cardiovascular prevention

Description Results NMA

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

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]

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

Sample size: 27400/0

Primary endpoint:

FU duration:

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

double-blind

Parallel groups

Sample size: 9152/9126

Primary endpoint: cardiovascular death, stroke, MI

FU duration: 23 months

warfarin (n=607)

vs.

placebo (n=607)

double-blind

Sample size: 607/607

Primary endpoint:

FU duration: 37 months

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]

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]

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

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

warfarin adjusted dose for INR of 1.5 + aspirin 75 mg daily (n=1277)

vs.

placebo (n=1272)

factorial design with aspirin and warfarin

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

cardiovascular death 1.11 [1.01; 1.21]

all-cause mortality 1.17 [1.03; 1.33]

cardiovascular death 1.26 [0.99; 1.61]

all-cause mortality 1.07 [0.79; 1.46]

all-cause mortality 0.51 [0.25; 1.05]

cardiovascular death 0.49 [0.18; 1.30]

all-cause mortality 0.09 [0.09; 0.10]

coronary events 0.09 [0.08; 0.10]

cardiovascular death 0.10 [0.09; 0.12]

all-cause cerebrovascular accident 0.09 [0.08; 0.10]

Cardiovascular Event 0.09 [0.09; 0.10]

all-cause mortality 1.07 [0.74; 1.55]

coronary events 0.84 [0.56; 1.27]

cardiovascular death 1.17 [0.54; 2.52]

all-cause cerebrovascular accident 1.42 [0.96; 2.09]

Cardiovascular Event 1.14 [0.87; 1.48]

all-cause mortality 1.03 [0.92; 1.16]

coronary events 0.97 [0.77; 1.23]

cardiovascular death 1.15 [0.95; 1.39]

Hemorrhagic Stroke 2.13 [0.92; 4.92]

non fatal stroke 1.10 [0.87; 1.40]

non fatla MI 1.09 [0.85; 1.40]

Ischemic Stroke 1.12 [0.88; 1.41]

all-cause cerebrovascular accident 1.18 [0.94; 1.47]

Cardiovascular Event 1.09 [0.96; 1.24]

coronary death 1.03 [0.77; 1.37]

coronary events 0.95 [0.78; 1.17]

non fatla MI 0.87 [0.64; 1.19]

beta carotene 20mg four times daily (n=14560)

vs.

placebo (n=14573)

factorial design of four regimens: alpha-tocopherol (50 mg per day) alone, beta carotene (20 mg per day) alone, both alpha-tocopherol and beta carotene, or placebo

double-blind

Factorial plan

Sample size: 14560/14573

Primary endpoint: not defined

FU duration: 6.1 median (range 5-8y)

combination of 30 mg of beta carotene per day and 25,000 IU of retinol (vitamin A) in the form of retinyl palmitate per day (n=9420)

vs.

placebo (n=8894)

double-blind

Parallel groups

Sample size: 9420/8894

Primary endpoint: lung cancer

FU duration: 4 y

beta carotene 50mg four times daily (n=913)

vs.

placebo (n=892)

double-blind

Parallel groups

Sample size: 913/892

Primary endpoint: basal cell or squamaous cell skin cancer

FU duration: 4.02 years

beta carotene 30mg four times daily (n=820)

vs.

placebo (n=801)

factorial design of sunscreen and betacarotene

double-blind

Factorial plan

Sample size: 820/801

Primary endpoint: skin cancer

FU duration: 4.5 y

beta carotene 50 mg on alternate days (n=11036)

vs.

placebo (n=1035)

factorial design that tested aspirin and beta carotene

double-blind

Factorial plan

Sample size: 11036/1035

Primary endpoint: neoplasm except nonmelanoma skin cancer

FU duration: 12 y

beta carotene 50mg four times daily (n=19939)

vs.

placebo (n=19937)

factorial edsign testing aspirin, vitamin E, and b-carotene

double-blind

Factorial plan

Sample size: 19939/19937

Primary endpoint: not defined

FU duration: 2.1y (range 0 - 2.72y)

beta carotene (Lurotin) 50 mg every two days (n=4084)

vs.

placebo (n=4087)

2x2x2 factorial design testing the effects of ascorbic acid (500 mg/d), vitamin E (600 IU every other day), and beta carotene (50 mg every other day)

double blind

Factorial plan

Sample size: 4084/4087

Primary endpoint: MI, stroke, coronary revascularization, CVD death

FU duration: 9.4 years

synthetic beta carotene 20 mg daily (n=876)

vs.

placebo (n=919)

factorial design of alpha tocopherol (vitamin E) 50 mg/day and beta carotene 20 mg/day

double-blind

Factorial plan

Sample size: 876/919

Primary endpoint: not defined

FU duration: 3.79 y

all-cause mortality 1.03 [0.91; 1.15]

coronary events 1.04 [0.83; 1.32]

cardiovascular death 1.09 [0.90; 1.32]

Hemorrhagic Stroke 1.08 [0.49; 2.37]

non fatal stroke 0.87 [0.68; 1.10]

non fatla MI 1.09 [0.85; 1.39]

Ischemic Stroke 0.83 [0.66; 1.05]

all-cause cerebrovascular accident 0.86 [0.69; 1.08]

Cardiovascular Event 1.01 [0.89; 1.15]

all-cause mortality 1.06 [0.97; 1.16]

cardiovascular death 1.01 [0.85; 1.20]

Hemorrhagic Stroke 0.94 [0.57; 1.54]

Ischemic Stroke 0.87 [0.71; 1.06]

all-cause cerebrovascular accident 0.88 [0.74; 1.06]

Cardiovascular Event 0.99 [0.89; 1.10]

vitamin C (ascorbic acid) 500 mg/d (n=4087)

vs.

placebo (n=4084)

2x2x2 factorial design testing the effects of ascorbic acid (500 mg/d), vitamin E (600 IU every other day), and beta carotene (50 mg every other day)

double blind

Sample size: 4087/4084

Primary endpoint: MI, stroke, coronary revascularization, CVD death

FU duration: 9.4 years

vitamin C 500mg daily (n=7329)

vs.

placebo (n=7312)

2x2x2x2 factorial trial evaluating vitamin E (400 IU synthetic alpha-tocopherol), vitaminC(500mg synthetic ascorbic acid), a multivitamin (Centrum Silver daily; Wyeth Pharmaceuticals) and beta carotene (50mg, Lurotin on alternate days)

double blind

Factorial plan

Sample size: 7329/7312

Primary endpoint: Cv death, MI, Stroke

FU duration: 8 years (mean)

Ischemic Stroke 0.86 [0.75; 0.99]

cardiovascular death 0.98 [0.89; 1.07]

Hemorrhagic Stroke 1.22 [0.92; 1.61]

all-cause cerebrovascular accident 0.93 [0.83; 1.05]

Cardiovascular Event 0.98 [0.89; 1.07]

non fatla MI 0.32 [0.18; 0.58]

Cardiovascular Event 0.60 [0.41; 0.88]

all-cause mortality 1.29 [0.79; 2.13]

cardiovascular death 1.10 [0.63; 1.90]

all-cause mortality 0.92 [0.82; 1.04]

cardiovascular death 0.94 [0.81; 1.10]

non fatal stroke 0.87 [0.65; 1.17]

non fatla MI 1.11 [0.92; 1.33]

all-cause cerebrovascular accident 0.87 [0.65; 1.17]

Cardiovascular Event 0.98 [0.88; 1.09]

cardiovascular death 1.05 [0.90; 1.21]

Hemorrhagic Stroke 1.31 [0.64; 2.70]

non fatal stroke 1.17 [0.96; 1.42]

non fatla MI 1.02 [0.91; 1.14]

Ischemic Stroke 1.15 [0.94; 1.41]

all-cause cerebrovascular accident 1.17 [0.96; 1.42]

Cardiovascular Event 1.05 [0.96; 1.15]

all-cause mortality 1.05 [0.89; 1.25]

all-cause mortality 1.07 [0.78; 1.49]

coronary events 0.89 [0.51; 1.58]

cardiovascular death 0.86 [0.49; 1.51]

Hemorrhagic Stroke ∞ [NaN; ∞]

non fatal stroke 1.56 [0.78; 3.13]

non fatla MI 1.07 [0.56; 2.04]

Ischemic Stroke 1.13 [0.60; 2.13]

all-cause cerebrovascular accident 1.24 [0.67; 2.31]

Cardiovascular Event 1.07 [0.74; 1.55]

coronary events 0.45 [0.21; 0.99]

Cardiovascular Event 0.54 [0.33; 0.89]

all-cause mortality 1.09 [0.72; 1.66]

cardiovascular death 0.61 [0.28; 1.33]

Ischemic Stroke 0.85 [0.27; 2.70]

all-cause cerebrovascular accident 0.85 [0.27; 2.70]

Cardiovascular Event 0.91 [0.77; 1.08]

all-cause mortality 1.02 [0.91; 1.15]

coronary events 0.92 [0.73; 1.16]

cardiovascular death 0.96 [0.79; 1.16]

Hemorrhagic Stroke 1.50 [0.68; 3.34]

non fatal stroke 0.82 [0.64; 1.04]

non fatla MI 0.89 [0.69; 1.14]

Ischemic Stroke 0.81 [0.64; 1.02]

all-cause cerebrovascular accident 0.85 [0.68; 1.07]

Cardiovascular Event 0.92 [0.81; 1.04]

Hemorrhagic Stroke 1.70 [1.02; 2.84]

all-cause mortality 1.03 [0.94; 1.12]

cardiovascular death 1.03 [0.87; 1.22]

Ischemic Stroke 0.98 [0.80; 1.19]

all-cause cerebrovascular accident 1.05 [0.87; 1.25]

Cardiovascular Event 0.99 [0.89; 1.10]

Hemorrhagic Stroke 0.92 [0.61; 1.38]

Ischemic Stroke 0.98 [0.81; 1.20]

all-cause cerebrovascular accident 0.98 [0.82; 1.17]

all-cause mortality 0.90 [0.69; 1.18]

coronary events 0.97 [0.73; 1.28]

cardiovascular death 0.99 [0.70; 1.40]

all-cause cerebrovascular accident 1.03 [0.60; 1.76]

Cardiovascular Event 1.04 [0.83; 1.32]

all-cause mortality 2.00 [0.37; 10.82]

coronary death 1.06 [0.79; 1.41]

coronary events 0.94 [0.77; 1.14]

non fatla MI 0.81 [0.60; 1.11]

vitamin E (alpha-tocopherol) 50mg/d (n=14564)

vs.

placebo (n=14569)

factorial design of four regimens: alpha-tocopherol (50 mg per day) alone, beta carotene (20 mg per day) alone, both alpha-tocopherol and beta carotene, or placebo

double-blind

Factorial plan

Sample size: 14564/14569

Primary endpoint: not defined

FU duration: 6.1 median (range 5-8y)

vitamin E 400-800UI/d (alpha tocopherol) (n=1035)

vs.

identical placebo (n=967)

double-blind

Parallel groups

Sample size: 1035/967

Primary endpoint: CV death, MI and non fatal MI alone

FU duration: 1.5y

2 primary endpoints but no procedure to control multiplicity

vitamin E 300mg/d (n=5660)

vs.

no vitamine E (n=5664)

randomization between 4 treatment: n-3 PUFA (1 g daily), vitamin E (300 mg daily), both or none (control)

open

Factorial plan

Sample size: 5660/5664

Primary endpoint: death, MI, stroke

FU duration: 3.5y

vitamin E 400IU/d from natural sources (n=4761)

vs.

matching placebo (n=4780)

factorial design of ramipril and vitamin E

double-blind

Factorial plan

Sample size: 4761/4780

Primary endpoint: CV death, MI, stroke

FU duration: 4.5y

daily supplementation of antioxidants (500 mg of vitamin C, 400 IU of vitamin E, and 15 mg of beta carotene) (n=2370)

vs.

placebo (n=2387)

patients with more than a few small drusen were also randomly assigned to receive tablets with or without zinc (80 mg of zinc as zinc oxide) and copper (2 mg of copper as cupric oxide) as part of the age-related macular degeneration trial

double-blind

Factorial plan

Sample size: 2370/2387

Primary endpoint: opacity grades or cataract surgery

FU duration: 6.3 y

vitamin E (300 mg/day) (n=2231)

vs.

no vitamin E (n=2264)

factorial design with aspirin

open

Factorial plan

Sample size: 2231/2264

Primary endpoint: CV events

FU duration: 3.6y

vitamin E 800 IU daily (n=97)

vs.

matching placebo (n=99)

double -blind

Parallel groups

Sample size: 97/99

Primary endpoint: MI, stroke, PVD, unstable angina

FU duration: 1.42 years

beta carotene, vitamin E, and selenium (n=14792)

vs.

(n=14792)

Sample size: 14792/14792

Primary endpoint:

FU duration: 5y

vitamin E (600IU every two days) (n=4083)

vs.

placebo (n=4088)

2x2x2 factorial design testing the effects of ascorbic acid (500 mg/d), vitamin E (600 IU every other day), and beta carotene (50 mg every 2day)

double blind

Factorial plan

Sample size: 4083/4088

Primary endpoint: MI, stroke, coronary revascularization, CVD death

FU duration: 9.4 years

vitamin E 400IU every two days (n=7315)

vs.

placebo (n=7326)

factorial trial evaluating vitamin E (400 IU every 2 days synthetic alpha-tocopherol), vitaminC(500mg synthetic ascorbic acid), a multivitamin (Centrum Silver daily; Wyeth Pharmaceuticals) and beta carotene (50mg, Lurotin on alternate days)

7641 partcipant from PHS I and 7000 new physicians

double blind

Sample size: 7315/7326

Primary endpoint: Cv death, MI, Stroke

FU duration: 8 years (mean)

vitamin E 600 IU every other day (á-tocopherol) (n=19937)

vs.

placebo (n=19939)

factorial design vitamin E or placebo and aspirin or placebo

double-blind

Factorial plan

Sample size: 19937/19939

Primary endpoint: major cardiovascular event

FU duration: 10.1 y

two primary endpoint specified without method for dealing with multiplicity

vitamin E 400 IU/day, natural (n=499)

vs.

placebo (n=494)

double-blind

Factorial plan

Sample size: 499/494

Primary endpoint: not defined

FU duration: 4.5y

subgroup analysis

d-alpha-tocopherol 91 mg (136 IU) twice daily (n=260)

vs.

placebo (n=260)

double-blind

Factorial plan

Sample size: 260/260

Primary endpoint: carotid artery mean intima-media thickness

FU duration: 3 years

after the double-blind 3-year period, the study was continued for another 3 years as an open study

alpha tocopherol (vitamin E) 50 mg/day (n=916)

vs.

placebo (n=879)

factorial design of alpha tocopherol (vitamin E) 50 mg/day and beta carotene 20 mg/day

double-blind

Factorial plan

Sample size: 916/879

Primary endpoint: not defined

FU duration: 3.79 y

fatal or nonfatal coronary event or stroke or revascularisation 1.03 [0.84; 1.27]

major haemorrhage requiring admission to hospital 1.71 [0.99; 2.96]

All cause mortality 0.95 [0.77; 1.17]

Major hemorrhage 1.70 [0.98; 2.94]

all vascular event 1.00 [0.85; 1.17]

gastrointestinal ulcer 1.75 [0.74; 4.16]

fatal hemorrhagic stroke 1.00 [0.20; 4.95]

non fatal hemorrhagic stroke 2.00 [0.18; 22.04]

aspirin 100mg daily (n=1675)

vs.

placebo (n=1675)

double blind

Parallel groups

Sample size: 1675/1675

Primary endpoint: fatal or nonfatal coronary event or stroke or revascularisation

FU duration: 8.2 y (mean)

Non fatal MI 0.84 [0.70; 1.00]

MI,stroke or CVdeath 0.92 [0.84; 1.00]

Death from any cause 0.98 [0.87; 1.10]

Death from cardiovascular causes 0.92 [0.80; 1.07]

severe bleeding 0.88 [0.70; 1.12]

non fatal stroke 0.94 [0.82; 1.07]

clopidogrel 75 mg once daily (n=9599)

vs.

aspirin 325 mg once daily (n=9586)

Double blind

Parallel groups

Sample size: 9599/9586

Primary endpoint: ischaemic stroke, myocardial infarction, or vascular death

FU duration: mean 1.91 years

non fatal stroke 0.81 [0.65; 1.00]

moderate bleeding 1.62 [1.27; 2.08]

nonfatal Ischemic stroke 0.82 [0.66; 1.04]

Death from any cause 0.99 [0.86; 1.14]

Death from cardiovascular causes 1.04 [0.87; 1.24]

severe bleeding 1.25 [0.97; 1.61]

Non fatal MI 0.92 [0.74; 1.15]

fatal bleeding 1.53 [0.83; 2.82]

MI,stroke or CVdeath 0.93 [0.83; 1.04]

clopidogrel (75 mg per day) plus low-dose aspirin (75 to 162 mg per day) (n=7802)

vs.

placebo plus low-dose aspirin (n=7801)

Double blind

Parallel groups

Sample size: 7802/7801

Primary endpoint: myocardial infarction, stroke or death from cardiovasculare causes

FU duration: median 28 months

Stroke (any) 0.75 [0.57; 0.98]

myocardial infarction 0.85 [0.73; 0.99]

all vascular event 0.85 [0.75; 0.95]

CV death, MI, stroke 0.85 [0.75; 0.95]

Major hemorrhage 2.16 [1.56; 2.99]

All cause mortality 0.89 [0.76; 1.04]

death from CHD 0.81 [0.63; 1.04]

cardiovascular death 0.83 [0.68; 1.01]

fatal bleeding 0.92 [0.41; 2.08]

Intracranial haemorrhage 1.10 [0.67; 1.81]

death from CHD 0.74 [0.57; 0.96]

myocardial infarction 0.82 [0.70; 0.95]

all vascular event 0.85 [0.76; 0.96]

CV death, MI, stroke 0.85 [0.76; 0.96]

Major hemorrhage 2.36 [1.72; 3.24]

All cause mortality 1.00 [0.86; 1.16]

cardiovascular death 0.87 [0.71; 1.06]

fatal bleeding 0.50 [0.19; 1.33]

Intracranial haemorrhage 1.26 [0.73; 2.18]

Stroke (any) 0.82 [0.63; 1.07]

ticagrelor at a dose of 60 mg twice daily (n=7045)

vs.

placebo (n=7067)

double-blind

Parallel groups

Sample size: 7045/7067

Primary endpoint: cardiovascular death, myocardial

FU duration: 2.75 y (median)

ticagrelor at a dose of 90 mg twice daily (n=7050)

vs.

(n=7067)

double-blind

Sample size: 7050/7067

Primary endpoint: cardiovascular death, myocardial

FU duration: 2.75 y (median)

myocardial infarction 0.84 [0.75; 0.93]

all vascular event 0.87 [0.80; 0.94]

CV death, MI, stroke 0.87 [0.81; 0.95]

major haemorrhage requiring admission to hospital 1.42 [1.32; 1.52]

Major hemorrhage 1.45 [1.21; 1.73]

Intracranial haemorrhage 1.92 [1.38; 2.68]

All cause mortality 0.96 [0.85; 1.07]

cardiovascular death 0.89 [0.76; 1.05]

fatal bleeding 1.45 [0.82; 2.56]

Stroke (any) 0.97 [0.83; 1.13]

all vascular event 0.84 [0.76; 0.93]

all vascular event 0.81 [0.73; 0.90]

Major hemorrhage 1.29 [1.02; 1.63]

All cause mortality 0.93 [0.79; 1.09]

fatal bleeding 1.56 [0.45; 5.41]

Intracranial haemorrhage 1.54 [0.54; 4.34]

fatal hemorrhagic stroke 1.53 [0.95; 2.46]

net benefit 0.92 [0.36; 2.33]

vorapaxar (SCH 530348) 2.5-mg daily (n=13225)

vs.

placebo (added to the existing standard of care for preventing heart attack and stroke (eg, aspirin, clopidogrel) (n=13244)

trial was discontinued in patients who experienced a stroke. The study drug will be continued in patients with previous MI or peripheral disease

double-blind

Parallel groups

Sample size: 13225/13244

Primary endpoint: CV death, MI, stroke, urgent revascularization

FU duration: 2.5 y (median)

vorapaxar (SCH 530348) 2.5-mg daily (n=20699)

vs.

placebo (added to the existing standard of care for preventing heart attack and stroke (eg, aspirin, clopidogrel) (n=0)

trial was discontinued in patients who experienced a stroke. The study drug will be continued in patients with previous MI or peripheral disease

double-blind

Parallel groups

Sample size: 20699/0

Primary endpoint: CV death, MI, stroke, urgent revascularization

FU duration: 2.5 y (median)

vorapaxar (SCH 530348) 2.5-mg daily (n=8898)

vs.

placebo (added to the existing standard of care for preventing heart attack and stroke (eg, aspirin, clopidogrel) (n=8881)

trial was discontinued in patients who experienced a stroke. The study drug will be continued in patients with previous MI or peripheral disease

double-blind

Parallel groups

Sample size: 8898/8881

Primary endpoint: CV death, MI, stroke, urgent revascularization

FU duration: 2.5 y (median)

Cv death 0.88 [0.79; 0.98]

CV events (nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular cause) 0.88 [0.79; 0.98]

major bleeding 1.29 [1.09; 1.52]

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

all-cause mortality 0.89 [0.74; 1.08]

coronary heart disease mortality 0.94 [0.67; 1.34]

total coronary heart disease events 0.96 [0.75; 1.23]

Cv death 0.93 [0.72; 1.22]

Hemorrhagic Stroke and Intracranial Hemorrhage 1.08 [0.41; 2.84]

non fatal stroke 1.13 [0.72; 1.77]

non fatal MI 0.97 [0.67; 1.41]

Ischemic Stroke 1.50 [0.64; 3.51]

fatal and nonfatal stroke 1.16 [0.80; 1.69]

CV events (nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular cause) 0.98 [0.81; 1.19]

Major gastrointestinal bleeding 1.00 [0.47; 2.13]

coronary heart disease mortality 0.64 [0.42; 0.99]

total coronary heart disease events 0.61 [0.51; 0.74]

non fatal MI 0.61 [0.49; 0.75]

CV events (nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular cause) 0.83 [0.71; 0.96]

Major gastrointestinal bleeding 1.60 [1.01; 2.52]

all-cause mortality 0.96 [0.79; 1.15]

Cv death 0.98 [0.72; 1.32]

Hemorrhagic Stroke and Intracranial Hemorrhage 1.92 [0.95; 3.85]

non fatal stroke 1.20 [0.91; 1.57]

Ischemic Stroke 1.11 [0.82; 1.49]

fatal and nonfatal stroke 1.21 [0.93; 1.58]

non fatal MI 0.68 [0.53; 0.89]

Major extracranial bleed 1.54 [0.77; 3.08]

all-cause mortality 1.03 [0.79; 1.33]

coronary heart disease mortality 1.06 [0.66; 1.68]

total coronary heart disease events 0.77 [0.58; 1.03]

Cv death 1.24 [0.93; 1.66]

Hemorrhagic Stroke and Intracranial Hemorrhage 2.00 [0.75; 5.31]

non fatal stroke 0.78 [0.50; 1.23]

Ischemic Stroke 0.64 [0.37; 1.09]

fatal and nonfatal stroke 0.69 [0.38; 1.26]

CV events (nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular cause) 0.88 [0.74; 1.04]

Major gastrointestinal bleeding 1.54 [0.77; 3.08]

total coronary heart disease events 0.65 [0.49; 0.85]

non fatal MI 0.60 [0.44; 0.80]

myocardial infarction (fatal and non fatal) 0.65 [0.49; 0.85]

CV events (nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular cause) 0.86 [0.74; 0.99]

Major extracranial bleed 1.93 [1.43; 2.62]

Gastrointestinal Bleeding 1.94 [1.41; 2.69]

Major gastrointestinal bleeding 2.08 [1.41; 3.07]

all-cause mortality 0.93 [0.79; 1.09]

coronary heart disease mortality 1.00 [0.48; 2.09]

Cv death 0.95 [0.75; 1.20]

Hemorrhagic Stroke and Intracranial Hemorrhage 0.93 [0.45; 1.93]

fatal bleeding 0.87 [0.32; 2.41]

fatal and nonfatal stroke 0.99 [0.79; 1.24]

Gastrointestinal Bleeding 3.47 [1.28; 9.38]

all-cause mortality 0.81 [0.58; 1.13]

coronary heart disease mortality 0.86 [0.39; 1.92]

total coronary heart disease events 0.76 [0.46; 1.25]

Hemorrhagic Stroke and Intracranial Hemorrhage 0.68 [0.11; 4.06]

non fatal MI 0.73 [0.38; 1.41]

Ischemic Stroke 0.95 [0.46; 1.97]

fatal and nonfatal stroke 0.68 [0.36; 1.28]

myocardial infarction (fatal and non fatal) 0.69 [0.39; 1.23]

CV events (nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular cause) 0.72 [0.49; 1.04]

Major gastrointestinal bleeding 2.04 [0.51; 8.14]

Ischemic Stroke 0.77 [0.63; 0.94]

fatal and nonfatal stroke 0.83 [0.70; 0.99]

Gastrointestinal Bleeding 1.21 [1.10; 1.33]

Peptic ulcer 1.31 [1.16; 1.49]

Hematuria 1.06 [1.01; 1.11]

Major gastrointestinal bleeding 1.40 [1.07; 1.83]

all-cause mortality 0.95 [0.85; 1.06]

coronary heart disease mortality 1.17 [0.54; 2.52]

total coronary heart disease events 0.97 [0.82; 1.16]

Hemorrhagic Stroke and Intracranial Hemorrhage 1.24 [0.83; 1.88]

non fatal MI 1.02 [0.83; 1.25]

myocardial infarction (fatal and non fatal) 1.03 [0.84; 1.25]

CV events (nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular cause) 0.91 [0.81; 1.03]

All cause mortality 0.93 [0.72; 1.21]

CHD death 1.35 [0.82; 2.21]

CHD events (fatal and non fatal) 1.10 [0.83; 1.45]

CV death 1.23 [0.80; 1.89]

fatal MI 1.35 [0.82; 2.21]

fatal stroke 0.89 [0.35; 2.29]

non fatal MI 0.98 [0.69; 1.40]

stroke (fatal and non fatal) 0.74 [0.49; 1.12]

CV events (fatal and non fatal) 0.99 [0.79; 1.25]

peripheral artery disease 0.91 [0.70; 1.17]

stable angina 0.90 [0.66; 1.22]

CV death 0.10 [0.01; 0.79]

CHD death 0.00 [0.00; NaN]

CHD events (fatal and non fatal) 0.81 [0.50; 1.32]

fatal MI 0.00 [0.00; NaN]

fatal stroke 0.20 [0.02; 1.73]

non fatal MI 1.35 [0.57; 3.19]

stroke (fatal and non fatal) 0.89 [0.54; 1.46]

CV events (fatal and non fatal) 0.80 [0.59; 1.09]

peripheral artery disease 0.64 [0.25; 1.66]

stable angina 1.10 [0.49; 2.49]

unstable angina 0.40 [0.13; 1.29]

non fatal MI 4.20 [1.10; 16.10]

All cause mortality 0.49 [0.13; 1.95]

CV death 0.49 [0.10; 2.42]

CV events (fatal and non fatal) 1.48 [0.68; 3.22]

CHD events (fatal and non fatal) 0.85 [0.73; 1.00]

All cause mortality 0.93 [0.81; 1.06]

CV death 0.92 [0.79; 1.07]

non fatal MI 0.78 [0.54; 1.11]

stroke (fatal and non fatal) 1.18 [0.88; 1.58]

CV events (fatal and non fatal) 0.95 [0.83; 1.07]

CHD events (fatal and non fatal) 0.40 [0.20; 0.79]

All cause mortality 1.23 [0.69; 2.19]

CHD events (fatal and non fatal) 0.49 [0.17; 1.43]

CV death 1.23 [0.49; 3.10]

revascularization procedure 0.79 [0.31; 1.98]

stroke (fatal and non fatal) 0.89 [0.36; 2.17]

all MI 0.49 [0.17; 1.43]

CV events (fatal and non fatal) 0.90 [0.50; 1.62]

peripheral artery disease 0.83 [0.38; 1.85]

stable angina 0.80 [0.39; 1.65]

stroke (fatal and non fatal) 0.48 [0.26; 0.88]

CHD events (fatal and non fatal) 1.50 [0.91; 2.47]

all MI 1.50 [0.91; 2.47]

CV events (fatal and non fatal) 0.93 [0.67; 1.31]

aspirin 500 mg/d (n=3429)

vs.

no aspirin (n=1710)

open

Parallel groups

Sample size: 3429/1710

Primary endpoint: not defined

FU duration: 5.5 years

aspirin 325 mg every other day (n=11037)

vs.

placebo (n=11034)

factorial design with beta caroten vs placebo

double blind

Parallel groups

Sample size: 11037/11034

Primary endpoint: cardiovascular mortality ?

FU duration: 60.2 months

aspirin 75 mg/d (controlled release) (n=2545)

vs.

placebo (n=2540)

factorial design of aspirin and warfarin (all two vs placebo)

double blind

Factorial plan

Sample size: 2545/2540

Primary endpoint: ischemic heart diseases

FU duration: median 6.8y

aspirin 75 mg daily (n=9399)

vs.

placebo (n=9391)

factorial design with as 2nd factor the comparison of 3 BP targets

Double blind

Factorial plan

Sample size: 9399/9391

Primary endpoint: non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death

FU duration: mean 3.8 y (range 3.3-4.9y)

aspirin 100 mg/d (n=2226)

vs.

no aspirin (open control) (n=2269)

factorial design with other comaprison: vitamin E vs control

Open

Factorial plan

Sample size: 2226/2269

Primary endpoint: cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke

FU duration: 3.6 y

aspirin 100mg daily (n=19934)

vs.

placebo (n=19942)

factorial design: vitamin E vs placebo

Double blind

Factorial plan

Sample size: 19934/19942

Primary endpoint: nonfatal myocardial infarction, nonfatal stroke, and death from cardiovascular causes

FU duration: 10.1 y mean (range 8.2 to 10.9

aspirin 100mg daily (n=638)

vs.

placebo (n=638)

factoral design with antioxidant capsule

double blind

Factorial plan

Sample size: 638/638

Primary endpoint: Cv events; CHD death+stroke

FU duration: nov 1997 - jul 2001

low-dose aspirin (81 or 100 mg per day) (n=1262)

vs.

no aspirin (n=1277)

open

Parallel groups

Sample size: 1262/1277

Primary endpoint: atherosclerotic events

FU duration: 4.37 y median

aspirin alone (330 mg 3 times daily) or in combination with dipyridamole (75 mg 3 times daily) (n=318)

vs.

placebo (n=157)

double blind

Parallel groups

Sample size: 318/157

Primary endpoint: number of microaneurysms

FU duration: 3 y

aspirin 650mg once daily (n=1856)

vs.

placebo (n=1855)

double blind

Parallel groups

Sample size: 1856/1855

Primary endpoint: Mortality from all causes

FU duration: 60 months

aspirin 325 mg every other day (n=275)

vs.

placebo (n=258)

double blind

Factorial plan

Sample size: 275/258

Primary endpoint: cardiovascular mortality

FU duration: 5 y

aspirin 100mg daily (n=519)

vs.

control (n=512)

factorial design evaluating aspirin and vitamin E

Initialy, PPP enrolled 4784 patients of whom 1031 had diabetes

open

Factorial plan

Sample size: 519/512

Primary endpoint: CV events

FU duration: 3.6 y

sub group study

aspirin 100mg on alternate days (n=514)

vs.

placebo (n=513)

factorial design of aspirin and vitamin E

trial enrolled 39876 patients of whom 1027 had diabetes (2.6%)

double blind

Parallel groups

Sample size: 514/513

Primary endpoint: cardiovascular event

FU duration: 10.1 y

sub group

CV death 0.00 [0.00; NaN]

non fatal MI 0.00 [0.00; NaN]

CV events (fatal and non fatal) 0.00 [0.00; NaN]

picotamide 300 mg TID (n=25)

vs.

placebo (n=25)

double blind

Parallel groups

Sample size: 25/25

Primary endpoint: not unique (carotid atherosclerotic lesions)

FU duration: 24 months

All cause mortality ∞ [NaN; ∞]

CV death ∞ [NaN; ∞]

non fatal MI 1.00 [0.05; 18.57]

CV events (fatal and non fatal) 2.07 [0.41; 10.46]

sulfinyrazone (n=30)

vs.

(n=31)

Parallel groups

Sample size: 30/31

Primary endpoint:

FU duration: 32 months

All cause mortality NaN [NaN; NaN]

CV death NaN [NaN; NaN]

non fatal MI 0.00 [0.00; NaN]

CV events (fatal and non fatal) 0.00 [0.00; NaN]

All cause mortality 1.05 [0.07; 16.24]

CV death 1.05 [0.07; 16.24]

non fatal MI NaN [NaN; NaN]

CV events (fatal and non fatal) 0.53 [0.05; 5.57]

All cause mortality 0.73 [0.17; 3.24]

CV death 0.49 [0.04; 5.35]

non fatal MI 0.33 [0.03; 3.84]

CV events (fatal and non fatal) 0.56 [0.17; 1.88]

All cause mortality NaN [NaN; NaN]

CV death NaN [NaN; NaN]

non fatal MI 0.00 [0.00; NaN]

CV events (fatal and non fatal) 0.00 [0.00; NaN]

All cause mortality ∞ [NaN; ∞]

CV death ∞ [NaN; ∞]

non fatal MI NaN [NaN; NaN]

CV events (fatal and non fatal) ∞ [NaN; ∞]

ticlopidine 100, 250, 500 mg (n=20)

vs.

(n=8)

Parallel groups

Sample size: 20/8

Primary endpoint:

FU duration: 2 months

ticlopidine 500mg (n=38)

vs.

(n=40)

Parallel groups

Sample size: 38/40

Primary endpoint:

FU duration: 12 months

ticlopidine 500mg (n=220)

vs.

(n=215)

Parallel groups

Sample size: 220/215

Primary endpoint:

FU duration: 32m

ticlopidine 500mg/d (n=49)

vs.

placebo (n=51)

double blind

Parallel groups

Sample size: 49/51

Primary endpoint: evolution of retinopathy

FU duration: 48 months

ticlopidine 500mg daily (n=12)

vs.

placebo (n=11)

double blind

Parallel groups

Sample size: 12/11

Primary endpoint:

FU duration: 12 months

myocardial infarction as adverse event 0.39 [0.20; 0.79]

death from all causes as adverse event 0.29 [0.09; 0.99]

General allergic reaction 1.06 [0.81; 1.37]

serious adverse events 0.96 [0.80; 1.14]

cardiovascular events as adverse events 0.91 [0.63; 1.33]

Neurocognitive disorder 2.28 [0.78; 6.72]

neurological SAE 0.94 [0.63; 1.41]

cardiovascular death as adverse event 0.41 [0.16; 1.02]

serious adverse events 1.19 [0.53; 2.65]

death from all causes as adverse event NaN [NaN; NaN]

myocardial infarction as adverse event ∞ [NaN; ∞]

cardiovascular death as adverse event NaN [NaN; NaN]

CHD events 0.85 [0.78; 0.93] Demonstrated

major CHD event 0.88 [0.80; 0.96] Demonstrated

cardiovascular events 0.87 [0.81; 0.94] Demonstrated

all causes deaths 0.85 [0.73; 0.98]

cardiovascular death 0.88 [0.74; 1.05]

CHD death 0.92 [0.76; 1.11]

cardiovascular death 0.88 [0.74; 1.05]

serious adverse events 0.98 [0.06; 15.26]

death from all causes as adverse event NaN [NaN; NaN]

cardiovascular death as adverse event NaN [NaN; NaN]

serious adverse events 0.97 [0.31; 3.01]

death from all causes as adverse event NaN [NaN; NaN]

cardiovascular death as adverse event NaN [NaN; NaN]

serious adverse events 0.56 [0.17; 1.86]

death from all causes as adverse event 0.00 [0.00; NaN]

cardiovascular death as adverse event 0.00 [0.00; NaN]

serious adverse events 0.74 [0.26; 2.04]

death from all causes as adverse event 0.00 [0.00; NaN]

cardiovascular death as adverse event 0.00 [0.00; NaN]

serious adverse events 0.95 [0.52; 1.74]

death from all causes as adverse event 0.51 [0.03; 8.11]

myocardial infarction as adverse event 0.51 [0.03; 8.11]

cardiovascular death as adverse event 0.34 [0.06; 2.01]

serious adverse events 1.05 [0.76; 1.46]

death from all causes as adverse event 0.50 [0.07; 3.55]

cardiovascular death as adverse event 0.25 [0.05; 1.36]

alirocumab 150 mg as a 1-ml subcutaneous injection every 2 weeks for 78 weeks. (n=1553)

vs.

placebo (n=788)

Sample size: 1553/788

Primary endpoint: change in LDL at week 24

FU duration: 78 wk

Alirocumab 75 mg with potential up-titration to 150 mg Q2W (n=-9)

vs.

Ezetimibe 10 mg (n=-9)

double-blind

Sample size: -9/-9

Primary endpoint: percent change in LDL-C from baseline to week 24

FU duration: 24 wk

Alirocumab (on top intensive or maximum-tolerated statin therapy) (n=9462)

vs.

placebo (n=9462)

double-blind

Parallel groups

Sample size: 9462/9462

Primary endpoint:

FU duration: 2.8 yr (median)

Alirocumab 75 mg Q2W (n=-9)

vs.

Ezetimibe 10 mg (n=-9)

double-blind

Sample size: -9/-9

Primary endpoint:

FU duration: 24 wk

Alirocumab 75 mg with potential up-titration to 150 mg Q2W (n=-9)

vs.

Placebo (n=-9)

double-blind

Sample size: -9/-9

Primary endpoint:

FU duration: 78 wk

Alirocumab 75 mg with potential up-titration to 150 mg Q2W (n=-9)

vs.

Placebo (n=-9)

double blind

Sample size: -9/-9

Primary endpoint:

FU duration: 78 wk

Alirocumab 150 mg Q2W (n=-9)

vs.

Placebo (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration: 52–78 wk

Alirocumab 75 mg with potential up-titration to 150 mg Q2W (n=-9)

vs.

Ezetimibe 10 mg (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration: 24 wk

Alirocumab 75 mg with potential up-titration to 150 mg Q2W (n=-9)

vs.

Ezetimibe 10 mg (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration: 24 wk

Alirocumab 75 mg with potential up-titration to 150 mg Q2W (n=-9)

vs.

Placebo (n=-9)

double-blind

Sample size: -9/-9

Primary endpoint:

FU duration: 52 wk

Alirocumab 75 mg with potential up-titration to 150 mg Q2W (n=-9)

vs.

Ezetimibe 10 mg (n=-9)

double-blind

Sample size: -9/-9

Primary endpoint:

FU duration: 104 wk

cardiovascular events ∞ [NaN; ∞]

oral anacetrapib 100 mg for 52 weeks (n=204)

vs.

placebo (n=102)

double-blind

Parallel groups

Sample size: 204/102

Primary endpoint: percentage change from baseline in LDL-C

FU duration: 52 weeks

all cause death 1.38 [0.56; 3.40]

Cardiovascular death 4.00 [0.45; 35.76]

Nonfatal stroke 1.00 [0.29; 3.45]

Nonfatal myocardial infarction 0.67 [0.24; 1.87]

Cardiovascular death, myocardial infarction, stroke 0.76 [0.40; 1.45]

cardiovascular events 0.76 [0.40; 1.45]

anacetrapib 100mg fr 18 months (n=811)

vs.

placebo (n=812)

double-blind

Parallel groups

Sample size: 811/812

Primary endpoint: percent change from baseline in LDL cholesterol at 24 weeks

FU duration:

Critère de jugement principal de l'étude 0.84 [0.55; 1.28]

Infarctus non mortel et décès coronariens 0.84 [0.55; 1.28]

AVC 0.67 [0.41; 1.08]

Cv events (CV death, MI, stroke) 0.84 [0.55; 1.28]

CV events (including revascularization) 0.65 [0.49; 0.84] Demonstrated

coronary events 0.65 [0.46; 0.93]

MI non fatal 0.60 [0.37; 0.99]

stroke (fatal et non fatal) 0.53 [0.31; 0.90]

cardiovascular events 0.63 [0.47; 0.86]

Pancreatitis 1.23 [0.33; 4.59]

all cause deaths 0.74 [0.53; 1.02]

coronary deaths 0.74 [0.40; 1.36]

adverse events 0.94 [0.50; 1.75]

cardiovascular death 0.65 [0.36; 1.15]

décès par cancer 0.66 [0.38; 1.15]

Haemorrhagic strokes NaN [NaN; NaN]

fatal stroke 0.14 [0.02; 1.15]

Rhabdomyolyses NaN [NaN; NaN]

Myopathies 0.99 [0.06; 15.78]

coronary events 0.72 [0.59; 0.87] Demonstrated

CV events (including revascularization) 0.80 [0.70; 0.90]

stroke (fatal et non fatal) 0.73 [0.56; 0.96]

Infarctus non mortel et décès coronariens 0.65 [0.50; 0.83]

Pancreatitis 0.50 [0.21; 1.16]

all cause deaths 0.87 [0.71; 1.05]

cardiovascular death 0.90 [0.66; 1.23]

Rhabdomyolyses ∞ [NaN; ∞]

non cardiovascular death 0.85 [0.66; 1.09]

incident diabetes 1.14 [0.89; 1.46]

coronary events 0.86 [0.74; 0.99]

CV events 0.96 [0.83; 1.10]

all cause death 0.95 [0.85; 1.07]

Cardiovascular death 0.83 [0.67; 1.03]

cardiovascular death, CV events (nonfatal MI, or nonfatal stroke) 0.96 [0.83; 1.10]

Noncardiovascular death 0.97 [0.80; 1.18]

Pancreatitis 0.59 [0.14; 2.48]

coronary events 0.74 [0.51; 1.05]

cardiovascular death 1.02 [0.65; 1.59]

CV events (including revascularization) 0.91 [0.75; 1.11]

stroke (fatal et non fatal) 0.89 [0.56; 1.40]

cardiovascular events 0.91 [0.75; 1.11]

Infarctus non mortel et décès coronariens 0.74 [0.51; 1.05]

Décès toutes causes 1.02 [0.74; 1.41]

Décès cardiovasculaires 1.02 [0.65; 1.59]

AVC 0.89 [0.56; 1.40]

Cv events (CV death, MI, stroke) 0.91 [0.75; 1.11]

all cause deaths 0.58 [0.35; 0.95]

coronary deaths 0.53 [0.33; 0.86]

coronary events 0.49 [0.39; 0.61]

stroke (fatal et non fatal) 0.53 [0.32; 0.89]

cardiac death 0.58 [0.35; 0.95]

Pancreatitis NaN [NaN; NaN]

Haemorrhagic strokes 1.00 [0.06; 15.96]

fatal stroke 0.00 [0.00; NaN]

Rhabdomyolyses NaN [NaN; NaN]

non cardiovascular death 1.50 [0.25; 8.95]

all cause deaths 1.06 [0.70; 1.60]

coronary events 0.97 [0.75; 1.26]

cardiovascular death 1.25 [0.69; 2.26]

stroke (fatal et non fatal) 0.92 [0.55; 1.54]

cardiovascular events 0.97 [0.75; 1.26]

non cardiovascular death 0.90 [0.49; 1.63]

CHD events 1.10 [0.57; 2.10]

Cv events 1.10 [0.57; 2.10]

10 mg atorvastatin (n=1258)

vs.

placebo (n=1274)

Sample size: 1258/1274

Primary endpoint:

FU duration:

atorvastatin 10mg/d (n=1429)

vs.

placebo (n=1412)

double blind

Parallel groups

Sample size: 1429/1412

Primary endpoint: Ev coronariens aigus, revascularisation ou AVC

FU duration: 3.9 years

atorvastatin 10mg/d (n=5168)

vs.

placebo (n=5137)

double blind

Parallel groups

Sample size: 5168/5137

Primary endpoint: Infractus non mortel et décès coronariens

FU duration: 3.3 years

atorvastatin 20mg daily (n=619)

vs.

matching placebo (n=636)

double blind

Parallel groups

Sample size: 619/636

Primary endpoint: cardiac death, stroke, MI

FU duration: 4 y (median)

atorvastatin 10mg (n=1211)

vs.

placebo (n=1199)

double blind

Parallel groups

Sample size: 1211/1199

Primary endpoint: cardiovascular events

FU duration: 4 year

atorvastatin 10mg daily (n=1211)

vs.

placebo (n=1199)

double blind

Parallel groups

Sample size: 1211/1199

Primary endpoint: CV death, mI, stroke, recanalization, CABG, worsening

FU duration: 4y

atorvastatin 10-80 mg/d (n=800)

vs.

usual care (n=800)

open

Parallel groups

Sample size: 800/800

Primary endpoint: CV events

FU duration: 3 years mean

atorvastatin (10 mg per day) (n=-9)

vs.

placebo (n=-9)

double blind

Sample size: -9/-9

Primary endpoint:

FU duration: 12 months

atorvastatin 10mg (n=959)

vs.

placebo (n=947)

double blind

Parallel groups

Sample size: 959/947

Primary endpoint: cardiovascular events

FU duration: 4 year

Atorvastatin 10 mg daily (n=979)

vs.

placebo (n=963)

double-blind

Parallel groups

Sample size: 979/963

Primary endpoint: non-fatal myocardial infarction and fatal CHD

FU duration: 3.3 y

AVC 0.70 [0.50; 0.98]

Cv events (CV death, MI, stroke) 0.77 [0.61; 0.97]

Décès toutes causes 1.10 [0.82; 1.49]

Evénement coronarien majeur 0.82 [0.62; 1.08]

atorvastatin 80 mg daily (n=748)

vs.

atorvastatin 10 mg daily (n=753)

double blind

Sample size: 748/753

Primary endpoint: major cardiovascular event

FU duration: 4.9 y

coronary deaths 1.08 [0.07; 17.12]

CV events (including revascularization) 0.64 [0.40; 1.04]

MI non fatal 0.86 [0.24; 3.16]

stroke (fatal et non fatal) NaN [NaN; NaN]

cardiac death 1.08 [0.07; 17.12]

cardiovascular events 0.64 [0.40; 1.04]

atorvastatin 80 mg/d (n=164)

vs.

recommended percutaneous revascularization procedure(angioplasty) followed by usual care, whichcould include lipid-lowering treatment (n=177)

open

Parallel groups

Sample size: 164/177

Primary endpoint: ischemic event

FU duration: 1.5 years

adverse events 0.95 [0.54; 1.70]

Rhabdomyolyses NaN [NaN; NaN]

stroke (fatal et non fatal) 1.00 [0.06; 15.92]

Infarctus non mortel et décès coronariens 0.57 [0.17; 1.93]

Myopathies NaN [NaN; NaN]

CV events (including revascularization) 0.76 [0.66; 0.88]

Pancreatitis 0.98 [0.06; 15.70]

adverse events 1.23 [0.87; 1.74]

Rhabdomyolyses NaN [NaN; NaN]

stroke (fatal et non fatal) 1.18 [0.62; 2.24]

Infarctus non mortel et décès coronariens 0.85 [0.69; 1.06]

cardiovascular events 0.79 [0.70; 0.89] Demonstrated

coronary events 0.80 [0.70; 0.92]

MI non fatal 0.79 [0.67; 0.93]

stroke (fatal et non fatal) 0.76 [0.60; 0.96]

Infarctus non mortel et décès coronariens 0.80 [0.70; 0.92]

AST >3 x ULN 6.68 [3.32; 13.45]

ALT >3 x ULN 6.68 [3.32; 13.45]

adverse events 1.36 [1.17; 1.59]

Myopathies 6.68 [3.32; 13.45]

CPK >10 x ULN NaN [NaN; NaN]

Pancreatitis 0.83 [0.52; 1.31]

all cause deaths 1.01 [0.86; 1.18]

coronary deaths 0.80 [0.62; 1.03]

Haemorrhagic strokes 0.84 [0.43; 1.64]

Rhabdomyolyses 0.67 [0.11; 4.00]

AST >3 x ULN 0.11 [0.03; 0.48]

ALT >3 x ULN 0.12 [0.05; 0.29]

MI non fatal 0.83 [0.71; 0.98]

adverse events 2.30 [1.94; 2.71]

Myopathies 9.02 [2.09; 38.85]

CPK >10 x ULN NaN [NaN; NaN]

Pancreatitis 1.00 [0.48; 2.10]

all cause deaths 0.98 [0.85; 1.13]

coronary deaths 0.99 [0.80; 1.21]

coronary events 0.89 [0.78; 1.01]

décès par cancer 0.89 [0.68; 1.16]

Rhabdomyolyses 0.67 [0.11; 4.00]

stroke (fatal et non fatal) 0.87 [0.70; 1.08]

Infarctus non mortel et décès coronariens 0.89 [0.78; 1.01]

all cause deaths ∞ [NaN; ∞]

CV events (including revascularization) 1.57 [0.59; 4.19]

stroke (fatal et non fatal) 0.52 [0.03; 8.27]

Infarctus non mortel et décès coronariens 2.09 [0.24; 18.47]

all cause deaths 0.33 [0.13; 0.83]

coronary deaths 0.33 [0.07; 1.64]

adverse events 1.04 [0.71; 1.53]

cardiovascular death 0.40 [0.13; 1.26]

décès par cancer 0.00 [0.00; NaN]

CV events (including revascularization) 0.72 [0.48; 1.08]

MI non fatal 0.94 [0.48; 1.84]

Rhabdomyolyses NaN [NaN; NaN]

stroke (fatal et non fatal) 0.33 [0.03; 3.19]

Infarctus non mortel et décès coronariens 0.81 [0.47; 1.41]

Myopathies NaN [NaN; NaN]

non cardiovascular death 0.33 [0.07; 1.64]

atorvastatin 80 mg daily (n=327)

vs.

Pravastatin(40 mg) (n=327)

double blind

Parallel groups

Sample size: 327/327

Primary endpoint: Percentagechange inatheromavolume

FU duration: 1.5 years

atorvastatin 80 mg daily (n=2099)

vs.

Pravastatin 40 mg (n=2063)

factorial design with gatifloxacin or placebo

double blind

Parallel groups

Sample size: 2099/2063

Primary endpoint: Cardiac events

FU duration: 2 years

80 mg of atorvastatin daily (n=4995)

vs.

10 mg of atorvastatin daily (n=5006)

double blind

Parallel groups

Sample size: 4995/5006

Primary endpoint: Cardiovascular events

FU duration: 4.9 years

atorvastatin 80mg daily (n=4439)

vs.

simvastatine 20mg/j (n=4449)

open

Parallel groups

Sample size: 4439/4449

Primary endpoint: Cardiac events

FU duration: 4.8 years

atorvastatin (80 mg) with or without vitamin C and E (n=197)

vs.

low dose lovastatin (5 mg) (n=103)

double blind

Parallel groups

Sample size: 197/103

Primary endpoint: No. andduration ofischemicepisodes onambulatory ECG

FU duration: 1 year

atorvastatin 80 mg daily (n=446)

vs.

pravastatin(40 mg) (n=445)

double blind

Parallel groups

Sample size: 446/445

Primary endpoint: Total duration of ischemia onambulatoryECG

FU duration: 1 years

coronary events 0.25 [0.08; 0.84]

CV events (including revascularization) 0.26 [0.08; 0.88]

all cause deaths ∞ [NaN; ∞]

coronary deaths ∞ [NaN; ∞]

cardiac death NaN [NaN; NaN]

non cardiovascular death NaN [NaN; NaN]

incident diabetes 0.57 [0.15; 2.26]

Pancreatitis 1.00 [0.32; 3.08]

all cause deaths 1.06 [0.86; 1.30]

coronary deaths 1.01 [0.71; 1.44]

coronary events 0.91 [0.76; 1.08]

CV events (including revascularization) 0.93 [0.84; 1.02]

MI non fatal 0.87 [0.71; 1.07]

stroke (fatal et non fatal) 0.93 [0.68; 1.27]

cardiac death 1.01 [0.71; 1.44]

Infarctus non mortel et décès coronariens 0.91 [0.76; 1.08]

non cardiovascular death 1.03 [0.73; 1.44]

coronary events 0.36 [0.15; 0.87]

all cause deaths 0.00 [0.00; NaN]

cardiac death NaN [NaN; NaN]

all cause deaths 1.05 [0.89; 1.24]

coronary events 0.81 [0.63; 1.05]

cardiac death 1.05 [0.84; 1.32]

cardiovascular events 0.94 [0.77; 1.15]

bezafibrate 200 mg three times daily (n=47)

vs.

placebo (n=45)

double blind

Parallel groups

Sample size: 47/45

Primary endpoint: change in mean minimum lumen diameter

FU duration: 5.0 years

bezafibrate 400 mg/d (n=1548)

vs.

placebo (n=1542)

double blind

Parallel groups

Sample size: 1548/1542

Primary endpoint: IDM fatal ou non fatal ou décès coronarien

FU duration: 6.2 y

bezafibrate 400 mg daily (n=81)

vs.

placebo (n=83)

double blind

Parallel groups

Sample size: 81/83

Primary endpoint: B-mode ultrasound

FU duration: 3.0 years

bezafibrate 400 mg daily (n=783)

vs.

placebo (n=785)

double-blind

Parallel groups

Sample size: 783/785

Primary endpoint: CHD, stroke

FU duration: 4.6y

all cause deaths 0.72 [0.24; 2.18]

coronary deaths 0.85 [0.27; 2.64]

non cardiovascular death 0.00 [0.00; NaN]

all cause deaths 0.95 [0.69; 1.32]

coronary deaths 0.79 [0.49; 1.26]

coronary events 0.83 [0.67; 1.01]

décès par cancer 1.06 [0.53; 2.14]

MI non fatal 0.82 [0.66; 1.03]

non cardiovascular death 1.15 [0.72; 1.82]

all cause deaths 0.00 [0.00; NaN]

cardiac death 0.00 [0.00; NaN]

non cardiovascular death NaN [NaN; NaN]

cholestyramine (n=71)

vs.

placebo (n=72)

double blind

Parallel groups

Sample size: 71/72

Primary endpoint: not defined

FU duration: 5.0 y

cholestyramine 24 g daily (n=1906)

vs.

placebo (n=1900)

double blind

Parallel groups

Sample size: 1906/1900

Primary endpoint: definite CHD death, MI

FU duration: 7.4 years

cholestyramine (n=30)

vs.

diet (n=30)

Sample size: 30/30

Primary endpoint:

FU duration: 3 years

all cause deaths 0.00 [0.00; NaN]

coronary deaths NaN [NaN; NaN]

non cardiovascular death 0.00 [0.00; NaN]

MI non fatal 0.75 [0.60; 0.94]

all cause deaths 1.27 [1.01; 1.59]

non cardiovascular death 1.41 [1.07; 1.85]

Pancreatitis ∞ [NaN; ∞]

coronary deaths 1.12 [0.76; 1.65]

coronary events 0.83 [0.68; 1.00]

décès par cancer 1.35 [0.96; 1.91]

cardiac death 1.12 [0.76; 1.65]

coronary deaths 0.85 [0.73; 0.98]

cardiac death 0.85 [0.73; 0.98]

non cardiovascular death 1.55 [1.20; 2.01]

venous thromboembolism 1.78 [1.08; 2.92]

Pancreatitis 0.00 [0.00; NaN]

all cause deaths 0.98 [0.87; 1.11]

coronary events 0.93 [0.83; 1.04]

décès par cancer 1.05 [0.51; 2.20]

MI non fatal 0.94 [0.79; 1.13]

all cause deaths 0.98 [0.66; 1.45]

coronary deaths 1.02 [0.65; 1.60]

coronary events 0.81 [0.60; 1.11]

MI non fatal 0.64 [0.38; 1.07]

cardiac death 1.02 [0.65; 1.60]

non cardiovascular death 0.84 [0.33; 2.10]

all cause deaths 0.63 [0.42; 0.95]

coronary deaths 0.59 [0.37; 0.93]

coronary events 0.63 [0.48; 0.84]

cardiac death 0.59 [0.37; 0.93]

MI non fatal 0.68 [0.44; 1.03]

non cardiovascular death 0.89 [0.30; 2.61]

all cause deaths 0.42 [0.14; 1.27]

coronary deaths 0.46 [0.15; 1.44]

cardiac death NaN [NaN; NaN]

coronary events 1.04 [0.65; 1.67]

colestipol (15 to 30mg/d) + clofibrate (2g/d) (n=48)

vs.

diet (n=49)

Parallel groups

Sample size: 48/49

Primary endpoint:

FU duration: 2.0 years

clofibrate 1.6 g daily (n=5331)

vs.

olive oil (n=5296)

double blind

Parallel groups

Sample size: 5331/5296

Primary endpoint: IDM et/ou mort subite et/ou ischémie

FU duration: 5.3 years

clofibrate 1.8 mg/d (n=1103)

vs.

placebo (n=2789)

double blind

Parallel groups

Sample size: 1103/2789

Primary endpoint: Mortalité totale

FU duration: 6.2 years

clofibrate 1.6-2 g daily (n=350)

vs.

placebo (n=367)

double blind

Parallel groups

Sample size: 350/367

Primary endpoint: Mort subite, IDM fatal

FU duration: 3.4 years

clofibrate 1.5-2 g daily (n=244)

vs.

placebo (n=253)

double blind

Parallel groups

Sample size: 244/253

Primary endpoint: Décès coronariens et idm non fatal

FU duration: 3.6 y

clofibrate (n=30)

vs.

placebo (n=33)

double-blind

Parallel groups

Sample size: 30/33

Primary endpoint:

FU duration: 1 years

clofibrate (n=76)

vs.

placebo (n=79)

Parallel groups

Sample size: 76/79

Primary endpoint:

FU duration: 3.5 y

clofibrate (n=-9)

vs.

placebo (n=-9)

NA

Parallel groups

Sample size: -9/-9

Primary endpoint:

FU duration: 6 years

clofibrate (n=268)

vs.

placebo (n=264)

Parallel groups

Sample size: 268/264

Primary endpoint:

FU duration: 1.8 years

clofibrate (n=20)

vs.

placebo (n=20)

Parallel groups

Sample size: 20/20

Primary endpoint:

FU duration: 2 years

clofibric acid 1.6 g/day (n=379)

vs.

placebo (n=382)

double-blind

Parallel groups

Sample size: 379/382

Primary endpoint: NA

FU duration: 5 years

all cause deaths 0.76 [0.50; 1.15]

coronary deaths 0.60 [0.34; 1.06]

décès par cancer 0.98 [0.14; 6.96]

cardiac death 0.60 [0.34; 1.06]

non cardiovascular death 1.05 [0.52; 2.11]

all cause deaths 0.00 [0.00; NaN]

coronary deaths 0.00 [0.00; NaN]

cardiac death 0.00 [0.00; NaN]

non cardiovascular death NaN [NaN; NaN]

colestipol hydrochloride 32 mg/dl (n=1149)

vs.

placebo (n=1129)

double blind

Parallel groups

Sample size: 1149/1129

Primary endpoint: death

FU duration: 1.9 years

colestipol (n=23)

vs.

placebo (n=29)

Parallel groups

Sample size: 23/29

Primary endpoint:

FU duration: 1.0 years

colestipol15 g/day (n=44)

vs.

placebo (n=48)

Parallel groups

Sample size: 44/48

Primary endpoint:

FU duration: 3.0 years

colestipol 10g twice daily (n=36)

vs.

placebo (n=30)

double-blind

Parallel groups

Sample size: 36/30

Primary endpoint:

FU duration: 0.8 years

colestipol (n=21)

vs.

placebo (n=19)

Parallel groups

Sample size: 21/19

Primary endpoint:

FU duration: 3.2 years

MI non fatal 0.41 [0.20; 0.86]

décès par cancer 1.81 [1.02; 3.23]

all cause deaths 0.98 [0.83; 1.15]

coronary deaths 0.82 [0.55; 1.21]

coronary events 0.80 [0.57; 1.12]

stroke (fatal et non fatal) 0.59 [0.30; 1.15]

all cause deaths 0.88 [0.55; 1.41]

coronary deaths 0.97 [0.58; 1.64]

coronary events 0.86 [0.61; 1.22]

décès par cancer 0.16 [0.02; 1.34]

MI non fatal 0.75 [0.43; 1.30]

cardiac death 0.97 [0.58; 1.64]

non cardiovascular death 0.16 [0.02; 1.34]

all cause deaths 1.49 [0.95; 2.34]

coronary deaths 1.44 [0.90; 2.32]

cardiac death 1.44 [0.90; 2.32]

non cardiovascular death 2.14 [0.40; 11.59]

coronary events 0.75 [0.57; 0.99]

all cause deaths 0.75 [0.52; 1.06]

coronary deaths 0.74 [0.51; 1.08]

MI non fatal 0.77 [0.47; 1.27]

non cardiovascular death 0.80 [0.22; 2.94]

all cause deaths 3.85 [0.51; 29.20]

coronary deaths 2.41 [0.30; 19.57]

coronary events 0.96 [0.41; 2.28]

MI non fatal 0.67 [0.24; 1.92]

cardiac death 3.85 [0.51; 29.20]

non cardiovascular death NaN [NaN; NaN]

all cause deaths 0.87 [0.51; 1.50]

coronary events 1.01 [0.73; 1.38]

coronary deaths 1.01 [0.83; 1.24]

coronary events 0.97 [0.87; 1.08]

CV events (including revascularization) 0.97 [0.90; 1.05]

MI non fatal 0.97 [0.86; 1.09]

stroke (fatal et non fatal) 1.01 [0.90; 1.14]

cardiovascular events 0.97 [0.91; 1.04]

all cause deaths 0.33 [0.04; 3.03]

cardiac death 0.33 [0.04; 3.03]

non cardiovascular death NaN [NaN; NaN]

all cause deaths ∞ [NaN; ∞]

cardiac death ∞ [NaN; ∞]

non cardiovascular death NaN [NaN; NaN]

all cause deaths 0.99 [0.92; 1.07]

cardiac death 0.95 [0.83; 1.09]

non cardiovascular death 1.01 [0.92; 1.11]

all cause deaths 0.98 [0.92; 1.04]

cardiac death 1.00 [0.90; 1.12]

non cardiovascular death 0.98 [0.91; 1.07]

all cause deaths 0.49 [0.05; 5.26]

cardiac death 0.00 [0.00; NaN]

non cardiovascular death ∞ [NaN; ∞]

all cause deaths 1.03 [0.83; 1.28]

coronary deaths 1.15 [0.73; 1.81]

coronary events 1.08 [0.85; 1.38]

décès par cancer 1.33 [0.63; 2.81]

cholesterol lowering diet (n=424)

vs.

usual diet (n=422)

double blind

Parallel groups

Sample size: 424/422

Primary endpoint: MI, sudden death

FU duration: 3.6 and 8 y

Régime pauvre en graisses saturées + 85 g/j d'huile de soja (n=199)

vs.

usual diet (n=194)

open, blind assessment

Parallel groups

Sample size: 199/194

Primary endpoint: MI

FU duration: 3.5 y

diet (n=221)

vs.

usual diet (n=237)

open

Parallel groups

Sample size: 221/237

Primary endpoint: death

FU duration: < 7 years

diet (n=206)

vs.

usual care (n=206)

open, blind assessment

Parallel groups

Sample size: 206/206

Primary endpoint: IDM fatal ou non fatal

FU duration: 5 y (11y)

Régime restreint en graisses + 80 g/j huile de maïs (n=28)

vs.

usual diet (n=26)

open

Parallel groups

Sample size: 28/26

Primary endpoint: Mort subite

FU duration: 1.2 years

(n=123)

vs.

(n=129)

open

Parallel groups

Sample size: 123/129

Primary endpoint: death, MI

FU duration: 3 y

dietary modification intervention to promote dietary change with the goals of reducing intake of total fat to 20% of energy and increasing consumption of vegetables and fruit to at least 5 servings daily and grains to at least 6 servings daily (n=19541)

vs.

usual diet (n=29294)

open

Parallel groups

Sample size: 19541/29294

Primary endpoint: Invasive breast cancer

FU duration: 8.1y mean

low-fat (n=-9)

vs.

Mediterranean-style diets (n=-9)

open

Parallel groups

Sample size: -9/-9

Primary endpoint: cardiovascular events

FU duration: 24 months

strict diet (n=204)

vs.

usual diet (n=202)

open

Parallel groups

Sample size: 204/202

Primary endpoint: not unique

FU duration: 2.0 years

dietary advice (n=30)

vs.

usual diet (n=30)

open, blind assessment

Sample size: 30/30

Primary endpoint: not defined

FU duration: 3.0 years

diet (n=424)

vs.

usual diet (n=422)

double blind

Parallel groups

Sample size: 424/422

Primary endpoint:

FU duration: 8.0 y

low-fat vegetarian diet, stopping smoking, stress management training, and moderate exercise (n=28)

vs.

usual-care (n=20)

open

Parallel groups

Sample size: 28/20

Primary endpoint: quantitative coronary angiography

FU duration: 1.0 y

diet (multifactorial intervention programme) (n=188)

vs.

usual diet (n=187)

open

Parallel groups

Sample size: 188/187

Primary endpoint: not defined

FU duration: 3.0 years

multifactor intervention program (n=6428)

vs.

usual diet (n=6438)

open

Parallel groups

Sample size: 6428/6438

Primary endpoint: CHD death

FU duration: 6.5 y

diet (n=604)

vs.

usual diet (n=628)

open

Parallel groups

Sample size: 604/628

Primary endpoint: not defined

FU duration: 6.5 years

cholesterol-lowering diet (low in saturated fats and cholesterol and relatively high in polyunsaturated fats) (n=612)

vs.

usual diet (n=610)

open, blind assessment

Cluster-randomized cross-ove

Sample size: 612/610

Primary endpoint:

FU duration: 6.0 years

multifactorial prevention (n=30489)

vs.

usual diet (n=26971)

open

Parallel groups

Sample size: 30489/26971

Primary endpoint:

FU duration: 5.5 years

multifactorial intervention programme (n=10004)

vs.

usual care (n=20028)

open

Parallel groups

Sample size: 10004/20028

Primary endpoint:

FU duration: 10.0 years

diet with 20 percent of total caloric intake as fat (n=56)

vs.

usual diet (n=55)

open

Parallel groups

Sample size: 56/55

Primary endpoint: not defined

FU duration: 2.0 years

multifactorial intervention programme (n=10004)

vs.

no intervention (n=20028)

open

Parallel groups

Sample size: 10004/20028

Primary endpoint: not defined

FU duration: 10 years

cholesterol lowering diet (n=2197)

vs.

control diet (n=2196)

double-blind

Parallel groups

Sample size: 2197/2196

Primary endpoint: not defined

FU duration: 1.1 y (max 4.5y)

all cause deaths 0.39 [0.25; 0.62]

coronary deaths 0.33 [0.15; 0.76]

non cardiovascular death 0.43 [0.24; 0.77]

estrogen (n=285)

vs.

placebo (n=147)

Parallel groups

Sample size: 285/147

Primary endpoint:

FU duration: 5.0 y

estrogen (n=156)

vs.

placebo (n=119)

Parallel groups

Sample size: 156/119

Primary endpoint:

FU duration: 5.0 years

estrogen (n=295)

vs.

placebo (n=287)

Parallel groups

Sample size: 295/287

Primary endpoint:

FU duration: 1.4 years

estrogen 5.0 mg daily (n=1119)

vs.

placebo (n=2788)

Parallel groups

Sample size: 1119/2788

Primary endpoint:

FU duration: 1.5 years

estrogen 2.5 mg daily (n=1101)

vs.

placebo (n=2789)

Parallel groups

Sample size: 1101/2789

Primary endpoint:

FU duration: 4.7 years

estrogen or thyroxine (n=427)

vs.

placebo (n=143)

Parallel groups

Sample size: 427/143

Primary endpoint:

FU duration: 3.2 years

etofibrate 1g/j (n=-9)

vs.

placebo (n=-9)

double-blind

Parallel groups

Sample size: -9/-9

Primary endpoint: not defined

FU duration: 12 months

serious adverse events 1.28 [0.68; 2.40]

death from all causes as adverse event ∞ [NaN; ∞]

cardiovascular events as adverse events 1.51 [0.31; 7.45]

serious adverse events ∞ [NaN; ∞]

death from all causes as adverse event NaN [NaN; NaN]

Muscle-related adverse events 0.81 [0.31; 2.12]

serious adverse events ∞ [NaN; ∞]

death from all causes as adverse event NaN [NaN; NaN]

serious adverse events 0.88 [0.45; 1.73]

death from all causes as adverse event 0.00 [0.00; NaN]

cardiovascular events as adverse events 1.25 [0.24; 6.42]

Neurocognitive disorder ∞ [NaN; ∞]

Muscle-related adverse events 1.85 [1.11; 3.09]

serious adverse events 3.01 [0.87; 10.45]

death from all causes as adverse event NaN [NaN; NaN]

serious adverse events 0.69 [0.23; 2.14]

death from all causes as adverse event NaN [NaN; NaN]

cardiovascular events as adverse events ∞ [NaN; ∞]

Muscle-related adverse events 4.95 [0.64; 38.21]

Neurocognitive disorder NaN [NaN; NaN]

cardiovascular events 0.80 [0.73; 0.88] Demonstrated

stroke (fatal and non fatal) 0.79 [0.66; 0.95]

MI ( (fatal and non fatal) 0.73 [0.65; 0.82]

cardiovascular death 1.05 [0.88; 1.25]

all causes deaths 1.04 [0.91; 1.19]

cardiovascular death 1.05 [0.88; 1.25]

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

evolocumab (420 mg) every 4 weeks (n=599)

vs.

placebo (n=302)

Sample size: 599/302

Primary endpoint:

FU duration: 52 weeks

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

subcutaneous injections of AMG 145 70 mg, 105 mg, or 140 mg, (n=-9)

vs.

placebo (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=95)

vs.

(n=32)

placebo- and ezetimibe-controlled

Sample size: 95/32

Primary endpoint:

FU duration:

AMG 145 350 mg, AMG 145 420 mg (n=111)

vs.

placebo (n=56)

Sample size: 111/56

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

evolucumab + statin (n=1117)

vs.

placebo + statin (n=558)

Sample size: 1117/558

Primary endpoint:

FU duration:

evolocumab 140 mg every two weeks (Q2W) or evolocumab 420 mg once monthly (QM) (n=102)

vs.

ezetimibe 10 mg (n=205)

Sample size: 102/205

Primary endpoint:

FU duration:

subcutaneous evolocumab 140 mg every 2 weeks, evolocumab 420 mg monthly (n=220)

vs.

placebo (n=109)

Sample size: 220/109

Primary endpoint:

FU duration:

evolocumab (either 140 mg every 2 weeks or 420 mg monthly) (n=-9)

vs.

placebo (n=-9)

3 arms

double-blind

Parallel groups

Sample size: -9/-9

Primary endpoint:

FU duration: 2.2 years

CV events (fatal and non fatal) 0.94 [0.89; 0.99] Demonstrated

Major coronary event 0.87 [0.80; 0.95]

all cause death or CV event 0.95 [0.90; 1.00]

all cause mortality 0.99 [0.91; 1.07]

Death from coronary heart disease 0.96 [0.84; 1.09]

Death from cardiovascular causes 1.00 [0.89; 1.13]

stroke 0.86 [0.73; 1.01]

CV events (fatal and non fatal) 0.87 [0.79; 0.95]

Any incident cancer 0.99 [0.87; 1.12]

all cause mortality 1.02 [0.95; 1.09]

Major coronary event 0.92 [0.77; 1.10]

fatal stroke 0.87 [0.63; 1.20]

cancer 0.99 [0.87; 1.12]

End-stage renal disease (ESRD) 0.97 [0.90; 1.04]

adverse events 1.32 [0.98; 1.78]

cardiovascular events 1.35 [0.55; 3.29]

non cardiovascular death 0.49 [0.09; 2.65]

ezetimibe 10mg + simvastatin daily (n=357)

vs.

simvastatin 80mg daily (n=363)

double blind

Parallel groups

Sample size: 357/363

Primary endpoint: change in the mean carotid-artery intima–media thickness

FU duration: 24 months

10 mg/day of ezetimibe and 40 mg/day of simvastatin (n=9067)

vs.

simvastatin 40 mg/day (n=9077)

If LDL-C response is inadequate, the dose of simvastatin may be increased to 80 mg

double blind

Parallel groups

Sample size: 9067/9077

Primary endpoint: CV death, MI, hospitalization for unstable angina, stroke and coronary revascularization

FU duration: 5.68 years

Simvastatin 20mg/Ezetimibe 10mg (n=4193)

vs.

placebo (n=4191)

3 arms: Simvastatin 20 mg, Simvastatin 20mg/Ezetimibe 10mg and placebo

double-blind

Parallel groups

Sample size: 4193/4191

Primary endpoint: vascular events: cardiac death, MI, any stroke, or any revascularization

FU duration: 4.9 years

There is a certain incertitude concerning the primary endpoint (apparently changed by the Steering committe before the trial ended but this change was not endorsed by the sponsor) Statistical analysis plan is not clear too, with or without the inclusion of patients initially allocated to simvastatin alone and re-randomized to either combination or placebo for the remainder of the study period

aggressive targets of LDL-C of 70 mg/dL or lower and SBP of 115 mm Hg or lower (n=252)

vs.

standard targets of LDL-C of 100 mg/dL or lower and SBP of 130 mm Hg or lower (n=247)

open

Parallel groups

Sample size: 252/247

Primary endpoint: common carotid artery intimal medial thickness (IMT)

FU duration: 3 years

addition of ezetimibe (10 mg/daily) to statin therapy (n=-9)

vs.

extended-release niacin 2000 mg/daily (n=-9)

open

Parallel groups

Sample size: -9/-9

Primary endpoint: carotid IMT

FU duration: 14 months

stopped early on the basis of a prespecified interim analysis showing that niacin was superior to ezetimibe on the end point of change in the carotid IMT

MI non fatal 0.76 [0.62; 0.94]

cardiovascular events 0.90 [0.81; 0.99]

Pancreatitis 1.74 [1.04; 2.90]

venous thromboembolism 1.50 [1.13; 1.99]

all cause deaths 1.10 [0.95; 1.28]

coronary deaths 1.18 [0.90; 1.56]

coronary events 0.89 [0.76; 1.05]

adverse events 1.58 [0.95; 2.64]

cardiovascular death 1.10 [0.87; 1.40]

décès par cancer 1.14 [0.91; 1.41]

Rhabdomyolyses 3.00 [0.31; 28.86]

stroke (fatal et non fatal) 0.90 [0.73; 1.12]

cardiac death 1.18 [0.90; 1.56]

Infarctus non mortel et décès coronariens 0.89 [0.76; 1.05]

Myopathies 2.00 [0.18; 22.07]

Cv events (CV death, MI, stroke) 0.90 [0.81; 0.99]

Critère de jugement principal de l'étude 0.89 [0.76; 1.05]

Infarctus non mortel et décès coronariens 0.89 [0.76; 1.05]

Décès toutes causes 1.10 [0.95; 1.28]

Evénement coronarien majeur 0.89 [0.76; 1.05]

Décès cardiovasculaires 1.10 [0.87; 1.40]

AVC 0.90 [0.73; 1.12]

all cause deaths 0.68 [0.25; 1.88]

coronary events 0.77 [0.53; 1.13]

cardiac death 0.61 [0.15; 2.53]

non cardiovascular death 0.51 [0.09; 2.75]

Critère de jugement principal de l'étude 0.93 [0.80; 1.09]

Décès toutes causes 0.91 [0.76; 1.10]

Evénement coronarien majeur 0.94 [0.81; 1.08]

Décès cardiovasculaires 0.86 [0.66; 1.13]

AVC 1.06 [0.72; 1.56]

Cv events (CV death, MI, stroke) 0.93 [0.80; 1.09]

fenofibrate 200mg/d (n=4895)

vs.

Placebo (n=4900)

double blind

Parallel groups

Sample size: 4895/4900

Primary endpoint: coronary events

FU duration: 5 years

fenofibrate 200 mg daily (n=4895)

vs.

placebo (n=4900)

Sample size: 4895/4900

Primary endpoint: coronary events

FU duration: 5y

fenofibrate 200 mg/day (n=207)

vs.

placebo (n=211)

double-blind

Parallel groups

Sample size: 207/211

Primary endpoint: QCA (minimum lumen diameter)

FU duration: 3.3 years

fenofibrate on top simvastatin (n=2765)

vs.

placebo (on top simvastatine) (n=2753)

participants were also randomized to either intensive or standard glycemic control and to either intensive or standard blood-pressure control. Glycemic-control ACCORD study was stopped early, in February 2008, because of higher mortality in the intensive-glycemic-control group. All patients were then transferred to a standard glycemia-control regimen

double-blind

Factorial plan

Sample size: 2765/2753

Primary endpoint: fatal cardiovascular events, nonfatal MI, or nonfatal stroke

FU duration: 4.7y

CV events (including revascularization) 0.80 [0.68; 0.96]

all cause deaths 0.73 [0.48; 1.10]

coronary deaths 0.53 [0.27; 1.04]

coronary events 0.69 [0.47; 1.01]

Rhabdomyolyses NaN [NaN; NaN]

cardiac death 0.53 [0.27; 1.04]

Infarctus non mortel et décès coronariens 0.69 [0.47; 1.01]

non cardiovascular death 0.86 [0.48; 1.54]

all cause death 1.04 [0.84; 1.29]

Cardiovascular death 0.67 [0.44; 1.01]

cardiovascular death, CV events (nonfatal MI, or nonfatal stroke) 0.84 [0.66; 1.06]

Noncardiovascular death 1.19 [0.86; 1.63]

Critère de jugement principal de l'étude 0.57 [0.37; 0.89]

Evénement coronarien majeur 0.57 [0.37; 0.89]

coronary events 0.67 [0.50; 0.90]

all cause deaths 1.04 [0.84; 1.29]

coronary deaths 0.67 [0.44; 1.01]

CV events (including revascularization) 0.84 [0.66; 1.06]

MI non fatal 0.70 [0.48; 1.01]

stroke (fatal et non fatal) 1.18 [0.85; 1.63]

cardiac death 0.67 [0.44; 1.01]

non cardiovascular death 1.19 [0.86; 1.63]

all cause deaths 0.96 [0.20; 4.67]

coronary events 0.62 [0.37; 1.04]

Rhabdomyolyses NaN [NaN; NaN]

cardiac death ∞ [NaN; ∞]

non cardiovascular death 0.64 [0.11; 3.77]

all cause deaths 0.48 [0.09; 2.57]

Rhabdomyolyses NaN [NaN; NaN]

cardiac death 0.48 [0.09; 2.57]

non cardiovascular death NaN [NaN; NaN]

all cause deaths 1.01 [0.33; 3.10]

cardiac death 0.50 [0.05; 5.53]

non cardiovascular death 1.26 [0.34; 4.66]

all cause deaths 0.45 [0.12; 1.71]

CV events (including revascularization) 0.97 [0.75; 1.24]

MI non fatal 0.31 [0.09; 1.12]

Rhabdomyolyses NaN [NaN; NaN]

All cause mortality 0.35 [0.07; 1.70]

Coronary Heart Disease Mortality 0.70 [0.12; 4.12]

Nonfatal Myocardial Infarction 0.58 [0.20; 1.70]

Revascularization 0.69 [0.51; 0.94]

All cause mortality 0.66 [0.40; 1.11]

Coronary Heart Disease Mortality 0.49 [0.21; 1.14]

Nonfatal Myocardial Infarction 0.69 [0.33; 1.44]

all cause deaths 0.81 [0.22; 2.97]

cardiovascular events 0.74 [0.35; 1.58]

fluvastatin, 80 mg/d (n=844)

vs.

placebo (n=833)

double blind

Parallel groups

Sample size: 844/833

Primary endpoint: MACE (cardiac death, MI, reintervention)

FU duration: 3.9 years

fluvastatin (n=1050)

vs.

placebo (n=1052)

double blind

Parallel groups

Sample size: 1050/1052

Primary endpoint: major adverse cardiac event

FU duration: 5.1 years

fluvastatin (n=120)

vs.

placebo (n=82)

double blind

Parallel groups

Sample size: 120/82

Primary endpoint: MACE

FU duration: 3.9y

fluvastatin (n=197)

vs.

placebo (n=199)

double blind

Parallel groups

Sample size: 197/199

Primary endpoint:

FU duration:

fluvastatin 40 mg daily (n=1050)

vs.

placebo (n=1052)

double-blind

Parallel groups

Sample size: 1050/1052

Primary endpoint: major adverse cardiac event

FU duration: 5.1 years

fluvastatin 20 mg twice daily (n=164)

vs.

placebo (n=157)

double-blind

Parallel groups

Sample size: 164/157

Primary endpoint: minimum lumen diameter

FU duration: 2.5 years

fluvastatin 40 mg (o.a.d. or b.i.d.) (n=187)

vs.

placebo (n=178)

double blind

Parallel groups

Sample size: 187/178

Primary endpoint:

FU duration: 1.0 years

fluvastatin 40 mg once daily (n=395)

vs.

placebo (n=398)

factorial design of fluvastatin versus placebo and metoprolol CR/XL vs placebo

double-blind

Factorial plan

Sample size: 395/398

Primary endpoint: not unique (IMT)

FU duration: 3.0 years

fluvastatin 40 mg twice daily (n=409)

vs.

placebo (n=425)

double blind

Parallel groups

Sample size: 409/425

Primary endpoint: angiographic restenosis

FU duration: 40 weeks

Fluvastatin 80mg (n=179)

vs.

(n=187)

double blind

parallel groups

Sample size: 179/187

Primary endpoint:

FU duration: 0.8y

Fluvastatin 80mg (n=324)

vs.

(n=299)

double blind

parallel groups

Sample size: 324/299

Primary endpoint:

FU duration: 3.9y

fluvastatin 40 mg daily (n=283)

vs.

placebo (n=285)

factorialdesign with 2nd randomization between intensive lifestyle intervention (physical activity and diet) or usual care (treatment of hypertension and other disorders by own private physician).

double blind

Factorial plan