| mechanism | treatment | Demonstrated benefit and harm | k | | | |
|---|
| anti-anginal drugs | ranolazine | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| MERLIN TIMI 36, 2007 | ranolazine vs placebo | Recurrent ischemia 0.87 [0.77; 0.98] | | Death from any cause 0.98 [0.80; 1.20] cardiovascular death 0.99 [0.80; 1.24] MI 0.97 [0.82; 1.16] |
| Trial | Treatments | Patients | Method |
|---|
| MERLIN TIMI 36, 2007 | ranolazine 1000 mg twice daily for the duration of the trial (intitialy 200 mg intravenously for 1 hour, followed by an 80 mg/h intravenous infusion) (n=3279) vs. placebo (n=3281) | Hospitalized with NSTE-ACS; ischemic symptoms at rest within 48 hours; and at least one indicator of moderate to high risk, defined as elevated troponin or creatine kinase-myocardial band, ST-depression >0.1 mV, diabetes, or TIMI risk score for unstable angina/NSTEMI >=3 | Double blind Parallel groups Sample size: 3279/3281 Primary endpoint: CV death, MI, or recurrent ischemia FU duration: median 11.4 months |
|
| antithrombotics | apixaban | 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 |
|
| antithrombotics | argatroban | versus heparin No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ARGAMI-2, 1998 | Argatroban vs heparin | | | |
| Trial | Treatments | Patients | Method |
|---|
| ARGAMI-2, 1998 | Argatroban 60–20 mg/kg bolus; 2–4 µg /kg/min infusion for 72h (n=-9) vs. UFH 5000 IU bolus; 1000 IU/h infusion (n=-9) | AMI | Sample size: -9/-9 Primary endpoint: FU duration: 30 days |
|
| antithrombotics | aspirin | versus placebo or control No demonstrated result for efficacy | 8 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| VA-pilot | aspirin vs placebo | | | Vasc events 0.23 [0.03; 1.92] Major bleeds NaN [NaN; NaN] Vasc deaths 0.31 [0.03; 2.76] Non-fatal stroke NaN [NaN; NaN] Non-fatal MI 0.00 [0.00; NaN] Non vasc deaths NaN [NaN; NaN] cardiovascular events 0.23 [0.03; 1.92] | | VA-main, 1983 | aspirin vs placebo | Vasc events 0.61 [0.43; 0.88] Non-fatal MI 0.56 [0.36; 0.89] cardiovascular events 0.61 [0.43; 0.88] | | Major bleeds NaN [NaN; NaN] Vasc deaths 0.64 [0.34; 1.21] Non-fatal stroke 1.54 [0.26; 9.17] Non vasc deaths NaN [NaN; NaN] | | Canadian (Aspirin + sulfinpyrazone), 1985 | aspirin + sulfinpyrazone vs placebo | | | Vasc events 0.90 [0.56; 1.45] Major bleeds NaN [NaN; NaN] Vasc deaths 0.72 [0.38; 1.35] Non-fatal stroke ∞ [NaN; ∞] Non-fatal MI 1.15 [0.50; 2.60] Non vasc deaths ∞ [NaN; ∞] cardiovascular events 0.90 [0.56; 1.45] | | RISC, 1990 | aspirin vs placebo | Vasc events 0.53 [0.38; 0.74] Non-fatal MI 0.52 [0.35; 0.76] cardiovascular events 0.53 [0.38; 0.74] | | Major bleeds NaN [NaN; NaN] Vasc deaths 0.56 [0.25; 1.25] Non-fatal stroke NaN [NaN; NaN] Non vasc deaths 0.99 [0.14; 7.03] | | ALDUSA-pilot | aspirin vs placebo | | | Vasc events 3.50 [0.45; 27.07] Major bleeds NaN [NaN; NaN] Vasc deaths 0.50 [0.03; 7.70] Non-fatal stroke ∞ [NaN; ∞] Non-fatal MI ∞ [NaN; ∞] Non vasc deaths NaN [NaN; NaN] cardiovascular events 3.50 [0.45; 27.07] | | Théroux, 1988 | aspirin vs placebo | Non-fatal MI 0.28 [0.09; 0.82] fatal and non fatal MI 0.28 [0.09; 0.82] | | Vasc events 0.63 [0.38; 1.04] cardiovascular events 0.63 [0.38; 1.04] refractory ischemia 0.72 [0.43; 1.21] | | ATACS-pilot, 1990 | aspirin vs control | | | Vasc events 0.00 [0.00; NaN] Major bleeds NaN [NaN; NaN] Vasc deaths 0.00 [0.00; NaN] Non-fatal MI 0.00 [0.00; NaN] Non vasc deaths NaN [NaN; NaN] cardiovascular events 0.00 [0.00; NaN] | | Canadian (Aspirin vs PBO), 1985 | aspirin vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| VA-pilot | Aspirin 324 mg/d (n=26) vs. (n=24) | | Sample size: 26/24 Primary endpoint: FU duration: 3m | | VA-main, 1983 | Aspirin 324mg/d (n=661) vs. placebo (n=677) | men with unstable angina | double blind Sample size: 661/677 Primary endpoint: FU duration: 3m | | Canadian (Aspirin + sulfinpyrazone), 1985 | Aspirin 1300mg/d + sulfinpyrazone 800mg/d (n=416) vs. placebo (n=139) | patients with unstable angina | double blind Sample size: 416/139 Primary endpoint: FU duration: 18m | | RISC, 1990 | Aspirin 75mg/d (n=474) vs. placebo (n=471) half of the patients received heparin in a 2x2 factorial design | men with unstable coronary artery disease (unstable angina or non-Q wave myocardial infarction | double blind Factorial plan Sample size: 474/471 Primary endpoint: FU duration: 12m | | ALDUSA-pilot | Aspirin 325mg/d, Aspirin 40mg/d (n=56) vs. (n=28) | | Sample size: 56/28 Primary endpoint: FU duration: 12m | | Théroux, 1988 | Aspirin 325 mg twice daily (n=121) vs. placebo (n=118) | acute unstable angina | double blind Sample size: 121/118 Primary endpoint: FU duration: 6d (3m) | | ATACS-pilot, 1990 | Aspirin 80mg/d (Heparin + Warfarin) (n=37) vs. full-dose heparin followed by warfarin (n=24) | acute coronary syndromes | Sample size: 37/24 Primary endpoint: FU duration: 3m | | Canadian (Aspirin vs PBO), 1985 | Aspirin 1300mg/d (n=-9) vs. placebo
(n=139)
| patients with unstable angina
| double blind Sample size: -9/139 Primary endpoint: FU duration: 18m
|
|
| antithrombotics | atopaxar | versus placebo or control No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| LANCELOT ACS | atopaxar vs placebo | | | | | J-LANCELOT, 2010 | atopaxar vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| LANCELOT ACS | 400-mg loading dose of atopaxar followed by a daily dose of 50 mg, 100 mg, or 200 mg for 12 weeks (n=603) vs. placebo (n=0) | unstable-angina or non-STEMI patients | Parallel groups Sample size: 603/0 Primary endpoint: FU duration: pahse 2 | | J-LANCELOT, 2010 | atopaxar at a loading dose of 400 mg followed by 50 mg per day, 100 mg per day, or 200 mg per day for 12 weeks (n=-9) vs. atopaxar at a loading dose of 400 mg followed by placebo (n=-9) | patients with acute coronary syndrome (unstable angina and NSTEMI) | Parallel groups Sample size: -9/-9 Primary endpoint: bleeding events FU duration: phase 2 study |
|
| antithrombotics | bivalirudin | versus No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ACUITY (biva alone vs hep+aGP2b3a), 2006 | bivalirudin vs heparin + GP2b3a inhibitors | major bleeding 0.77 [0.69; 0.87] major bleeding not related to CABG 0.53 [0.43; 0.65] ischemic events + bleeding 0.86 [0.77; 0.97] major bleeding TIMI 0.50 [0.35; 0.72] | | all cause death 1.19 [0.85; 1.67] MI 1.09 [0.92; 1.30] death, MI, unplanned revascularization 1.08 [0.93; 1.24] 1 yer MI 1.12 [0.97; 1.30] 1 year death from any cause 0.98 [0.80; 1.21] I year Unplanned revascularization for ischemia 1.04 [0.91; 1.20] 1 year composite ischemia 1.05 [0.96; 1.16] | | ACUITY (biva+aGP2b3a vs hep+aGP2b3a), 2006 | bivalirudin + GP2b3a inhibitors vs heparin + GP2b3a inhibitors | | | all cause death 1.13 [0.80; 1.58] major bleeding 0.94 [0.84; 1.06] MI 1.01 [0.84; 1.21] death, MI, unplanned revascularization 1.07 [0.92; 1.23] major bleeding not related to CABG 0.93 [0.78; 1.10] ischemic events + bleeding 1.01 [0.90; 1.12] major bleeding TIMI 0.88 [0.65; 1.20] 1 yer MI 1.03 [0.89; 1.20] 1 year death from any cause 1.01 [0.82; 1.24] I year Unplanned revascularization for ischemia 1.09 [0.95; 1.24] 1 year composite ischemia 1.04 [0.95; 1.15] |
| Trial | Treatments | Patients | Method |
|---|
| ACUITY (biva alone vs hep+aGP2b3a), 2006 | bivalirudin alone (n=4612) vs. unfractionated heparin or enoxaparin plus a glycoprotein IIb/IIIa inhibitor (n=4603) 3 arms: unfractionated heparin or enoxaparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin alone | in patients with moderate- or high-risk acute coronary syndromes who were undergoing an early invasive strategy. | double blind Parallel groups Sample size: 4612/4603 Primary endpoint: hierarchical endpoint testing FU duration: 30 days | | ACUITY (biva+aGP2b3a vs hep+aGP2b3a), 2006 | bivalirudin plus a glycoprotein IIb/IIIa inhibitor
(n=4604) vs. unfractionated heparin or enoxaparin plus a glycoprotein IIb/IIIa inhibitor
(n=4603) 3 arms: unfractionated heparin or enoxaparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin alone
| in patients with moderate- or high-risk acute coronary syndromes who were undergoing an early invasive strategy.
| double blind Sample size: 4604/4603 Primary endpoint: hierarchical endpoint testing FU duration: 30 days
|
|
| antithrombotics | bivalirudin | versus eptifibatide + heparin No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| PROTECT-TIMI 30, 2006 | bivalirudin vs eptifibatide + heparin | | | |
| Trial | Treatments | Patients | Method |
|---|
| PROTECT-TIMI 30, 2006 | bivalirudin alone (n=284) vs. eptifibatide plus either unfractionated heparin or enoxaparin (n=573) 3 arms trial: eptifibatide reduced dose unfractionated heparin (n=298), eptifibatide reduced-dose enoxaparin (n=275), or bivalirudin monotherapy (n=284) | non ST elevation ACS patients undergoing PCI | open Parallel groups Sample size: 284/573 Primary endpoint: Coronary flow reserve FU duration: hospital stay |
|
| antithrombotics | bivalirudin | versus heparin No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| HERO, 1997 | bivalirudin vs heparin | Major bleeding 0.61 [0.42; 0.89] transfusion 0.51 [0.31; 0.85] | | Death 0.80 [0.36; 1.80] MI 0.60 [0.29; 1.26] coronary event 0.74 [0.46; 1.18] Minor bleeding 1.02 [0.84; 1.23] hemorrhagic stroke ∞ [NaN; ∞] | | BAT (Bittl), 1995 | bivalirudin vs heparin | Major bleeding 0.39 [0.30; 0.50] | | Death 2.23 [0.69; 7.22] MI 0.80 [0.58; 1.11] coronary event 0.89 [0.68; 1.16] long term death 1.62 [0.96; 2.74] long term CV event 0.98 [0.88; 1.09] |
| Trial | Treatments | Patients | Method |
|---|
| HERO, 1997 | Bivalirudin 0.125–0.250 mg/kg bolus; 0.125–0.500 mg /kg/min infusion for 72h (n=272) vs. UFH 5000 IU bolus; 1000–1200 IU/h infusion (n=140) 3 arms: low-dose, high dose hirulog and heparin | AMI (patients presenting within 12 hours with ST-segment elevation) | double blind Parallel groups Sample size: 272/140 Primary endpoint: TIMI3 of the infarct-related artery at 90 to 120 minutes FU duration: 35 days dose-finding study | | BAT (Bittl), 1995 | Bivalirudin 1.0 mg/kg bolus; 2.5 mg /kg/h for 4 h, then 0.2 mg /kg/h infusion for 24h (n=2059) vs. UFH 175 IU/kg bolus; 15 IU mg /kg/h infusion (n=2039) | patients undergoing angioplasty for unstable or postinfarction angina | double blind Parallel groups Sample size: 2059/2039 Primary endpoint: death, MI, abrupt vessel closure, clinical deterioration FU duration: 6 months |
|
| antithrombotics | bivalirudin | versus heparin+aGP2b3a No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ACUITY (sub groups PCI, bivalirudin +aGP2b3a) importé, 2007 | bivalirudin + GP2b3a inhibitors vs heparin + GP2b3a inhibitors | | | all cause death 1.28 [0.75; 2.20] Major bleeding (non-CABG related) 1.11 [0.91; 1.35] Myocardial infarction 1.17 [0.94; 1.45] Death, MI, urgent revascularization 1.14 [0.95; 1.36] ischemic event + bleeding 1.12 [0.98; 1.28] TIMI major bleeding 1.07 [0.75; 1.52] TIMI minor bleeding 1.08 [0.90; 1.31] | | ACUITY (sub groups PCI, bivalirudin alone) importé, 2007 | bivalirudin vs heparin + GP2b3a inhibitors | Major bleeding (non-CABG related) 0.52 [0.40; 0.66] TIMI major bleeding 0.55 [0.44; 0.69] TIMI minor bleeding 0.37 [0.23; 0.60] | | all cause death 1.19 [0.69; 2.06] Myocardial infarction 1.15 [0.93; 1.43] Death, MI, urgent revascularization 1.07 [0.90; 1.28] ischemic event + bleeding 0.87 [0.75; 1.00] |
| Trial | Treatments | Patients | Method |
|---|
| ACUITY (sub groups PCI, bivalirudin +aGP2b3a) importé, 2007 | bivalirudin +
(n=2609) vs. heparin (either unfractionated or
enoxaparin) plus glycoprotein
IIb/IIIa inhibitors
(n=2561) 2×2 factorial design with upstream
glycoprotein IIb/IIIa inhibitor initiation immediately after randomisation versus deferred glycoprotein
IIb/IIIa inhibitor initiation for selective use in the
catheterisation laboratory starting immediately before
percutaneous coronary intervention
| patients with moderate and high-risk acute coronary syndromes undergoing percutaneous
coronary intervention after angiography.
| open Sample size: 2609/2561 Primary endpoint: FU duration: 30 days
| | ACUITY (sub groups PCI, bivalirudin alone) importé, 2007 | bivalirudin alone (n=2619) vs. heparin (either unfractionated or enoxaparin) plus glycoprotein IIb/IIIa inhibitors (n=2561) 2×2 factorial design with upstream
glycoprotein IIb/IIIa inhibitor initiation immediately after randomisation versus deferred glycoprotein
IIb/IIIa inhibitor initiation for selective use in the
catheterisation laboratory starting immediately before
percutaneous coronary intervention | patients with moderate and high-risk acute coronary syndromes undergoing percutaneous
coronary intervention after angiography (sub group). | open Factorial plan Sample size: 2619/2561 Primary endpoint: FU duration: 30 days |
|
| antithrombotics | clopidogrel | versus placebo No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| CURE (PCI sub study), 2001 | clopidogrel vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| CURE (PCI sub study), 2001 | pretreatment with clopidogrel -+aspirin 75–325 mg) (n=1313) vs. placebo (+ aspirin 75–325 mg) (n=1345) | patients with non-ST-elevation acute coronary syndrome undergoing PCI | double blind Parallel groups Sample size: 1313/1345 Primary endpoint: ardiovascular death, MI, or urgent TVR FU duration: |
|
| antithrombotics | clopidogrel | versus aspirin No demonstrated result for efficacy clopidogrel + aspirin inferior to aspirin in terms of Major bleeds in CURE, 2001 | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| CURE, 2001 | clopidogrel + aspirin vs aspirin | Vasc events 0.82 [0.73; 0.90] fatal and non fatal MI 0.78 [0.68; 0.90] cardiovascular events 0.82 [0.73; 0.90] | Major bleeds 1.38 [1.13; 1.67] | Vasc deaths 0.93 [0.80; 1.08] Non vasc deaths 0.92 [0.60; 1.40] fatala and non fatal stroke 0.87 [0.64; 1.18] refractory ischemia 0.93 [0.83; 1.04] fatal bleeding 0.74 [0.34; 1.61] |
| Trial | Treatments | Patients | Method |
|---|
| CURE, 2001 | clopidogrel 300 mg immediately, followed by 75 mg once daily + aspirin for 3 to 12 months (n=6259) vs. aspirin (+placebo) (n=6303) | acute coronary syndromes without ST-segment elevation within 24 hours after the onset of symptoms | double blind Parallel groups Sample size: 6259/6303 Primary endpoint: CV death, MI, stroke FU duration: NA (median <9 months) |
|
| antithrombotics | clopidogrel | versus clopidogrel No demonstrated result for efficacy clopidogrel high-dose regimen inferior to clopidogrel standard-dose in terms of Major bleeds in CURRENT OASIS 7 (clopidogrel), 2010 | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| CURRENT OASIS 7 (clopidogrel), 2010 | clopidogrel high-dose regimen vs clopidogrel standard-dose | | Major bleeds 1.24 [1.05; 1.46] | vascular death, MI, stroke 0.94 [0.83; 1.06] Severe recurrent ischemia 0.93 [0.64; 1.36] Hemorrhagic stoke 0.67 [0.19; 2.37] Vasc events 0.94 [0.84; 1.06] all cause death 0.96 [0.82; 1.13] Vasc deaths 0.95 [0.81; 1.13] fatala and non fatal stroke 0.99 [0.70; 1.39] fatal and non fatal MI 0.86 [0.72; 1.02] cardiovascular events 0.94 [0.84; 1.06] fatal bleeding 1.07 [0.53; 2.16] |
| Trial | Treatments | Patients | Method |
|---|
| CURRENT OASIS 7 (clopidogrel), 2010 | Double-dose clopidogrel (n=12520) vs. Standard-dose clopidogrel (n=12566) patients were also assigned in an open-label manner to 300 to 325 mg of aspirin once daily or 75- to 100-mg aspirin once daily | ACS patients referred for an invasive strategy (scheduled for percutaneous coronary intervention no more than 72 hours after randomization) about two thirds eventually underwent PCI (although PCI was planned for everyone who was randomized, about a third of the patients did not undergo the procedure because they were not considered suitable based on angiography findings) | open Factorial plan Sample size: 12520/12566 Primary endpoint: CV death/MI/stroke FU duration: 30 days |
|
| antithrombotics | coumadin | 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 |
|
| antithrombotics | coumadin | 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)
|
|
| antithrombotics | dabigatran | 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 |
|
| antithrombotics | dalteparin | versus placebo or control No demonstrated result for efficacy | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| FRISC (long term), 1996 | dalteparin vs placebo (on top of aspirin) | myocardial infarction 0.70 [0.49; 0.99] | | long term MI or death 0.91 [0.71; 1.16] death 0.85 [0.46; 1.54] all revascularisations 0.78 [0.60; 1.01] myocardial infarction or death 0.75 [0.54; 1.03] | | FRIC prolonged treatment phase (LWMH vs PBO), 1997 | dalteparin vs placebo (on top of aspirin) | | | long term MI or death 1.05 [0.72; 1.51] death 1.61 [0.83; 3.13] all revascularisations 1.00 [0.79; 1.27] myocardial infarction 0.86 [0.56; 1.32] recurrent angina 1.12 [0.87; 1.45] myocardial infarction or death 1.05 [0.72; 1.51] | | FRISC (short term), 1996 | dalteparin vs placebo (on top of aspirin) | | | |
| Trial | Treatments | Patients | Method |
|---|
| FRISC (long term), 1996 | dalteparin SC 120 IU per kg bodyweight [maximum 10 000 IU] twice daily for 6 days with 7500 IU once daily for 34-45 days +aspirin (n=746) vs. matched placebo + aspirin (n=760) the primary aims was to compare the difference during the first 6 days between dalteparin and placebo | patients with unstable CAD (unstable angina or non-Q-wave myocardial infarction) within the previous 72 hours | double blind Parallel groups Sample size: 746/760 Primary endpoint: death or new myocardial infarction FU duration: 40 days | | FRIC prolonged treatment phase (LWMH vs PBO), 1997 | dalteparin SC 120 i.u./kg twice-daily for 6 days followed by dalteparin 7500UI daily up to day 45 (+aspirin) (n=731) vs. unfractionated heparin dose-adjusted intravenous infusion (for at least 48h) then by subcutaneous injection up to day 6 (then placebo) (+aspirin)
(n=751)
| Patients with unstable angina or non-Q-wave myocardial infarction
| double blind Parallel groups Sample size: 731/751 Primary endpoint: death MI recurrence of angina FU duration: 45 days the second phase is bliding but the first one is open. Perfommence biais is not discarded | | FRISC (short term), 1996 | dalteparin SC 120 IU per kg bodyweight [maximum 10 000 IU] twice daily for 6 days with 7500 IU once daily for 34-45 days +aspirin
(n=746) vs. matched placebo + aspirin
(n=760)
| patients with unstable CAD (unstable angina or non-Q-wave myocardial infarction) within the previous 72 hours
| double blind Sample size: 746/760 Primary endpoint: death or new myocardial infarction FU duration: 6 days
|
|
| antithrombotics | dalteparin | versus UFH No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| FRIC (acute phase LMWH vs UFH), 1997 | dalteparin vs UFH (on top of aspirin) | | | death 3.57 [1.00; 12.74] all revascularisations 0.90 [0.58; 1.40] myocardial infarction 0.80 [0.44; 1.46] myocardial infarction or death 1.09 [0.65; 1.83] |
| Trial | Treatments | Patients | Method |
|---|
| FRIC (acute phase LMWH vs UFH), 1997 | twice-daily weight-adjusted subcutaneous injections of dalteparin (120 i.u./kg) (+aspirin)
(n=751) vs. dose-adjusted intravenous infusion of unfractionated heparin (+aspirin)
(n=731) | Patients with unstable angina or non-Q-wave myocardial infarction
| open Sample size: 751/731 Primary endpoint: FU duration: 6 days
|
|
| antithrombotics | dipyridamol | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Prandoni, 1991 | aspirin + dipyridamol vs placebo | | | Vasc events 0.55 [0.22; 1.35] Major bleeds NaN [NaN; NaN] Vasc deaths ∞ [NaN; ∞] Non-fatal stroke NaN [NaN; NaN] Non-fatal MI 0.45 [0.17; 1.20] Non vasc deaths ∞ [NaN; ∞] cardiovascular events 0.55 [0.22; 1.35] |
| Trial | Treatments | Patients | Method |
|---|
| Prandoni, 1991 | Aspirin 50mg/d + Dipyridamol 400mg/d (n=44) vs. placebo (n=44) | patients with acute unstable angina | double blind Sample size: 44/44 Primary endpoint: FU duration: 12m |
|
| antithrombotics | Efegatran | versus heparin No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Klootwijk, 1999 | Efegatran vs heparin | | | |
| Trial | Treatments | Patients | Method |
|---|
| Klootwijk, 1999 | Efegatran 0.1–0.3 mg/kg bolus; 0.105–1.200 mg /kg/h infusion for 48h (n=432) vs. UFH 5000 IU bolus; 1000 IU/h infusion (n=0) | patients with unstable angina | open Parallel groups Sample size: 432/0 Primary endpoint: none defined FU duration: 30 days |
|
| antithrombotics | enoxaparin | versus No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| RESCUE | enoxaparin vs unfractionated heparin | | | |
| Trial | Treatments | Patients | Method |
|---|
| RESCUE | Enoxaparin (n=-9) vs. unfractionated heparin (n=-9) | patients diagnosed with acute coronary syndrome in the emergency department | open Parallel groups Sample size: -9/-9 Primary endpoint: death, MI, recurrent angina requiring revasc FU duration: 30 days |
|
| antithrombotics | enoxaparin | versus LMWH No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| EVET, 2005 | enoxaparin vs tinzaparin | recurrent angina 0.61 [0.39; 0.96] death, myocardial infarction, or recurrent at 30 days 0.63 [0.44; 0.90] | | death 0.50 [0.05; 5.42] myocardial infarction 0.25 [0.03; 2.20] death at 30 days 0.50 [0.05; 5.42] myocardial infarction at 30 days 0.17 [0.02; 1.36] |
| Trial | Treatments | Patients | Method |
|---|
| EVET, 2005 | enoxaparin, 100 IU/kg subcutaneously twice daily +aspirin for 7 days (n=220) vs. tinzaparin, 175 IU/kg subcutaneously once daily +aspirin for 7 days (n=218) | patients with non-ST-segment elevation acute coronary syndromes | open Parallel groups Sample size: 220/218 Primary endpoint: FU duration: 30 days |
|
| antithrombotics | enoxaparin | versus UFH No demonstrated result for efficacy enoxaparin inferior to UFH (on top of aspirin) in terms of minor bleeding in ESSENCE, 1997 enoxaparin inferior to UFH (on top of aspirin) in terms of minor bleeding in TIMI 11 B (short term), 1998 enoxaparin inferior to UFH (on top of aspirin) in terms of major bleeding in SYNERGY, 2005 enoxaparin inferior to UFH (on top of aspirin) in terms of minor bleeding in INTERACT, 2006 enoxaparin inferior to UFH (on top of aspirin) in terms of major bleeding in TIMI 11 B (long term), 1998 enoxaparin inferior to UFH (on top of aspirin) in terms of minor bleeding in TIMI 11 B (long term), 1998 | 5 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ESSENCE, 1997 | enoxaparin vs UFH (on top of aspirin) | death, MI and recurrence 0.84 [0.72; 0.97] all revascularisations 0.84 [0.75; 0.93] recurrent angina 0.83 [0.70; 0.98] death, myocardial infarction, or recurrent at 14 days 0.84 [0.72; 0.97] death, myocardial infarction, or recurrent at 30 days 0.85 [0.74; 0.97] | minor bleeding 1.66 [1.33; 2.08] | recurrent angina at 14 days 0.87 [0.75; 1.02] death 0.97 [0.62; 1.54] major bleeding 0.93 [0.71; 1.21] stroke at 30 days 0.97 [0.34; 2.77] myocardial infarction 0.71 [0.50; 1.01] Drop in platelet count of 50% 0.68 [0.45; 1.01] myocardial infarction or death 0.83 [0.43; 1.57] death at 30 days 0.79 [0.54; 1.15] myocardial infarction at 30 days 0.74 [0.54; 1.03] | | TIMI 11 B (short term), 1998 | enoxaparin vs UFH (on top of aspirin) | myocardial infarction 0.71 [0.52; 0.97] | minor bleeding 3.66 [2.68; 5.01] | death, MI and revascularization 0.85 [0.73; 1.00] death 0.83 [0.53; 1.30] all revascularisations 0.88 [0.72; 1.07] major bleeding 1.52 [0.86; 2.71] myocardial infarction or death 0.78 [0.60; 1.03] | | SYNERGY, 2005 | enoxaparin vs UFH (on top of aspirin) | | major bleeding 1.19 [1.05; 1.36] | long term MI or death 0.96 [0.87; 1.06] death 1.04 [0.84; 1.30] minor bleeding 1.01 [0.91; 1.12] myocardial infarction 0.94 [0.85; 1.05] myocardial infarction or death 0.96 [0.87; 1.06] death at 30 days 1.04 [0.84; 1.30] myocardial infarction at 30 days 0.92 [0.83; 1.03] | | INTERACT, 2006 | enoxaparin vs UFH (on top of aspirin) | long term MI or death 0.55 [0.32; 0.96] major bleeding 0.40 [0.17; 0.95] myocardial infarction or death 0.55 [0.32; 0.96] | minor bleeding 1.31 [1.04; 1.65] | death, MI and revascularization 0.87 [0.61; 1.22] death, MI and recurrence 1.30 [0.86; 1.98] death 0.58 [0.26; 1.30] all revascularisations 1.35 [0.77; 2.35] myocardial infarction 0.69 [0.36; 1.31] recurrent angina 0.45 [0.19; 1.09] death, myocardial infarction, or recurrent at 30 days 0.71 [0.47; 1.08] death at 30 days 0.58 [0.26; 1.30] myocardial infarction at 30 days 0.69 [0.36; 1.31] | | TIMI 11 B (long term), 1998 | enoxaparin vs UFH (on top of aspirin) | | major bleeding 1.90 [1.08; 3.34] minor bleeding 3.68 [2.81; 4.82] | long term MI or death 0.89 [0.73; 1.10] death, MI and revascularization 0.88 [0.77; 1.00] death 0.96 [0.71; 1.31] all revascularisations 0.84 [0.71; 1.00] myocardial infarction 0.83 [0.65; 1.07] myocardial infarction or death 0.89 [0.73; 1.10] |
| Trial | Treatments | Patients | Method |
|---|
| ESSENCE, 1997 | enoxaparin 1mg/kg, twice daily during 48h-8days (n=1607) vs. continuous intravenous unfractionated heparin (n=1564) | patients with angina at rest or non–Q-wave myocardial infarction | Double blind Parallel groups Sample size: 1607/1564 Primary endpoint: FU duration: 14 days (30 days) | | TIMI 11 B (short term), 1998 | enoxaprin during both the acute phase and outpatient phase (n=1953) vs. intravenous UFH for >=3 days (followed by
subcutaneous placebo injections) (n=1957) | unstable angina/non–Q-wave myocardial infarction | double blind Parallel groups Sample size: 1953/1957 Primary endpoint: death, myocardial infarction, or urgent revascularization FU duration: 8 days (43 days) | | SYNERGY, 2005 | Enoxaparin 1 mg/kg twice daily (n=4993) vs. unfractionated heparin (n=4985) | high-risk patients with acute coronary syndromes | open Parallel groups Sample size: 4993/4985 Primary endpoint: death/MI FU duration: 30 days | | INTERACT, 2006 | enoxaparin (1 mg/kg subcutaneously twice daily) for 48 hours (+eptifibatide and aspirin) (n=380) vs. intravenous UFH (70 U/kg bolus followed by 15 U/kg per hour adjusted to an activated partial thromboplastin time of 1.5-2 times control) for 48 hours (+eptifibatide and aspirin) (n=366) | high-risk patients with ACS receiving aspirin and eptifibatide | open Parallel groups Sample size: 380/366 Primary endpoint: 96-hour non–CABG related major bleeding FU duration: 30 days (2.5y) | | TIMI 11 B (long term), 1998 | enoxaprin during both the acute phase (IV) and outpatient phase (SC)
(n=1953) vs. intravenous UFH for >=3 days (followed by subcutaneous placebo injections) (n=1957)
| unstable angina/non–Q-wave myocardial infarction
| double blind Sample size: 1953/1957 Primary endpoint: death, MI or urgent revascularization FU duration: 43 days |
|
| antithrombotics | fondaparinux | versus LMWH No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| PENTUA, 2004 | fondaparinux vs enoxaparin | | | | | OASIS 5, 2006 | fondaparinux vs enoxaparin | | | |
| Trial | Treatments | Patients | Method |
|---|
| PENTUA, 2004 | Four doses fondaparinux (2.5, 4, 8, or 12 mg once daily) for three to seven days (n=908) vs. enoxaparin (1 mg/kg twice daily) for three to seven days (n=230) | patients with ACS without persistent
ST-segment elevation | Sample size: 908/230 Primary endpoint: FU duration: 9 days | | OASIS 5, 2006 | fondaparinux 2.5 mg daily until hospital discharge or for up
to eight days (n=10057) vs. enoxaparin 1 mg per kilogram of body weight twice daily for two to eight days or
until the patient was in clinically stable condition (n=10021) | patients with acute coronary syndromes | double blind Parallel groups Sample size: 10057/10021 Primary endpoint: death, myocardial infarction, or refractory ischemia FU duration: 9 days (180 days) |
|
| antithrombotics | hirudin | versus heparin No demonstrated result for efficacy | 7 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| HIT-4, 1999 | Hirudin vs heparin | | | | | TIMI 9B, 1996 | Hirudin vs heparin | | | | | GUSTO IIB, 1996 | Hirudin vs heparin | | | | | OASIS pilot, 1997 | Hirudin vs heparin | | | | | HELVETICA (Serruys), 1995 | Hirudin vs heparin | | | | | OASIS 2, 1999 | Hirudin vs heparin | | | | | OASIS, 1997 | Hirudin vs heparin | | | |
| Trial | Treatments | Patients | Method |
|---|
| HIT-4, 1999 | Hirudin 0.2 mg/kg bolus; 0.5 mg/kg twice daily 0.1 mg/kg 0.1 mg /kg/h infusion for 5-7 days (n=447) vs. Placebo bolus, UFH 12 500 IU twice daily (n=0) | patients with AMI <=6 h were treated with aspirin and streptokinase | double blind Parallel groups Sample size: 447/0 Primary endpoint: TIMI 3 flow at 90 min FU duration: 30 days | | TIMI 9B, 1996 | Hirudin 0.1 mg/kg bolus; 0.1 mg /kg/h infusion for 96h (n=3002) vs. UFH 5000 IU bolus; 1000 IU/h infusion (n=0) | Unstable angina or AMI | open Parallel groups Sample size: 3002/0 Primary endpoint: death,MI, HF, cardiogenic shock FU duration: 30 days | | GUSTO IIB, 1996 | Hirudin 0.1 mg/kg bolus; 0.1 mg /kg/h infusion for 72h (n=12142) vs. UFH 5000 IU bolus; 1000 IU/h infusion for 72H (n=0) | patients with acute coronary syndromes | open Parallel groups Sample size: 12142/0 Primary endpoint: death, MI FU duration: 30days (1 year) | | OASIS pilot, 1997 | Hirudin 0.2–0.4 mg/kg bolus; 0.10–0.15 mg /kg/h infusion for 72h (n=909) vs. UFH 5000 IU bolus; 1000–1200 IU/h infusion (n=0) | patients with unstable angina or suspected acute MI without ST-segment elevation | open Parallel groups Sample size: 909/0 Primary endpoint: death, MI, refrectory angina FU duration: 6 months | | HELVETICA (Serruys), 1995 | Hirudin 40 mg intravenous bolus; 0.2 mg /kg/h infusion for 24 h, then 40 mg or placebo twice daily for 72h (n=1141) vs. UFH 10 000 IU bolus; 15 IU /kg/h infusion for 24 h, then placebo twice daily (n=0) | patients with unstable angina who were scheduled for angioplasty | double blind Parallel groups Sample size: 1141/0 Primary endpoint: MACE FU duration: 6 months | | OASIS 2, 1999 | Hirudin 0.4 mg/kg bolus; 0.15 mg /kg/h infusion for 72h (n=5083) vs. UFH 5000 IU bolus; 15 IU /kg/h infusion (n=5058) | patients with unstable angina or suspected acute myocardial infarction without ST elevation | double blind Parallel groups Sample size: 5083/5058 Primary endpoint: death, MI at 7 days FU duration: 7 days (6 months) | | OASIS, 1997 | low-dose hirudin (0.2 mg/kg bolus+0.10 mg/kg/h infusion) or medium-dose hirudin (0.4 mg/kg bolus+0.15 mg/kg/h infusion) for 72h (n=538) vs. heparin 5000 IU bolus+1000 to 1200 U/h (n=371) 3 arms trial; high, medium dose of hirudin and heparin | patients with unstable angina or suspected acute MI without ST-segment elevation | open Parallel groups Sample size: 538/371 Primary endpoint: death, MI, refractory angina FU duration: 7 days |
|
| antithrombotics | inogatran | versus heparin No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| TRIM, 1997 | Inogatran vs heparin | | | |
| Trial | Treatments | Patients | Method |
|---|
| TRIM, 1997 | Inogatran 0.1–5.5 mg bolus; 2.0–10.0 mg/h infusion for 72h (n=1209) vs. UFH 5000 IU bolus; 1200 IU/h infusion (n=0) | patients with suspected unstable angina, or non-Q wave myocardial infarction | double blind Parallel groups Sample size: 1209/0 Primary endpoint: death, MI, refractory angina, recurrent angina FU duration: 30 days |
|
| antithrombotics | nadroparin | versus UFH No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| FRAXIS (6days), 1998 | nadroparin vs UFH (on top of aspirin) | | | recurrent angina at 14 days 0.93 [0.76; 1.14] long term MI or death 1.10 [0.83; 1.44] death 1.06 [0.51; 2.18] all revascularisations 0.95 [0.67; 1.36] myocardial infarction 1.09 [0.66; 1.79] recurrent angina 0.84 [0.67; 1.06] death, myocardial infarction, or recurrent at 14 days 0.99 [0.83; 1.18] myocardial infarction or death 0.99 [0.63; 1.56] death at 30 days 1.18 [0.79; 1.77] myocardial infarction at 30 days 1.10 [0.79; 1.52] | | FRAXIS (14 days), 1998 | nadroparin vs UFH (on top of aspirin) | | | recurrent angina at 14 days 1.11 [0.92; 1.35] long term MI or death 1.15 [0.87; 1.50] death 1.26 [0.70; 2.29] all revascularisations 0.95 [0.78; 1.14] myocardial infarction 0.98 [0.64; 1.49] recurrent angina 1.11 [0.92; 1.35] myocardial infarction or death 1.08 [0.74; 1.56] |
| Trial | Treatments | Patients | Method |
|---|
| FRAXIS (6days), 1998 | nadroparin for 6 days (+aspirin) (n=1166) vs. unfractionated heparin for 6 days (+aspirin) (n=1151) | unstable angina or non-Q wave myocardial
infraction | Double blind Parallel groups Sample size: 1166/1151 Primary endpoint: death, MI, recurent or refractory angina FU duration: 14 days | | FRAXIS (14 days), 1998 | nadroparin for 14 days
(n=1151) vs. unfractionated heparin for 14 days
(n=1151)
| unstable angina or non-Q wave myocardial
infraction
| double blind Sample size: 1151/1151 Primary endpoint: death, MI, recurent or refractory angina FU duration: 14 days
|
|
| antithrombotics | otamixaban | 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 |
|
| antithrombotics | prasugrel | versus clopidogrel No demonstrated result for efficacy prasugrel inferior to clopidogrel in terms of all bleeding (major and minor) in TRITON-TIMI 38, 2007 prasugrel inferior to clopidogrel in terms of Major bleeds in TRITON-TIMI 38, 2007 prasugrel inferior to clopidogrel in terms of fatal bleeding in TRITON-TIMI 38, 2007 | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| TRILOGY ACS (overall population), 2012 | prasugrel vs clopidogrel | | | all cause death 0.94 [0.82; 1.08] all bleeding (major and minor) 1.26 [0.94; 1.69] Major bleeds 1.21 [0.83; 1.77] Vasc deaths 0.93 [0.80; 1.08] fatala and non fatal stroke 0.90 [0.64; 1.26] fatal and non fatal MI 0.96 [0.84; 1.10] fatal bleeding 0.78 [0.29; 2.09] death, MI, stroke 0.96 [0.87; 1.06] | | TRITON-TIMI 38, 2007 | prasugrel vs clopidogrel | Vasc events 0.82 [0.74; 0.91] revascularization 0.67 [0.55; 0.82] Non-fatal MI 0.76 [0.68; 0.86] | all bleeding (major and minor) 1.31 [1.11; 1.55] Major bleeds 1.31 [1.03; 1.68] fatal bleeding 4.19 [1.58; 11.10] | all cause death 0.95 [0.78; 1.16] Vasc deaths 0.88 [0.70; 1.11] Non-fatal stroke 1.01 [0.71; 1.45] |
| Trial | Treatments | Patients | Method |
|---|
| TRILOGY ACS (overall population), 2012 | prasugrel 10 mg daily (n=4663) vs. clopidogrel 75 mg daily (n=4663) | patients with acute coronary syndromes selected for a final treatment
strategy of medical management without revascularization
within 10 days after the index event | double-blind Parallel groups Sample size: 4663/4663 Primary endpoint: cardiovascular events FU duration: 17 months (median) | | TRITON-TIMI 38, 2007 | prasugrel 60-mg loading dose
and 10-mg daily maintenance dose, for 6 to 15 months (n=6813) vs. clopidogrel (a 300-mg loading dose and a
75-mg daily maintenance dose) for 6 to 15 months (n=6795) | patients with moderate-to-high-risk acute coronary syndromes (UA, NSTEMI,STEMI) with scheduled
percutaneous coronary intervention | double blind Parallel groups Sample size: 6813/6795 Primary endpoint: cardiovascular death, nonfatal MI, or nonfatal FU duration: |
|
| antithrombotics | rivaroxaban | 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
|
|
| antithrombotics | sulfinpyrazone | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Canadian (sulfinpyrazone alone), 1985 | sulfinpyrazone vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| Canadian (sulfinpyrazone alone), 1985 | sulfinpyrazone 800mg/d
(n=-9) vs. placebo
(n=139)
| patients with unstable angina
| double blind Sample size: -9/139 Primary endpoint: FU duration: 18m
|
|
| antithrombotics | ticagrelor | versus clopidogrel No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| PLATO, 2009 | ticagrelor vs clopidogrel | vascular death, MI, stroke 0.85 [0.78; 0.92] Vasc events 0.88 [0.82; 0.95] all cause death 0.78 [0.69; 0.89] Vasc deaths 0.80 [0.69; 0.91] fatal and non fatal MI 0.85 [0.75; 0.95] cardiovascular events 0.85 [0.78; 0.92] death, MI, stroke 0.84 [0.77; 0.92] | | Severe recurrent ischemia 0.87 [0.75; 1.01] Hemorrhagic stoke 1.76 [0.89; 3.47] all bleeding (major and minor) 1.04 [0.95; 1.13] Major bleeds 1.03 [0.92; 1.14] Ischemic stroke 1.05 [0.79; 1.40] Non vasc deaths 0.72 [0.49; 1.04] fatala and non fatal stroke 1.17 [0.91; 1.52] fatal bleeding 0.87 [0.48; 1.58] | | DISPERSE-2 (90mg), 2007 | ticagrelor vs clopidogrel | | | Vasc events 1.09 [0.58; 2.07] all cause death 1.37 [0.44; 4.27] all bleeding (major and minor) 1.11 [0.70; 1.77] Major bleeds 0.98 [0.58; 1.65] Vasc deaths 1.47 [0.42; 5.16] fatala and non fatal stroke 1.96 [0.18; 21.49] fatal and non fatal MI 0.78 [0.37; 1.65] cardiovascular events 1.09 [0.58; 2.07] |
| Trial | Treatments | Patients | Method |
|---|
| PLATO, 2009 | ticagrelor 90mg twice daily (n=9333) vs. clopidogrel 75mg once daily (n=9291) Patients undergoing PCI after randomization received,
in a blind fashion, an additional dose of
their study drug at the time of PCI | patients with an acute coronary syndrome, with or without
ST-segment elevation (onset
of symptoms within the previous 24h). | double blind Parallel groups Sample size: 9333/9291 Primary endpoint: Cv death, MI, stroke FU duration: 1 y | | DISPERSE-2 (90mg), 2007 | ticagrelor 90 mg twice daily (n=334) vs. clopidogrel (n=327) 3 arms trial: AZD6140 90 mg and 180mg twice daily, Clopidogrel 75 mg
daily | patients with NSTE-ACS, treated with aspirin and standard therapy for ACS | double blind Parallel groups Sample size: 334/327 Primary endpoint: major or minor bleeding through 4 weeks FU duration: 12 weeks |
|
| antithrombotics | ticlopidine | versus placebo or control No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| STAI, 1990 | ticlopidine vs control | Vasc events 0.52 [0.32; 0.83] Non-fatal MI 0.54 [0.30; 0.98] cardiovascular events 0.52 [0.32; 0.83] | | Major bleeds NaN [NaN; NaN] Vasc deaths 0.54 [0.23; 1.24] Non-fatal stroke 0.00 [0.00; NaN] Non vasc deaths NaN [NaN; NaN] | | Florida UA | ticlopidine vs placebo | | | Vasc events 1.00 [0.17; 5.98] Major bleeds NaN [NaN; NaN] Vasc deaths NaN [NaN; NaN] Non-fatal stroke NaN [NaN; NaN] Non-fatal MI 1.00 [0.17; 5.98] Non vasc deaths NaN [NaN; NaN] cardiovascular events 1.00 [0.17; 5.98] |
| Trial | Treatments | Patients | Method |
|---|
| STAI, 1990 | ticlopidine 250 mg b.i.d (n=314) vs. untreated control (n=338) | patients with unstable angina <=48hrs from the pain onset | single blind Sample size: 314/338 Primary endpoint: FU duration: 6m | | Florida UA | Ticlopidine 500mg/d (n=12) vs. (n=12) | | Sample size: 12/12 Primary endpoint: FU duration: 14d |
|
| antithrombotics | trapidil | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Modena | trapidil vs placebo | Vasc events 0.21 [0.05; 0.91] cardiovascular events 0.21 [0.05; 0.91] | | Vasc deaths 0.21 [0.02; 1.72] Non-fatal MI 0.21 [0.02; 1.72] |
| Trial | Treatments | Patients | Method |
|---|
| Modena | trapidil (n=71) vs. (n=73) | | Sample size: 71/73 Primary endpoint: FU duration: 6m |
|
| antithrombotics | triflusal | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Plaza, 1993 | triflusal vs placebo | Non-fatal MI 0.34 [0.14; 0.84] | | Vasc events 0.45 [0.20; 1.02] revascularization 0.83 [0.51; 1.35] Major bleeds NaN [NaN; NaN] Vasc deaths ∞ [NaN; ∞] Non vasc deaths NaN [NaN; NaN] cardiovascular events 0.45 [0.20; 1.02] |
| Trial | Treatments | Patients | Method |
|---|
| Plaza, 1993 | triflusal 300 mg three times daily (n=143) vs. placebo (n=138) | patients with unstable angina | double blind Parallel groups Sample size: 143/138 Primary endpoint: FU duration: 6m |
|
| antithrombotics | UFH | versus placebo or control No demonstrated result for efficacy | 10 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| ATACS (Cohen), 1994 | UFH, warfarin vs control (on top of aspirin) | | | death 1.04 [0.15; 7.24] major bleeding 7.06 [0.41; 120.87] myocardial infarction 0.69 [0.26; 1.88] recurrent angina 0.62 [0.32; 1.21] myocardial infarction or death 0.46 [0.15; 1.45] | | Holdright, 1994 | UFH vs control (on top of aspirin) | | | major bleeding 0.85 [0.08; 8.71] myocardial infarction or death 0.89 [0.62; 1.29] | | Cohen (ATACS pilot) (heparin+aspirin vs asp), 1990 | UFH, warfarin vs control (on top of aspirin) | | | death NaN [NaN; NaN] all revascularisations 1.59 [0.94; 2.67] major bleeding NaN [NaN; NaN] minor bleeding 0.86 [0.06; 13.28] myocardial infarction 0.00 [0.00; NaN] recurrent angina 1.24 [0.81; 1.91] | | RISC (heparin+aspirin vs ASP), 1990 | UFH vs control (on top of aspirin) | | | myocardial infarction or death 0.80 [0.32; 2.03] | | Theroux (heparin+aspirin vs PBO), 1988 | UFH + aspirin vs placebo | myocardial infarction 0.14 [0.03; 0.59] recurrent angina 0.47 [0.25; 0.86] myocardial infarction or death 0.14 [0.03; 0.60] | | death 0.00 [0.00; NaN] | | Gurfinkel (UFH+aspririn vs aspirin), 1995 | UFH vs placebo (on top of aspirin) | | | death NaN [NaN; NaN] all revascularisations 0.81 [0.32; 2.06] major bleeding 5.21 [0.29; 92.25] minor bleeding ∞ [NaN; ∞] myocardial infarction 0.60 [0.18; 1.95] recurrent angina 1.20 [0.80; 1.78] myocardial infarction or death 0.60 [0.18; 1.95] | | Theroux (heparin vs PBO), 1988 | UFH vs placebo | death, MI and recurrence 0.35 [0.19; 0.67] myocardial infarction 0.07 [0.01; 0.53] recurrent angina 0.37 [0.19; 0.73] myocardial infarction or death 0.07 [0.01; 0.53] | | death 0.00 [0.00; NaN] major bleeding 1.00 [0.14; 6.98] minor bleeding 2.00 [0.62; 6.46] | | RISC (heparin vs PBO), 1990 | UFH vs placebo | | | myocardial infarction or death 0.90 [0.54; 1.48] | | Theroux (heparin+ASP vs ASP), 1988 | UFH vs control (on top of aspirin) | death, MI and recurrence 0.45 [0.25; 0.80] | | | | RISC (ASP+ heparin vs PBO), 1990 | UFH + aspirin vs placebo | myocardial infarction or death 0.24 [0.07; 0.83] | | |
| Trial | Treatments | Patients | Method |
|---|
| ATACS (Cohen), 1994 | aspirin 162.5 mg daily plus heparin (activated partial thromboplastin time, two times control) followed by aspirin 162.5 mg daily plus warfarin (international normalized ratio, 2 to 3) for 12 weeks. (n=105) vs. aspirin alone (162.5 mg daily) for 12 weeks. (n=109) | patients with unstable rest angina or non-Q-wave myocardial infarction with last episode of pain within 48 hours of randomization and who were nonprior aspirin users | single blind Parallel groups Sample size: 105/109 Primary endpoint: FU duration: 12 weeks | | Holdright, 1994 | intravenous heparin plus oral aspirin (150 mg once daily) (n=154) vs. aspirin alone 150 mg/d (n=131) | unstable angina | single blind Parallel groups Sample size: 154/131 Primary endpoint: FU duration: hospital stay | | Cohen (ATACS pilot) (heparin+aspirin vs asp), 1990 | aspirin (80 mg/day) plus heparin and then warfarin (n=37) vs. aspirin (325 mg/day) (n=32) | Patients between 21 and 75 years with unstable angina or non-Q-wave MI with last episode of pain within 48 hours of screening. | open Parallel groups Sample size: 37/32 Primary endpoint: FU duration: 12 weeks | | RISC (heparin+aspirin vs ASP), 1990 | 5 days of intermittent intravenous heparin + oral aspirin 75 mg/day (n=210) vs. oral aspirin 75 mg/day (n=189) | unstable angina or non-Q-wave myocardial infarction | open Parallel groups Sample size: 210/189 Primary endpoint: FU duration: 90 days | | Theroux (heparin+aspirin vs PBO), 1988 | heparin (1000 units per hour by intravenous infusion)+ aspirin (325 mg twice daily) (n=122) vs. aspirin (325 mg twice daily) (n=118) | | double blind Sample size: 122/118 Primary endpoint: FU duration: 3-9 days | | Gurfinkel (UFH+aspririn vs aspirin), 1995 | aspirin plus UFH 5000 IU iv then 400 IU/kg body weight per day intravenously and titered by activated partial thromboplastin time (n=70) vs. aspirin 200 mg/day (n=73) | patients greater than 21 years with ustable angina within 24 hours of randomizationcatio | double blind Parallel groups Sample size: 70/73 Primary endpoint: FU duration: 5-7 days | | Theroux (heparin vs PBO), 1988 | heparin (1000 units per hour by intravenous infusion) (n=118) vs. placebo (n=118) | patients with acute unstable angina pectoris | double blind Sample size: 118/118 Primary endpoint: FU duration: 3-9 days | | RISC (heparin vs PBO), 1990 | 5 days of intermittent intravenous heparin (n=198) vs. placebo (n=199) | men with unstable coronary artery disease (unstable angina or non-Q-wave myocardial infarction) | Factorial plan Sample size: 198/199 Primary endpoint: FU duration: 1y (5,30 and 90 days) | | Theroux (heparin+ASP vs ASP), 1988 | aspirin 325 mg/d + heparin 1000 UI/hr IV (n=122) vs. aspirin 325 mg/d (n=121) |
| double blind Sample size: 122/121 Primary endpoint: FU duration: 3-9 days
| | RISC (ASP+ heparin vs PBO), 1990 | oral apsirin 75mg/d + intermittent IV heparin 10000UI/d followed by 7500 UI 6-hourly for 4 days (n=210) vs. placebo
(n=199) | men with unstable coronary artery disease (unstable angina or non-Q-wave myocardial infarction) | Sample size: 210/199 Primary endpoint: FU duration: 1y (5,30 and 90 days)
|
|
| antithrombotics | UFH | versus aspirin No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Cohen (ATACS pilot) (heparin vs asp), 1990 | UFH, warfarin vs aspirin | | | death NaN [NaN; NaN] all revascularisations 1.33 [0.73; 2.43] major bleeding NaN [NaN; NaN] minor bleeding 0.00 [0.00; NaN] recurrent angina 0.83 [0.46; 1.50] myocardial infarction or death 4.00 [0.44; 36.12] |
| Trial | Treatments | Patients | Method |
|---|
| Cohen (ATACS pilot) (heparin vs asp), 1990 | heparin followed by warfarin (without aspirin) (n=24) vs. aspirin 325 mg/day (n=32) | Patients between 21 and 75 years with unstable angina or non-Q-wave MI with last episode of pain within 48 hours of screening | open Parallel groups Sample size: 24/32 Primary endpoint: FU duration: 12 weeks |
|
| antithrombotics | warfarin | 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 |
|
| antithrombotics | ximelagatran | 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 |
|
| calcium channel blockers | diltiazem | versus placebo or control No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| T1 vs T0 | | | | | T1 vs T0 | | | |
| Trial | Treatments | Patients | Method |
|---|
| Göbel (Dutch study), 1995 | diltiazem intravenously (n=129) vs. glyceryl trinitrate intravenously (n=0) | patients with unstable angina | double blind Parallel groups Sample size: 129/0 Primary endpoint: refractory angina or myocardial infarction FU duration: ND | | DRS, 1986 | diltiazem 90 mg every six hours up to 14 days (n=287) vs. placebo (n=289) | patients with non-Q-wave myocardial infarct, 24 to 72 hours after the onset of infarction | double blind Sample size: 287/289 Primary endpoint: reinfarction FU duration: ND |
|
| calcium channel blockers | nifedipine | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| T1 vs T0 | | | |
| Trial | Treatments | Patients | Method |
|---|
| HINT (nifedipine vs metoprolol), 1988 | nifedipine (n=-9) vs. metoprolol (n=-9) | patients with unstable angina not pretreated with a beta-blocker and of nifedipine | ND Parallel groups Sample size: -9/-9 Primary endpoint: recurrent ischemia or myocardial infarction within 48 h FU duration: ND |
|
| cholesterol lowering intervention | atorvastatin | versus placebo or control No demonstrated result for efficacy | 3 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| MIRACL, 2001 | atorvastatin vs placebo | Non fatal stroke 0.41 [0.19; 0.89] Recurrent ischaemia 0.74 [0.57; 0.95] | | Death 0.95 [0.68; 1.32] fatal MI 0.95 [0.49; 1.84] Revascularisation 1.02 [0.87; 1.20] Non fatal acute MI 0.90 [0.69; 1.17] Death or MI 0.92 [0.75; 1.13] Stroke (fatal & non fatal) 0.50 [0.25; 1.00] Death from CHD 0.86 [0.59; 1.23] Major cardiovascular events 0.92 [0.75; 1.13] CABG 0.97 [0.75; 1.25] PTCA 1.06 [0.85; 1.31] death, MI and stroke - 4 month 0.89 [0.73; 1.09] death, MI and stroke - 1 month 1.06 [0.81; 1.39] | | Colivicchi, 2002 | atorvastatin vs usual care | | | Death 0.77 [0.18; 3.22] fatal MI 0.68 [0.12; 3.88] Revascularisation NaN [NaN; NaN] Non fatal acute MI 0.44 [0.12; 1.58] Stroke (fatal & non fatal) 0.51 [0.05; 5.43] Death from CHD 0.68 [0.12; 3.88] Major cardiovascular events 0.57 [0.21; 1.55] death, MI and stroke - 4 month 0.57 [0.21; 1.55] death, MI and stroke - 1 month 0.00 [0.00; NaN] | | ESTABLISH, 2004 | atorvastatin vs usual care | | | Death 0.00 [0.00; NaN] fatal MI NaN [NaN; NaN] Revascularisation 1.00 [0.42; 2.36] Non fatal acute MI NaN [NaN; NaN] Stroke (fatal & non fatal) NaN [NaN; NaN] Death from CHD NaN [NaN; NaN] Major cardiovascular events 0.00 [0.00; NaN] death, MI and stroke - 4 month 0.00 [0.00; NaN] |
| Trial | Treatments | Patients | Method |
|---|
| MIRACL, 2001 | Atorvastatin, 80 mg (early initiation) (n=1538) vs. Placebo (n=1548) | unstable angina or non–Q-wave acute MI | Double blind Parallel groups Sample size: 1538/1548 Primary endpoint: death, MI, recurrent ischemia requiring hospitalization FU duration: 1 and 4 months | | Colivicchi, 2002 | Atorvastatin, 80 mg daily early initiation (n=40) vs. Usual care (n=41) | unstable angina pectoris or non-Q-wave myocardial infarction | open Parallel groups Sample size: 40/41 Primary endpoint: cardiac death, MI, objective recurrent ischemia FU duration: 1, 3, and 6 months | | ESTABLISH, 2004 | Atorvastatin, 20 mg early initiation (n=35) vs. Usual care (n=35) | patients with ACS undergoing emergency coronary angiography and percutaneous coronary intervention | open Parallel groups Sample size: 35/35 Primary endpoint: none defined FU duration: 1, 4, and 6 months |
|
| cholesterol lowering intervention | atorvastatin | versus statin No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| PROVE IT - TIMI 22, 2004 | atorvastatin vs pravastatin | Major cardiovascular events 0.76 [0.66; 0.88] | | Death 0.72 [0.50; 1.03] |
| Trial | Treatments | Patients | Method |
|---|
| PROVE IT - TIMI 22, 2004 | 80 mg of atorvastatin daily (intensive therapy). (n=2099) vs. 40 mg of pravastatin daily (standard therapy) (n=2063) | patients who had been hospitalized for an acute coronary syndrome
within the preceding 10 days | double blind Parallel groups Sample size: 2099/2063 Primary endpoint: death, MI, unstable angina, revascularization, stroke FU duration: 24 mo (18-36 mo) |
|
| cholesterol lowering intervention | fluvastatin | versus placebo or control No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| LIPS (sub groups), 2002 | fluvastatin vs placebo | | | Death 0.73 [0.16; 3.25] fatal MI NaN [NaN; NaN] Revascularisation 0.88 [0.67; 1.15] Non fatal acute MI 1.30 [0.46; 3.72] Stroke (fatal & non fatal) NaN [NaN; NaN] Death from CHD 0.65 [0.11; 3.87] Major cardiovascular events 2.60 [0.70; 9.74] death, MI and stroke - 4 month 2.60 [0.70; 9.74] death, MI and stroke - 1 month 2.93 [0.31; 28.03] | | FLORIDA, 2002 | fluvastatin vs placebo | | | Death 0.66 [0.26; 1.68] fatal MI 0.00 [0.00; NaN] Revascularisation 0.91 [0.60; 1.38] Non fatal acute MI 1.63 [0.64; 4.14] Stroke (fatal & non fatal) 0.00 [0.00; NaN] Death from CHD 0.52 [0.13; 2.05] Major cardiovascular events 0.95 [0.70; 1.28] Recurrent ischaemia 1.04 [0.57; 1.88] CABG 0.66 [0.32; 1.32] death, MI and stroke - 4 month 1.04 [0.44; 2.45] death, MI and stroke - 1 month 1.04 [0.30; 3.54] |
| Trial | Treatments | Patients | Method |
|---|
| LIPS (sub groups), 2002 | Fluvastatin, 80 mg (n=417) vs. Placebo (n=407) | patients with unstable angina and successful first percutaneous coronary intervention initially this study included patients with unstable or stable coronary heart disease (844 vs 833) | double blind Parallel groups Sample size: 417/407 Primary endpoint: MACE FU duration: 1, 4, and 6 months sub group of patients with unstable angina | | FLORIDA, 2002 | Fluvastatin, 80 mg (early initiation) (n=265) vs. Placebo (n=275) | patients with an AMI and total cholesterol of <6.5 mmol.l | double blind Parallel groups Sample size: 265/275 Primary endpoint: FU duration: 1, 4, and 6 months |
|
| cholesterol lowering intervention | pravastatin | versus placebo or control No demonstrated result for efficacy | 6 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| LAMIL, 1997 | pravastatin vs placebo | | | fatal MI ∞ [NaN; ∞] death, MI and stroke - 4 month 0.92 [0.20; 4.23] | | RECIFE, 1999 | pravastatin vs placebo | | | Death NaN [NaN; NaN] fatal MI NaN [NaN; NaN] Revascularisation NaN [NaN; NaN] Non fatal acute MI 0.00 [0.00; NaN] Stroke (fatal & non fatal) NaN [NaN; NaN] Death from CHD NaN [NaN; NaN] death, MI and stroke - 1 month 0.00 [0.00; NaN] | | L-CAD, 2000 | pravastatin vs usual care | Revascularisation 0.40 [0.16; 1.00] | | Death 0.80 [0.05; 12.51] fatal MI NaN [NaN; NaN] Non fatal acute MI NaN [NaN; NaN] Stroke (fatal & non fatal) NaN [NaN; NaN] Death from CHD NaN [NaN; NaN] Major cardiovascular events 0.80 [0.05; 12.51] death, MI and stroke - 4 month 0.80 [0.05; 12.51] death, MI and stroke - 1 month ∞ [NaN; ∞] | | PAIS, 2001 | pravastatin vs placebo | | | fatal MI 1.96 [0.18; 20.92] death, MI and stroke - 4 month 0.98 [0.26; 3.70] death, MI and stroke - 1 month 0.65 [0.11; 3.74] | | PTT, 2002 | pravastatin vs usual care | death, MI and stroke - 1 month 0.31 [0.11; 0.89] | | fatal MI 0.00 [0.00; NaN] death, MI and stroke - 4 month 0.31 [0.07; 1.44] | | PACT, 2004 | pravastatin vs placebo | Non fatal acute MI 0.09 [0.04; 0.23] | | Death 0.69 [0.42; 1.12] fatal MI 0.81 [0.39; 1.67] Stroke (fatal & non fatal) 0.79 [0.31; 2.01] Death from CHD 0.76 [0.46; 1.26] death, MI and stroke - 1 month 0.89 [0.67; 1.18] |
| Trial | Treatments | Patients | Method |
|---|
| LAMIL, 1997 | Pravastatin, 10-20 mg (starting at D3) (n=36) vs. Placebo (n=33) | patients suffering an acute myocardial infarction | double blind Parallel groups Sample size: 36/33 Primary endpoint: FU duration: 1 and 3 months | | RECIFE, 1999 | Pravastatin, 40 mg (n=30) vs. Placebo (n=30) | Patients with acute myocardial infarction or unstable angina and total cholesterol levels at admission >=5.2 mmol/L or LDL >=3.4 mmol/L | double blind Parallel groups Sample size: 30/30 Primary endpoint: none defined FU duration: 1.5 months | | L-CAD, 2000 | Pravastatin, 20-40 mg (strating on average at D6) (n=70) vs. Usual care (n=56) | patients with acute coronary syndrome | open Parallel groups Sample size: 70/56 Primary endpoint: death, MI, stroke, coronary intervention, PVD FU duration: 1, 4, and 6 months | | PAIS, 2001 | Pravastatin, 40 mg (initiated within 48 hours of hospital admission) (n=50) vs. Placebo (n=49) | patients with acute coronary syndromes | double blind Parallel groups Sample size: 50/49 Primary endpoint: FU duration: 1 and 3 months | | PTT, 2002 | Pravastatin, 40 mg (n=79) vs. Usual care (n=85) | patients who underwent coronary balloon angioplasty of the infarct-related artery during the first month of acute myocardial infarction | open Parallel groups Sample size: 79/85 Primary endpoint: FU duration: 1 and 6 months | | PACT, 2004 | Pravastatin, 20-40 mg within 24 hours of the onset of symptoms in (n=1710) vs. Placebo (n=1698) | patients with unstable angina, non-ST-segment elevation myocardial infarction, or ST-segment elevation myocardial infarction within 24 hours of the onset of symptoms | double blind Parallel groups Sample size: 1710/1698 Primary endpoint: death, recurrence of MI, or rehospital for unstable angina FU duration: 1 months |
|
| cholesterol lowering intervention | simvastatin | versus placebo or control No demonstrated result for efficacy | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| A to Z, 2004 | simvastatin vs placebo | | | Death 0.90 [0.60; 1.35] fatal MI 0.62 [0.35; 1.11] Revascularisation 0.95 [0.74; 1.21] Non fatal acute MI 0.99 [0.77; 1.29] Stroke (fatal & non fatal) 0.79 [0.48; 1.29] Death from CHD 0.86 [0.57; 1.30] Major cardiovascular events 0.89 [0.77; 1.02] death, MI and stroke - 4 month 0.99 [0.80; 1.22] death, MI and stroke - 1 month 0.93 [0.71; 1.22] |
| Trial | Treatments | Patients | Method |
|---|
| A to Z, 2004 | Simvastatin, 40-80 mg early initiation (n=2265) vs. Placebo (n=2232) | patient with an acute coronary syndrome (ACS) | Double aveugle Parallel groups Sample size: 2265/2232 Primary endpoint: cardiovascular death, MI, rehospitalization for ACS or stroke FU duration: 4 months |
|
| myocardial revascularization | anistreplase | versus placebo or control No demonstrated result for efficacy anistreplase inferior to placebo in terms of bleeding in UNASEM, 1992 | 1 trial | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| UNASEM, 1992 | anistreplase vs placebo | | bleeding 2.96 [1.34; 6.57] | |
| Trial | Treatments | Patients | Method |
|---|
| UNASEM, 1992 | anistreplase IV 30 UI over 5 minutes (n=80) vs. placebo (n=79) | Patients without a previous myocardial infarction, with a typical history of unstable angina and ECG abnormalities indicative of ischemia | double blind Parallel groups Sample size: 80/79 Primary endpoint: CA FU duration: hospital stay, 1y |
|
| myocardial revascularization | t-pa | versus placebo or control No demonstrated result for efficacy t-PA inferior to placebo in terms of bleeding in Williams, 1990 | 10 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| Nicklas, 1989 | t-PA vs placebo | | | MI 1.00 [0.16; 6.42] In hospital death ∞ [NaN; ∞] | | Gold, 1987 | t-PA vs placebo | | | | | Williams, 1990 | t-PA vs placebo | | bleeding 2.35 [1.04; 5.32] | MI 1.47 [0.16; 13.30] In hospital death NaN [NaN; NaN] | | Freeman, 1992 | t-PA vs placebo | | | Death 1.00 [0.07; 15.36] MI 2.00 [0.19; 21.06] In hospital death 1.00 [0.07; 15.36] | | van der Brand, 1991 | t-PA vs placebo | | | bleeding ∞ [NaN; ∞] MI 1.19 [0.31; 4.59] | | charbonnier, 1992 | t-PA vs placebo | | | | | Ardissino, 1990 | t-PA vs placebo | | | MI 0.50 [0.05; 4.81] In hospital death 0.00 [0.00; NaN] | | TIMI 3B, 1995 | t-PA vs placebo | | | | | Topol, 1988 | t-PA vs placebo | | | In hospital death ∞ [NaN; ∞] | | TIMI 3A, 1993 | t-PA vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| Nicklas, 1989 | rt-PA, 150 mg/8 h (n=20) vs. placebo (n=20) | patients with rest angina, angiographically documented coronary artery disease and pacing-induced ischemia | Double blind Parallel groups Sample size: 20/20 Primary endpoint: ischemic pacing threshold FU duration: | | Gold, 1987 | intravenous recombinant human tissue-type plasminogen activator (rt-PA). (n=12) vs. placebo (n=12) | chest pain at rest with transient ST segment deviation of at least 1 mm | Parallel groups Sample size: 12/12 Primary endpoint: FU duration: | | Williams, 1990 | tissue-type plasminogen activator (rt-PA) (0.75 mg/kg over 1 hour or (0.75 mg/kg over 1 hour; total dose, 100 mg over 6 hours) (n=45) vs. placebo (n=22) 3 arms study comparing low-dose and high dose of rt-PA to placebo | rest angina and angiographic evidence of coronary stenosis | double blind Parallel groups Sample size: 45/22 Primary endpoint: change in luminal diameter FU duration: | | Freeman, 1992 | tissue-type plasminogen activator (t-PA) (0.49 MU/kg for 1 hour followed by 0.07 MU/kg per hour for 9 hours) (n=35) vs. placebo (n=35) | patients with unstable angina | double blind Parallel groups Sample size: 35/35 Primary endpoint: in-hospital death, myocardial infarction, and urgent revascularization FU duration: in hospital | | van der Brand, 1991 | alteplase 100 mg in 3 h (n=19) vs. placebo (n=17) | patients with angina at rest, despite bedrest and medical treatment | double blind Parallel groups Sample size: 19/17 Primary endpoint: FU duration: hospital stay | | charbonnier, 1992 | rt-PA 100 mg/90 minutes (10 mg bolus + 90 mg/90 minutes (n=25) vs. placebo (n=25) | unstable angina pectoris | double blind Parallel groups Sample size: 25/25 Primary endpoint: FU duration: | | Ardissino, 1990 | recombinant tissue-type plasminogen activator (rt-PA) followed by heparin (n=12) vs. heparin alone (n=12) | unstable angina refractory to conventional medical treatment | double blind Parallel groups Sample size: 12/12 Primary endpoint: FU duration: in hospital | | TIMI 3B, 1995 | tissue-type plasminogen activator (t-PA) (n=729) vs. placebo (n=744) factorial design: early invasive management strategy with coronary arteriography at 18 to 48 h, followed by revascularization as soon as possible if appropriate, compared to an early conservative strategy with arteriography and revascularization reserved for failure of initial therapy to prevent recurrent ischemia | patients with unstable angina and non-Q wave myocardial infarction | Double blind Factorial plan Sample size: 729/744 Primary endpoint: death or MI FU duration: 1 year | | Topol, 1988 | intravenous tissue plasminogen activator (t-PA) (n=20) vs. placebo (n=20) | patients with angina at rest and provocable ischemia (pacing induced) | open Parallel groups Sample size: 20/20 Primary endpoint: FU duration: hospital stay | | TIMI 3A, 1993 | 90-minute front-loaded infusion of t-PA (0.8 mg/kg i.v.; maximum, 80 mg) (n=150) vs. placebo (n=156) | patients with unstable angina or non-Q wave myocardial infarction | double blind Parallel groups Sample size: 150/156 Primary endpoint: culprit lesion caliber FU duration: hospital stay |
|
| nitrates | nitroglycerin | versus placebo or control No demonstrated result for efficacy | 2 trials | meta-analysis | | | Trial | control | p<0.05 | harm | NS |
|---|
| T1 vs T0 | | | | | T1 vs T0 | | | |
| Trial | Treatments | Patients | Method |
|---|
| Doucet, 2000 | intravenous nitroglycerin (n=47) vs. placebo (n=48) 4 groups: (1) intravenous
nitroglycerin infusion plus placebo heparin, (2) intravenous heparin
5000 U bolus followed by infusion at 1000 U/h (1200 U/h for
patients weighing $80 kg) plus placebo nitroglycerin, (3) intravenous
nitroglycerin plus intravenous heparin, and (4) placebo nitroglycerin
plus placebo heparin | patients hospitalized for unstable angina within 6 months after angioplasty (excluding those with intracoronary stents) | double blind Factorial plan Sample size: 47/48 Primary endpoint: Recurrence of angina FU duration: NA | | Karlberg, 1998 | 48-hour titrated intravenous infusionof NTG (n=73) vs. placebo (n=70) | patients with ahistory and electrocardiographic changes suggestingunstable angina pectoris | double blind Sample size: 73/70 Primary endpoint: FU duration: |
|
