hypertension clinical trials results

ACE inhibitor versus CCB
STOP-2 (ACEI vs CCB) (diabetic subgroup), 2000
ACE inhibitor
versus
calcium antagonists
diabetic (subgroup) elderly patients aged 70-84 years open with blind assessment
Follow-up duration: 5.03y
Sweden
ACE inhibitor versus diuretic or beta-blocker
STOP-2 ACEI (diabetic subgroup), 2000
ACE inhibitor
versus
conventional treatment (diuretic or beta-blocker)
diabetic (subgroup) elderly patients aged 70-84 years with hypertensionopen with blind assessment
Follow-up duration: 5.03y
Sweden
ACE inhibitor versus placebo
HOPE (diabetic subgroup), 2000
ramipril 10 mg once per day orally
versus
placebo
patients with diabetes (sub group), aged 55 years or older, who had a previous cardiovascular event or at least one other cardiovascular risk factor, no clinical proteinuria, heart failure, or low ejection fractiondouble-blind
Follow-up duration: 4.5 years
North, South america, Europe
aliskiren versus hydrochlorothiazide
Schmieder (vs HCTZ), 2009
aliskiren 300 mg
versus
hydrochlorothiazide 25 mg
patients with essential hypertension double blind
Follow-up duration: 20 weeks
aliskiren versus losartan
ALLAY, 2009
aliskiren 300 mg
versus
losartan 100 mg
patients with hypertension, increased ventricular wall thickness, and body mass index >25 kg/m2open
Follow-up duration: 9 months
aliskiren versus placebo
AVOID, 2008
NCT00097955
aliskiren (150 mg daily for 3 months, followed by an increase in dosage to 300 mg daily for another 3 months
versus
placebo
patients with hypertension and type 2 diabetes with nephropathydouble blind
Follow-up duration: 6 months
15 countries
aliskiren versus ramipril
Andersen, 2008
aliskiren 150 mg (up to 300mg) daily
versus
ramipril 5 mg (up to 10mg) daily
double blind
Follow-up duration: 26 weeks
amlodipine versus atenolol
ASCOT-BPLA, 2005
amlodipine5–10 mg adding perindopril 4–8 mg as required
versus
atenolol 50–100 mg adding bendroflumethiazide 1·25–2·5 mg and potassium as required
patients with hypertension who were aged 40–79 years and had at least three other cardiovascular risk factors.ÿopen
Follow-up duration: 5.5 y
Nordic countries and UK
amlodipine versus chlorthalidone
ALLHAT (CCB vs diu), 2002
Amlodipine 2.5 to 10g/d , Amlodipine 2.5 to 10g/d , Amlodipine 2.5 to 10g/d , Amlodipine 2.5 to 10g/d
versus
chlorthalidone 12.5 to 25 mg/d
participants aged 55 years or older with hypertension and at least 1 other CHD risk factor Double aveugle
Follow-up duration: 4.9y
US
ALLHAT (amlodipine vs chlor, diabetic subgroup), 2002
amlodipine
versus
chlorthalidone
diabetic (subgroup) participants aged 55 years or older with hypertensiondouble-blind
Follow-up duration: 4.9 y
amlodipine versus fosinopril
FACET, 1997
amlodipine (long acting) 10 mg daily
versus
fosinopril 20 mg daily
hypertensive patients with NIDDMopen
Follow-up duration: 3.5 y
Italy
amlodipine versus lisinopril
ALLHAT (CCB vs ACEI), 2002
Amlodipine 2.5 to 10g/d , Amlodipine 2.5 to 10g/d , Amlodipine 2.5 to 10g/d
versus
lisinopril 10 to 40 mg/d
participants aged 55 years or older with hypertension and at least 1 other CHD risk factorDouble aveugle
Follow-up duration: 4.9y
US
amlodipine versus metoprolol
AASK (vs metoprolol), 2002
Amlodipine 5-10 mg/d
versus
metoprolol 50-200 mg/d
African Americans aged 18 to 70 years with hypertensive renal disease (GFR, 20-65 mL/min per 1.73m2)
Follow-up duration: 3·0y
US
amlodipine versus placebo
IDNT, 2001
Amlodipine 10mg/d
versus
placebo
hypertensive patients with nephropathy due to type 2 diabetesDouble blind
Follow-up duration: 2·6
IDNT amlodipine, 2001
Amlodipine 10 mg daily
versus
placebo
hypertensive patients with nephropathy due to type 2 diabetesdouble-blind
Follow-up duration: 2.6 years
Worldwide
Tepel et al, 2008
NCT00124969
Amlodipine 10 mg/day
versus
matched placebo
hypertensive haemodialysis patients double blind
Follow-up duration: 19 montsh median (8-30)
amlodipine versus ramipril
AASK (vs ramipril), 2002
Amlodipine 5-10 mg/d
versus
ramipril 2.5-10 mg/d
African Americans aged 18 to 70 years with hypertensive renal disease (GFR, 20-65 mL/min per 1.73m2) Double blind
Follow-up duration: 3·0
US
amlodipine plus benazepril versus hydrochlorothiazide plus benazepril
ACCOMPLISH, 2008
NCT00170950
benazepril 40mg plus amlodipine 5mg daily
versus
benazepril 40mg plus hydrochlorothiazide 12.5mg daily
patients with hypertension who were at high risk for cardiovascular eventsdouble blind
Follow-up duration: 36 months
US, Sweden, Norway, Denmark, Finland
angioplasty versus medical therapy
EMMA, 1998
angioplasty
versus
antihypertensive drug treatment
hypertensive patients with atherosclerotic renal artery stenosis.open
Follow-up duration: 6 months
France
SNRASCG, 1998
percutaneous transluminal angioplasty
versus
medical therapy
hypertensive patients with unilateral or bilateral disease
Follow-up duration: 12 months
United Kingdom
DRASTIC, 2000
percutaneous transluminal renal angioplasty
versus
drug therapy
patients with hypertension who had atherosclerotic renal-artery stenosis (defined as a decrease in luminal diameter of 50 percent or more) and a serum creatinine concentration of 2.3 mg per deciliter (200 micromol per liter) or less open
Follow-up duration: 12 months
Netherlands
ASTRAL, 2009
revascularization in addition to medical therapy
versus
medical therapy alone
patients with atherosclerotic renovascular diseaseopen
Follow-up duration: 33.6 months
United Kingdom, Australia, New Zealand
STAR, 2009
stent placement and medical treatment
versus
medical treatment alone (antihypertensive treatment, statin, aspirin)
patients with atherosclerotic renal artery stenosis and impaired renal functionopen
Follow-up duration: 24 months
Netherlands, France
NITER, 2009

versus

Follow-up duration: 43 months
Italy
ARBs versus control
Suzuki, 2008
ARBs (valsartan, candesartan, and losartan)
versus
no ARBs
patients with diabetes and chronic kidney disease on dialysisopen
aspirin versus placebo
HOT, 1998
aspirin 75 mg daily
versus
placebo
patients aged 50-80 with hypertension and diastolic blood pressure between 100 mmHG and 115 mmHGDouble blind
Follow-up duration: mean 3.8 y (range 3.3-4.9y)
Europe, North and South America, and Asia
atenolol versus amlodipine
ASCOT-BPLA, 2005
atenolol 50–100 mg adding bendroflumethiazide 1·25–2·5 mg and potassium as required
versus
Amlodipine 5–10 mg adding perindopril 4–8 mg as required
hypertensif patients aged 40-79y with at least three other cardiovascular risk factorsOpen
Follow-up duration: 5·7y
atenolol versus bendroflumethiazide
MRC I (vs diuretics), 1985
Propranolol
versus
Bendroflumethiazide.
men and women aged 35-64 years with mild hypertension (diastolic pressure 90-109 mm Hgdouble blind
Follow-up duration: 5·5y
atenolol versus captopril
UKPDS, 1998
Atenolol 50-100 mg/
versus
Captopril 25-50 mg twice daily
hypertensive patients with type 2 diabetesOpen
Follow-up duration: 9y
England,Scotland, and Northern Ireland.m
atenolol versus control
Coope (subgroup ), 1986
atenolol and bendrofluazide
versus
control
patients aged 60 to 79 years double-blind
Follow-up duration: 3·8y
atenolol versus hydrochlorothiazide+amiloride
MRC old (vs diuretics), 1992
Atenolol
versus
Hydrochlorothiazide/amiloride
hypertensive patients aged 65-74double blind
Follow-up duration: 5·8y
UK
atenolol versus lacidipine
ELSA, 2002
Atenolol 50 mg once daily
versus
Lacidipine 4 mg once daily
Subjects aged 45 to 75 years with sitting systolic blood pressure (SBP) of 150 to 210 mm Hg and diastolic blood pressure (DBP) of 95 to 115 mm HgDouble blind
Follow-up duration: 3·75y
Europe
atenolol versus Losartan
LIFE, 2002
Atenolol 50mg/d
versus
Losartan 50mg/d
participants aged 55–80 years with essential hypertension (sitting blood pressure 160–200/ 95–115 mm Hg) and LVH ascertained by electrocardiography (ECG).Double blind
Follow-up duration: 4.8y
Denmark, Finland, Iceland, Norway, Sweden, UK, US
atenolol versus open control
Coope, 1986
atenolol and bendrofluazide , Atenolol
versus
Open control
patients aged 60 to 79 years open
Follow-up duration: 4·4y
atenolol versus placebo
MRC I (vs placebo), 1985
Propranolol
versus
Placebo
men and women aged 35-64 yearswith mild hypertension (diastolic pressure 90-109 mm Hgdouble blind
Follow-up duration: 5.5y
MRC old (vs placebo), 1992
Atenolol
versus
Placebo
patients aged 65-74double blind
Follow-up duration: 5.8y
UK
Dutch TIA, 1993
Atenolol 50mg/d
versus
Placebo
aspirin-treated patients with transient ischemic attack or nondisabling ischemic stroke double blind
Follow-up duration: 2·6y
TEST, 1995
Atenolol
versus
Placebo
post stroke
Follow-up duration: 2·6y
atenolol versus verapamil
INVEST, 2003
NCT00133692
Atenolol 50mg/d
versus
Verapamil SR 250 mg/d
hypertensive with coronary artery disease patients aged 50 years or olderopen
Follow-up duration: 2·7y
Atenolol or hydrochlorothiazide versus verapamil
CONVINCE, 2003
Atenolol 50mg/d or hydrochlorothiazide 12.5 mg/d
versus
Verapamil 180mg/d
hypertension and 1 or more additional risk factors for cardiovascular disease double blind
Follow-up duration: 3.0y
15 countries
atorvastatin versus placebo
ASCOT, 2003
atorvastatin 10mg/d
versus
placebo
hypertensive patients aged 40-79 years with at least three other cardiovascular risk factorsdouble blind
Follow-up duration: 3.3 years
UK et Scandinavie
benazepril + amlodipine versus benazepril + hydrochlorothiazide
ACCOMPLISH (diabetic subgroup), 2010
NCT00170950
benazepril, combined with amlodipine
versus
benazepril, combined with hydrochlorothiazide
patients with diabetes (subgroup) and hypertension at high risk of cardiovascular and related eventsdouble-blind
Follow-up duration: 36 months
US, Norway, Denmark, Finland
beta-blockers + diuretics versus placebo
CASTEL (subgroup ), 1994
active antihypertensive therapy (thiazide or beta-blockers)
versus
control
open
Follow-up duration: 6·8y
beta-blockers or diuretics versus placebo
STOP (subgroup ), 1991
active antihypertensive therapy (three beta-blockers and one diuretic)
versus
placebo
hypertensive Swedish men and women aged 70-84 yearsdouble-blind
Follow-up duration: 2·1 y
Sweden
calcium-channel blocker versus diuretic or beta-blocker
STOP-2 CCB (diabetic subgroup), 2000
Calcium-channel blocker
versus
diuretic or beta-blocker
diabetic (subgroup) elderly patients aged 70-84 years open with blind assessment
Follow-up duration: 5.03y
Sweden
candesartan versus amlodipine
CASE-J, 2008
candesartan-based regimen
versus
amlodipine-based regimen
high-risk Japanese hypertensive patientsopen (blinded assessment)
Follow-up duration: 3.2 years
Japan
candesartan versus control
Takahashi, 2006
candesartan
versus
control
patients on chronic haemodialysis in stable condition and with no clinical evidence of cardiac disorders open
Follow-up duration: 19.4 months
candesartan versus conventional treatment
E-COST, 2005
candesartan, 2 to 12 mg daily
versus
conventional antihypertensive drugs other than angiotensin converting enzyme inhibitors or ARBs
Japanese essential hypertensive subjects (sitting blood pressure 140-180/90-110 mmHg) aged 35-79 yearssingle-blind
Japan
E-COST-R, 2005
candesartan
versus
conventional treatment
hypertensive subjects 60 to 75 years old with non-diabetic chronic renal insufficiencyopen
HIJ-CREATE, 2009
angiotensin II receptor blocker-based therapy
versus
non-angiotensin II receptor blocker-based therapy
patients with angiographically documented coronary artery disease and hypertensionopen
Follow-up duration: 4.2 y (median)
Japan
candesartan versus hydrochlorothiazide
ALPINE, 2003
candesartan
versus
hydrochlorothiazide
newly detected hypertensivesdouble-blind
Follow-up duration: 1 year
Sweden
candesartan versus placebo
TROPHY, 2006
NCT00227318
candesartan during 2y followed by 2y of placebo
versus
placebo
subjects with repeated measurements of systolic pressure of 130 to 139 mm Hg and diastolic pressure of 89 mm Hg or lower, or systolic pressure of 139 mm Hg or lower and diastolic pressure of 85 to 89 mm Hgdouble-blind
Follow-up duration: 4y
USA
SCOPE, 2003
candesartan, 8–16 mg once daily (target 160/90)
versus
placebo
patients aged 70–89 years, with systolic blood pressure 160– 179 mmHg, and/or diastolic blood pressure 90–99 mmHg, and a Mini Mental State Examination (MMSE) test score > 24double-blind
Follow-up duration: 3.7 y (mean)
15 countries
Candesartan versus usual care
HIJ-CREATE, 2009
cardesartan adjusted dose for target arterial pressure of <130/85 mmHg
versus
usual care (non-ARB-based pharmacotherapy including angiotensin-converting enzyme-inhibitors)
hypertension with angiographically documented coronary artery disease (acute or stable)open
Follow-up duration: up to 60 months
japan
candesartan versus usual care
Takahashi et al, 2006
Candesartan 4-8mg/day
versus
Conventional treatment
chronic haemodialysis patients open
Suzuki et al, 2008
Candesartan 12 mg/day, losartan 100 mg/day, or valsartan 160 mg/day
versus
Conventional treatment
patients undergoing hemodialysisopen
Follow-up duration: 1-5 years
captopril versus atenolol
UKPDS 39, 1998
captopril 25 mg/d aiming at a BP <150/85
versus
atenolol 50mg/d aiming at a BP <150/85
hypertensive patients with type 2 diabetesopen
Follow-up duration: ND
UK
captopril versus diuretic and/or beta-blockers
CAPP (diabetic subgroup), 1999
Captopril initial dose of 50 mg daily given in one or two doses
versus
thiazide diuretic or beta-blocker
Patients aged 25-66 years with a measured diastolic blood pressure of 100 mm Hg or more on two occasions; subgroup of diabetic patientsopen with blinded assessment
Follow-up duration: 6.1 year
Sweden, Finland
captopril versus diuretic or beta-blocker
CAPPP, 1999
captopril 50mg/d
versus
beta-blocker (not specified) or diuretic (not specified)
Patients aged 25–66 years with a measured diastolic bloodpressure of 100 mm Hg or more on two occasionsOpen
Follow-up duration: 6.1 y
Sweden and Finland
UKPDS-HDS, 1998
captopril started at 25mg twice daily up to 50 mg twice dialy (target blood pressure of <150/<85 mmHG)
versus
atenolol started at 50mg daily up to 100mg if required(target blood pressure of <150/<85 mmHG)
HBP+DMOpen
Follow-up duration: 8·4 y
England, Scotland, and Northern Ireland
captopril or atenolol versus control
UKPDS 38, 1998
tight control of blood pressure aiming at a BP <150/85 (with the use of captopril or atenolol as main treatment, other treatment were added if the control criteria were not met)
versus
less tight control aiming at a blood pressure of <180/105 (avoiding treatment with ACE inhibitors or beta-blockers)
hypertensive patients with type 2 diabetes open
Follow-up duration: 8.4y (median)
UK
carvedilol versus placebo
Cice et al, 2003
Carvedilol 50 mg/day
versus
matched placebo
dialysis patients with dilated cardiomyopathy
Follow-up duration: 12 months
Nakao et al, 2007
Carvedilol 20 mg/day
versus
matched placebo
chlorthalidone versus placebo
SHEP-pilot, 1989
chlorthalidone
versus
placebo
elderly participants with untreated blood pressures of greater than 160/less than 90 mm Hg double blind
Follow-up duration: 2.8y
VA-NHLBI, 1977
chlorthalidone 50mg/d
versus
placebo
patients aged 21 to 50 years with diastolic BP between 85 to 105 mm HgDouble aveugle
Follow-up duration: 1.4 y
USA
SHEP, 1991
NCT00000514
chlorthalidone, 12.5 mg/d , chlorthalidone, 12.5 mg/d , chlorthalidone, 12.5 mg/d
versus
placebo
patients aged 60 years and above with Systolic BP between 160 and 219 mm Hg and diastolic BP less than 90 mm Hg Double blind
Follow-up duration: 4.4 y
SHEP (diabetic subgroup), 1996
low dose of chlorthalidone (12.5-25.0 mg/d) with a step-up to atenolol (25.0-50.0 mg/d) or reserpine (0.05-0.10 mg/d) if needed
versus
placebo
men and women aged 60 years and older , non-insulin-treated diabetic (sub group) patients with isolated systolic hypertension (systolic BP >= 160 mm Hg; diastolic BP, <90 mm Hg)double-blind
Follow-up duration: 5 year
SHEP-P (subgroup ), 1989
chlorthalidone
versus
placebo
elderly participants with untreated blood pressures of greater than 160/less than 90 mm Hg double-blind
Follow-up duration: 2·8y
SHEP (subgroup ), 1991
chlorthalidone, 12.5 mg/d for step 1
versus
placebo
patients aged 60 years and above double blind
Follow-up duration: 4·2y
darusentan versus placebo
DORADO-AC,

versus
DORADO, 2009
NCT00330369
darusentan 50 mg, 100 mg or 300 mg
versus
placebo
patients with treatment-resistant hypertensiondouble blind
Follow-up duration: 14 weeks
North and South America, Europe, New Zealand, Australia
deserpidine +methylclothiazide versus placebo
HSCS, 1974
deserpidine 1mg/d + methylclothiazide 10mg/d
versus
placebo
strokeDouble blind
Follow-up duration: 2.3y
USA
diltiazem versus diuretic or beta-blocker
NORDIL, 2000
diltiazem 180-360 daily
versus
beta-blocker (not specified) or diuretic (not specified)
hypertensive patients, aged 50–74 yearsOpen
Follow-up duration: up to 5 years
Norway, Sweden
NORDIL (diabetic subgroup), 2000
Diltiazem 180–360 mg diltiazem daily at step one
versus
thiazide diuretic or a beta-blocker at step one
diabetic patients (subgroup), aged 50-74 years who had diastolic blood pressure of 100 mm Hg or moreopen
Follow-up duration: 4.5 y
Norway, Sweden
diuretic and rauwolfia serpentina versus placebo
USPHS, 1977
diuretic and rauwolfia serpentina
versus
placebo
subjects, ages 21-55, with diastolic blood pressures between 90 and 115 mm Hg double blind
Follow-up duration: 7.0 y
enalapril versus diuretics
ANBP2, 2003
enalapril
versus
hydrochlorothiazide
subjects with hypertension 65 to 84 years open
Follow-up duration: 4.1 y
Australia
enalapril versus nisoldipine
ABCD (H), 1998
enalapril
versus
nisoldipine
patients with non-insulin-dependent diabetes and hypertensiondouble blind
Follow-up duration: 5·3 y
felopidine or israpidine versus diuretic or beta-blocker
STOP 2 (vs diurectic or beta-blocker), 1999
felodipine 2·5 mg or isradipine 2–5 mg daily
versus
conventional antihypertensivedrugs (atenolol 50 mg, metoprolol 100 mg,pindolol 5 mg, or hydrochlorothiazide 25 mg plus amiloride2.5 mg daily
patients aged 70–84 years with hypertension (blood pressure >180 mm Hg systolic, >105 mm Hg diastolic, or both). Open
Follow-up duration: up to 6 years
fluvastatin versus placebo
HYRIM, 2005
fluvastatin 40 mg daily
versus
placebo
drug-treated hypertensive men aged 40-74 years with total cholesterol 4.5-8.0 mmol/L, triglycerides <4.5 mmol/L, body mass index 25-35 kg/m2, and a sedentary lifestyledouble blind
Follow-up duration: 4 year
Norway
fosinopril versus placebo
Zannad et al, 2006
Fosinopril 20 mg/day
versus
matched placebo
chronic hemodialysis patients.double blind
Follow-up duration: 24 months
High-dose diuretics versus beta-blockers
MRC (diu vs BB), 1985
High-dose diuretics
versus
ß-Blockers

Follow-up duration: 4.9y
High-dose diuretics versus control
HDFP, 1979
NCT00000485?acronym=
High-dose diuretics
versus
Usual careb
persons with high blood pressure aged 30 to 69 years
Follow-up duration: 5 y
US
High-dose diuretics versus placebo
VA II, 1970
High-dose diuretics
versus
Placebo

Follow-up duration: 3.3y
VA-I, 1967
High-dose diuretics
versus
Placebo

Follow-up duration: 1.5y
Barraclough, 1973
High-dose diuretics
versus
Placebo

Follow-up duration: 2.0 y
hydrochlorothiazide versus placebo
EWPHE (subgroup ), 1985
hydrochlorothiazide + triamterene
versus
placebo
patients over the age of 60double-blind
Follow-up duration: 3·1y
hydrochlorothiazide + triamterene versus placebo
Kuramoto, 1981
hydrochlorothiazide + triamterene
versus
placebo
patients over the age of 60 with sitting diastolic blood pressure on placebo treatment in the range 90-119 mm Hg and a systolic pressure in the range 160-239 mm Hgdouble blind
Follow-up duration: 4.0y
EWPHE, 1985
hydrochlorothiazide + triamterene , hydrochlorothiazide + triamterene
versus
placebo
patients over the age of 60 with sitting diastolic blood pressure on placebo treatment in the range 90-119 mm Hg and a systolic pressure in the range 160-239 mm Hg Double blind
Follow-up duration: 4.3 y
indapamide versus placebo
HYVET, 2008
NCT00122811
indapamide sustained release 1.5 mg/d + perindopril 2-4mg/d to obtain SBP<150 and DBP<80
versus
placebo
patients 80 years or older with persistent hypertension defined as a sustained systolic BP of 160 mm Hg or higherDouble blind
Follow-up duration: 1.8y (median)
Western and Eastern Europe, China, Australasia, and North Africa
PATS, 1995
indapamide 2.5 mg/d
versus
placebo
Double blind
Follow-up duration: 2y
China
intensive versus usual
ACCORD blood pressure, 2010
NCT00000620
intensive blood-pressure control, targeting a systolic pressure of less than 120 mm Hg
versus
standard blood-pressure control
high-risk patients with type 2 diabetes, high HbA1c concentrations (>7.5%), and cardiovascular disease (or >=2 cardiovascular risk factors)open
Follow-up duration: 4.7 y
United States, Canada
irbesartan versus amlodipine
IDNT (vs amlodipine), 2001
Irbesartan 300mg/d (with a target of 135/85)
versus
amlodipine 10mg/d (with a target of 135/85)
hypertensive patients with nephropathy due to type 2 diabetes double-blind
Follow-up duration: 2·6y
worldwide
IDNT (irbesartan vs amlodipine), 2001
Irbesartan 300 mg daily
versus
amlodipine 10 mg daily
hypertensive patients with nephropathy due to type 2 diabetes double blind
Follow-up duration: 2.6 years
Worldwide
irbesartan versus placebo
IDNT (vs placebo), 2001
Irbesartan 300mg/d (target 135/85)
versus
placebo
hypertensive patients with nephropathy due to type 2 diabetesdouble-blind
Follow-up duration: 2.6 y
worldwide
IRMA 2, 2001
irbesartan 150 mg daily or 300 mg daily
versus
placebo
hypertensive patients with type 2 diabetes and microalbuminuriadouble-blind
Follow-up duration: 2 years
multinational
IDNT irbesartan, 2001
Irbesartan 300 mg daily
versus
placebo
hypertensive patients with nephropathy due to type 2 diabetes double blind
Follow-up duration: 2.6 years
Worldwide
IPDM 150mg, 2001
irbesartan 150 mg daily
versus
placebo
hypertensive patients with type 2 diabetes and microalbuminuriadouble-blind
Follow-up duration: 2 years
Worldwide
isradipine versus hydrochlorothiazide
MIDAS, 1996
isradipine 2.5-5.0 mg twice daily
versus
hydrochlorothiazide 12.5-25 mg Twice daily
HBP
Follow-up duration: 3y
lacidipine versus atenolol
ELSA, 2002
Lacidipine
versus
atenolol
patients with hypertensionDouble blind
Follow-up duration: 4·0y
lacidipine versus chlorthalidone
SHELL, 2003
lacidipine 4 mg/d
versus
chlorthalidone 12.5 mg/d
elderly patients with isolated systolic hypertension > or = 60 years
Follow-up duration: 3·6?y
LCZ696 versus placebo
Ruilope, 2010
LCZ696 for 8 weeks
versus
placebo
patients with mild to moderate hypertension double blind
Follow-up duration: 8 weeks
18 countries
lisinopril versus amlodipine
ALLHAT (vs amlodipine), 2002
Lisinopril 10 to 40 mg/d
versus
amlodipine 2.5 to 10 mg/d
participants aged 55 years or older with hypertension and at least 1 other CHD risk factDouble blind
Follow-up duration: 4.9 y
US
lisinopril versus chlorthalidone
ALLHAT (lisi vs chlor, diabetic subgroup), 2002
lisinopril 10 to 40 mg/d
versus
chlorthalidone 12.5 to 25 mg/d
diabetic (subgroup) participants aged 55 years or older with hypertensiondouble-blind
Follow-up duration: 4.9 y
lisinopril versus diuretics
ALLHAT (vs chlorthalidone), 2002
lisinopril 10 to 40 mg/d
versus
chlorthalidone 12.5 to 25 mg/d
participants aged 55 years or older with hypertension and at least 1 other CHD risk factorDouble blind
Follow-up duration: 4·9 y
US
losartan versus atenolol
LIFE, 2002
losartan
versus
atenolol
patients aged 55–80 years, with previously treated or untreated hypertension (sitting blood pressure 160–200/95–115 mm Hg) and ECG signs of LVH.Double blind
Follow-up duration: 4.8 y (mean)
USA, Europe
LIFE (diabetic subgroup), 2002
losartan 50mg daily at step 1
versus
atenolol 50mg daily at step 1
patients with diabetes (subgroup) , hypertension, and signs of left-ventricular hypertrophy on electrocardiogramsdouble-blind
Follow-up duration: 4.7 years
USA, UK, Nordic countries
Losartan versus Captopril
ELITE-II, 2000
Losartan titrated to 50 mg once daily
versus
Captopril titrated to 50 mg three times daily
patients aged 60 years or older with New York Heart Association class II-IV heart failure and ejection fraction of 40% or less. Patientsdouble-blind
Follow-up duration: 1.5 y
OPTIMAAL, 2001
losartan (titrated to 50 mg once daily)
versus
Captopril (titrated to 50 mg three times daily)
patients 50 years of age or older, with confirmed acute myocardial infarction and heart failure during the acute phase or a new Q-wave anterior infarction or reinfarctionNA
Follow-up duration: 2.7 y
Europe (7 countries)
ELITE, 1997
Losartan titrated to 50 mg once daily for 48 weeks
versus
Captopril titrated to 50 mg three times daily for 48 weeks
naive patients (aged 65 years or more) with NYHA class II-IV heart failure and ejection fractions of 40% or less double-blind
Follow-up duration: 1 y
losartan versus placebo
RENAAL, 2001
lLosartan 50 to 100 mg once daily
versus
placebo
patients with type 2 diabetes and nephropathydouble-blind
Follow-up duration: 3.4 years
RENAAL, 2001
losartan 50 to 100 mg once daily
versus
placebo
patients with type 2 diabetes and nephropathydouble-blind
Follow-up duration: 3.4 y
America, Europe, Asia
more intensive blood pressure lowering strategie versus less intensive blood pressure lowering strategie
PAST-BP, 2015

versus
Wei, 2013
BP <=140/90 mm Hg
versus
BP <=150/90 mm Hg
Chinese hypertensive patients older than 70 years
Follow-up duration: 4 years (mean)
China
SPS3, 2013
NCT00059306.
less than 130 mm Hg
versus
130-149 mm Hg
patients lived in North America, Latin America, and Spain and had recent, MRI-defined symptomatic lacunar infarctionsopen-label
HOMED-BP, 2012
tight control (<125/<80 mm Hg (TC)) of HBP
versus
usual control (125-134/80-84 mm Hg (UC))
with an untreated systolic/diastolic HBP of 135-179/85-119 mm Hg
Follow-up duration: 5.3 years (median)
VANLISH, 2010
strict blood pressure control (<140 mm Hg)
versus
moderate blood pressure control (> or =140 mm Hg to <150 mm Hg)
patients aged 70 to 84 years with isolated systolic hypertension (sitting blood pressure 160 to 199 mm Hg)open-label
Follow-up duration: 3.07 years (median)
JATOS, 2008
strict treatment to maintain systolic blood pressure below 140 mmHg
versus
mild treatment to maintain systolic blood pressure below 160 but at or above 140 mmHg
elderly hypertensive patients with essential hypertension (65-85 years old, with a pretreatment systolic blood pressure of above 160 mmHg)open-label
UKPDS-HDS, 1998
blood pressure of <150/85 mm Hg (with the use of an angiotensin converting enzyme inhibitor captopril or a beta blocker atenolol as main treatment)
versus
less tight control aiming at a blood pressure of <180/105 mm Hg
patients with type 2 diabetesopen-label
Follow-up duration: 8.4 years
UK
SPRINT, 2015
NCT01206062
target of 120 mm Hg
versus
target of 140 mm Hg
high-risk hypertensive adults 50 years of age and older with one additional cardiovascular risk factor or preexisting kidney diseaseopen
Cardio-Sis, 2009
NCT00421863
tighter control of systolic BP with a goal of <130 mm Hg
versus
usual control, with a goal of <140 mm Hg
nondiabetic patients with hypertension and with SBP of 150 mm Hg or higher confirmed at two different timesopen
Follow-up duration: 2 years
Italy
AASK, 2002
arterial pressure goal of 92 mm Hg or lower
versus
usual mean arterial pressure goal of 102 to 107 mm Hg/pj
African-Americans,with diastolic blood pressure higher than 94mmHg and a glomerular filtration rate between 20 and 65 ml/min per 1.73 m2open
Follow-up duration: (range 3-6.4y)
USA
ABCD (H), 2000
intensive treatment with a diastolic blood pressure goal of 75 mmHg
versus
moderate treatment with a diastolic blood pressure goal of 80-89 mmHg
diabetes patients with DBP >=90 mmHgopen
Follow-up duration: 5 year
ABCD (N), 2002
intensive treatment (diastolic blood pressure decrease of 10 mmHg below baseline DBP)
versus
moderate treatment (diastolic blood pressure goal of 80-89 mmHg)
diabetes patients with diastolic blood pressure between 80 and 89mmHgopen
HOT, 1994
less or equal than 85 mmHg, or less or equal than 80 mmHg
versus
less or equal than 90 mmHg
patients with diastolic blood pressure between 100 mmHg and 115 mmHgopen
Follow-up duration: 3.8 y
26 countries
REIN-2, 2005
intensified (systolic/diastolic <130/80 mm Hg) blood-pressure control
versus
conventional (diastolic <90 mm Hg) blood-pressure control
patients with non-diabetic proteinuric nephropathies receiving background treatment with the ACE inhibitor ramipril open
Follow-up duration: 36 months
MDRD, 1994
low target blood pressure (mean arterial pressure < 92 mm Hg)
versus
usual target blood pressure (mean arterial pressure < 107 mm Hg)
patients with predominantly nondiabetic kidney disease and a glomerular filtration rate of 13 to 55 mL/min per 1.73 m2open
Follow-up duration: 2.2 y
Toto, 1995
strict blood pressure control (DBP 65 to 80 mm Hg)
versus
usual blood pressure control (DBP 85 to 95 mm Hg)
non-diabetic patients (age 25 to 73) with long-standing hypertension (DBP > or = 95 mm Hg), chronic renal insufficiency (GFR < or = 70 m/min/1.73 m2) and a normal urine sediment open
ACCORD blood pressure, 2008
NCT00000620
intensive therapy, targeting a systolic pressure of less than 120 mm Hg
versus
standard therapy, targeting a systolic pressure of less than 140 mm Hg
patients with a median glycated hemoglobin level of 8.1% at high risk for cardiovascular eventsopen
Follow-up duration: 4.7y
USA, Canada
nicardipine versus trichlormethiazide
NICS-EH, 1999
Nicardipine SR 20mg twice daily
versus
trichlormethiazide 2mg once daily
>=60 years of age with systolic blood pressure of 160 to 220 mm Hg and diastolic blood pressure <115 mm Hg Double blind
Follow-up duration: 4.5 years
nidrendipine versus placebo
Syst-Eur (subgroup ), 1997
nitrendipine 10-40 mg daily in first step
versus
placebo
patients aged 60 years or olderdouble blind
Follow-up duration: 2·9 y
nifedipine versus atenolol+chlorthalidone
Castel, 1994
Nifedipine 20mg/d
versus
Clonidine 0.15mg/d (n=61) or atenolol 100mg/d + chlorthalidone 25mg/d
nifedipine versus coamilozide
INSIGHT (diabetic subgroup), 2000
Nifedipine GITS 30 mg daily
versus
co-amilozide hydrochlorothiazide 25 mg plus amiloride 2.5 mg
diabetic (subgroup) patients aged 55-80 years with hypertension (blood pressure >= 150/95 mm Hg, or >= 160 mmHg systolic)double-blind
Follow-up duration: 4 y
Europe, Israel
nifedipine versus hydrochlorothiazide+amiloride
INSIGHT, 2000
nifedipine GITS 30mg/d
versus
hydrochlorothiazide 25mg/d + amiloride 2.5mg/d
HBP + RFDouble blind
Follow-up duration: at least 3 years
nisoldipine versus enalapril
ABCD hypertension, 1998
nisoldipine (long acting)
versus
enalapril
patients with non-insulin-dependent diabetes and hypertensionDouble blind
Follow-up duration: 5 y
USA
nitrendipine versus placebo
SYST-EUR, 1997
nitrendipine 10-40 mg daily , nitrendipine 10-40 mg daily
versus
placebo
HBP, >=60 years Double aveugle
Follow-up duration: 2·6y
23 countries across Europe
Syst-Eur (diabetic subgroup), 1999
Calcium-channel blocker
versus
placebo
subgroup of diabetic patients, age, >=60 years) with systolic blood pressure of 160 to 219 mm Hg and diastolic pressure below 95 mm Hgdouble blind
Follow-up duration: 2 years
olmesartan 40 mg versus olmesartan 20 mg plus a calcium-channel blocker
OSCAR, 2011
NCT00134160
high-dose olmesartan 40 mg per day
versus
20-mg/day olmesartan comined with standard dose of amlodipine or azelnidipine
high-risk elderly Japanese hypertension patients
Japan
oxprenolol versus placebo
IPPPSH, 1985
Oxprenolol
versus
Placebo
men and women aged 40-64 years with uncomplicated essential hypertension (diastolic blood pressures 100-125 mmHg)Double blind
Follow-up duration: 4·0y
propranolol versus bendroflumethiazide
Berglund, 1986
Propranolol
versus
Bendroflumethiazide.
patients 21 to 70 years with essential hypertension (sitting diastolic blood pressures 100-120 mm Hg)
Follow-up duration: 10y
ramipril versus amlodipine
AASK (vs amlodipine), 2002
ramipril 2.5-10 mg/d
versus
amlodipine 5-10 mg/d
African Americans aged 18 to 70 years with hypertensive renal disease (GFR, 20-65 mL/min per 1.73 m(2))Double blind
Follow-up duration: 3·0 y
US
ramipril versus metoprolol
AASK (vs metoprolol), 2002
ramipril 2.5-10 mg/d
versus
metoprolol 50-200 mg/d
African Americans aged 18 to 70 years with hypertensive renal disease (GFR, 20-65 mL/min per 1.73 m(2))Double blind
Follow-up duration: 4·1 y
US
ramipril versus usual care
Li et al, 2003
Ramipril 5 mg/day
versus
Conventional treatment
patients with end-stage renal failure treated with peritoneal dialysisopen
Follow-up duration: 12 months
telmisartan versus enalapril
DETAIL, 2004
telmisartan 80 mg daily
versus
enalapril 20 mg daily
subjects with type 2 diabetes and early nephropathy double-blind
Follow-up duration: 5 year
Telmisartan versus Enalapril
DETAIL, 2004
Telmisartan 80 mg daily
versus
Enalapril 20 mg daily
pateintspatients with type 2 diabetes and early nephropathy double-blind
Follow-up duration: 5 y
telmisartan versus placebo
PROPHESS, 2008
NCT00153062
telmisartan 80 mg daily
versus
placebo
patients who recently had an ischemic strokedouble blind
Follow-up duration: 2.5 y
35 countries
Cice et al, 2006
Telmisartan 80 mg/day
versus
matched placebo
Telmisartan versus Ramipril
ONTARGET/Tel, 2008
Telmisartan 80 mg daily
versus
Ramipril 10 mg daily
patients with vascular disease or high-risk diabetesdouble-blind
Follow-up duration: 4.7 y
Telmisartan + ramipril versus Ramipril
ONTARGET/Tel+Ram, 2008
Telmisartan + ramipril
versus
Ramipril
patients with vascular disease or high-risk diabetesdouble-blind
Follow-up duration: 4.7 y
thiazide diuretics versus control
Carter, 1970
thiazide
versus
?
Open
Follow-up duration: 3.6 y
NA
Oslo (Hegeland), 1980
step 1: hydrochlorothiazide 50mg/d, step 2: alpha methyldopa 250-500mg x2/d or propranolol 40-160mg x2/d,
versus
no treatment
men, aged 40 to 49 years, without target organ damage, with systolic blood pressures between 150 and 179 mm Hg and diastolic blood pressure below 110 mm HgOpen
Follow-up duration: 5.5 y
Oslo
ANBPS (Australian ), 1980
step 1:chlorothiazide 500 mg/d, step 2: chlorothoazide 500mg x2/d or methyldopa, propranolol, pindolol added, step 3: hydralazine or clonidine added
versus
placebo (without adjustement according to the BP!)
Double blind
Follow-up duration: 4 y
Australia
thiazide diuretics versus placebo
MCR 35-64 (diuretics vs pbo), 1985
bendrofluazide 10 mg/d (step 2: methyldopa)
versus
placebo
mild hypertension single blind
Follow-up duration: 4.9y
NA
valsartan versus amlodipine
NAGOYA HEART,
NCT00129233
blood-pressure-lowering therapy based on valsartan; blood-pressure goal of <130/80 mm Hg
versus
blood-pressure-lowering therapy based on amlodipine; blood-pressure goal of <130/80 mm Hg
patients with hypertension with type 2 diabetes or impaired glucose toleranceopen
Japan
VALUE, 2004
NCT00129233
valsartan based regimen
versus
amlodipine based regimen
patients, aged 50 years or older with treated or untreated hypertension and high risk of cardiac eventsDouble blind
Follow-up duration: 4.2 y (mean)
31 countries
NAGOYA HEART, 2011
NCT00129233
blood-pressure-lowering therapy based on valsartan; blood-pressure goal of <130/80 mm Hg
versus
blood-pressure-lowering therapy based on amlodipine; blood-pressure goal of <130/80 mm Hg
patients with hypertension with type 2 diabetes or impaired glucose toleranceopen
Follow-up duration: 3.2 y median
Japan
Valsartan versus Captopril
VALIANT/Val, 2003
Valsartan
versus
Captopril
patients with myocardial infarction complicated by left ventricular systolic dysfunction, heart failure, or bothdouble-blind
Follow-up duration: 2.1 y
Valsartan + captopril versus Captopril
VALIANT/Val+Cap, 2003
Valsartan + captopril
versus
Captopril
patients with myocardial infarction complicated by left ventricular systolic dysfunction, heart failure, or bothdouble-blind
Follow-up duration: 2.1 y
various ACEI versus calcium-channel blocker
STOP-2 (vs felodipine or isradipine), 1999
Enalapril or lisinopril , enalapril 10 mg or lisinopril 10 mg daily
versus
felodipine 2.5 mg or isradipine 2-5 mg daily
patients aged 70-84 years with hypertension (blood pressure > or = 180 mm Hg systolic, > or = 105 mm Hg diastolic, or both) Open
Follow-up duration: 5·0 y
Sweden
various ACEI versus diuretic or beta-blocker
STOP 2 (vs conventional drugs), 1999
enalapril 10 mg or lisinopril10 mg daily
versus
conventional antihypertensive drugs (atenolol 50 mg, metoprolol 100 mg, pindolol 5 mg, or hydrochlorothiazide 25 mg plus amiloride 2·5 mg daily)
patients aged 70–84 years with hypertension (blood pressure >180 mm Hg systolic, >105 mm Hg diastolic, or both).Open
Follow-up duration: 5.0 y
Sweden
various ACEI versus nifedipine
JMIC-B, 2002
ACE inhibitor
versus
nifedipine
HBP+CHDOpen
Follow-up duration: 3·0 y
Japan
various beta-blockers versus ACEI or calcium-blockers
STOP-2, 1999
Atenolol, Metoprolol, Pindolol, HCTZ/Ami
versus
Enalapril, Lisinopril, Felodipine, Isradipine
patients aged 70-84 years with hypertension (blood pressure > or = 180 mm Hg systolic, > or = 105 mm Hg diastolic, or both). open
Follow-up duration: 5·0y
various beta-blockers versus diuretics
Yurenev, 1992
hypotensive drugs including beta-blockers
versus
same combination of drugs including diuretics
hypertensive patients with different degrees of left ventricular hypertrophy (LVH)
Follow-up duration: 4·0y
HAPPHY, 1988
Atenolol, Metoprolol, Propranolol
versus
Hydrochlorothiazide, Bendroflumethiazide
Men aged 40-64 years with mild to moderate hypertension (diastolic blood pressure 100-130 mmHg)open
Follow-up duration: 3·8y
various beta-blockers versus placebo
STOP, 1991
active antihypertensive therapy (Thiazide and amiloride or beta-blocker) , Atenolol, Metoprolol, Pindolol, HCTZ/Ami
versus
Placebo
hypertensive men and women aged 70-84 years Double blind
Follow-up duration: 2·1y
Swezden
verapamil versus atenolol
INVEST (Pepine), 2003
NCT00133692
verapamil sustained release 240mg/d
versus
atenolol 50mg/d
patients with hypertension and CAD
Follow-up duration: 2.7 y
14 countries
verapamil versus chlorthalidone
VHAS, 1998
verapamil SR 240 mg/d
versus
chlorthalidone 25mg/d
HBPOpen
Follow-up duration: 2 years
verapamil versus diuretic or beta-blocker
CONVINCE, 2003
controlled-onset extendedrelease(COER) verapamil 180mg/d
versus
hydrochlorothiazide 12.5 mg/d or atenolol 50 mg/d(investigator choice prior to randomization)
hypertension with 1 or more additional risk factors for cardiovascular diseaseDouble blind
Follow-up duration: 3 y
15 countries