarin 1mg/d + aspirin 80mg/d
(n=2028) vs. aspirin 160 mg/d
(n=3393)
| patients who had had myocardial infarction
| double blind Parallel groups Sample size: 2028/3393 Primary endpoint: reinfarction, non-fatal ischaemic stroke, or cardiovascular death FU duration: 14 months
| | WARIS II (warfarin+ASA), 2002 | warfarin target INR 2-2.5 +ASA 75mg/d (n=4927) vs. ASA 160mg/d (n=4669) | patients hospitalized for acute myocardial
infarction | open Parallel groups Sample size: 4927/4669 Primary endpoint: death, MI, ischaemic stroke FU duration: 4 years |
|
| acute myocardial infarction | warfarin | not classified | versus antiplatelet drugs No demonstrated result for efficacy warfarin inferior to aspirin in terms of Major Bleeding in WARIS II (warfarin alone), 2002 warfarin inferior to aspirin in terms of Minor Bleeding in WARIS II (warfarin alone), 2002 | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| WARIS II (warfarin alone), 2002 | warfarin vs aspirin | cardiovascular event 0.84 [0.71; 0.99] non fatal MI 0.76 [0.59; 0.99] Thrombotic Stroke 0.53 [0.29; 0.94] all cause death, MI, thrombo-embolic stroke 0.81 [0.69; 0.95] | Major Bleeding 4.09 [1.90; 8.82] Minor Bleeding 2.62 [1.83; 3.75] | Death 1.03 [0.79; 1.36] intrcranial major bleeding 4.96 [0.58; 42.38] |
| Trial | Treatments | Patients | Method |
|---|
| WARIS II (warfarin alone), 2002 | warfarin target INR 2.8-4.2
(n=1216) vs. ASA 160mg/d
(n=1206)
| patients hospitalized for acute myocardial
infarction
| NA Parallel groups Sample size: 1216/1206 Primary endpoint: death, MI, ischaemic stroke FU duration: 48 months
|
|
| cardiovascular prevention | dicoumarol | not classified | versus No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| T1 vs T0 | | | |
| Trial | Treatments | Patients | Method |
|---|
| Apenstrom and Korsan-Bengtsen, 1964 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: |
|
| cardiovascular prevention | rivaroxaban | secondary prevention | versus No demonstrated result for efficacy rivaroxaban + aspirin inferior to aspirin in terms of major bleeding in COMPASS (rivaroxaban + aspirin), 2017 (secondary prevention patients) rivaroxaban + aspirin inferior to aspirin in terms of CV events in COMPASS (rivaroxaban + aspirin), 2017 (secondary prevention patients) rivaroxaban + aspirin inferior to aspirin in terms of all causes deaths in COMPASS (rivaroxaban + aspirin), 2017 (secondary prevention patients) rivaroxaban + aspirin inferior to aspirin in terms of CV death (IHD+stroke) in COMPASS (rivaroxaban + aspirin), 2017 (secondary prevention patients) rivaroxaban + aspirin inferior to aspirin in terms of fatal stroke in COMPASS (rivaroxaban + aspirin), 2017 (secondary prevention patients) rivaroxaban + aspirin inferior to aspirin in terms of ischemic stroke in COMPASS (rivaroxaban + aspirin), 2017 (secondary prevention patients) rivaroxaban + aspirin inferior to aspirin in terms of all stroke in COMPASS (rivaroxaban + aspirin), 2017 (secondary prevention patients) | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| COMPASS (rivaroxaban alone), 2017 | rivaroxaban vs aspirin | | | | | COMPASS (rivaroxaban + aspirin), 2017 | rivaroxaban + aspirin vs aspirin | | major bleeding 17.00 [6.50; 44.44] CV events 76.00 [66.58; 86.75] all causes deaths 82.00 [70.52; 95.35] CV death (IHD+stroke) 78.00 [63.69; 95.53] fatal stroke 78.00 [63.69; 95.53] ischemic stroke 51.00 [38.12; 68.22] all stroke 58.00 [44.13; 76.23] | |
| Trial | Treatments | Patients | Method |
|---|
| COMPASS (rivaroxaban alone), 2017 | Rivaroxaban 2.5 mg twice daily alone (n=27400) vs. aspirin 100 mg once daily (n=0) 3 arms rivaroxaban and aspirin, rivaroxaban alone, aspirin alone | Patients With Coronary or Peripheral Artery Disease | Sample size: 27400/0 Primary endpoint: FU duration: | | COMPASS (rivaroxaban + aspirin), 2017 | rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily) (n=9152) vs. aspirin 100 mg once daily
(n=9126) 3 arms rivaroxaban and aspirin, rivaroxaban alone, aspirin alone
| Patients With Coronary or Peripheral Artery Disease
| double-blind Parallel groups Sample size: 9152/9126 Primary endpoint: cardiovascular death, stroke, MI FU duration: 23 months
|
|
| cardiovascular prevention | wafarin | not classified | versus No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| T1 vs T0 | | | |
| Trial | Treatments | Patients | Method |
|---|
| WARIS, 1990 | warfarin (n=607) vs. placebo (n=607) | patients who had recovered from acute myocardial infarction (mean interval from the onset of symptoms to randomization, 27 days) | double-blind Sample size: 607/607 Primary endpoint: FU duration: 37 months |
|
| cardiovascular prevention | warfarin | primary prevention | versus placebo or control No demonstrated result for efficacy warfarin inferior to placebo in terms of fatal stroke in Thrombosis Prevention trial (Warfarin), 1998 (primary prevention patients) warfarin + aspirin inferior to placebo in terms of fatal stroke in Thrombosis Prevention trial (W plus A), 1998 (primary prevention patients) | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Thrombosis Prevention trial (Warfarin), 1998 | warfarin vs placebo | all causes deaths 0.83 [0.70; 0.99] IHD death 0.61 [0.44; 0.85] ischemic heart disease 0.79 [0.66; 0.95] | fatal stroke 2.81 [1.11; 7.11] | major bleeding 2.48 [0.96; 6.38] CV death (IHD+stroke) 0.75 [0.55; 1.01] Haemorrhagic stroke 2.97 [0.81; 10.97] non fatal IHD 0.91 [0.72; 1.14] ischemic stroke 0.96 [0.57; 1.60] all stroke 1.15 [0.79; 1.68] | | Thrombosis Prevention trial (W plus A), 1998 | warfarin + aspirin vs placebo | ischemic heart disease 0.66 [0.49; 0.88] non fatal IHD 0.64 [0.45; 0.92] | fatal stroke 11.95 [1.56; 91.79] | major bleeding 2.99 [0.97; 9.24] all causes deaths 0.93 [0.72; 1.21] IHD death 0.70 [0.42; 1.18] CV death (IHD+stroke) 1.06 [0.72; 1.55] Haemorrhagic stroke ∞ [NaN; ∞] ischemic stroke 0.61 [0.29; 1.28] all stroke 1.11 [0.66; 1.88] |
| Trial | Treatments | Patients | Method |
|---|
| Thrombosis Prevention trial (Warfarin), 1998 | warfarin started at 2.5mg/d adjusted for a target INR 1.5
(n=2762) vs. placebo
(n=2737) factorial design with aspirin and warfarin
| men aged between 45 years and 69 years at high risk of IHD
| double blind Factorial plan Sample size: 2762/2737 Primary endpoint: coronary death and fatal and non-fatal myocardial infarction FU duration: median 6.8 y
| | Thrombosis Prevention trial (W plus A), 1998 | warfarin adjusted dose for INR of 1.5 + aspirin 75 mg daily
(n=1277) vs. placebo
(n=1272) factorial design with aspirin and warfarin
| men aged between 45 years and 69 years at high risk of IHD
| double blind NA Sample size: 1277/1272 Primary endpoint: coronary death and fatal and non-fatal myocardial infarction FU duration: median 6.8 y separate group analysis of a factorial design
|
|
| coronary artery disease | dicoumarol | not classified | versus No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| T1 vs T0 | | | |
| Trial | Treatments | Patients | Method |
|---|
| Apenstrom and Korsan-Bengtsen, 1964 | (n=-9) vs. (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: |
|
| coronary artery disease | wafarin | not classified | versus No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| T1 vs T0 | | | |
| Trial | Treatments | Patients | Method |
|---|
| WARIS, 1990 | warfarin (n=607) vs. placebo (n=607) | patients who had recovered from acute myocardial infarction (mean interval from the onset of symptoms to randomization, 27 days) | double-blind Sample size: 607/607 Primary endpoint: FU duration: 37 months |
|
| heart failure | rivaroxaban | not classified | versus No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| COMMANDER HF, 2018 | rivaroxaban vs placebo | | | death 0.98 [0.87; 1.10] |
| Trial | Treatments | Patients | Method |
|---|
| COMMANDER HF, 2018 | rivaroxaban at a dose of 2.5 mg twice daily (n=2507) vs. placebo (n=2515) | patients who had chronic heart failure, a left ventricular ejection fraction of 40% or less, coronary artery disease, and elevated plasma concentrations of natriuretic peptides and who did not have atrial fibrillation | Sample size: 2507/2515 Primary endpoint: death all cause, MI, stroke FU duration: 21.1 months |
|
| heart failure | warfarin | not classified | versus placebo or no treatment No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| HELAS (warfarin vs placebo), 2006 | warfarin vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| HELAS (warfarin vs placebo), 2006 | warfarin (target
INR of 2–3) (n=38) vs. placebo (n=44) | HF due to dilated cardiomyopathy | double blind Parallel groups Sample size: 38/44 Primary endpoint: stroke, PE, MI, hospitalization, death FU duration: 21.9 months |
|
| heart failure | warfarin | not classified | versus antiplatelet drugs No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| HELAS (warfarin vs aspirin), 2006 | warfarin vs aspirin | | | | | WATCH (warfarin vs aspirin), 2009 | warfarin vs aspirin | Ischemic stroke 0.24 [0.07; 0.85] | | death 0.95 [0.73; 1.23] bleeding 1.43 [0.81; 2.52] stroke (fatal and non fatal) 0.58 [0.26; 1.32] |
| Trial | Treatments | Patients | Method |
|---|
| HELAS (warfarin vs aspirin), 2006 | warfarin (n=54) vs. aspirin 325mg/d (n=61) | HF related to ischemic heart disease with LVFE<35% | Double blind Parallel groups Sample size: 54/61 Primary endpoint: stroke, PE, ME, hospitalisation, death FU duration: 21.9 months | | WATCH (warfarin vs aspirin), 2009 | warfarin (target INR 2.5-3.0) (n=540) vs. aspirin 162 mg daily (n=523) | symptomatic heart failure patients in sinus rhythm with ejection fractions 35% taking angiotensin-converting enzyme inhibitors (unless not tolerated) and diuretics | open Parallel groups Sample size: 540/523 Primary endpoint: death from all causes, nonfatal FU duration: |
|
| percutaneous coronary intervention | bivalirudin | not classified | versus heparin No demonstrated result for efficacy | 4 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ISAR-REACT 3, 2008 | bivalirudin vs UFH | | | | | REPLACE-1, 2004 | bivalirudin vs UFH | | | death, MI, urgent TVR, in-hospital major bleeding 0.77 [0.35; 1.69] All cause death 0.00 [0.00; NaN] MI 0.95 [0.56; 1.60] death, MI, revascularization 0.82 [0.51; 1.31] Unplanned revascularisation for ischaemia 0.56 [0.17; 1.91] | | BAT (Bittl), 1995 | bivalirudin vs UFH | major bleeding 0.39 [0.30; 0.50] | | All cause death 2.23 [0.69; 7.22] Ischaemic complication 0.93 [0.79; 1.10] MI 0.80 [0.58; 1.11] Unplanned revascularisation for ischaemia 0.99 [0.62; 1.58] | | ARMYDA BIVALVE | bivalirudin vs UFH | | | |
| Trial | Treatments | Patients | Method |
|---|
| ISAR-REACT 3, 2008 | UFH bolus of 140 U/kg (n=2289) vs. bivalirudin (bolus of 0.75 mg/kg, followed by infusion of 1.75 mg/kg/hr) (n=2281) | troponin-negative patients undergoing PCI | double blind Parallel groups Sample size: 2289/2281 Primary endpoint: death, MI, urgent TVR, in-hospital major bleeding, FU duration: 30 days (mean) | | REPLACE-1, 2004 | bivalirudin (0.75 mg/kg bolus, 1.75 mg/kg/h infusion during the procedure (n=532) vs. heparin (70 U/kg initial bolus) adjusted to ACT of 200 to 300s (n=524) | patients undergoing elective or urgent revascularization | Parallel groups Sample size: 532/524 Primary endpoint: death, MI, repeat revascularization FU duration: hospital stay (48h min) | | BAT (Bittl), 1995 | bivalirudin immediately before angioplasty. (n=2059) vs. heparin immediately before angioplasty (n=2039) | patients undergoing urgent angioplasty for unstable or postinfarction angina | double blind Parallel groups Sample size: 2059/2039 Primary endpoint: death, MI, abrupt clossure, rapide deterioration FU duration: hospital stay Although two parallel studies were
specified to meet regulatory requirements, the protocol specified that scientific analysis and safety monitoring would
involve the combined cohort of 4000 patients | | ARMYDA BIVALVE | bivalirudin (0.75 mg/kg bolus followed by 1.75 mg/kg per hour during the procedure) (n=140) vs. unfractionated heparin (75 IU/kg) (n=0) | patients at high bleeding risk (over 75 years of age, diabetes, reduced renal function) scheduled for PCI | Parallel groups Sample size: 140/0 Primary endpoint: death, MI, target vessel revascularization, or stent thrombosis FU duration: |
|
| percutaneous coronary intervention | bivalirudin | not classified | versus heparin + anti Gp2b3a No demonstrated result for efficacy | 5 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| REPLACE-2, 2003 | bivalirudin vs heparin + GP2b3a inhibitors | | | | | HORIZONS-AMI (Stone), 2008 | bivalirudin vs heparin + GP2b3a inhibitors | All cause death 0.66 [0.44; 1.00] safety criteria 0.60 [0.46; 0.77] major bleeding 0.61 [0.44; 0.84] minor bleeding 0.62 [0.44; 0.88] net benefit 0.76 [0.63; 0.92] | | Ischaemic complication 0.99 [0.76; 1.30] MI 1.14 [0.64; 2.01] death, MI, revascularization 0.99 [0.76; 1.30] Unplanned revascularisation for ischaemia 1.34 [0.87; 2.07] | | ACUITY (Stone) (bivalirudin alone), 2006 | bivalirudin vs heparin + GP2b3a inhibitors | | | | | Kleiman, 2002 | bivalirudin + eptifibatide vs heparin + GP2b3a inhibitors | | | | | NAPLES (Tavano), 2009 | bivalirudin vs UFH plus tirofiban | death, MI, urgent TVR, in-hospital major bleeding 0.57 [0.38; 0.84] minor bleeding 0.42 [0.23; 0.78] | | All cause death NaN [NaN; NaN] major bleeding 0.25 [0.03; 2.23] Unplanned revascularisation for ischaemia NaN [NaN; NaN] |
| Trial | Treatments | Patients | Method |
|---|
| REPLACE-2, 2003 | bivalirudin, with glycoprotein IIb/IIIa (Gp IIb/IIIa) inhibition on a provisional basis for complications during PCI (n=2994) vs. heparin plus planned Gp IIb/IIIa blockade (n=3008) | patients undergoing urgent or elective PCI | double blind Parallel groups Sample size: 2994/3008 Primary endpoint: death, MI, urgent revascularization, or in-hospital FU duration: 30 days | | HORIZONS-AMI (Stone), 2008 | Bivalirudin (n=1800) vs. Heparin plus GP IIb/IIIa inhibitor (n=1802) | patients with ST-segment elevation myocardial infarction
who presented within 12 hours after the onset of symptoms and who were
undergoing primary PCI | open Parallel groups Sample size: 1800/1802 Primary endpoint: MACE, major bleeding FU duration: 30 days | | ACUITY (Stone) (bivalirudin alone), 2006 | bivalirudin alone (n=9216) vs. unfractionated heparin or enoxaparin plus a glycoprotein IIb/IIIa inhibitor (n=4603) | patients with acute coronary syndromes | open Parallel groups Sample size: 9216/4603 Primary endpoint: ischemia events and bleeding FU duration: 30 days | | Kleiman, 2002 | bivalirudin + eptifibatide (n=-9) vs. heparin + eptifibatide (n=-9) | patients who underwent elective percutaneous coronary intervention | open Parallel groups Sample size: -9/-9 Primary endpoint: none defined FU duration: | | NAPLES (Tavano), 2009 | bivalirudin monotherapy (n=167) vs. unfractionated heparin plus tirofiban (n=168) | patients with diabetes mellitus undergoing elective percutaneous coronary intervention | open Parallel groups Sample size: 167/168 Primary endpoint: MACE FU duration: 30 days |
|
| percutaneous coronary intervention | dalteparin | not classified | versus heparin No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Natarajan (without antiGp2b3a), 2003 | dalteparin vs UFH | | | |
| Trial | Treatments | Patients | Method |
|---|
| Natarajan (without antiGp2b3a), 2003 | Dalteparin 100 IU/kg bolus (n=-9) vs. UFH 100 IU/kg bolus (n=-9) | Elective or urgent PCI | Sample size: -9/-9 Primary endpoint: FU duration: |
|
| percutaneous coronary intervention | dalteparin | not classified | versus heparin + anti Gp2b3a No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Natarajan (+ antiGp2b3a), 2003 | dalteparin vs UFH + anti Gp2b3a | | | |
| Trial | Treatments | Patients | Method |
|---|
| Natarajan (+ antiGp2b3a), 2003 | Dalteparin 70 IU/kg bolus + GP IIb/IIIa inhibitorse/p (n=-9) vs. UFH 70 IU/kg bolus +GPIIb/IIIa inhibitors (n=-9) | | Sample size: -9/-9 Primary endpoint: FU duration: |
|
| percutaneous coronary intervention | enoxaparin | not classified | versus heparin No demonstrated result for efficacy | 9 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| STEEPLE, 2006 | enoxaparin vs UFH | | | | | Rabah, 1999 | enoxaparin vs UFH | | | safety criteria 1.00 [0.07; 15.26] Ischaemic complication 1.00 [0.22; 4.56] | | CRUISE, 2003 | enoxaparin vs UFH | | | safety criteria 0.00 [0.00; NaN] Ischaemic complication 1.13 [0.50; 2.56] | | Galeote, 2001 | enoxaparin vs UFH | | | safety criteria 0.25 [0.03; 2.12] Ischaemic complication 1.63 [0.41; 6.47] | | Dudek, 2000 | enoxaparin vs UFH | | | safety criteria NaN [NaN; NaN] Ischaemic complication 1.25 [0.50; 3.10] | | Dudek b (enox alone), 2000 | enoxaparin vs UFH | | | | | Drozd, 2001 | enoxaparin vs UFH | | | safety criteria NaN [NaN; NaN] Ischaemic complication 1.00 [0.21; 4.72] | | Dubek b (+abciximal), 2001 | enoxaparin+abciximab vs UFH | | | | | ATOLL, 2010 | enoxaparin vs UFH | | | |
| Trial | Treatments | Patients | Method |
|---|
| STEEPLE, 2006 | enoxaparin (0.5 or 0.75 mg per kilogram of body weight) (n=-9) vs. unfractionated heparin (adjusted for activated clotting time) (n=-9) | elective percutaneous coronary intervention. | open Parallel groups Sample size: -9/-9 Primary endpoint: major or minor bleeding FU duration: | | Rabah, 1999 | Enoxaparin 1 mg/kg bolus (n=30) vs. UFH 10,000 IU bolus, then titrated to ACT > 300 (n=30) | PCI for stable angina | open Parallel groups Sample size: 30/30 Primary endpoint: none defined FU duration: | | CRUISE, 2003 | Enoxaparin 0.75 mg/kg bolus (n=129) vs. UFH 60 IU/kg bolus, then titrated to ACT > 200 (n=132) | Urgent or elective PCI | open Parallel groups Sample size: 129/132 Primary endpoint: hemoglobin FU duration: 2,7 +30 days | | Galeote, 2001 | Enoxaparin 0.75 mg/kg bolus (n=50) vs. UFH 70 U/kg bolus, then titrated to ACT > 200 (n=49) | PTCA patients with stable/unstable angina or AMI | Sample size: 50/49 Primary endpoint: FU duration: | | Dudek, 2000 | Enoxaparin 1 mg/kg bolus (n=200) vs. UFH titrated to ACT > 300 (n=200) | PCI | Sample size: 200/200 Primary endpoint: FU duration: 3à days | | Dudek b (enox alone), 2000 | Enoxaparin 1 mg/kg bolus (n=-9) vs. UFH titrated to ACT > 300 (n=50) | PTCA complex lesionsCI | Sample size: -9/50 Primary endpoint: FU duration: | | Drozd, 2001 | Enoxaparin 1 mg/kg bolus (n=50) vs. UFH 100 IU/kg bolus (n=50) | PCI for stable angina | Sample size: 50/50 Primary endpoint: FU duration: 24hrs, 30 days | | Dubek b (+abciximal), 2001 | Enoxaparin 0.75 mg/kg bolus + abciximab (n=-9) vs. UFH titrated to ACT > 300 (n=50) | | Sample size: -9/50 Primary endpoint: FU duration: | | ATOLL, 2010 | IV enoxaparin (n=450) vs. UFH (n=460) | patients undergoing PCI for acute STEMI | open Parallel groups Sample size: 450/460 Primary endpoint: Death, Complication of MI, Procedure Failure or Major Bleeding FU duration: 30 days |
|
| percutaneous coronary intervention | reviparin | not classified | versus heparin No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| REDUCE, 1996 | reviparin vs UFH | Ischaemic complication 0.48 [0.25; 0.94] | | safety criteria 0.88 [0.32; 2.38] |
| Trial | Treatments | Patients | Method |
|---|
| REDUCE, 1996 | Reviparin 7,000 IU anti-Xa (n=306) vs. UFH 10,000 IU bolus (n=306) | PTCA with stable/unstable angina | double blind Parallel groups Sample size: 306/306 Primary endpoint: MACE FU duration: 3 days |
|
| peripheral vascular diseases | warfarin | not classified | versus No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| warfarin vs contrôle | | | | | warfarin vs contrôle | | | |
| Trial | Treatments | Patients | Method |
|---|
| Johnson, 2002 | warfarin 5 mg/j au 2ème ou 3ème j post-opératoire. INR cible : 1.4 à 2.8 (n=308) vs. contrôle (n=306) | stades II à IV
614 patients inclus | Ouvert Parallel groups Sample size: 308/306 Primary endpoint: perméabilité du pontage FU duration: 5 ans | | Sarac, 1998 | héparine (6 à 24 h avant l'intervention) puis warfarin pour un INR entre 2 et 3. (n=32) vs. pas d'anti-coagulation (n=24) | AOMI stade non précisé | Ouvert Parallel groups Sample size: 32/24 Primary endpoint: perméabilité du pontage FU duration: 3 ans |
|
| post myocardial infarction | coumadin | not classified | versus placebo or control No demonstrated result for efficacy coumadin inferior to placebo in terms of Major Bleeding in ASPECT, 1994 coumadin inferior to control (on top of aspirin) in terms of Minor Bleeding in ASPECT-2 (coumadin+ASA vs ASA), 2002 | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ASPECT, 1994 | coumadin vs placebo | Thrombotic Stroke 0.60 [0.40; 0.89] myocardial infarction 0.47 [0.38; 0.58] | Major Bleeding 3.85 [2.34; 6.35] | Death 0.90 [0.74; 1.10] | | ASPECT-2 (coumadin+ASA vs ASA), 2002 | coumadin vs control (on top of aspirin) | | Minor Bleeding 3.03 [1.77; 5.20] | Death 0.58 [0.26; 1.31] Revascularization 0.80 [0.51; 1.23] Major Bleeding 2.26 [0.59; 8.67] Thrombotic Stroke 0.00 [0.00; NaN] myocardial infarction 0.69 [0.31; 1.53] |
| Trial | Treatments | Patients | Method |
|---|
| ASPECT, 1994 | nicoumalone or phenprocoumon, target INR 2.8–4.8 (n=1700) vs. placebo (n=1704) | hospital survivors of myocardial infarction | double blind Parallel groups Sample size: 1700/1704 Primary endpoint: FU duration: 37 months (range 6-76) | | ASPECT-2 (coumadin+ASA vs ASA), 2002 | coumadin(INR mean 2.4) +aspirin
(n=298) vs. aspirin
(n=289)
| Acute MI, unstable angina
| open Parallel groups Sample size: 298/289 Primary endpoint: death, MI or stroke FU duration: 1 year
|
|
| post myocardial infarction | coumadin | not classified | versus antiplatelet drugs No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ASPECT-2 (coumadin alone), 2002 | coumadin vs aspirin | Death 0.28 [0.09; 0.82] | | Revascularization 0.90 [0.58; 1.39] Major Bleeding 1.03 [0.21; 5.09] Minor Bleeding 1.68 [0.92; 3.07] intrcranial major bleeding NaN [NaN; NaN] myocardial infarction 0.96 [0.46; 2.01] all cause death, MI, thrombo-embolic stroke 0.57 [0.32; 1.00] |
| Trial | Treatments | Patients | Method |
|---|
| ASPECT-2 (coumadin alone), 2002 | coumadin (phenprocoumon or acenocoumarol) target INR 3-4 (n=325) vs. aspirin 80mg daily (n=336)
| Acute MI, unstable angina
| open Parallel groups Sample size: 325/336 Primary endpoint: death, MI or stroke FU duration: 1 year (range 0-26 months)
|
|
| post myocardial infarction | warfarin | not classified | versus placebo or control No demonstrated result for efficacy warfarin inferior to control (on top of aspirin) in terms of Minor Bleeding in Zibaeenezhad, 2004 warfarin inferior to control (on top of aspirin) in terms of Major Bleeding in CHAMP, 2002 warfarin inferior to control (on top of aspirin) in terms of Minor Bleeding in CHAMP, 2002 warfarin inferior to control (on top of aspirin) in terms of Major Bleeding in LoWASA, 2004 warfarin inferior to control (on top of aspirin) in terms of Minor Bleeding in LoWASA, 2004 warfarin inferior to control (on top of aspirin) in terms of cardiovascular event in CARS (warfarin 1mg), 1997 warfarin inferior to control (on top of aspirin) in terms of non fatal MI in CARS (warfarin 1mg), 1997 warfarin inferior to control (on top of aspirin) in terms of Thrombotic Stroke in CARS (warfarin 1mg), 1997 warfarin inferior to control (on top of aspirin) in terms of Major Bleeding in WARIS II (warfarin+ASA), 2002 warfarin inferior to control (on top of aspirin) in terms of Minor Bleeding in WARIS II (warfarin+ASA), 2002 | 9 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| APRICOT-2, 2002 | warfarin vs control (on top of aspirin) | Revascularization 0.33 [0.19; 0.57] myocardial infarction 0.28 [0.08; 0.98] | | Death ∞ [NaN; ∞] Major Bleeding 1.03 [0.15; 7.21] Minor Bleeding 2.57 [0.51; 13.04] | | Williams, 1997 | warfarin vs placebo (on top of aspirin) | myocardial infarction 0.17 [0.03; 1.00] | | Death 0.00 [0.00; NaN] Revascularization 1.11 [0.45; 2.77] Major Bleeding ∞ [NaN; ∞] Minor Bleeding ∞ [NaN; ∞] Thrombotic Stroke NaN [NaN; NaN] | | Zibaeenezhad, 2004 | warfarin vs control (on top of aspirin) | | Minor Bleeding 6.50 [1.52; 27.75] | Death 0.33 [0.07; 1.60] Major Bleeding 2.50 [0.50; 12.46] Thrombotic Stroke NaN [NaN; NaN] myocardial infarction 0.67 [0.20; 2.26] | | WARIS, 1999 | warfarin vs control (on top of aspirin) | | | | | CHAMP, 2002 | warfarin vs control (on top of aspirin) | | Major Bleeding 1.75 [1.24; 2.47] Minor Bleeding 4.56 [3.58; 5.80] | Death 1.02 [0.90; 1.15] Thrombotic Stroke 0.89 [0.66; 1.20] intrcranial major bleeding 0.94 [0.45; 1.94] myocardial infarction 1.02 [0.88; 1.17] | | CARS (warafrin 3mg), 1997 | warfarin vs control (on top of aspirin) | cardiovascular event 0.60 [0.52; 0.70] non fatal MI 0.57 [0.48; 0.69] cardiovascular death 0.69 [0.52; 0.92] Death 0.73 [0.56; 0.94] | | Major Bleeding 1.09 [0.70; 1.70] Thrombotic Stroke 0.93 [0.53; 1.61] | | LoWASA, 2004 | warfarin vs control (on top of aspirin) | Thrombotic Stroke 0.68 [0.48; 0.94] stroke 0.67 [0.50; 0.88] | Major Bleeding 2.23 [1.24; 3.99] Minor Bleeding 2.21 [1.55; 3.14] | cardiovascular event 0.97 [0.87; 1.09] cardiovascular death 0.91 [0.77; 1.07] Death 0.95 [0.83; 1.10] intrcranial major bleeding 1.98 [0.68; 5.78] myocardial infarction 1.04 [0.90; 1.22] | | CARS (warfarin 1mg), 1997 | warfarin vs control (on top of aspirin) | | cardiovascular event 1.29 [1.10; 1.51] non fatal MI 1.31 [1.09; 1.58] Thrombotic Stroke 2.23 [1.27; 3.92] | cardiovascular death 1.07 [0.77; 1.49] Death 1.03 [0.76; 1.41] Major Bleeding 1.45 [0.86; 2.44] | | WARIS II (warfarin+ASA), 2002 | warfarin vs control (on top of aspirin) | cardiovascular event 0.71 [0.59; 0.86] non fatal MI 0.56 [0.42; 0.75] Thrombotic Stroke 0.50 [0.28; 0.91] myocardial infarction 0.56 [0.42; 0.75] all cause death, MI, thrombo-embolic stroke 0.71 [0.59; 0.86] | Major Bleeding 3.32 [1.51; 7.27] Minor Bleeding 3.23 [2.27; 4.61] | Death 0.98 [0.74; 1.30] Revascularization 0.90 [0.79; 1.02] intrcranial major bleeding 2.84 [0.30; 27.32] |
| Trial | Treatments | Patients | Method |
|---|
| APRICOT-2, 2002 | moderate-intensity coumarin target INR 2-3 (+aspirin)
(n=135) vs. aspirin
(n=139)
| Acute MI after thrombolytics
| open Parallel groups Sample size: 135/139 Primary endpoint: reocclusion of the infarct-related artery FU duration: 3 months
| | Williams, 1997 | warfarin target INR 2–2.5 +aspirin
(n=6) vs. placebo +aspirin
(n=5)
| Acute MI, unstable angina
| double blind Parallel groups Sample size: 6/5 Primary endpoint: quantitative angiography FU duration: 2.5 months
| | Zibaeenezhad, 2004 | Warfarin target INR 2–3 +aspirin (n=70) vs. aspirin 100 mg/day (n=70)
| Acute MI
| open Parallel groups Sample size: 70/70 Primary endpoint: FU duration: 1 year
| | WARIS, 1999 | warfarin 2.8–4.8 (n=1208) vs. placebo (n=1206)
| survivors of acute myocardial infarction
| double blind Parallel groups Sample size: 1208/1206 Primary endpoint: FU duration: 37 months
| | CHAMP, 2002 | warfarin target INR 1.5-2.5 + aspirin 81 mg daily (n=2522) vs. aspirin 162 mg/d (n=2537) | AMI (patients enrolled within 14 days of infarction) | open Parallel groups Sample size: 2522/2537 Primary endpoint: all cause mortality FU duration: 2.7 years | | CARS (warafrin 3mg), 1997 | warfarin fixed dose 3mg/d + 80 mg ASA
(n=5410) vs. aspirin 160 mg/d
(n=3393)
| AMI
| double blind Parallel groups Sample size: 5410/3393 Primary endpoint: reinfarction, non-fatal ischaemic stroke, or cardiovascular death FU duration: 14 months
| | LoWASA, 2004 | warfarin fixed dose 1.25mg/d + ASA 75mg/d (n=1659) vs. aspirin alone (n=1641)
| AMI
| open Parallel groups Sample size: 1659/1641 Primary endpoint: Cardiovascular event and CV death FU duration: 5 years
| | CARS (warfarin 1mg), 1997 | warfarin 1mg/d + aspirin 80mg/d
(n=2028) vs. aspirin 160 mg/d
(n=3393)
| patients who had had myocardial infarction
| double blind Parallel groups Sample size: 2028/3393 Primary endpoint: reinfarction, non-fatal ischaemic stroke, or cardiovascular death FU duration: 14 months
| | WARIS II (warfarin+ASA), 2002 | warfarin target INR 2-2.5 +ASA 75mg/d (n=4927) vs. ASA 160mg/d (n=4669) | patients hospitalized for acute myocardial
infarction | open Parallel groups Sample size: 4927/4669 Primary endpoint: death, MI, ischaemic stroke FU duration: 4 years |
|
| post myocardial infarction | warfarin | not classified | versus antiplatelet drugs No demonstrated result for efficacy warfarin inferior to aspirin in terms of Major Bleeding in WARIS II (warfarin alone), 2002 warfarin inferior to aspirin in terms of Minor Bleeding in WARIS II (warfarin alone), 2002 | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| WARIS II (warfarin alone), 2002 | warfarin vs aspirin | cardiovascular event 0.84 [0.71; 0.99] non fatal MI 0.76 [0.59; 0.99] Thrombotic Stroke 0.53 [0.29; 0.94] all cause death, MI, thrombo-embolic stroke 0.81 [0.69; 0.95] | Major Bleeding 4.09 [1.90; 8.82] Minor Bleeding 2.62 [1.83; 3.75] | Death 1.03 [0.79; 1.36] intrcranial major bleeding 4.96 [0.58; 42.38] |
| Trial | Treatments | Patients | Method |
|---|
| WARIS II (warfarin alone), 2002 | warfarin target INR 2.8-4.2
(n=1216) vs. ASA 160mg/d
(n=1206)
| patients hospitalized for acute myocardial
infarction
| NA Parallel groups Sample size: 1216/1206 Primary endpoint: death, MI, ischaemic stroke FU duration: 48 months
|
|
| post stroke | dicoumarol | not classified | versus No demonstrated result for efficacy dicoumarol inferior to placebo in terms of Major extracranial haemorrhage in Nat-Coop, 1962 | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Howard, 1963 | dicoumarol vs placebo | | | Deaths from any cause 1.00 [0.24; 4.18] Vascular deaths 1.00 [0.24; 4.18] Symptomatic intracranial haemorrhage NaN [NaN; NaN] Major extracranial haemorrhage NaN [NaN; NaN] | | Nat-Coop, 1962 | dicoumarol vs placebo | Non-fatal stroke/intracranial haemorrhage or vascular death 0.73 [0.54; 1.00] | Major extracranial haemorrhage 10.51 [2.50; 44.16] | Recurrent ischaemic/unknown stroke 0.56 [0.26; 1.20] Symptomatic intracranial haemorrhage 2.23 [0.58; 8.51] Any recurrent stroke or symptomatic intracranial haemorrhage 0.63 [0.36; 1.08] Myocardial infarction 0.76 [0.31; 1.90] |
| Trial | Treatments | Patients | Method |
|---|
| Howard, 1963 | dicumarol, TP 15 to 25% of normal (n=-9) vs. placebo (n=-9) | | single-blind Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: 1 year | | Nat-Coop, 1962 | heparin 50 mg 4-hourly iv then dicumarol, Quick test 15% to 25% of control (n=-9) vs. placebo (n=-9) | | single-blind Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: 13 months |
|
| post stroke | phenindione | not classified | versus No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Enger, 1965 | phenindione vs placebo | | | Death or dependency 1.11 [0.92; 1.34] Non-fatal stroke, myocardial infarction or vascular death 0.70 [0.48; 1.04] Deaths from any cause 1.12 [0.65; 1.90] Vascular deaths 0.91 [0.50; 1.65] Recurrent ischaemic/unknown stroke 0.51 [0.24; 1.07] Symptomatic intracranial haemorrhage 2.55 [0.27; 23.77] Any recurrent stroke or symptomatic intracranial haemorrhage 0.64 [0.33; 1.22] Major extracranial haemorrhage ∞ [NaN; ∞] Myocardial infarction 1.06 [0.30; 3.75] Other embolic events 0.85 [0.05; 13.25] Non-fatal stroke/intracranial haemorrhage or vascular death 0.72 [0.48; 1.09] | | Thygesen, 1964 | phenindione vs placebo | | | Deaths from any cause 1.41 [0.34; 5.85] Vascular deaths 2.12 [0.42; 10.82] Recurrent ischaemic/unknown stroke 1.48 [0.52; 4.22] Symptomatic intracranial haemorrhage ∞ [NaN; ∞] Any recurrent stroke or symptomatic intracranial haemorrhage 1.91 [0.71; 5.11] Myocardial infarction 0.00 [0.00; NaN] Non-fatal stroke/intracranial haemorrhage or vascular death 1.52 [0.65; 3.51] |
| Trial | Treatments | Patients | Method |
|---|
| Enger, 1965 | phenindione thrombotest 10% to 25% of normal, started in hospital (n=-9) vs. placebo (n=-9) | | single-blind Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: 22.7 months | | Thygesen, 1964 | phenindione, prothrombin-proconvertin test 10% to 20% (n=-9) vs. placebo (n=-9) | | single-blind Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: 29.5 months |
|
| post stroke | rivaroxaban | not classified | versus No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| NAVIGATE ESUS, 2018 | rivaroxaban vs aspirin | | | |
| Trial | Treatments | Patients | Method |
|---|
| NAVIGATE ESUS, 2018 | rivaroxaban (at a daily dose of 15 mg) (n=3609) vs. aspirin (at a daily dose of 100 mg) (n=3604) | patients with recent ischemic stroke that was presumed to be from cerebral embolism but without arterial stenosis, lacune, or an identified cardioembolic source | Sample size: 3609/3604 Primary endpoint: first recurrence of ischemic or hemorrhagic stroke or systemic embolism FU duration: |
|
| post stroke | warfarin | not classified | versus No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| SWAT, 1998 | warfarin vs aspirin | | | Deaths from any cause 1.43 [0.25; 8.23] Recurrent ischaemic/unknown stroke 0.63 [0.11; 3.66] Any recurrent stroke or symptomatic intracranial haemorrhage 0.63 [0.11; 3.66] Major extracranial haemorrhage 1.27 [0.47; 3.43] Myocardial infarction 2.85 [0.31; 26.65] Non-fatal stroke/intracranial haemorrhage or vascular death 0.95 [0.29; 3.11] |
| Trial | Treatments | Patients | Method |
|---|
| SWAT, 1998 | warfarin (INR 2.0 to 3.0) (n=-9) vs. Enteric-coated aspirin 650 mg 12-hourly (n=-9) 3 arms: Enteric-coated aspirin 650 mg 12-hourly; warfarin (INR 2.0 to 3.0) and warfarin plus aspirin 80
mg 24-hourly | | open Parallel groups Sample size: -9/-9 Primary endpoint: FU duration: 2 years |
|
| thrombosis prevention | acenocoumarol | not classified | versus Low molecular weight heparin No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Hamulyak, 1994 | Acenocoumarol vs Nadroparin | | | DVT 1.18 [0.81; 1.70] | | Samama, 2001 | Acenocoumarol vs Reviparin | | | DVT 1.35 [0.70; 2.61] |
| Trial | Treatments | Patients | Method |
|---|
| Hamulyak, 1994 | Acenocoumarol (n=342) vs. Nadroparin 60 anti-Xa IU /kg x1 (n=330) | THR or TKR (stratified) | single blind Sample size: 342/330 Primary endpoint: FU duration: Day 10 ± 2 | | Samama, 2001 | Acenocoumarol (n=645) vs. Reviparin 4200 anti-Xa IU x1 (n=644) | THR | Open Sample size: 645/644 Primary endpoint: FU duration: 6 weeks |
|
| thrombosis prevention | acenocoumarol | not classified | versus unfractionated heparin No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Acenocoumarol vs unfractionated heparin | | | |
| Trial | Treatments | Patients | Method |
|---|
| van Geloven, 1977 | Acenocoumarol (n=11) vs. UFH 4000 ·x2 (n=11) | THR | double blind Sample size: 11/11 Primary endpoint: FU duration: NA |
|
| thrombosis prevention | apixaban | hip surgery | versus Low molecular weight heparin No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ADVANCE 3, 2010 | apixaban vs enoxaparin | DVT (asymptomatic or symptomatic) 0.32 [0.20; 0.51] proximal DVT 0.35 [0.15; 0.82] asymptomatic DVT 0.33 [0.20; 0.54] total VTE and all-cause mortality 0.36 [0.23; 0.56] major VTE (fatal and non fatal DVT,PE) 0.40 [0.17; 0.94] | | death 2.99 [0.31; 28.73] coronary events 1.66 [0.40; 6.93] major bleeding 1.22 [0.65; 2.26] myocardial infarction 2.24 [0.69; 7.27] non-fatal PE 0.40 [0.08; 2.05] Symptomatic venous thromboembolism 0.40 [0.04; 4.00] symptomatic DVT 0.20 [0.02; 1.71] major or clinically relevant non-major bleeding 0.96 [0.76; 1.21] |
| Trial | Treatments | Patients | Method |
|---|
| ADVANCE 3, 2010 | apixaban 2.5mg twice daily for 35 days (n=2708) vs. enoxaparin 40mg once daily for 35 days (n=2699) | patients undergoing elective total hip replacement surgery | double blind Parallel groups Sample size: 2708/2699 Primary endpoint: asymptomatic and symptomatic DVT, PE,all-cause death FU duration: 35 days (+60) |
|
| thrombosis prevention | apixaban | knee surgery | versus Low molecular weight heparin No demonstrated result for efficacy | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| APROPOS 2.5mg, 2007 | apixaban vs enoxaparin (US regimen) | | | death ∞ [NaN; ∞] major bleeding NaN [NaN; NaN] proximal DVT 0.33 [0.03; 3.10] asymptomatic DVT 0.63 [0.29; 1.40] total VTE and all-cause mortality 0.39 [0.08; 1.98] major VTE (fatal and non fatal DVT,PE) 0.58 [0.28; 1.20] symptomatic DVT 0.98 [0.06; 15.50] all bleeding 0.73 [0.26; 2.04] | | ADVANCE-1, 2008 | apixaban vs enoxaparin (US regimen) | major or clinically relevant non-major bleeding 0.67 [0.47; 0.97] | | death 1.00 [0.20; 4.94] coronary events 0.50 [0.05; 5.48] major bleeding 0.50 [0.24; 1.02] myocardial infarction 0.40 [0.08; 2.05] DVT (asymptomatic or symptomatic) 0.95 [0.72; 1.26] proximal DVT 0.79 [0.33; 1.89] total VTE and all-cause mortality 1.02 [0.78; 1.32] Symptomatic venous thromboembolism 1.46 [0.72; 2.94] | | ADVANCE 2, 2010 | apixaban vs enoxaparin (europe regimen) | DVT (asymptomatic or symptomatic) 0.60 [0.50; 0.72] proximal DVT 0.35 [0.16; 0.74] total VTE and all-cause mortality 0.62 [0.51; 0.74] major VTE (fatal and non fatal DVT,PE) 0.50 [0.26; 0.97] | | death ∞ [NaN; ∞] coronary events 1.00 [0.06; 16.05] major bleeding 0.65 [0.28; 1.49] myocardial infarction 1.00 [0.06; 15.98] Symptomatic venous thromboembolism 1.00 [0.35; 2.85] symptomatic DVT 0.43 [0.11; 1.66] major or clinically relevant non-major bleeding 0.74 [0.52; 1.05] |
| Trial | Treatments | Patients | Method |
|---|
| APROPOS 2.5mg, 2007 | apixaban 2.5mg BID for 12 days (n=153) vs. enoxaparin 30mg twice daily for 12 days (n=152) 8 arms: apixaban 2.5mg BID, 5mg BID, 10mg BID, 5mgQD, 20mg QD for 12 days, enoxaparin 30mg twice daily, warfarin INR 1.8-3.0 | patients undergoing elective total knee replacement surgery | double blind Parallel groups Sample size: 153/152 Primary endpoint: VTE events and all-cause death FU duration: 12 days phase 2 dose ranging study | | ADVANCE-1, 2008 | apixaban 2.5 mg orally twice daily for 10 to 14 days (n=1599) vs. enoxaparin 30mg subcutaneously every 12 hours for 10-14 days (n=1596) | patients undergoing knee-replacement surgery | double blind Parallel groups Sample size: 1599/1596 Primary endpoint: a- and symptomatic DVT, non fatal PE, death FU duration: 10-14 days | | ADVANCE 2, 2010 | apixaban 2.5mg twice daily during 12 days (n=1528) vs. enoxaparin 40mg once daily 12 days (n=1529) "European" enoxaprin regimen | patients undergoing elective unilateral or bilateral total knee replacement | double blind Parallel groups Sample size: 1528/1529 Primary endpoint: asymptomatic and symptomatic proximal DVT, PE, VTE-related death FU duration: 12 days |
|
| thrombosis prevention | dabigatran | hip surgery | versus Low molecular weight heparin No demonstrated result for efficacy dabigatran 150mg inferior to enoxaparin in terms of symptomatic DVT in RE-NOVATE (150mg), 2007 (hip surgery patients) | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| RE-NOVATE (220mg), 2007 | dabigatran 220mg vs enoxaparin | | | death ∞ [NaN; ∞] major bleeding 1.29 [0.70; 2.37] proximal DVT 0.57 [0.32; 1.00] distal DVT 0.94 [0.53; 1.66] non-fatal PE 1.70 [0.41; 7.09] asymptomatic DVT 0.73 [0.49; 1.08] total VTE and all-cause mortality 0.90 [0.63; 1.29] major VTE (fatal and non fatal DVT,PE) 0.78 [0.48; 1.27] symptomatic DVT 6.03 [0.73; 49.98] | | RE-NOVATE (150mg), 2007 | dabigatran 150mg vs enoxaparin | | symptomatic DVT 8.89 [1.13; 70.07] | death NaN [NaN; NaN] coronary events 0.72 [0.31; 1.68] major bleeding 0.83 [0.42; 1.63] proximal DVT 0.90 [0.55; 1.49] distal DVT 1.50 [0.90; 2.50] non-fatal PE 0.33 [0.03; 3.16] asymptomatic DVT 1.15 [0.82; 1.63] total VTE and all-cause mortality 1.28 [0.93; 1.78] major VTE (fatal and non fatal DVT,PE) 1.09 [0.70; 1.70] | | RE-NOVATE 2 | dabigatran 220mg vs enoxaparin | | | coronary events 0.99 [0.06; 15.86] |
| Trial | Treatments | Patients | Method |
|---|
| RE-NOVATE (220mg), 2007 | dabigatran etexilate 220 mg q.d. for 28-35 days (n=1157) vs. Enoxaparin 40 mg q.d. for 23-35 days (n=1162) 3 arms dabigatran 220mg, 150mg and placebo | Total hip replacement | double blind Parallel groups Sample size: 1157/1162 Primary endpoint: total VTE and all-cause mortality FU duration: 28-35 days, median 33d | | RE-NOVATE (150mg), 2007 | dabigatran etexilate 150 mg q.d. 28-35 days
(n=1174) vs. Enoxaparin 40 mg q.d. for 28-25 days (n=1162) 3 arms dabigatran 220mg, 150mg and placebo
| Total hip replacement
| double blind Sample size: 1174/1162 Primary endpoint: total VTE and all-cause mortality FU duration: 28-35 days, median 33d
| | RE-NOVATE 2 | dabigatran 220mg once daily for 28-35 Days (n=1010) vs. enoxaparin 40mg subcutaneous once daily for 28-35 Days (n=1003) | patients undergoing total hip-replacement surgery | double-blind Parallel groups Sample size: 1010/1003 Primary endpoint: venous thromboembolism or death FU duration: 28-35 days (mean 32d) |
|
| thrombosis prevention | dabigatran | knee surgery | versus Low molecular weight heparin No demonstrated result for efficacy dabigatran 220mg inferior to enoxaparin (US regimen) in terms of total VTE and all-cause mortality in RE-MOBILIZE (220mg), 2008 (knee surgery patients) dabigatran 150mg inferior to enoxaparin (US regimen) in terms of distal DVT in RE-MOBILIZE (150mg), 2008 (knee surgery patients) dabigatran 150mg inferior to enoxaparin (US regimen) in terms of total VTE and all-cause mortality in RE-MOBILIZE (150mg), 2008 (knee surgery patients) | 4 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| RE-MOBILIZE (220mg), 2008 | dabigatran 220mg vs enoxaparin (US regimen) | | total VTE and all-cause mortality 1.23 [1.03; 1.47] | coronary events 1.05 [0.48; 2.31] major bleeding 0.42 [0.15; 1.19] proximal DVT 1.49 [0.67; 3.33] distal DVT 1.20 [0.99; 1.45] major VTE (fatal and non fatal DVT,PE) 1.51 [0.79; 2.91] major or clinically relevant non-major bleeding 0.86 [0.52; 1.41] | | RE-MODEL (220mg), 2007 | dabigatran 220mg vs enoxaparin (europe regimen) | | | death 1.01 [0.06; 16.19] coronary events 1.26 [0.40; 3.99] major bleeding 1.14 [0.46; 2.78] proximal DVT 0.82 [0.40; 1.69] distal DVT 1.02 [0.85; 1.21] asymptomatic DVT 1.00 [0.85; 1.18] total VTE and all-cause mortality 0.97 [0.82; 1.13] major VTE (fatal and non fatal DVT,PE) 0.73 [0.36; 1.47] symptomatic DVT 0.13 [0.02; 1.01] major or clinically relevant non-major bleeding 1.11 [0.76; 1.63] | | RE-MODEL (150mg), 2007 | dabigatran 150mg vs enoxaparin (europe regimen) | | | death 0.98 [0.06; 15.70] major bleeding 0.99 [0.39; 2.47] proximal DVT 1.03 [0.54; 1.98] distal DVT 1.07 [0.91; 1.27] non-fatal PE ∞ [NaN; ∞] asymptomatic DVT 1.10 [0.94; 1.29] total VTE and all-cause mortality 1.07 [0.92; 1.25] major VTE (fatal and non fatal DVT,PE) 1.08 [0.58; 2.01] symptomatic DVT 0.37 [0.10; 1.37] major or clinically relevant non-major bleeding 1.22 [0.84; 1.78] | | RE-MOBILIZE (150mg), 2008 | dabigatran 150mg vs enoxaparin (US regimen) | | distal DVT 1.33 [1.10; 1.59] total VTE and all-cause mortality 1.33 [1.12; 1.58] | death ∞ [NaN; ∞] major bleeding 0.42 [0.15; 1.17] non-fatal PE 0.00 [0.00; NaN] major VTE (fatal and non fatal DVT,PE) 1.36 [0.70; 2.63] major or clinically relevant non-major bleeding 0.82 [0.49; 1.34] |
| Trial | Treatments | Patients | Method |
|---|
| RE-MOBILIZE (220mg), 2008 | dabigatran etexilate 220 mg for 12-15 days
(n=862) vs. Enoxaparin 30mg SC BID after surgery for 12-15 days (n=876)
| Total knee replacement
| double blind Parallel groups Sample size: 862/876 Primary endpoint: total VTE and all-cause mortality FU duration: 12-15 days, median 14d
| | RE-MODEL (220mg), 2007 | dabigatran etexilate 220 mg q.d. 6-10 days
(n=694) vs. Enoxaparin 40 mg q.d. for 6-10 days (n=699)
| patients undergoing total knee replacement | double blind Sample size: 694/699 Primary endpoint: total VTE and all-cause mortality FU duration: 6-10 days, mean 8 days
| | RE-MODEL (150mg), 2007 | dabigatran etexilate 150 mg q.d. for 6-10 days (n=708) vs. Enoxaparin 40 mg q.d. for 6-10 days (n=699)
| Total knee replacement
| double blind Parallel groups Sample size: 708/699 Primary endpoint: total VTE and all-cause mortality FU duration: 6-10 days, mean 8 days
| | RE-MOBILIZE (150mg), 2008 | dabigatran etexilate 150 mg q.d. for 12-15 days
(n=877) vs. enoxaparin 30 mg SC BID after surgery for 12-15 days
(n=876)
| Total knee replacement
| double blind Sample size: 877/876 Primary endpoint: total VTE and all-cause mortality FU duration: 12-15 days, median 14d
|
|
| thrombosis prevention | edoxaban | hip surgery | versus No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| STARS J-V | edoxaban vs enoxaparin (short duration) | distal DVT 0.36 [0.15; 0.92] asymptomatic DVT 0.38 [0.16; 0.89] major VTE (fatal and non fatal DVT,PE) 0.34 [0.14; 0.86] | | proximal DVT 0.49 [0.04; 5.33] symptomatic DVT NaN [NaN; NaN] |
| Trial | Treatments | Patients | Method |
|---|
| STARS J-V | edoxaban 30 mg once daily for 11 to 14 days (n=255) vs. subcutaneous enoxaparin 2,000 IU, equivalent to 20 mg, twice daily (BID) for 11 to 14 days (n=248) | total hip arthroplasty | double-blind Parallel groups Sample size: 255/248 Primary endpoint: all DVT,PE FU duration: |
|
| thrombosis prevention | phenindione | not classified | versus placebo or no treatment No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Phenindione vs no treatment | | | | | Phenindione vs no treatment | | | |
| Trial | Treatments | Patients | Method |
|---|
| Eskeland, 1966 | Phenindione (n=100) vs. No treatment (n=100) | HFS | Open Sample size: 100/100 Primary endpoint: FU duration: 3 months | | Hamilton, 1970 | Phenindione (n=38) vs. No treatment (n=38) | HFS | Open Sample size: 38/38 Primary endpoint: FU duration: 3–10 months |
|
| thrombosis prevention | rivaroxaban | hip surgery | versus Low molecular weight heparin No demonstrated result for efficacy | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ODIXa-HIP 10mg, 2006 | rivaroxaban vs enoxaparin (short duration) | DVT (asymptomatic or symptomatic) 0.42 [0.22; 0.79] distal DVT 0.36 [0.17; 0.73] total VTE and all-cause mortality 0.42 [0.22; 0.79] | | proximal DVT 0.95 [0.20; 4.59] non-fatal PE NaN [NaN; NaN] | | RECORD 1, 2008 | rivaroxaban vs enoxaparin | DVT (asymptomatic or symptomatic) 0.23 [0.12; 0.43] proximal DVT 0.03 [0.00; 0.23] total VTE and all-cause mortality 0.30 [0.18; 0.51] major VTE (fatal and non fatal DVT,PE) 0.12 [0.04; 0.34] | | death 0.98 [0.24; 3.90] coronary events 0.49 [0.12; 1.95] major bleeding 3.02 [0.61; 14.95] distal DVT 0.49 [0.24; 1.00] non-fatal PE 3.91 [0.44; 34.92] Symptomatic venous thromboembolism 0.55 [0.20; 1.48] | | RECORD 2, 2008 | rivaroxaban (long duration) vs enoxaparin (short duration) | DVT (asymptomatic or symptomatic) 0.20 [0.11; 0.35] proximal DVT 0.11 [0.05; 0.29] distal DVT 0.34 [0.16; 0.71] total VTE and all-cause mortality 0.21 [0.13; 0.35] Symptomatic venous thromboembolism 0.20 [0.06; 0.69] major VTE (fatal and non fatal DVT,PE) 0.12 [0.05; 0.28] | | death 0.34 [0.07; 1.66] coronary events 1.33 [0.30; 5.95] major bleeding 1.00 [0.06; 15.98] non-fatal PE 0.25 [0.03; 2.25] major or clinically relevant non-major bleeding 1.20 [0.93; 1.54] |
| Trial | Treatments | Patients | Method |
|---|
| ODIXa-HIP 10mg, 2006 | rivaroxaban 10mg daily for 5–9 days (n=142) vs. once-daily subcutaneous enoxaparin dose of 40 mg for 5–9 days (n=157) dose finding study (doses of 5, 10, 20, 30, or 40 mg) | patients undergoing elective total hip replacement | double blind Parallel groups Sample size: 142/157 Primary endpoint: any DVT, PE, all cause death FU duration: 5-9 days | | RECORD 1, 2008 | rivaroxaban 10mg once daily for 35 days (n=2266) vs. enoxaparin 40mg subcutaneous once daily for 31-39 days (n=2275) | patients undergoing total hip arthroplasty | double blind Parallel groups Sample size: 2266/2275 Primary endpoint: DVT, PE, death FU duration: 36 days (range 30-42) | | RECORD 2, 2008 | extended thromboprophylaxis with rivaroxaban 10mg once daily for 31-39 days (n=1252) vs. enoxaparin 40mg subcutaneous once daily for 10-14 days (n=1257) | patients undergoing elective total hip replacement | double blind Parallel groups Sample size: 1252/1257 Primary endpoint: DVT, PE , all cause death FU duration: 30-42 days |
|
| thrombosis prevention | rivaroxaban | knee surgery | versus Low molecular weight heparin No demonstrated result for efficacy | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ODIXa-KNEE, 2005 | rivaroxaban vs enoxaparin (US regimen) | | | major bleeding 0.00 [0.00; NaN] | | RECORD 3, 2008 | rivaroxaban vs enoxaparin (europe regimen) | DVT (asymptomatic or symptomatic) 0.53 [0.41; 0.68] distal DVT 0.53 [0.41; 0.70] total VTE and all-cause mortality 0.51 [0.39; 0.65] Symptomatic venous thromboembolism 0.34 [0.15; 0.75] major VTE (fatal and non fatal DVT,PE) 0.38 [0.18; 0.82] | | death 0.00 [0.00; NaN] coronary events 0.51 [0.05; 5.59] major bleeding 1.19 [0.40; 3.53] myocardial infarction 0.51 [0.05; 5.61] proximal DVT 0.48 [0.22; 1.05] non-fatal PE 0.00 [0.00; NaN] | | RECORD 4, 2009 | rivaroxaban vs enoxaparin (US regimen) | proximal DVT 0.23 [0.07; 0.80] total VTE and all-cause mortality 0.69 [0.51; 0.92] | | death 0.66 [0.11; 3.94] coronary events 0.33 [0.03; 3.16] major bleeding 2.47 [0.78; 7.86] myocardial infarction 0.20 [0.02; 1.69] distal DVT 0.82 [0.57; 1.17] non-fatal PE 0.49 [0.15; 1.64] asymptomatic DVT 0.72 [0.51; 1.01] Symptomatic venous thromboembolism 0.60 [0.29; 1.27] major VTE (fatal and non fatal DVT,PE) 0.59 [0.30; 1.16] symptomatic DVT 0.60 [0.22; 1.63] major or clinically relevant non-major bleeding 1.34 [0.86; 2.07] |
| Trial | Treatments | Patients | Method |
|---|
| ODIXa-KNEE, 2005 | BAY 59-7939 5mg b.i.d. for 5–9 days (n=102) vs. enoxaparin 30 mg b.i.d. for 5–9 days (n=105) dose ranging study with doses 2.5, 5, 10, 20, and 30 mg | patients undergoing elective total knee replacement | double blind Parallel groups Sample size: 102/105 Primary endpoint: FU duration: 5-9 days | | RECORD 3, 2008 | rivaroxaban 10 mg once daily for 10- 14 days (n=1254) vs. enoxaparin 40 mg subcutaneous once daily for 10-14 days (n=1277) | patients undergoing total knee arthroplasty | double blind Parallel groups Sample size: 1254/1277 Primary endpoint: DVT, PE all cause mortality FU duration: 13-17 days | | RECORD 4, 2009 | rivaroxaban 10mg once daily for 10 to 14 days (n=1584) vs. enoxaparin 30 mg twice daily by subcutaneous injection for 10-14 days (n=1564) | patients who had undergone total-knee-replacement surgery | double blind Parallel groups Sample size: 1584/1564 Primary endpoint: total VTE events FU duration: 40 days |
|
| thrombosis prevention | warfarin | not classified | versus placebo or no treatment No demonstrated result for efficacy | 5 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Warfarin vs placebo | | | | | Warfarin vs no treatment | | | | | Warfarin vs no treatment | | | | | Warfarin vs no treatment | | | | | Warfarin vs no treatment | | | |
| Trial | Treatments | Patients | Method |
|---|
| Myrhe, 1969 | Wwarfarin (n=50) vs. Placebo (n=55) | HFS | double blind Sample size: 50/55 Primary endpoint: FU duration: 3 weeks | | Pinto, 1970 | Warfarin (n=25) vs. No treatment (n=25) | Hip surgery | Open Sample size: 25/25 Primary endpoint: FU duration: > 3 weeks | | Hume, 1973 | Warfarin (n=17) vs. No treatment (n=19) | THR | Open Sample size: 17/19 Primary endpoint: FU duration: Discharge | | Morris, 1976 | Warfarin (n=80) vs. No treatment (n=80) | HFS | Open Sample size: 80/80 Primary endpoint: FU duration: 3 months | | Powers, 1989 | Warfarin (n=65) vs. No treatment (n=63) | HFS | Open Sample size: 65/63 Primary endpoint: FU duration: 3 months |
|
| thrombosis prevention | warfarin | not classified | versus antiplatelet drugs No demonstrated result for efficacy | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Warfarin vs Sudoxicam | | | | | Warfarin vs Aspirin | | | | | Warfarin vs Aspirin | | | |
| Trial | Treatments | Patients | Method |
|---|
| Hume, 1973 | Warfarin (n=52) vs. Sudoxicam (n=51) | THR | single blind Sample size: 52/51 Primary endpoint: FU duration: Discharge | | Powers, 1989 | Warfarin (n=65) vs. Aspirin 650 mg x2 (n=66) | HFS | Open Sample size: 65/66 Primary endpoint: FU duration: 3 months | | Lotke, 1997 | Warfarin (n=146) vs. Aspirin 325 mg x2 (n=166) | THR or TKR (stratified) | Open Sample size: 146/166 Primary endpoint: FU duration: 6 months |
|
| thrombosis prevention | warfarin | not classified | versus Danaparoid No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Warfarin vs Danaparoid | | | | | Warfarin vs Danaparoid | | | |
| Trial | Treatments | Patients | Method |
|---|
| Gerhart, 1991 | Warfarin (n=131) vs. Danaparoid 750 U x2 (n=132) | HFS | Open Sample size: 131/132 Primary endpoint: FU duration: 9 days | | van Comp, 1998 | Warfarin (n=247) vs. Danaparoid 750 U x2 (n=241) | THR | Open Sample size: 247/241 Primary endpoint: FU duration: 3 months |
|
| thrombosis prevention | warfarin | not classified | versus Dextran No demonstrated result for efficacy | 4 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Warfarin vs Dextran | | | | | Warfarin vs Dextran | | | | | Warfarin vs Dextran | | | | | Warfarin vs Dextran | | | |
| Trial | Treatments | Patients | Method |
|---|
| Myrhe, 1969 | Warfarin (n=50) vs. Dextran 70 (n=55) | HFS | double blind Sample size: 50/55 Primary endpoint: FU duration: 3 weeks | | Harris, 1972 | Warfarin (n=114) vs. Dextran 40 (n=113) | THR | Open Sample size: 114/113 Primary endpoint: FU duration: NA | | Barber, 1977 | Warfarin (n=58) vs. Dextran 70 (n=51) | THR | Open Sample size: 58/51 Primary endpoint: FU duration: 11–14 days | | Francis, 1983 | Warfarin (n=57) vs. Dextran 40 (n=43) | THR or TKR (stratified) | Open Sample size: 57/43 Primary endpoint: FU duration: 5–7 days |
|
| thrombosis prevention | warfarin | not classified | versus intermittent pneumatic compression No demonstrated result for efficacy | 4 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Warfarin vs Intermittent pneumatic compression | | | | | Warfarin vs Intermittent pneumatic compression | | | | | Warfarin vs Intermittent pneumatic compression | | | | | Warfarin vs Intermittent pneumatic compression | | | |
| Trial | Treatments | Patients | Method |
|---|
| Paiement, 1987 | Warfarin (n=80) vs. IPC (n=83) | THR | Open Sample size: 80/83 Primary endpoint: FU duration: 12 days | | Bailey, 1991 | Warfarin (n=45) vs. IPC (n=50) | THR | Open Sample size: 45/50 Primary endpoint: FU duration: 5–7 days | | Kaempffe, 1991 | Warfarin (n=52) vs. IPC (n=48) | THR or TKR (stratified) | Open Sample size: 52/48 Primary endpoint: FU duration: At least 2 months | | Francis, 1992 | Warfarin (n=103) vs. IPC (n=98) | THR | Open Sample size: 103/98 Primary endpoint: FU duration: 6–8 days |
|
| thrombosis prevention | warfarin | not classified | versus Low molecular weight heparin No demonstrated result for efficacy | 8 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Hull, 1993 | Warfarin vs Logiparin | DVT 1.19 [1.02; 1.40] | | | | RD Heparin, 1994 | Warfarin vs Ardeparin | DVT 1.44 [1.12; 1.86] | | | | Leclerc, 1996 | Warfarin vs Enoxaparin | DVT 1.40 [1.12; 1.75] | | | | Francis, 1997 | Warfarin vs Dalteparin | DVT 1.77 [1.16; 2.69] | | | | Heit, 1997 | Warfarin vs Ardeparin | DVT 1.31 [1.05; 1.63] | | | | Colwell, 1999 | Warfarin vs Enoxaparin | DVT 5.07 [1.47; 17.48] | | | | Hull, 2000 | Warfarin vs Dalteparin | DVT 2.02 [1.52; 2.67] | | | | Fitzgerald, 2001 | Warfarin vs Enoxaparin | DVT 1.51 [1.08; 2.11] | | |
| Trial | Treatments | Patients | Method |
|---|
| Hull, 1993 | Warfarin (n=721) vs. Logiparin 75 anti-Xa IU /kg x1 (n=715) | THR or TKR (stratified) | double blind Sample size: 721/715 Primary endpoint: FU duration: Day 14 or discharge | | RD Heparin, 1994 | Warfarin (n=403) vs. Ardeparin 50 anti-Xa IU /kg or 90 anti-Xa IU /kg x1 (n=770) | THR or TKR | Open Sample size: 403/770 Primary endpoint: FU duration: 3 months | | Leclerc, 1996 | Warfarin (n=334) vs. Enoxaparin 30 mg x2 (n=336) | TKR | double blind Sample size: 334/336 Primary endpoint: FU duration: 6 months | | Francis, 1997 | Warfarin (n=292) vs. Dalteparin 5000 anti-Xa IU x1 (n=288) | THR | Open Sample size: 292/288 Primary endpoint: FU duration: Day 7 ± 2 | | Heit, 1997 | Warfarin (n=279) vs. Ardeparin 25, 35, 50 anti-Xa U /kg x2 (n=554) | TKR | double blind Sample size: 279/554 Primary endpoint: FU duration: Days 5–14 | | Colwell, 1999 | Warfarin (n=1495) vs. Enoxaparin 30 mg x2 (n=1516) | THR | Open Sample size: 1495/1516 Primary endpoint: FU duration: 3 months | | Hull, 2000 | Warfarin (n=489) vs. Dalteparin 5000 anti-Xa IU x1 (n=983) | THR | double blind Sample size: 489/983 Primary endpoint: FU duration: Day 6 ± 2 | | Fitzgerald, 2001 | Warfarin (n=176) vs. Enoxaparin 30 mg x2 (n=173) | TKR | Open Sample size: 176/173 Primary endpoint: FU duration: 3 weeks |
|
| thrombosis prevention | warfarin | not classified | versus unfractionated heparin No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Warfarin vs unfractionated heparin | | | | | Warfarin vs unfractionated heparin | | | |
| Trial | Treatments | Patients | Method |
|---|
| Hume, 1973 | Warfarin (n=17) vs. UFH 5000 x3 (n=18) | THR | Open Sample size: 17/18 Primary endpoint: FU duration: Discharge | | Barber, 1977 | Warfarin (n=58) vs. UFH 5000 x2 (n=19) | THR | Open Sample size: 58/19 Primary endpoint: FU duration: 11–14 days |
|
