Mechanism

Endpoint	TE [95% CI]	p val	I2	n	k
cardiovascular events	0.89 [0.84 0.94]	p=0.04	0	89154	6	Physicians Health Study, Thrombosis Prevention Trial, HOT, Women’s Health Study, AAA, ASCEND,
Cardiovascular death	0.92 [0.85 1.01]	p=1.00	0	45928	4	Physicians Health Study, Thrombosis Prevention Trial, HOT, ASCEND,
myocardial infarction (fatal and non fatal)	0.88 [0.75 1.03]	p=1.00	0	58666	2	HOT, Women’s Health Study,
stroke (fatal and non fatal)	0.94 [0.83 1.06]	p=1.00	0	85822	4	Physicians Health Study, Thrombosis Prevention Trial, HOT, Women’s Health Study,
Coronary event	0.76 [0.68 0.85]	p=0.04	0	85822	4	Physicians Health Study, Thrombosis Prevention Trial, HOT, Women’s Health Study,
ischemic stroke	0.84 [0.72 0.99]	p=0.04	0	67032	3	Physicians Health Study, Thrombosis Prevention Trial, Women’s Health Study,
Coronary death	0.87 [0.66 1.14]	p=1.00	0	85822	4	Physicians Health Study, Thrombosis Prevention Trial, HOT, Women’s Health Study,
cardiovascular death, MI, stroke	no data
Gastrointestinal Bleeding	1.26 [1.15 1.39]	p=0.04	0	58666	2	HOT, Women’s Health Study,
Non fatal MI	0.74 [0.66 0.83]	p=0.04	0	85822	4	Physicians Health Study, Thrombosis Prevention Trial, HOT, Women’s Health Study,
All cause death	0.95 [0.88 1.03]	p=1.00	0	89172	5	Physicians Health Study, Thrombosis Prevention Trial, HOT, Women’s Health Study, AAA,
Non fatal stroke	1.07 [0.84 1.35]	p=1.00	0	27156	2	Physicians Health Study, Thrombosis Prevention Trial,
Haemmorhagic stroke	1.34 [0.99 1.82]	p=1.00	0	85822	4	Physicians Health Study, Thrombosis Prevention Trial, HOT, Women’s Health Study,
fatal hemorrhagic stroke	1.00 [0.20 4.96]	p=1.00	0	3350	1	AAA,
non fatal hemorrhagic stroke	2.00 [0.18 22.08]	p=1.00	0	3350	1	AAA,
Peptic ulcer	1.32 [1.16 1.50]	p=0.04	0	43226	2	Women’s Health Study, AAA,
Hematuria	1.06 [1.00 1.12]	p=1.00	0	39876	1	Women’s Health Study,
Major gastrointestinal bleeding	1.58 [1.31 1.92]	p=0.04	0	85822	4	Physicians Health Study, Thrombosis Prevention Trial, HOT, Women’s Health Study,
intracranial hemorrhage	no data
Major bleeding	1.32 [1.13 1.55]	p=0.04	0	3332	2	AAA, ASCEND,
Fatal bleeding	0.87 [0.32 2.41]	p=1.00	0	18790	1	HOT,
net benefit	no data

Trial	Studied treatment	Control	Patients
Physicians Health Study, 1989	aspirin 325 mg every other day	placebo	Healthy men
Thrombosis Prevention Trial, 1998	aspirin 75 mg/d (controlled release)	placebo	Men at high risk of CHD
HOT, 1998	aspirin 75 mg daily	placebo	patients aged 50-80 with hypertension and diastolic blood pressure between 100 mmHG and 115 mmHG
Women’s Health Study, 2005	aspirin 100mg daily	placebo	initially healthy women 45 years of age or older
AAA, 2009	aspirin 100mg daily	placebo	men and women aged 50 to 80 years with asymptomatic atherosclerosis detected by low ankle brachial index (<=0.95)
ASPREE, 2018
ASCEND, 2018

Aspirin

cardiovascular prevention, in primary prevention

Gastrointestinal Bleeding by 247% suggested

Aspirin

Peptic ulcer by 32% adverse event

Major gastrointestinal bleeding by 58% adverse event

Major bleeding by 32% adverse event

cardiovascular events by 11% suggested

Coronary event by 24% suggested

ischemic stroke by 16% suggested

Gastrointestinal Bleeding by 26% suggested

Non fatal MI by 26% suggested

Endpoint	TE [95% CI]	p val	I2	n	k
cardiovascular events	0.89 [0.84 0.94]	p=0.04	0	89154	6	Physicians Health Study, Thrombosis Prevention Trial, HOT, Women’s Health Study, AAA, ASCEND,
Cardiovascular death	0.92 [0.85 1.01]	p=1.00	0	45928	4	Physicians Health Study, Thrombosis Prevention Trial, HOT, ASCEND,
myocardial infarction (fatal and non fatal)	0.88 [0.75 1.03]	p=1.00	0	58666	2	HOT, Women’s Health Study,
stroke (fatal and non fatal)	0.94 [0.83 1.06]	p=1.00	0	85822	4	Physicians Health Study, Thrombosis Prevention Trial, HOT, Women’s Health Study,
Coronary event	0.76 [0.68 0.85]	p=0.04	0	85822	4	Physicians Health Study, Thrombosis Prevention Trial, HOT, Women’s Health Study,
ischemic stroke	0.84 [0.72 0.99]	p=0.04	0	67032	3	Physicians Health Study, Thrombosis Prevention Trial, Women’s Health Study,
Coronary death	0.87 [0.66 1.14]	p=1.00	0	85822	4	Physicians Health Study, Thrombosis Prevention Trial, HOT, Women’s Health Study,
cardiovascular death, MI, stroke	no data
Gastrointestinal Bleeding	1.26 [1.15 1.39]	p=0.04	0	58666	2	HOT, Women’s Health Study,
Non fatal MI	0.74 [0.66 0.83]	p=0.04	0	85822	4	Physicians Health Study, Thrombosis Prevention Trial, HOT, Women’s Health Study,
All cause death	0.95 [0.88 1.03]	p=1.00	0	89172	5	Physicians Health Study, Thrombosis Prevention Trial, HOT, Women’s Health Study, AAA,
Non fatal stroke	1.07 [0.84 1.35]	p=1.00	0	27156	2	Physicians Health Study, Thrombosis Prevention Trial,
Haemmorhagic stroke	1.34 [0.99 1.82]	p=1.00	0	85822	4	Physicians Health Study, Thrombosis Prevention Trial, HOT, Women’s Health Study,
fatal hemorrhagic stroke	1.00 [0.20 4.96]	p=1.00	0	3350	1	AAA,
non fatal hemorrhagic stroke	2.00 [0.18 22.08]	p=1.00	0	3350	1	AAA,
Peptic ulcer	1.32 [1.16 1.50]	p=0.04	0	43226	2	Women’s Health Study, AAA,
Hematuria	1.06 [1.00 1.12]	p=1.00	0	39876	1	Women’s Health Study,
Major gastrointestinal bleeding	1.58 [1.31 1.92]	p=0.04	0	85822	4	Physicians Health Study, Thrombosis Prevention Trial, HOT, Women’s Health Study,
intracranial hemorrhage	no data
Major bleeding	1.32 [1.13 1.55]	p=0.04	0	3332	2	AAA, ASCEND,
Fatal bleeding	0.87 [0.32 2.41]	p=1.00	0	18790	1	HOT,
net benefit	no data

Trial	Studied treatment	Control	Patients
Physicians Health Study, 1989	aspirin 325 mg every other day	placebo	Healthy men
Thrombosis Prevention Trial, 1998	aspirin 75 mg/d (controlled release)	placebo	Men at high risk of CHD
HOT, 1998	aspirin 75 mg daily	placebo	patients aged 50-80 with hypertension and diastolic blood pressure between 100 mmHG and 115 mmHG
Women’s Health Study, 2005	aspirin 100mg daily	placebo	initially healthy women 45 years of age or older
AAA, 2009	aspirin 100mg daily	placebo	men and women aged 50 to 80 years with asymptomatic atherosclerosis detected by low ankle brachial index (<=0.95)
ASPREE, 2018
ASCEND, 2018

Aspirin

cardiovascular prevention, in patients without established disease

Gastrointestinal Bleeding by 247% suggested

Endpoint	TE [95% CI]	p val	I2	n	k
stable angina	1.10 [0.49 2.51]	p=1.00	0	2539	1	JPAD,
unstable angina	0.40 [0.13 1.29]	p=1.00	0	2539	1	JPAD,
Peripheral vascular events	0.64 [0.25 1.67]	p=1.00	0	2539	1	JPAD,
cardiovascular events	0.89 [0.75 1.04]	p=1.00	0	12173	3	British Doctor’s Trial, Primary Prevention Project, JPAD,
Cardiovascular death	0.90 [0.68 1.18]	p=1.00	0	7678	2	British Doctor’s Trial, JPAD,
myocardial infarction (fatal and non fatal)	0.69 [0.39 1.24]	p=1.00	0	4495	1	Primary Prevention Project,
stroke (fatal and non fatal)	0.97 [0.74 1.28]	p=1.00	0	12173	3	British Doctor’s Trial, Primary Prevention Project, JPAD,
Coronary event	0.89 [0.72 1.10]	p=1.00	0	12173	3	British Doctor’s Trial, Primary Prevention Project, JPAD,
ischemic stroke	1.15 [0.66 2.01]	p=1.00	0	9634	2	British Doctor’s Trial, Primary Prevention Project,
Coronary death	0.90 [0.65 1.25]	p=1.00	0	12173	3	British Doctor’s Trial, Primary Prevention Project, JPAD,
Gastrointestinal Bleeding	3.47 [1.28 9.41]	p=0.04	0	4495	1	Primary Prevention Project,
Fatal MI	0.09 [0.01 1.67]	p=1.00	0	2539	1	JPAD,
Non fatal MI	0.95 [0.70 1.30]	p=1.00	0	12173	3	British Doctor’s Trial, Primary Prevention Project, JPAD,
Revascularization	no data
All cause death	0.87 [0.73 1.04]	p=1.00	0	9634	2	British Doctor’s Trial, Primary Prevention Project,
Fatal stroke	0.20 [0.02 1.73]	p=1.00	0	2539	1	JPAD,
Non fatal stroke	1.13 [0.71 1.78]	p=1.00	0	5139	1	British Doctor’s Trial,
Haemmorhagic stroke	0.97 [0.41 2.28]	p=1.00	0	9634	2	British Doctor’s Trial, Primary Prevention Project,
Peptic ulcer	no data
Hematuria	no data
Major gastrointestinal bleeding	1.18 [0.60 2.29]	p=1.00	0	9634	2	British Doctor’s Trial, Primary Prevention Project,
Major bleeding	no data
Fatal bleeding	no data

Trial	Studied treatment	Control	Patients
British Doctor’s Trial, 1988	aspirin 500 mg/d	no aspirin	apparently healthy male doctors
Primary Prevention Project, 2001	aspirin 100 mg/d	no aspirin (open control)	men and women aged 50 years or greater, with at least one of the major recognised cardiovascular risk factors.
JPAD, 2008	low-dose aspirin (81 or 100 mg per day)	no aspirin	patients with type 2 diabetes without a history of atherosclerotic disease

Aspirin

Peptic ulcer by 32% adverse event

Major gastrointestinal bleeding by 58% adverse event

Major bleeding by 32% adverse event

cardiovascular events by 11% suggested

Coronary event by 21% suggested

ischemic stroke by 16% suggested

Gastrointestinal Bleeding by 26% suggested

Non fatal MI by 24% suggested

Endpoint	TE [95% CI]	p val	I2	n	k
stable angina	0.90 [0.64 1.26]	p=1.00	0	1276	1	POPADAD aspirin,
unstable angina	no data
Peripheral vascular events	0.91 [0.67 1.22]	p=1.00	0	1276	1	POPADAD aspirin,
cardiovascular events	0.89 [0.85 0.95]	p=0.04	0	90430	7	Physicians Health Study, Thrombosis Prevention Trial, HOT, Women’s Health Study, POPADAD aspirin, AAA, ASCEND,
Cardiovascular death	0.93 [0.86 1.01]	p=1.00	0	47204	5	Physicians Health Study, Thrombosis Prevention Trial, HOT, POPADAD aspirin, ASCEND,
myocardial infarction (fatal and non fatal)	0.88 [0.75 1.03]	p=1.00	0	58666	2	HOT, Women’s Health Study,
stroke (fatal and non fatal)	0.92 [0.82 1.04]	p=1.00	0	87098	5	Physicians Health Study, Thrombosis Prevention Trial, HOT, Women’s Health Study, POPADAD aspirin,
Coronary event	0.79 [0.71 0.88]	p=0.04	0	87098	5	Physicians Health Study, Thrombosis Prevention Trial, HOT, Women’s Health Study, POPADAD aspirin,
ischemic stroke	0.84 [0.72 0.99]	p=0.04	0	67032	3	Physicians Health Study, Thrombosis Prevention Trial, Women’s Health Study,
Coronary death	0.96 [0.75 1.22]	p=1.00	0	87098	5	Physicians Health Study, Thrombosis Prevention Trial, HOT, Women’s Health Study, POPADAD aspirin,
cardiovascular death, MI, stroke	no data
Gastrointestinal Bleeding	1.26 [1.15 1.39]	p=0.04	0	58666	2	HOT, Women’s Health Study,
Fatal MI	1.35 [0.80 2.26]	p=1.00	0	1276	1	POPADAD aspirin,
Non fatal MI	0.76 [0.68 0.85]	p=0.04	0	87098	5	Physicians Health Study, Thrombosis Prevention Trial, HOT, Women’s Health Study, POPADAD aspirin,
Revascularization	no data
All cause death	0.95 [0.88 1.02]	p=1.00	0	90448	6	Physicians Health Study, Thrombosis Prevention Trial, HOT, Women’s Health Study, POPADAD aspirin, AAA,
Fatal stroke	0.89 [0.34 2.32]	p=1.00	0	1276	1	POPADAD aspirin,
Non fatal stroke	1.07 [0.84 1.35]	p=1.00	0	27156	2	Physicians Health Study, Thrombosis Prevention Trial,
Haemmorhagic stroke	1.34 [0.99 1.82]	p=1.00	0	85822	4	Physicians Health Study, Thrombosis Prevention Trial, HOT, Women’s Health Study,
fatal hemorrhagic stroke	1.00 [0.20 4.96]	p=1.00	0	3350	1	AAA,
non fatal hemorrhagic stroke	2.00 [0.18 22.08]	p=1.00	0	3350	1	AAA,
Peptic ulcer	1.32 [1.16 1.50]	p=0.04	0	43226	2	Women’s Health Study, AAA,
Hematuria	1.06 [1.00 1.12]	p=1.00	0	39876	1	Women’s Health Study,
Major gastrointestinal bleeding	1.58 [1.31 1.92]	p=0.04	0	85822	4	Physicians Health Study, Thrombosis Prevention Trial, HOT, Women’s Health Study,
intracranial hemorrhage	no data
Major bleeding	1.32 [1.13 1.55]	p=0.04	0	3332	2	AAA, ASCEND,
Fatal bleeding	0.87 [0.32 2.41]	p=1.00	0	18790	1	HOT,
net benefit	no data

Trial	Studied treatment	Control	Patients
Physicians Health Study, 1989	aspirin 325 mg every other day	placebo	Healthy men
Thrombosis Prevention Trial, 1998	aspirin 75 mg/d (controlled release)	placebo	Men at high risk of CHD
HOT, 1998	aspirin 75 mg daily	placebo	patients aged 50-80 with hypertension and diastolic blood pressure between 100 mmHG and 115 mmHG
Women’s Health Study, 2005	aspirin 100mg daily	placebo	initially healthy women 45 years of age or older
POPADAD aspirin, 2008	aspirin 100mg daily	placebo	patients with diabetes mellitus and asymptomatic peripheral arterial disease
AAA, 2009	aspirin 100mg daily	placebo	men and women aged 50 to 80 years with asymptomatic atherosclerosis detected by low ankle brachial index (<=0.95)
ASPREE, 2018
ASCEND, 2018

Aspirin

cardiovascular prevention, in diabetic patients

all NS

Aspirin

all NS

Aspirin

diabetes type 2, in patients without cardiovascular disease

all NS

Aspirin

all NS

Aspirin

diabetes type 2, in all type of patients

all NS

Aspirin

all NS

Aspirin

Major gastrointestinal bleeding by 108% adverse event

cardiovascular events by 14% suggested

myocardial infarction (fatal and non fatal) by 35% suggested

Coronary event by 35% suggested

Gastrointestinal Bleeding by 94% suggested

Non fatal MI by 40% suggested

Aspirin

peripheral vascular diseases, in all type of patient

all NS

Aspirin

Cardiovascular death by 28% suggested

Fatal MI by 58% suggested

Non fatal MI by 29% suggested

Aspirin

post stroke, in all type of patients

stroke (fatal and non fatal) by 21% suggested

Aspirin

thrombosis prevention, in general surgery

all NS

Aspirin

Deep vein thrombosis by 31% suggested

fatal pulmonary embolism by 61% suggested

Major bleeding by 24% suggested

Aspirin

thrombosis prevention, in all type of patients

all NS

Aspirin

Deep vein thrombosis by 30% suggested

fatal pulmonary embolism by 58% suggested

non-fatal pulmonary embolism by 35% suggested

proximal DVT by 56% suggested

Major bleeding by 24% suggested

Endpoint	TE [95% CI]	p val	n	k
Deep vein thrombosis	0.70 [0.57 0.85]	p=0.04	21263	13	PEP hip-fracture, MRC, Loew DVT, Erfurt-A, Zekert V, Vinazzer I, Vinazzer II, PEP elective arthroplasty, Stockholm-I, Harris-I, McKenna-I, Sautter, McBride,
non pulmonary embolism death	1.05 [0.87 1.27]	p=1.00	20871	8	PEP hip-fracture, MRC, Loew DVT, Erfurt-A, Zekert V, Vinazzer I, Vinazzer II, PEP elective arthroplasty,
fatal pulmonary embolism	0.42 [0.26 0.67]	p=0.04	21263	13	PEP hip-fracture, MRC, Loew DVT, Erfurt-A, Zekert V, Vinazzer I, Vinazzer II, PEP elective arthroplasty, Stockholm-I, Harris-I, McKenna-I, Sautter, McBride,
non-fatal pulmonary embolism	0.65 [0.45 0.95]	p=0.04	21263	13	PEP hip-fracture, MRC, Loew DVT, Erfurt-A, Zekert V, Vinazzer I, Vinazzer II, PEP elective arthroplasty, Stockholm-I, Harris-I, McKenna-I, Sautter, McBride,
proximal DVT	0.44 [0.24 0.80]	p=0.04	298	3	Harris-I, McKenna-I, Sautter,
wound haematoma / infection	1.24 [0.39 3.99]	p=1.00	262	2	Harris-I, Sautter,
Bleeding	1.17 [0.18 7.58]	p=1.00	349	4	Stockholm-I, Harris-I, McKenna-I, Sautter,
Major bleeding	1.24 [1.01 1.52]	p=0.04	20568	7	PEP hip-fracture, Loew DVT, Erfurt-A, Zekert V, Vinazzer I, Vinazzer II, PEP elective arthroplasty,

Trial	Studied treatment	Control	Patients
PEP hip-fracture, 2000	aspirin 160mg/d started preoperatively and continued for 35 days	placebo	patients undergoing surgery for hip fracture
MRC, 1972	A600	placebo	general surgery
Loew DVT, 1974	A600	Placebo
Erfurt-A, 1979	A1500	Placebo
Zekert V, 1980	A1500+Hep???	Placebo
Vinazzer I, 1980	A1500+Hep v Hep	Placebo
Vinazzer II, 1977	A1000+Hepv Hep	Placebo
PEP elective arthroplasty, 2000	aspirin 160mg/d started preoperatively and continued for 35 daysA	placebo	Patients undergoing elective hip or knee arthroplasty
Stockholm-I, 1975	Aspirin 2000mg daily	placebo	elective surgery of the hip
Harris-I, 1977	Aspirin 1200mg daily	placebo	patients over 40 years of age, who had undergone total hip replacement
McKenna-I, 1980	Aspirin 975mg or 3900mg daily	placebo	total knee replacement
Sautter, 1983	Aspirin 900mg daily + sulfinpyrazone	placebo	patient with total hip replacement
McBride, 1983	A1800+Dipyridamole	placebo	Elective orthopaedic surgery

Aspirin

Deep vein thrombosis by 67% suggested

Aspirin

thrombosis prevention, in orthopedic surgery

Deep vein thrombosis by 67% suggested

Aspirin

Deep vein thrombosis by 29% suggested

proximal DVT by 59% suggested

non-fatal pulmonary embolism by 59% suggested

Aspirin

thrombosis prevention, in elective orthopedic surgery

Deep vein thrombosis by 67% suggested

Aspirin

proximal DVT by 56% suggested

Dipyridamol

acute coronary syndrome, in ACS (excluding AMI)

all NS

Dipyridamol

acute coronary syndrome, in all type of patients

all NS

Dipyridamol

all NS

Dipyridamol

all NS

Dipyridamol

cardiovascular prevention, in secondary prevention in patients with CAD

all NS

Dipyridamol

Non fatal MI by 31% suggested

stroke (fatal and non fatal) by 39% suggested

Dipyridamol

all NS

Dipyridamol

cardiovascular prevention, in secondary prevention in patients with intermittent claudication

all NS

Dipyridamol

peripheral vascular diseases, in all type of patient

all NS

Dipyridamol

Non fatal MI by 31% suggested

stroke (fatal and non fatal) by 39% suggested

Dipyridamol

all NS

Dipyridamol

thrombosis prevention, in general surgery

Deep vein thrombosis by 50% suggested

Dipyridamol

all NS

Dipyridamol

thrombosis prevention, in all type of patients

Deep vein thrombosis by 50% suggested

Dipyridamol

all NS

Dipyridamol

all NS

Dipyridamol

thrombosis prevention, in orthopedic surgery

all NS

Dipyridamol

all NS

Dipyridamol

thrombosis prevention, in elective orthopedic surgery

all NS

Dipyridamol

all NS

Dipyridamol

thrombosis prevention, in medical patients

all NS

Dipyridamol

all NS

Ketanserine

cardiovascular prevention, in secondary prevention in patients with intermittent claudication

all NS

Ketanserine

peripheral vascular diseases, in all type of patient

all NS

Picotamide

cardiovascular prevention, in secondary prevention in patients with intermittent claudication

all NS

Picotamide

cardiovascular prevention, in diabetic patients

all NS

Picotamide

diabetes type 2, in patients without cardiovascular disease

all NS

Picotamide

diabetes type 2, in all type of patients

all NS

Picotamide

peripheral vascular diseases, in all type of patient

all NS

Sulfinpyrazone

acute coronary syndrome, in STEMI patients

all NS

Sulfinpyrazone

all NS

Sulfinpyrazone

acute coronary syndrome, in ACS (excluding AMI)

all NS

Sulfinpyrazone

acute coronary syndrome, in all type of patients

Sulfinpyrazone

Sulfinpyrazone

Sulfinpyrazone

Sulfinpyrazone

cardiovascular prevention, in diabetic patients

all NS

Sulfinpyrazone

diabetes type 2, in patients without cardiovascular disease

all NS

Sulfinpyrazone

diabetes type 2, in all type of patients

all NS

Suloctidil

cardiovascular prevention, in secondary prevention in patients with intermittent claudication

all NS

Suloctidil

peripheral vascular diseases, in all type of patient

all NS

Suloctidil

thrombosis prevention, in general surgery

all NS

Suloctidil

thrombosis prevention, in all type of patients

all NS

Sulotroban

CABG surgery, in all type of patients

all NS

Trapidil

acute coronary syndrome, in ACS (excluding AMI)

cardiovascular events by 79% suggested

Trapidil

acute coronary syndrome, in all type of patients

cardiovascular events by 79% suggested

Triflusal

acute coronary syndrome, in ACS (excluding AMI)

Non fatal MI by 66% suggested

Triflusal

acute coronary syndrome, in all type of patients

Non fatal MI by 66% suggested

Various

cardiovascular prevention, in secondary prevention in patients with intermittent claudication

all NS

Various

peripheral vascular diseases, in all type of patient

all NS

Vorapaxar

acute coronary syndrome, in all type of patients

all NS

Vorapaxar

intracranial hemorrhage by 92% adverse event

Major bleeding by 45% adverse event

cardiovascular events by 13% suggested

myocardial infarction (fatal and non fatal) by 16% suggested

cardiovascular death, MI, stroke by 13% suggested

Vorapaxar

cardiovascular prevention, in secondary prevention in patients with intermittent claudication

intracranial hemorrhage by 92% adverse event

Major bleeding by 45% adverse event

cardiovascular events by 13% suggested

myocardial infarction (fatal and non fatal) by 16% suggested

cardiovascular death, MI, stroke by 13% suggested

Vorapaxar

cardiovascular prevention, in secondary prevention in patients with CAD

intracranial hemorrhage by 92% adverse event

Major bleeding by 45% adverse event

cardiovascular events by 13% suggested

myocardial infarction (fatal and non fatal) by 16% suggested

cardiovascular death, MI, stroke by 13% suggested

Vorapaxar

cardiovascular prevention, in secondary prevention

intracranial hemorrhage by 92% adverse event

Major bleeding by 39% adverse event

cardiovascular events by 15% suggested

myocardial infarction (fatal and non fatal) by 16% suggested

cardiovascular death, MI, stroke by 13% suggested

Endpoint	TE [95% CI]	p val	I2	n	k
cardiovascular events	0.85 [0.80 0.89]	p=0.04	0	70668	3	TRA-2P TIMI 50, TRA-2P TIMI 50 (no prior stroke sub group), TRA-2P TIMI 50 (MI subgroup),
Cardiovascular death	0.89 [0.76 1.05]	p=1.00	0	26449	1	TRA-2P TIMI 50,
myocardial infarction (fatal and non fatal)	0.84 [0.75 0.94]	p=0.04	0	26449	1	TRA-2P TIMI 50,
stroke (fatal and non fatal)	0.97 [0.83 1.14]	p=1.00	0	26449	1	TRA-2P TIMI 50,
Coronary death	no data
cardiovascular death, MI, stroke	0.87 [0.80 0.95]	p=0.04	0	26449	1	TRA-2P TIMI 50,
All cause death	0.95 [0.86 1.04]	p=1.00	0	44228	2	TRA-2P TIMI 50, TRA-2P TIMI 50 (MI subgroup),
fatal hemorrhagic stroke	1.53 [0.95 2.47]	p=1.00	0	17779	1	TRA-2P TIMI 50 (MI subgroup),
non fatal hemorrhagic stroke	no data
Peptic ulcer	no data
intracranial hemorrhage	1.92 [1.38 2.68]	p=0.04	0	26352	1	TRA-2P TIMI 50,
Major bleeding	1.39 [1.20 1.60]	p=0.04	0	44131	2	TRA-2P TIMI 50, TRA-2P TIMI 50 (MI subgroup),
Fatal bleeding	1.45 [0.82 2.56]	p=1.00	0	26352	1	TRA-2P TIMI 50,
net benefit	no data

Trial	Studied treatment	Control	Patients
TRA-2P TIMI 50, 2012	vorapaxar (SCH 530348) 2.5-mg daily	placebo (added to the existing standard of care for preventing heart attack and stroke (eg, aspirin, clopidogrel)	patients with a known history of atherosclerosis (MI, ischemic stroke, or peripheral vascular disease)
TRA-2P TIMI 50 (no prior stroke sub group), 2012	vorapaxar (SCH 530348) 2.5-mg daily	placebo (added to the existing standard of care for preventing heart attack and stroke (eg, aspirin, clopidogrel)	patients with a known history of atherosclerosis (MI, ischemic stroke, or peripheral vascular disease), sub group of patient with no prior stroke
TRA-2P TIMI 50 (MI subgroup), 2012	vorapaxar (SCH 530348) 2.5-mg daily	placebo (added to the existing standard of care for preventing heart attack and stroke (eg, aspirin, clopidogrel)	prespecified subgroup of patients with a qualifying myocardial infarction among the overall population of patients with a known history of atherosclerosis (MI, ischemic stroke, or peripheral vascular disease)

Vorapaxar

post myocardial infarction, in all type of patient

intracranial hemorrhage by 92% adverse event

Major bleeding by 45% adverse event

cardiovascular events by 13% suggested

myocardial infarction (fatal and non fatal) by 16% suggested

cardiovascular death, MI, stroke by 13% suggested

Clopidogrel

acute coronary syndrome, in STEMI patients

cardiovascular events by 8% suggested

Non fatal MI by 18% suggested

Clopidogrel

acute coronary syndrome, in ACS (excluding AMI)

Major bleeding by 38% adverse event

cardiovascular events by 18% suggested

myocardial infarction (fatal and non fatal) by 22% suggested

Clopidogrel

Major bleeding by 24% adverse event

Clopidogrel

acute coronary syndrome, in all type of patients

Major bleeding by 38% adverse event

cardiovascular events by 18% suggested

myocardial infarction (fatal and non fatal) by 22% suggested

Clopidogrel

Major bleeding by 24% adverse event

Clopidogrel

acute coronary syndrome, in patients with scheduled percutaneous coronary intervention

Major bleeding by 24% adverse event

Clopidogrel

acute myocardial infarction, in all type of patients

cardiovascular events by 8% suggested

Non fatal MI by 18% suggested

Clopidogrel

all NS

Clopidogrel

cardiovascular prevention, in secondary prevention in patients with intermittent claudication

myocardial infarction (fatal and non fatal) by 37% suggested

Fatal MI by 38% suggested

Non fatal MI by 18% suggested

Clopidogrel

cardiovascular prevention, in all type of patients

Non fatal MI by 16% suggested

Clopidogrel

all NS

Clopidogrel

cardiovascular prevention, in secondary prevention in patients with CAD

Non fatal MI by 16% suggested

Clopidogrel

all NS

Clopidogrel

cardiovascular prevention, in secondary prevention

Non fatal MI by 16% suggested

Clopidogrel

all NS

Clopidogrel

percutaneous coronary intervention, in all type of patients

all NS

Clopidogrel

all NS

Clopidogrel

all NS

Clopidogrel

peripheral vascular diseases, in all type of patient

myocardial infarction (fatal and non fatal) by 37% suggested

Fatal MI by 38% suggested

Clopidogrel

all NS

Prasugrel

acute coronary syndrome, in ACS (excluding AMI)

Bleeding by 30% adverse event

Major bleeding by 28% adverse event

Non fatal MI by 24% suggested

Revascularization by 33% suggested

Prasugrel

acute coronary syndrome, in all type of patients

Bleeding by 30% adverse event

Major bleeding by 28% adverse event

Non fatal MI by 24% suggested

Revascularization by 33% suggested

Prasugrel

acute coronary syndrome, in patients not initialy planned for PCI

all NS

Prasugrel

acute coronary syndrome, in patients with scheduled percutaneous coronary intervention

fatal bleeding by 319% adverse event

Bleeding by 31% adverse event

Major bleeding by 31% adverse event

Non fatal MI by 24% suggested

Revascularization by 33% suggested

Ticlopidine

acute coronary syndrome, in ACS (excluding AMI)

cardiovascular events by 48% suggested

Ticlopidine

all NS

Ticlopidine

acute coronary syndrome, in all type of patients

cardiovascular events by 48% suggested

Ticlopidine

all NS

Ticlopidine

acute coronary syndrome, in STEMI patients

all NS

Ticlopidine

acute myocardial infarction, in all type of patients

all NS

Ticlopidine

all NS

Ticlopidine

all NS

Ticlopidine

cardiovascular prevention, in secondary prevention in patients with intermittent claudication

Vascular death by 40% suggested

Endpoint	TE [95% CI]	p val	I2	n	k
Amputation	no data
myocardial infarction (fatal and non fatal)	0.86 [0.59 1.24]	p=1.00	0	2071	7	EMATAP, Stiegler, Ellis, Cloarec, Arcan, Balsano, STIMS,
Vascular death	0.60 [0.39 0.92]	p=0.04	0	2313	10	EMATAP, Katsumara, Aukland, Ellis, Balsano, Cloarec, Arcan, Hurlow, Krause, STIMS,
Fatal MI	0.63 [0.35 1.14]	p=1.00	0	2071	7	EMATAP, Stiegler, Ellis, Cloarec, Arcan, Balsano, STIMS,
Non fatal MI	0.99 [0.65 1.51]	p=1.00	0	2427	11	EMATAP, Katsumara, Aukland, Stiegler, Ellis, Cloarec, Arcan, Balsano, STIMS, Hurlow, Krause,
Vascular events	0.75 [0.55 1.01]	p=1.00	0	2120	9	EMATAP, Aukland, Ellis, Cloarec, Arcan, Balsano, STIMS, Hurlow, Krause,
All cause death	0.73 [0.53 1.01]	p=1.00	0	2427	11	EMATAP, Katsumara, Aukland, Stiegler, Ellis, Cloarec, Arcan, Balsano, STIMS, Hurlow, Krause,
Fatal stroke	0.49 [0.15 1.56]	p=1.00	0	2071	7	EMATAP, Stiegler, Ellis, Cloarec, Arcan, Balsano, STIMS,
Non fatal stroke	0.81 [0.47 1.40]	p=1.00	0	2427	11	EMATAP, Katsumara, Aukland, Stiegler, Ellis, Cloarec, Arcan, Balsano, STIMS, Hurlow, Krause,
Non cerebral major bleeding	1.88 [0.58 6.02]	p=1.00	0	2362	10	EMATAP, Katsumara, Stiegler, Ellis, Cloarec, Arcan, Balsano, Hurlow, Krause, STIMS,
Fatal bleeding	1.01 [0.27 3.77]	p=1.00	0	2230	9	EMATAP, Katsumara, Stiegler, Ellis, Arcan, Balsano, STIMS, Hurlow, Krause,

Trial	Studied treatment	Control	Patients
EMATAP, 1993	Ticlopidine 500 mg/j	Placebo	AOMI stade non précisé
Katsumara, 1982	Ticlopidine 500 mg/j	Placebo	patients with ischemic ulcers due to chronic arterial occlusion
Aukland, 1982	Ticlopidine 500 mg/j	Placebo	men with atherosclerotic intermittent claudication and haemorheological abnormalities
Stiegler, 1984	Ticlopidine 500 mg/j	Placebo	AOMI stade II
Ellis, 1986	Ticlopidine 500 mg/j	Placebo	AOMI stade II
Cloarec, 1986	Ticlopidine 500 mg/j	Placebo	AOMI stade non précisé
Arcan, 1988	Ticlopidine 500 mg/j	Placebo	patients with chronic intermittent claudication due to obstructive peripheral vascular disease (stade II)
Balsano, 1989	Ticlopidine 500 mg/j	Placebo	patients with intermittent claudication (stade II)
STIMS, 1990	Ticlopidine 500 mg/j	Placebo	patients with intermittent claudication (stade II)
Hurlow, 1980	Ticlopidine : 100 -500 mg / jour pendant 2 mois.	Placebo	Données non disponibles
Krause, 1980	Ticlopidine : 500 mg pendant 4 mois	Placebo	Données non disponibles

Ticlopidine

cardiovascular prevention, in secondary prevention in patients with CAD

all NS

Ticlopidine

cardiovascular prevention, in diabetic patients

all NS

Ticlopidine

diabetes type 2, in patients without cardiovascular disease

all NS

Ticlopidine

diabetes type 2, in all type of patients

all NS

Ticlopidine

MACE by 59% suggested

Ticlopidine

MACE by 73% suggested

Ticlopidine

peripheral vascular diseases, in all type of patient

Vascular death by 40% suggested

Endpoint	TE [95% CI]	p val	I2	n	k
Amputation	no data
myocardial infarction (fatal and non fatal)	0.86 [0.59 1.24]	p=1.00	0	2071	7	EMATAP, Stiegler, Ellis, Cloarec, Arcan, Balsano, STIMS,
Vascular death	0.60 [0.39 0.92]	p=0.04	0	2313	10	EMATAP, Katsumara, Aukland, Ellis, Balsano, Cloarec, Arcan, Hurlow, Krause, STIMS,
Fatal MI	0.63 [0.35 1.14]	p=1.00	0	2071	7	EMATAP, Stiegler, Ellis, Cloarec, Arcan, Balsano, STIMS,
Non fatal MI	0.99 [0.65 1.51]	p=1.00	0	2427	11	EMATAP, Katsumara, Aukland, Stiegler, Ellis, Cloarec, Arcan, Balsano, STIMS, Hurlow, Krause,
Vascular events	0.75 [0.55 1.01]	p=1.00	0	2120	9	EMATAP, Aukland, Ellis, Cloarec, Arcan, Balsano, STIMS, Hurlow, Krause,
All cause death	0.73 [0.53 1.01]	p=1.00	0	2427	11	EMATAP, Katsumara, Aukland, Stiegler, Ellis, Cloarec, Arcan, Balsano, STIMS, Hurlow, Krause,
Fatal stroke	0.49 [0.15 1.56]	p=1.00	0	2071	7	EMATAP, Stiegler, Ellis, Cloarec, Arcan, Balsano, STIMS,
Non fatal stroke	0.81 [0.47 1.40]	p=1.00	0	2427	11	EMATAP, Katsumara, Aukland, Stiegler, Ellis, Cloarec, Arcan, Balsano, STIMS, Hurlow, Krause,
Non cerebral major bleeding	1.88 [0.58 6.02]	p=1.00	0	2362	10	EMATAP, Katsumara, Stiegler, Ellis, Cloarec, Arcan, Balsano, Hurlow, Krause, STIMS,
Fatal bleeding	1.01 [0.27 3.77]	p=1.00	0	2230	9	EMATAP, Katsumara, Stiegler, Ellis, Arcan, Balsano, STIMS, Hurlow, Krause,

Trial	Studied treatment	Control	Patients
EMATAP, 1993	Ticlopidine 500 mg/j	Placebo	AOMI stade non précisé
Katsumara, 1982	Ticlopidine 500 mg/j	Placebo	patients with ischemic ulcers due to chronic arterial occlusion
Aukland, 1982	Ticlopidine 500 mg/j	Placebo	men with atherosclerotic intermittent claudication and haemorheological abnormalities
Stiegler, 1984	Ticlopidine 500 mg/j	Placebo	AOMI stade II
Ellis, 1986	Ticlopidine 500 mg/j	Placebo	AOMI stade II
Cloarec, 1986	Ticlopidine 500 mg/j	Placebo	AOMI stade non précisé
Arcan, 1988	Ticlopidine 500 mg/j	Placebo	patients with chronic intermittent claudication due to obstructive peripheral vascular disease (stade II)
Balsano, 1989	Ticlopidine 500 mg/j	Placebo	patients with intermittent claudication (stade II)
STIMS, 1990	Ticlopidine 500 mg/j	Placebo	patients with intermittent claudication (stade II)
Hurlow, 1980	Ticlopidine : 100 -500 mg / jour pendant 2 mois.	Placebo	Données non disponibles
Krause, 1980	Ticlopidine : 500 mg pendant 4 mois	Placebo	Données non disponibles