anti hypertensive agents

Description Results NMA

All deaths 0.88 [0.66; 1.18]

Cardiovascular events 0.88 [0.69; 1.12]

microvascular events 1.04 [0.86; 1.25]

Amlodipine 10 mg daily (n=567)

vs.

placebo (n=569)

double-blind

Parallel groups

Sample size: 567/569

Primary endpoint: renal death

FU duration: 2.6 years

Cardiovascular events 0.49 [0.26; 0.93]

All deaths 0.81 [0.22; 2.99]

Stroke 2.47 [0.79; 7.75]

Fatal and nonfatal MI 1.29 [0.58; 2.86]

amlodipine (long acting) 10 mg daily (n=191)

vs.

fosinopril 20 mg daily (n=189)

if blood pressure was not controlled, the other study drug was added

open

Parallel groups

Sample size: 191/189

Primary endpoint: not defined

FU duration: 3.5 y

All deaths 0.96 [0.87; 1.06]

Stroke 0.89 [0.74; 1.07]

Fatal and nonfatal MI 1.02 [0.93; 1.12]

Cardiovascular events 1.06 [0.98; 1.14]

amlodipine (n=2664)

vs.

chlorthalidone (n=4498)

double-blind

Parallel groups

Sample size: 2664/4498

Primary endpoint: fatal CHD or nonfatal MI

FU duration: 4.9 y

Stroke 0.91 [0.48; 1.76]

Cardiovascular events 0.82 [0.57; 1.19]

candesartan (n=313)

vs.

control (n=284)

double-blind

Parallel groups

Sample size: 313/284

Primary endpoint: not defined

FU duration: 3.7 years

Stroke 0.58 [0.37; 0.90]

microvascular events 0.65 [0.46; 0.91]

All deaths 0.83 [0.65; 1.06]

Fatal and nonfatal MI 0.80 [0.60; 1.05]

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) (n=758)

vs.

less tight control aiming at a blood pressure of <180/105 (avoiding treatment with ACE inhibitors or beta-blockers) (n=390)

open

Parallel groups

Sample size: 758/390

Primary endpoint: not unique (3)

FU duration: 8.4y (median)

All deaths 1.14 [0.83; 1.55]

Stroke 1.38 [0.74; 2.57]

Fatal and nonfatal MI 1.19 [0.83; 1.69]

microvascular events 1.28 [0.81; 2.03]

captopril 25 mg/d aiming at a BP <150/85 (n=400)

vs.

atenolol 50mg/d aiming at a BP <150/85 (n=358)

open

Parallel groups

Sample size: 400/358

Primary endpoint: not unique (3)

FU duration: ND

All deaths 0.54 [0.31; 0.95]

Cardiovascular events 0.59 [0.38; 0.91]

Fatal and nonfatal MI 0.38 [0.20; 0.73]

Cardiovascular death 0.48 [0.21; 1.10]

Stroke 1.03 [0.57; 1.85]

Captopril initial dose of 50 mg daily given in one or two doses (n=309)

vs.

thiazide diuretic or beta-blocker (n=263)

open with blinded assessment

Parallel groups

Sample size: 309/263

Primary endpoint: CV events

FU duration: 6.1 year

Cardiovascular events 0.66 [0.46; 0.94]

Fatal and nonfatal MI 0.56 [0.32; 0.97]

All deaths 0.74 [0.46; 1.19]

Stroke 0.74 [0.45; 1.19]

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 (n=283)

vs.

placebo (n=300)

double-blind

Parallel groups

Sample size: 283/300

Primary endpoint: not defined

FU duration: 5 year

Total Mortality 0.45 [0.22; 0.92]

Cardiovascular mortality 0.54 [0.20; 1.43]

Congestive heart failure 0.98 [0.40; 2.43]

stroke 0.98 [0.40; 2.43]

MI 1.12 [0.56; 2.25]

Major CV events 0.91 [0.60; 1.37]

non cardiovascular mortality 0.36 [0.12; 1.11]

stroke 0.32 [0.10; 0.95]

Total Mortality 0.92 [0.50; 1.70]

Cardiovascular mortality 1.48 [0.65; 3.40]

Congestive heart failure 1.12 [0.50; 2.49]

MI 1.30 [0.68; 2.50]

Major CV events 0.97 [0.64; 1.47]

non cardiovascular mortality 0.47 [0.16; 1.32]

intensive treatment with a diastolic blood pressure goal of 75 mmHg (n=237)

vs.

moderate treatment with a diastolic blood pressure goal of 80-89 mmHg (n=233)

factorial design: nisoldipine or enalapril as the initial antihypertensive

open

Parallel groups

Sample size: 237/233

Primary endpoint:

FU duration: 5 year

intensive treatment (diastolic blood pressure decrease of 10 mmHg below baseline DBP) (n=237)

vs.

moderate treatment (diastolic blood pressure goal of 80-89 mmHg) (n=243)

patients randomized to intensive therapy received either nisoldipine or enalapril in a blinded manner as the initial antihypertensive medication

open

Parallel groups

Sample size: 237/243

Primary endpoint:

FU duration:

microvascular events 0.30 [0.14; 0.64]

microvascular events 0.80 [0.66; 0.97]

All deaths 0.92 [0.69; 1.23]

Cardiovascular events 0.91 [0.72; 1.15]

irbesartan 150 mg daily (n=195)

vs.

placebo (n=201)

3 arms trial: irbesartan 150 and 300 mg daily, placebo

double-blind

Parallel groups

Sample size: 195/201

Primary endpoint: diabetic nephropathy

FU duration: 2 years

Irbesartan 300 mg daily (n=579)

vs.

placebo (n=569)

double blind

Parallel groups

Sample size: 579/569

Primary endpoint: renal death

FU duration: 2.6 years

microvascular events 0.77 [0.63; 0.94]

All deaths 1.04 [0.77; 1.40]

Cardiovascular events 1.03 [0.81; 1.31]

Irbesartan 300 mg daily (n=579)

vs.

amlodipine 10 mg daily (n=567)

double blind

Parallel groups

Sample size: 579/567

Primary endpoint: renal death

FU duration: 2.6 years

All deaths 0.99 [0.89; 1.10]

Stroke 1.06 [0.89; 1.26]

Fatal and nonfatal MI 1.03 [0.94; 1.13]

Cardiovascular events 1.07 [0.99; 1.15]

lisinopril 10 to 40 mg/d (n=2431)

vs.

chlorthalidone 12.5 to 25 mg/d (n=4498)

double-blind

Parallel groups

Sample size: 2431/4498

Primary endpoint: fatal CHD or nonfatal MI

FU duration: 4.9 y

microvascular events 0.79 [0.66; 0.95]

All deaths 1.02 [0.80; 1.30]

losartan 50 to 100 mg once daily (n=751)

vs.

placebo (n=762)

double-blind

Parallel groups

Sample size: 751/762

Primary endpoint: doubling of the creatinine, end-stage renal disease, death

FU duration: 3.4 y

All deaths 0.61 [0.45; 0.83]

Cardiovascular death 0.65 [0.44; 0.96]

Cardiovascular events 0.76 [0.58; 0.99]

Stroke 0.82 [0.58; 1.16]

Fatal and nonfatal MI 0.85 [0.57; 1.27]

losartan 50mg daily at step 1 (n=586)

vs.

atenolol 50mg daily at step 1 (n=609)

of all 9193 patients included in the trial, 1195 had diabetes

double-blind

Parallel groups

Sample size: 586/609

Primary endpoint: CV events

FU duration: 4.7 years

All deaths 0.81 [0.57; 1.15]

Fatal and nonfatal MI 1.30 [0.69; 2.46]

metoprolol CR/XL (n=495)

vs.

placebo (n=490)

double-blind

Parallel groups

Sample size: 495/490

Primary endpoint: all-cause death

FU duration: 1y

Cardiovascular death 0.30 [0.11; 0.80]

Stroke 0.32 [0.12; 0.86]

Cardiovascular events 0.38 [0.19; 0.76]

All deaths 0.59 [0.31; 1.11]

Fatal and nonfatal MI 0.44 [0.18; 1.07]

Calcium-channel blocker (n=252)

vs.

placebo (n=240)

of all 4695 patients included in the study, 492 had diabetes

double blind

Parallel groups

Sample size: 252/240

Primary endpoint: persisting neurologic deficit

FU duration: 2 years

All deaths 0.75 [0.52; 1.09]

Cardiovascular death 1.01 [0.54; 1.88]

Stroke 0.90 [0.47; 1.72]

Fatal and nonfatal MI 1.13 [0.66; 1.91]

Cardiovascular events 0.99 [0.69; 1.42]

Nifedipine GITS 30 mg daily (n=649)

vs.

co-amilozide hydrochlorothiazide 25 mg plus amiloride 2.5 mg (n=653)

double-blind

Parallel groups

Sample size: 649/653

Primary endpoint: CV events

FU duration: 4 y

Fatal and nonfatal MI 5.00 [1.95; 12.84]

Cardiovascular events 0.43 [0.25; 0.73]

All deaths 0.77 [0.36; 1.65]

Cardiovascular death 2.00 [0.69; 5.76]

Stroke 1.57 [0.62; 3.98]

nisoldipine (long acting) (n=235)

vs.

enalapril (n=235)

Double blind

Factorial plan

Sample size: 235/235

Primary endpoint: 24-hour creatinine clearance

FU duration: 5 y

onset of microalbuminuria 0.77 [0.63; 0.94]

CV death 4.96 [1.44; 17.12]

all cause death 1.72 [0.91; 3.24]

non fatal stroke 1.74 [0.73; 4.13]

non fatal MI 0.65 [0.35; 1.19]

CV events 0.88 [0.63; 1.23]

all cause death 0.96 [0.52; 1.75]

CV death 3.36 [0.93; 12.07]

non fatal stroke 0.73 [0.30; 1.79]

non fatal MI 0.43 [0.11; 1.65]

olmesartan at 40 mg/day (n=2232)

vs.

placebo (n=2215)

double-blind

Parallel groups

Sample size: 2232/2215

Primary endpoint: microalbuminuria

FU duration: 3.2 y

olmesartan (n=282)

vs.

placebo (n=284)

double-blind

Parallel groups

Sample size: 282/284

Primary endpoint:

FU duration:

All deaths 1.04 [0.90; 1.20]

Cardiovascular death 1.07 [0.85; 1.35]

non fatal stroke 1.07 [0.80; 1.44]

non fatal MI 0.89 [0.62; 1.29]

Stroke 1.03 [0.80; 1.32]

Fatal and nonfatal MI 0.79 [0.57; 1.10]

Cardiovascular events 0.97 [0.85; 1.11]

All deaths 0.98 [0.60; 1.60]

Cardiovascular death 1.21 [0.52; 2.80]

Stroke 0.50 [0.15; 1.67]

Fatal and nonfatal MI 1.28 [0.58; 2.82]

Cardiovascular events 0.94 [0.56; 1.58]

ramipril 1.25 mg/day (n=2443)

vs.

placebo (n=2469)

double-blind

Parallel groups

Sample size: 2443/2469

Primary endpoint: cardiovascular death, non-fatal MI, stroke, HF, end-stage renal failure

FU duration: median 4 years

conducted mostly by general practitioners in 16 countries

ramipril(up to 15 mg per day) (n=2623)

vs.

placebo (n=2646)

factorial design with 2nd randomization between rosiglytazone vs placebo

open

Factorial plan

Sample size: 2623/2646

Primary endpoint: development of diabetes or death

FU duration: 3 years

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

death 0.00 [0.00; NaN]

Any serious adverse event 0.95 [0.58; 1.58]

Any adverse event 0.99 [0.89; 1.11]

Discontinuation due to adverse event 0.89 [0.47; 1.67]

aliskiren (150 mg daily for 3 months, followed by an increase in dosage to 300 mg daily for another 3 months (n=301)

vs.

placebo (n=298)

double blind

Parallel groups

Sample size: 301/298

Primary endpoint: ratio of albumin to creatinine

FU duration: 6 months

death NaN [NaN; NaN]

Any serious adverse event 0.76 [0.34; 1.68]

Any adverse event 1.10 [0.90; 1.33]

Discontinuation due to adverse event 0.39 [0.13; 1.23]

aliskiren 300 mg (n=154)

vs.

losartan 100 mg (n=152)

3rd arms with combination

open

Parallel groups

Sample size: 154/152

Primary endpoint: LV mass index

FU duration: 9 months

aliskiren 150 mg (up to 300mg) daily (n=-9)

vs.

ramipril 5 mg (up to 10mg) daily (n=-9)

Dose titration (to aliskiren 300 mg/ramipril 10 mg) and subsequent hydrochlorothiazide addition (12.5 mg, titrated to 25 mg if required) were permitted at weeks 6, 12, 18 and 21 for inadequate blood pressure control

double blind

Parallel groups

Sample size: -9/-9

Primary endpoint: BP change

FU duration: 26 weeks

Any serious adverse event 1.17 [0.67; 2.03]

Any adverse event 1.06 [0.97; 1.16]

Discontinuation due to adverse event 0.70 [0.44; 1.11]

aliskiren 300 mg (n=567)

vs.

hydrochlorothiazide 25 mg (n=557)

double blind

Parallel groups

Sample size: 567/557

Primary endpoint: BP reduction

FU duration: 20 weeks

All deaths 0.88 [0.66; 1.18]

Cardiovascular events 0.88 [0.69; 1.12]

microvascular events 1.04 [0.86; 1.25]

all cause death 0.90 [0.68; 1.18]

all cause mortality 0.78 [0.42; 1.45]

cardiovascular event 0.62 [0.37; 1.03]

Amlodipine 10 mg daily (n=567)

vs.

placebo (n=569)

double-blind

Parallel groups

Sample size: 567/569

Primary endpoint: renal death

FU duration: 2.6 years

Amlodipine 10mg/d (n=567)

vs.

placebo (n=569)

Double blind

Parallel groups

Sample size: 567/569

Primary endpoint:

FU duration: 2·6

Amlodipine 10 mg/day (n=123)

vs.

matched placebo (n=128)

double blind

Sample size: 123/128

Primary endpoint:

FU duration: 19 montsh median (8-30)

Cardiovascular events 0.49 [0.26; 0.93]

All deaths 0.81 [0.22; 2.99]

Stroke 2.47 [0.79; 7.75]

Fatal and nonfatal MI 1.29 [0.58; 2.86]

stroke (fatal & non fatal) 0.83 [0.72; 0.94]

all cause death 0.96 [0.89; 1.03]

coronary heart disease 1.00 [0.91; 1.10]

cardiovascular death 0.97 [0.87; 1.09]

fatal MI 1.07 [0.86; 1.33]

Coronary revascularization 1.01 [0.92; 1.12]

fatal stroke 0.79 [0.60; 1.03]

Major cardiovascular events 0.97 [0.92; 1.02]

Angina 0.93 [0.86; 1.01]

Peripheral arterial disease 0.85 [0.73; 1.00]

End stage renal disease 1.02 [0.80; 1.31]

amlodipine (long acting) 10 mg daily (n=191)

vs.

fosinopril 20 mg daily (n=189)

if blood pressure was not controlled, the other study drug was added

open

Parallel groups

Sample size: 191/189

Primary endpoint: not defined

FU duration: 3.5 y

Amlodipine 2.5 to 10g/d , Amlodipine 2.5 to 10g/d , Amlodipine 2.5 to 10g/d (n=9048)

vs.

lisinopril 10 to 40 mg/d (n=9054)

Double aveugle

Parallel groups

Sample size: 9048/9054

Primary endpoint: fatal CHD or nonfatal myocardial infarction

FU duration: 4.9y

all cause death 0.90 [0.82; 0.99]

cardiovascular death 0.77 [0.66; 0.90]

stroke (fatal & non fatal) 0.77 [0.67; 0.89]

Major cardiovascular events 0.85 [0.77; 0.93]

coronary heart disease 0.90 [0.79; 1.03]

heart failure 0.84 [0.67; 1.06]

all cause death 0.70 [0.38; 1.28]

amlodipine5–10 mg adding perindopril 4–8 mg as required (n=9639)

vs.

atenolol 50–100 mg adding bendroflumethiazide 1·25–2·5 mg and potassium as required (n=9618)

open

Parallel groups

Sample size: 9639/9618

Primary endpoint: non-fatal myocardial infarction and fatal CHD

FU duration: 5.5 y

Amlodipine 5-10 mg/d (n=217)

vs.

metoprolol 50-200 mg/d (n=441)

compare the effects of 2 levels of blood pressure (BP) control and 3 antihypertensive drug classe

Sample size: 217/441

Primary endpoint: rate of change in GFR (GFR slope)

FU duration: 3·0y

heart failure 1.37 [1.24; 1.51]

Coronary revascularization 1.10 [1.00; 1.20]

all cause death 0.96 [0.90; 1.03]

coronary heart disease 0.99 [0.91; 1.07]

cardiovascular death 1.01 [0.91; 1.11]

fatal MI 0.95 [0.79; 1.15]

fatal stroke 0.94 [0.73; 1.21]

stroke (fatal & non fatal) 0.94 [0.83; 1.07]

Major cardiovascular events 1.04 [1.00; 1.09]

Angina 0.99 [0.90; 1.08]

Peripheral arterial disease 0.88 [0.76; 1.01]

End stage renal disease 1.13 [0.90; 1.41]

coronary heart disease 0.79 [0.63; 0.99]

Major cardiovascular events 0.82 [0.73; 0.91]

all cause death 0.90 [0.76; 1.07]

cardiovascular death 0.80 [0.62; 1.03]

Coronary revascularization 0.87 [0.75; 1.00]

stroke (fatal & non fatal) 0.84 [0.66; 1.08]

All deaths 0.96 [0.87; 1.06]

Stroke 0.89 [0.74; 1.07]

Fatal and nonfatal MI 1.02 [0.93; 1.12]

Cardiovascular events 1.06 [0.98; 1.14]

Amlodipine 2.5 to 10g/d , Amlodipine 2.5 to 10g/d , Amlodipine 2.5 to 10g/d , Amlodipine 2.5 to 10g/d (n=9048)

vs.

chlorthalidone 12.5 to 25 mg/d (n=15255)

Double aveugle

Sample size: 9048/15255

Primary endpoint: fatal CHD or nonfatal myocardial infarction

FU duration: 4.9y

benazepril 40mg plus amlodipine 5mg daily (n=5744)

vs.

benazepril 40mg plus hydrochlorothiazide 12.5mg daily (n=5762)

double blind

Parallel groups

Sample size: 5744/5762

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

FU duration: 36 months

amlodipine (n=2664)

vs.

chlorthalidone (n=4498)

double-blind

Parallel groups

Sample size: 2664/4498

Primary endpoint: fatal CHD or nonfatal MI

FU duration: 4.9 y

cardiovascular events 0.82 [0.67; 0.99]

all cause death 0.93 [0.75; 1.15]

cardiovascular death 0.92 [0.69; 1.23]

stroke (fatal & non fatal) 0.76 [0.53; 1.08]

Myocardial infarction (fatal & non fatal) 0.87 [0.69; 1.09]

stroke (fatal & non fatal) 0.57 [0.34; 0.96]

all cause death 0.97 [0.70; 1.33]

cardiovascular death 0.78 [0.51; 1.17]

heart failure 0.68 [0.41; 1.13]

Myocardial infarction (fatal & non fatal) 1.02 [0.66; 1.59]

all cause death 1.06 [0.90; 1.27]

cardiovascular death 1.06 [0.84; 1.34]

stroke (fatal & non fatal) 0.84 [0.62; 1.14]

Myocardial infarction (fatal & non fatal) 1.01 [0.78; 1.31]

cardiovascular events 0.98 [0.82; 1.18]

cardiovascular death 0.48 [0.33; 0.68]

all cause death 1.12 [0.79; 1.57]

stroke (fatal & non fatal) 0.85 [0.60; 1.21]

Myocardial infarction (fatal & non fatal) 1.14 [0.75; 1.72]

cardiovascular events 1.03 [0.79; 1.35]

all cause death 0.80 [0.56; 1.12]

cardiovascular death 0.82 [0.53; 1.26]

stroke (fatal & non fatal) 1.01 [0.77; 1.33]

Myocardial infarction (fatal & non fatal) 0.75 [0.47; 1.20]

cardiovascular events 0.99 [0.77; 1.26]

All cause death NaN [NaN; NaN]

coronary death NaN [NaN; NaN]

coronary event NaN [NaN; NaN]

cardiovascular death NaN [NaN; NaN]

Heart failure NaN [NaN; NaN]

fatla stroke NaN [NaN; NaN]

Stroke 0.00 [0.00; NaN]

cardiovascular event 0.00 [0.00; NaN]

Propranolol (n=4403)

vs.

Placebo (n=8654)

double blind

Parallel groups

Sample size: 4403/8654

Primary endpoint:

FU duration: 5.5y

atenolol and bendrofluazide , Atenolol (n=419)

vs.

Open control (n=465)

open

Parallel groups

Sample size: 419/465

Primary endpoint:

FU duration: 4·4y

Atenolol (n=1102)

vs.

Placebo (n=2213)

double blind

Sample size: 1102/2213

Primary endpoint:

FU duration: 5.8y

Atenolol 50mg/d (n=732)

vs.

Placebo (n=741)

double blind

Sample size: 732/741

Primary endpoint:

FU duration: 2·6y

Atenolol (n=372)

vs.

Placebo (n=348)

Sample size: 372/348

Primary endpoint:

FU duration: 2·6y

atenolol and bendrofluazide (n=3)

vs.

control (n=4)

double-blind

Sample size: 3/4

Primary endpoint:

FU duration: 3·8y

Myocardial infarction (fatal & non fatal) 1.63 [1.15; 2.32]

all cause death 1.22 [0.99; 1.51]

cardiovascular death 0.92 [0.66; 1.29]

stroke (fatal & non fatal) 1.22 [0.83; 1.79]

cardiovascular events 1.02 [0.81; 1.28]

cardiovascular death 1.41 [1.04; 1.91]

Myocardial infarction (fatal & non fatal) 6.96 [4.90; 9.90]

cardiovascular events 1.38 [1.10; 1.75]

all cause death 1.22 [0.99; 1.51]

stroke (fatal & non fatal) 1.22 [0.83; 1.79]

Propranolol (n=4403)

vs.

Bendroflumethiazide. (n=4297)

double blind

Parallel groups

Sample size: 4403/4297

Primary endpoint:

FU duration: 5·5y

Atenolol (n=1102)

vs.

Hydrochlorothiazide/amiloride (n=1081)

double blind

Sample size: 1102/1081

Primary endpoint:

FU duration: 5·8y

hypertension 0.84 [0.75; 0.95]

cancer 1.32 [0.30; 5.84]

death cancer ∞ [NaN; ∞]

lung cancer 1.00 [0.14; 7.08]

Serious adverse events 0.60 [0.31; 1.15]

cardiovascular events 0.16 [0.02; 1.36]

candesartan during 2y followed by 2y of placebo (n=409)

vs.

placebo (n=400)

double-blind

Parallel groups

Sample size: 409/400

Primary endpoint: new-onset hypertension

FU duration: 4y

cardiovascular death 0.74 [0.39; 1.42]

All-cause death 1.02 [0.60; 1.72]

Coronary event 0.94 [0.31; 2.87]

Cardiovascular death 0.74 [0.39; 1.42]

Heart failure 0.00 [0.00; NaN]

Stroke 0.83 [0.55; 1.24]

cardiovascular event 0.73 [0.51; 1.03]

cardiovascular death 0.95 [0.76; 1.18]

all cause death 0.97 [0.82; 1.14]

coronary event 1.10 [0.79; 1.54]

Cardiovascular death 0.95 [0.76; 1.18]

cancer 1.08 [0.89; 1.31]

stroke (fatal and non fatal) 0.77 [0.59; 1.01]

Myocardial infarction ( fatal and non fatal) 1.10 [0.79; 1.54]

cardiac death 0.99 [0.52; 1.90]

cardiovascular event 0.90 [0.76; 1.06]

New onset diabetes 0.80 [0.63; 1.03]

cardiovascular event 0.35 [0.17; 0.76]

all cause mortality 0.00 [0.00; NaN]

cardiovascular event 0.58 [0.40; 0.83]

all cause mortality 0.66 [0.41; 1.04]

Cardiovascular mortality 0.60 [0.30; 1.19]

stroke (fatal and non fatal) 0.58 [0.41; 0.82]

Myocardial infarction ( fatal and non fatal) 0.41 [0.20; 0.86]

all cause death 0.94 [0.24; 3.77]

Cardiovascular death ∞ [NaN; ∞]

Heart failure 0.81 [0.52; 1.26]

all cause death 1.04 [0.27; 4.01]

Cardiovascular death 1.04 [0.27; 4.01]

Heart failure 0.68 [0.34; 1.34]

stroke (fatal and non fatal) 0.89 [0.51; 1.55]

Myocardial infarction ( fatal and non fatal) 2.09 [0.39; 11.03]

New onset diabetes 0.39 [0.16; 0.93]

all cause death 1.17 [0.84; 1.64]

Cardiovascular death 1.12 [0.66; 1.91]

Heart failure 0.91 [0.60; 1.38]

stroke (fatal and non fatal) 0.92 [0.62; 1.36]

Myocardial infarction ( fatal and non fatal) 1.12 [0.66; 1.88]

all cause death 0.00 [0.00; NaN]

Heart failure 0.39 [0.15; 1.02]

deserpidine 1mg/d + methylclothiazide 10mg/d (n=233)

vs.

placebo (n=219)

Double blind

Parallel groups

Sample size: 233/219

Primary endpoint:

FU duration: 2.3y

candesartan, 8–16 mg once daily (target 160/90) (n=2477)

vs.

placebo (n=2460)

double-blind

Parallel groups

Sample size: 2477/2460

Primary endpoint: major cardiovascular events

FU duration: 3.7 y (mean)

Candesartan 4-8mg/day (n=43)

vs.

Conventional treatment (n=37)

open

Sample size: 43/37

Primary endpoint:

FU duration:

Candesartan 12 mg/day, losartan 100 mg/day, or valsartan 160 mg/day (n=180)

vs.

Conventional treatment (n=180)

open

Sample size: 180/180

Primary endpoint:

FU duration: 1-5 years

candesartan, 2 to 12 mg daily (n=1053)

vs.

conventional antihypertensive drugs other than angiotensin converting enzyme inhibitors or ARBs (n=995)

single-blind

Parallel groups

Sample size: 1053/995

Primary endpoint: CV hospitalization

FU duration:

candesartan (n=69)

vs.

conventional treatment (n=72)

open

Parallel groups

Sample size: 69/72

Primary endpoint: cardiovascular event

FU duration:

angiotensin II receptor blocker-based therapy (n=1024)

vs.

non-angiotensin II receptor blocker-based therapy (n=1025)

open

Parallel groups

Sample size: 1024/1025

Primary endpoint: CV events

FU duration: 4.2 y (median)

candesartan (n=43)

vs.

control (n=37)

open

Parallel groups

Sample size: 43/37

Primary endpoint: cardiovascular events

FU duration: 19.4 months

New onset diabetes 0.64 [0.42; 0.96]

all cause death 0.85 [0.62; 1.15]

Heart failure 1.25 [0.65; 2.40]

stroke (fatal and non fatal) 1.27 [0.87; 1.86]

Myocardial infarction ( fatal and non fatal) 0.94 [0.49; 1.82]

candesartan-based regimen (n=2354)

vs.

amlodipine-based regimen (n=2349)

open (blinded assessment)

Parallel groups

Sample size: 2354/2349

Primary endpoint:

FU duration: 3.2 years

New onset diabetes 0.12 [0.02; 0.99]

cardiovascular death NaN [NaN; NaN]

all cause death NaN [NaN; NaN]

coronary event 0.99 [0.06; 15.80]

Cardiovascular death NaN [NaN; NaN]

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

Myocardial infarction ( fatal and non fatal) 0.99 [0.06; 15.80]

cardiovascular event 0.99 [0.06; 15.80]

candesartan (n=197)

vs.

hydrochlorothiazide (n=196)

double-blind

Parallel groups

Sample size: 197/196

Primary endpoint: diabetes

FU duration: 1 year

Stroke 0.58 [0.37; 0.90]

microvascular events 0.65 [0.46; 0.91]

All deaths 0.83 [0.65; 1.06]

Fatal and nonfatal MI 0.80 [0.60; 1.05]

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) (n=758)

vs.

less tight control aiming at a blood pressure of <180/105 (avoiding treatment with ACE inhibitors or beta-blockers) (n=390)

open

Parallel groups

Sample size: 758/390

Primary endpoint: not unique (3)

FU duration: 8.4y (median)

All deaths 1.14 [0.83; 1.55]

Stroke 1.38 [0.74; 2.57]

Fatal and nonfatal MI 1.19 [0.83; 1.69]

microvascular events 1.28 [0.81; 2.03]

captopril 25 mg/d aiming at a BP <150/85 (n=400)

vs.

atenolol 50mg/d aiming at a BP <150/85 (n=358)

open

Parallel groups

Sample size: 400/358

Primary endpoint: not unique (3)

FU duration: ND

All deaths 0.54 [0.31; 0.95]

Cardiovascular events 0.59 [0.38; 0.91]

Fatal and nonfatal MI 0.38 [0.20; 0.73]

Cardiovascular death 0.48 [0.21; 1.10]

Stroke 1.03 [0.57; 1.85]

Captopril initial dose of 50 mg daily given in one or two doses (n=309)

vs.

thiazide diuretic or beta-blocker (n=263)

open with blinded assessment

Parallel groups

Sample size: 309/263

Primary endpoint: CV events

FU duration: 6.1 year

microvascular disease 1.28 [0.81; 2.03]

all cause death 1.14 [0.83; 1.55]

coronary heart disease 1.19 [0.83; 1.69]

cardiovascular death 1.34 [0.88; 2.05]

fatal MI 1.31 [0.79; 2.15]

heart failure 1.19 [0.51; 2.80]

fatal stroke 0.72 [0.19; 2.65]

stroke (fatal & non fatal) 1.11 [0.59; 2.06]

Peripheral arterial disease 1.49 [0.36; 6.20]

end stage renal disease 0.90 [0.23; 3.55]

stroke (fatal & non fatal) 1.28 [1.03; 1.58]

all cause death 0.97 [0.79; 1.18]

coronary heart disease 0.96 [0.78; 1.18]

cardiovascular death 0.80 [0.59; 1.08]

heart failure 1.14 [0.82; 1.58]

Major cardiovascular events 1.08 [0.94; 1.24]

captopril started at 25mg twice daily up to 50 mg twice dialy (target blood pressure of <150/<85 mmHG) (n=400)

vs.

atenolol started at 50mg daily up to 100mg if required(target blood pressure of <150/<85 mmHG) (n=358)

Open

Parallel groups

Sample size: 400/358

Primary endpoint:

FU duration: 8·4 y

captopril 50mg/d (n=5492)

vs.

beta-blocker (not specified) or diuretic (not specified) (n=5493)

Open

Parallel groups

Sample size: 5492/5493

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

FU duration: 6.1 y

Cardiovascular mortality 0.43 [0.28; 0.67]

cardiovascular event 0.42 [0.27; 0.65]

Carvedilol 50 mg/day (n=58)

vs.

matched placebo (n=56)

Sample size: 58/56

Primary endpoint:

FU duration: 12 months

Carvedilol 20 mg/day (n=57)

vs.

matched placebo (n=51)

Sample size: 57/51

Primary endpoint:

FU duration:

cardiovascular death ∞ [NaN; ∞]

All-cause death ∞ [NaN; ∞]

Coronary event 1.59 [0.52; 4.82]

Cardiovascular death ∞ [NaN; ∞]

Heart failure 1.59 [0.52; 4.82]

Stroke NaN [NaN; NaN]

cardiovascular event 1.59 [0.52; 4.82]

cardiovascular event 0.70 [0.61; 0.80]

Coronary event 0.74 [0.58; 0.95]

Heart failure 0.52 [0.38; 0.71]

Stroke 0.65 [0.51; 0.83]

cardiovascular death 0.81 [0.61; 1.06]

All-cause death 0.88 [0.74; 1.05]

Cardiovascular death 0.81 [0.61; 1.06]

cardiovascular death 0.68 [0.25; 1.85]

cardiovascular event 0.65 [0.35; 1.22]

Cardiovascular events 0.66 [0.46; 0.94]

Fatal and nonfatal MI 0.56 [0.32; 0.97]

All deaths 0.74 [0.46; 1.19]

Stroke 0.74 [0.45; 1.19]

Stroke 0.21 [0.05; 0.96]

All cause death ∞ [NaN; ∞]

coronary death ∞ [NaN; ∞]

coronary event ∞ [NaN; ∞]

cardiovascular death ∞ [NaN; ∞]

Heart failure ∞ [NaN; ∞]

fatla stroke NaN [NaN; NaN]

cardiovascular event 0.64 [0.20; 2.10]

Heart failure 0.35 [0.18; 0.67]

Stroke 0.53 [0.32; 0.89]

cardiovascular event 0.67 [0.47; 0.94]

All cause death 0.93 [0.67; 1.30]

coronary death 0.75 [0.38; 1.48]

coronary event 0.70 [0.40; 1.25]

cardiovascular death 0.83 [0.50; 1.39]

fatla stroke 0.72 [0.16; 3.20]

chlorthalidone 50mg/d (n=508)

vs.

placebo (n=504)

Double aveugle

Sample size: 508/504

Primary endpoint:

FU duration: 1.4 y

chlorthalidone, 12.5 mg/d , chlorthalidone, 12.5 mg/d , chlorthalidone, 12.5 mg/d (n=2365)

vs.

placebo (n=2371)

Double blind

Sample size: 2365/2371

Primary endpoint:

FU duration: 4.4 y

chlorthalidone (n=443)

vs.

placebo (n=108)

double blind

Sample size: 443/108

Primary endpoint:

FU duration: 2.8y

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 (n=283)

vs.

placebo (n=300)

double-blind

Parallel groups

Sample size: 283/300

Primary endpoint: not defined

FU duration: 5 year

chlorthalidone (n=70)

vs.

placebo (n=15)

double-blind

Sample size: 70/15

Primary endpoint:

FU duration: 2·8y

chlorthalidone, 12.5 mg/d for step 1 (n=331)

vs.

placebo (n=319)

double blind

Sample size: 331/319

Primary endpoint: Nonfatal and fatal (total) stroke

FU duration: 4·2y

non fatal stroke 0.80 [0.64; 1.00]

all cause death 1.02 [0.86; 1.23]

coronary heart disease 1.14 [0.95; 1.37]

cardiovascular death 1.15 [0.90; 1.48]

fatal MI 1.13 [0.66; 1.94]

heart failure 1.18 [0.82; 1.69]

fatal stroke 0.97 [0.53; 1.75]

non fatal MI 1.19 [0.94; 1.49]

stroke (fatal & non fatal) 0.82 [0.67; 1.01]

Major cardiovascular events 1.04 [0.92; 1.18]

Diabetes onset 0.87 [0.73; 1.04]

diltiazem 180-360 daily (n=5410)

vs.

beta-blocker (not specified) or diuretic (not specified) (n=5471)

Open

Parallel groups

Sample size: 5410/5471

Primary endpoint: Stroke, MI, all CV deaths

FU duration: up to 5 years

coronary heart disease 0.35 [0.19; 0.66]

Major cardiovascular events 0.60 [0.39; 0.92]

all cause death 0.78 [0.40; 1.53]

cardiovascular death 0.55 [0.21; 1.45]

heart failure 1.25 [0.50; 3.11]

stroke (fatal & non fatal) 0.64 [0.25; 1.61]

enalapril (n=235)

vs.

nisoldipine (n=235)

double blind

Sample size: 235/235

Primary endpoint: complications of diabetes

FU duration: 5·3 y

all cause death 0.93 [0.77; 1.12]

coronary heart disease 0.89 [0.73; 1.08]

heart failure 0.88 [0.64; 1.22]

stroke (fatal & non fatal) 1.05 [0.81; 1.36]

Major cardiovascular events 0.92 [0.83; 1.03]

enalapril (n=3044)

vs.

hydrochlorothiazide (n=3039)

The ACE inhibitor enalapril and the diuretic hydrochlorothiazide were recommended as initial therapy; however, the choice of the specific agent and dose was made by the family practitioner

open

Parallel groups

Sample size: 3044/3039

Primary endpoint: all cardiovascular events or death from any cause

FU duration: 4.1 y

all cause mortality 1.09 [0.78; 1.52]

Cardiovascular mortality 1.06 [0.67; 1.68]

cardiovascular event 1.15 [0.86; 1.53]

Fosinopril 20 mg/day (n=196)

vs.

matched placebo (n=201)

double blind

Sample size: 196/201

Primary endpoint:

FU duration: 24 months

cardiovascular death 1.07 [0.23; 5.02]

cardiovascular event 0.47 [0.16; 1.43]

cardiovascular death 0.73 [0.55; 0.97]

cardiovascular event 0.73 [0.55; 0.97]

All cause death 1.17 [0.99; 1.40]

coronary death 1.37 [0.56; 3.35]

cardiovascular death 1.21 [0.85; 1.73]

fatla stroke 1.48 [0.65; 3.38]

hydrochlorothiazide + triamterene (n=44)

vs.

placebo (n=47)

double blind

Sample size: 44/47

Primary endpoint:

FU duration: 4.0y

hydrochlorothiazide + triamterene , hydrochlorothiazide + triamterene (n=416)

vs.

placebo (n=424)

Double blind

Sample size: 416/424

Primary endpoint:

FU duration: 4.3 y

hydrochlorothiazide + triamterene (n=70)

vs.

placebo (n=85)

double-blind

Sample size: 70/85

Primary endpoint:

FU duration: 3·1y

bendroflumethiazide (n=426)

vs.

no treatment (n=426)

Open

Parallel groups

Sample size: 426/426

Primary endpoint:

FU duration: 1.1y

Stroke 0.73 [0.60; 0.89]

cardiovascular event 1.27 [1.06; 1.53]

fatal stroke 0.78 [0.56; 1.09]

coronary death 1.31 [0.64; 2.69]

cardiovascular death 0.86 [0.65; 1.14]

All-cause death 0.92 [0.74; 1.15]

Coronary event 1.19 [0.67; 2.12]

Cardiovascular death 0.86 [0.65; 1.14]

cardiovascular event 0.71 [0.57; 0.87]

All-cause death 0.82 [0.69; 0.99]

Heart failure 0.38 [0.23; 0.62]

fatal stroke 0.64 [0.39; 1.03]

coronary death 0.75 [0.45; 1.26]

cardiovascular death 0.81 [0.63; 1.05]

Coronary event 0.74 [0.31; 1.76]

Cardiovascular death 0.81 [0.63; 1.05]

Stroke 0.73 [0.51; 1.04]

indapamide 2.5 mg/d (n=2841)

vs.

placebo (n=2841)

Double blind

Parallel groups

Sample size: 2841/2841

Primary endpoint:

FU duration: 2y

indapamide sustained release 1.5 mg/d + perindopril 2-4mg/d to obtain SBP<150 and DBP<80 (n=1933)

vs.

placebo (n=1912)

Double blind

Parallel groups

Sample size: 1933/1912

Primary endpoint: fatal and non fatal stroke

FU duration: 1.8y (median)

cardiovascular death 1.06 [0.74; 1.52]

cardiovascular event 0.98 [0.81; 1.19]

diuretic (n=3272)

vs.

beta-blocker (n=3297)

open

Sample size: 3272/3297

Primary endpoint:

FU duration: 3.8y

Total Mortality 0.45 [0.22; 0.92]

Cardiovascular mortality 0.54 [0.20; 1.43]

Congestive heart failure 0.98 [0.40; 2.43]

stroke 0.98 [0.40; 2.43]

MI 1.12 [0.56; 2.25]

Major CV events 0.91 [0.60; 1.37]

non cardiovascular mortality 0.36 [0.12; 1.11]

stroke 0.32 [0.10; 0.95]

Total Mortality 0.92 [0.50; 1.70]

Cardiovascular mortality 1.48 [0.65; 3.40]

Congestive heart failure 1.12 [0.50; 2.49]

MI 1.30 [0.68; 2.50]

Major CV events 0.97 [0.64; 1.47]

non cardiovascular mortality 0.47 [0.16; 1.32]

intensive treatment with a diastolic blood pressure goal of 75 mmHg (n=237)

vs.

moderate treatment with a diastolic blood pressure goal of 80-89 mmHg (n=233)

factorial design: nisoldipine or enalapril as the initial antihypertensive

open

Parallel groups

Sample size: 237/233

Primary endpoint:

FU duration: 5 year

intensive treatment (diastolic blood pressure decrease of 10 mmHg below baseline DBP) (n=237)

vs.

moderate treatment (diastolic blood pressure goal of 80-89 mmHg) (n=243)

patients randomized to intensive therapy received either nisoldipine or enalapril in a blinded manner as the initial antihypertensive medication

open

Parallel groups

Sample size: 237/243

Primary endpoint:

FU duration:

microvascular events 0.30 [0.14; 0.64]

microvascular events 0.80 [0.66; 0.97]

All deaths 0.92 [0.69; 1.23]

Cardiovascular events 0.91 [0.72; 1.15]

all cause death 0.92 [0.70; 1.20]

coronary event 0.91 [0.72; 1.15]

Cardiovascular death 1.11 [0.76; 1.62]

Heart failure 0.82 [0.59; 1.13]

stroke (fatal and non fatal) 1.06 [0.63; 1.78]

Myocardial infarction ( fatal and non fatal) 0.94 [0.63; 1.40]

all cause death 1.13 [0.40; 3.20]

Myocardial infarction ( fatal and non fatal) 0.51 [0.15; 1.75]

irbesartan 150 mg daily (n=195)

vs.

placebo (n=201)

3 arms trial: irbesartan 150 and 300 mg daily, placebo

double-blind

Parallel groups

Sample size: 195/201

Primary endpoint: diabetic nephropathy

FU duration: 2 years

Irbesartan 300 mg daily (n=579)

vs.

placebo (n=569)

double blind

Parallel groups

Sample size: 579/569

Primary endpoint: renal death

FU duration: 2.6 years

Irbesartan 300mg/d (target 135/85) (n=579)

vs.

placebo (n=569)

double-blind

Parallel groups

Sample size: 579/569

Primary endpoint: doubling of the base-line serum creatinine concentration, end-stage renal disease, or death

FU duration: 2.6 y

irbesartan 150 mg daily or 300 mg daily (n=404)

vs.

placebo (n=207)

double-blind

Parallel groups

Sample size: 404/207

Primary endpoint: onset of diabetic nephropathy

FU duration: 2 years

microvascular events 0.77 [0.63; 0.94]

All deaths 1.04 [0.77; 1.40]

Cardiovascular events 1.03 [0.81; 1.31]

Irbesartan 300 mg daily (n=579)

vs.

amlodipine 10 mg daily (n=567)

double blind

Parallel groups

Sample size: 579/567

Primary endpoint: renal death

FU duration: 2.6 years

all cause death 0.89 [0.35; 2.28]

coronary heart disease 1.20 [0.37; 3.89]

heart failure ∞ [NaN; ∞]

non fatal MI 1.20 [0.37; 3.89]

stroke (fatal & non fatal) 2.00 [0.50; 7.93]

Major cardiovascular events 1.54 [0.73; 3.25]

isradipine 2.5-5.0 mg twice daily (n=442)

vs.

hydrochlorothiazide 12.5-25 mg Twice daily (n=441)

Sample size: 442/441

Primary endpoint: intimal-medial thickness

FU duration: 3y

Lacidipine (n=1177)

vs.

atenolol (n=1157)

Double blind

Parallel groups

Sample size: 1177/1157

Primary endpoint: intima-media thicknesses

FU duration: 4·0y

lacidipine 4 mg/d (n=-9)

vs.

chlorthalidone 12.5 mg/d (n=-9)

Sample size: -9/-9

Primary endpoint: cardiovascular and cerebrovascular events

FU duration: 3·6?y

heart failure 0.87 [0.78; 0.96]

stroke (fatal & non fatal) 1.21 [1.06; 1.38]

all cause death 1.05 [0.97; 1.12]

coronary heart disease 1.00 [0.91; 1.09]

cardiovascular death 1.03 [0.92; 1.15]

fatal MI 0.93 [0.75; 1.16]

fatal stroke 1.27 [0.97; 1.67]

Major cardiovascular events 1.03 [0.99; 1.08]

end stage renal disease 0.98 [0.76; 1.25]

non cardiovascular death 1.08 [0.97; 1.21]

Lisinopril 10 to 40 mg/d (n=9054)

vs.

amlodipine 2.5 to 10 mg/d (n=9048)

Double blind

Parallel groups

Sample size: 9054/9048

Primary endpoint: fatal CHD or nonfatal myocardial infarction

FU duration: 4.9 y

heart failure 1.19 [1.07; 1.31]

stroke (fatal & non fatal) 1.14 [1.02; 1.28]

Major cardiovascular events 1.07 [1.03; 1.12]

all cause death 1.00 [0.94; 1.07]

coronary heart disease 0.98 [0.91; 1.07]

cardiovascular death 1.03 [0.94; 1.14]

fatal MI 0.89 [0.73; 1.08]

fatal stroke 1.20 [0.95; 1.52]

end stage renal disease 1.10 [0.88; 1.37]

non cardiovascular death 0.97 [0.88; 1.06]

All deaths 0.99 [0.89; 1.10]

Stroke 1.06 [0.89; 1.26]

Fatal and nonfatal MI 1.03 [0.94; 1.13]

Cardiovascular events 1.07 [0.99; 1.15]

lisinopril 10 to 40 mg/d (n=9054)

vs.

chlorthalidone 12.5 to 25 mg/d (n=15255)

Double blind

Parallel groups

Sample size: 9054/15255

Primary endpoint: fatal CHD or nonfatal myocardial infarction

FU duration: 4·9 y

lisinopril 10 to 40 mg/d (n=2431)

vs.

chlorthalidone 12.5 to 25 mg/d (n=4498)

double-blind

Parallel groups

Sample size: 2431/4498

Primary endpoint: fatal CHD or nonfatal MI

FU duration: 4.9 y

microvascular events 0.79 [0.66; 0.95]

All deaths 1.02 [0.80; 1.30]

losartan 50 to 100 mg once daily (n=751)

vs.

placebo (n=762)

double-blind

Parallel groups

Sample size: 751/762

Primary endpoint: doubling of the creatinine, end-stage renal disease, death

FU duration: 3.4 y

lLosartan 50 to 100 mg once daily (n=751)

vs.

placebo (n=762)

double-blind

Parallel groups

Sample size: 751/762

Primary endpoint: doubling of the base-line serum creatinine concentration, end-stage renal disease, or death

FU duration: 3.4 years

apparition d'un premier évènement cardiovasculaire 0.86 [0.77; 0.96]

PAS inférieure à 140 1.08 [1.03; 1.12]

PA inférieure à140/90 1.07 [1.02; 1.11]

stroke (fatal and non fatal) 0.75 [0.63; 0.88]

cardiovascular event 0.86 [0.77; 0.96]

New onset diabetes 0.75 [0.64; 0.89]

PAD inférieure à 90 0.98 [0.97; 1.00]

lung cancer 2.41 [1.23; 4.71]

cardiovascular death 0.87 [0.72; 1.04]

cancer occurence(prespecified endpoint) 1.11 [0.96; 1.29]

cancer occurence 1.11 [0.96; 1.29]

all cause death 0.89 [0.78; 1.01]

coronary event 1.05 [0.86; 1.28]

Cardiovascular death 0.87 [0.72; 1.04]

Heart failure 0.95 [0.76; 1.18]

cancer 1.11 [0.96; 1.29]

Myocardial infarction ( fatal and non fatal) 1.05 [0.86; 1.28]

cancer death 1.03 [0.80; 1.34]

All deaths 0.61 [0.45; 0.83]

Cardiovascular death 0.65 [0.44; 0.96]

Cardiovascular events 0.76 [0.58; 0.99]

Stroke 0.82 [0.58; 1.16]

Fatal and nonfatal MI 0.85 [0.57; 1.27]

losartan (n=4605)

vs.

atenolol (n=4588)

Double blind

Parallel groups

Sample size: 4605/4588

Primary endpoint: Cardiovascular mortality, stroke, and myocardial infarction

FU duration: 4.8 y (mean)

losartan 50mg daily at step 1 (n=586)

vs.

atenolol 50mg daily at step 1 (n=609)

of all 9193 patients included in the trial, 1195 had diabetes

double-blind

Parallel groups

Sample size: 586/609

Primary endpoint: CV events

FU duration: 4.7 years

all cause death 1.00 [0.14; 7.00]

coronary heart disease 1.00 [0.14; 7.00]

cardiovascular death ∞ [NaN; ∞]

fatal MI NaN [NaN; NaN]

heart failure 0.00 [0.00; NaN]

fatal stroke ∞ [NaN; ∞]

non fatal stroke 1.03 [0.39; 2.69]

non fatal MI 1.03 [0.15; 7.24]

stroke (fatal & non fatal) 0.75 [0.26; 2.12]

Major cardiovascular events 0.69 [0.30; 1.58]

Nicardipine SR 20mg twice daily (n=215)

vs.

trichlormethiazide 2mg once daily (n=214)

Double blind

Parallel groups

Sample size: 215/214

Primary endpoint: CV events

FU duration: 4.5 years

stroke (fatal & non fatal) 0.59 [0.41; 0.83]

Major cardiovascular events 0.71 [0.57; 0.87]

all cause death 0.86 [0.68; 1.09]

coronary heart disease 0.75 [0.50; 1.13]

cardiovascular death 0.73 [0.53; 1.03]

fatal MI 0.45 [0.18; 1.09]

heart failure 0.75 [0.50; 1.13]

fatal stroke 0.73 [0.38; 1.40]

Cardiovascular death 0.30 [0.11; 0.80]

Stroke 0.32 [0.12; 0.86]

Cardiovascular events 0.38 [0.19; 0.76]

All deaths 0.59 [0.31; 1.11]

Fatal and nonfatal MI 0.44 [0.18; 1.07]

All cause death 1.23 [0.91; 1.67]

coronary death 1.16 [0.54; 2.49]

coronary event 1.10 [0.56; 2.18]

cardiovascular death 1.08 [0.67; 1.74]

Heart failure 0.85 [0.42; 1.72]

fatla stroke 1.01 [0.42; 2.44]

Stroke 0.77 [0.42; 1.43]

cardiovascular event 0.95 [0.65; 1.41]

nitrendipine 10-40 mg daily , nitrendipine 10-40 mg daily (n=2398)

vs.

placebo (n=2297)

Double aveugle

Parallel groups

Sample size: 2398/2297

Primary endpoint:

FU duration: 2·6y

Calcium-channel blocker (n=252)

vs.

placebo (n=240)

of all 4695 patients included in the study, 492 had diabetes

double blind

Parallel groups

Sample size: 252/240

Primary endpoint: persisting neurologic deficit

FU duration: 2 years

nitrendipine 10-40 mg daily in first step (n=231)

vs.

placebo (n=210)

double blind

Sample size: 231/210

Primary endpoint:

FU duration: 2·9 y

all cause death 1.72 [1.20; 2.46]

heart failure 3.16 [1.41; 7.07]

Major cardiovascular events 1.73 [1.08; 2.77]

coronary heart disease 1.09 [0.42; 2.87]

stroke (fatal & non fatal) 1.40 [0.41; 4.76]

Nifedipine 20mg/d (n=146)

vs.

Clonidine 0.15mg/d (n=61) or atenolol 100mg/d + chlorthalidone 25mg/d (n=205)

Sample size: 146/205

Primary endpoint:

FU duration:

Diabetes onset 0.70 [0.54; 0.91]

fatal MI 3.21 [1.18; 8.74]

all cause death 1.03 [0.84; 1.26]

coronary heart disease 1.10 [0.83; 1.46]

cardiovascular death 1.17 [0.84; 1.63]

heart failure 1.75 [0.95; 3.24]

fatal stroke 1.09 [0.48; 2.47]

non fatal stroke 0.87 [0.61; 1.25]

non fatal MI 1.09 [0.76; 1.56]

stroke (fatal & non fatal) 0.94 [0.70; 1.28]

Major cardiovascular events 1.07 [0.89; 1.29]

All deaths 0.75 [0.52; 1.09]

Cardiovascular death 1.01 [0.54; 1.88]

Stroke 0.90 [0.47; 1.72]

Fatal and nonfatal MI 1.13 [0.66; 1.91]

Cardiovascular events 0.99 [0.69; 1.42]

nifedipine GITS 30mg/d (n=3157)

vs.

hydrochlorothiazide 25mg/d + amiloride 2.5mg/d (n=3164)

Double blind

Parallel groups

Sample size: 3157/3164

Primary endpoint: Total CV morbidity

FU duration: at least 3 years

Nifedipine GITS 30 mg daily (n=649)

vs.

co-amilozide hydrochlorothiazide 25 mg plus amiloride 2.5 mg (n=653)

double-blind

Parallel groups

Sample size: 649/653

Primary endpoint: CV events

FU duration: 4 y

Fatal and nonfatal MI 5.00 [1.95; 12.84]

Cardiovascular events 0.43 [0.25; 0.73]

All deaths 0.77 [0.36; 1.65]

Cardiovascular death 2.00 [0.69; 5.76]

Stroke 1.57 [0.62; 3.98]

nisoldipine (long acting) (n=235)

vs.

enalapril (n=235)

Double blind

Factorial plan

Sample size: 235/235

Primary endpoint: 24-hour creatinine clearance

FU duration: 5 y

all cause death 0.94 [0.73; 1.22]

stroke (fatal & non fatal) 0.97 [0.65; 1.47]

Myocardial infarction (fatal & non fatal) 0.92 [0.70; 1.21]

Oxprenolol (n=3185)

vs.

Placebo (n=3172)

Double blind

Parallel groups

Sample size: 3185/3172

Primary endpoint:

FU duration: 4·0y

all cause death 1.25 [0.36; 4.40]

Propranolol (n=-9)

vs.

Bendroflumethiazide. (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration: 10y

all cause mortality 1.00 [0.22; 4.56]

Cardiovascular mortality 1.00 [0.15; 6.64]

cardiovascular event 1.00 [0.32; 3.10]

Ramipril 5 mg/day (n=30)

vs.

Conventional treatment (n=30)

open

Sample size: 30/30

Primary endpoint:

FU duration: 12 months

all cause death 0.77 [0.48; 1.23]

ramipril 2.5-10 mg/d (n=436)

vs.

metoprolol 50-200 mg/d (n=441)

Double blind

Parallel groups

Sample size: 436/441

Primary endpoint: glomerular filtration rate (GFR) decline

FU duration: 4·1 y

all cause death 1.11 [0.59; 2.09]

cardiovascular death 0.50 [0.07; 3.51]

Major cardiovascular events 1.37 [0.44; 4.25]

ramipril 2.5-10 mg/d (n=436)

vs.

amlodipine 5-10 mg/d (n=217)

Double blind

Parallel groups

Sample size: 436/217

Primary endpoint: Rate of change in GFR

FU duration: 3·0 y

cardiovascular death 0.85 [0.71; 1.02]

cancer occurence 0.96 [0.83; 1.12]

all cause death 1.02 [0.93; 1.13]

Cardiovascular death 0.85 [0.71; 1.02]

cancer 0.96 [0.83; 1.12]

stroke (fatal and non fatal) 0.95 [0.87; 1.03]

Myocardial infarction ( fatal and non fatal) 1.00 [0.81; 1.23]

cardiovascular event 0.94 [0.88; 1.01]

New onset diabetes 0.83 [0.66; 1.05]

lung cancer 1.24 [0.77; 2.00]

all cause mortality 0.71 [0.53; 0.95]

Cardiovascular mortality 0.79 [0.61; 1.02]

cardiovascular event 0.79 [0.61; 1.02]

telmisartan 80 mg daily (n=10146)

vs.

placebo (n=10186)

double blind

Factorial plan

Sample size: 10146/10186

Primary endpoint: recurrent stroke

FU duration: 2.5 y

Telmisartan 80 mg/day (n=151)

vs.

matched placebo (n=152)

Sample size: 151/152

Primary endpoint:

FU duration:

Stroke 0.45 [0.21; 0.95]

cardiovascular death 0.44 [0.19; 1.01]

All-cause death 0.71 [0.43; 1.18]

Coronary event 0.99 [0.61; 1.60]

Cardiovascular death 0.44 [0.19; 1.01]

Heart failure 0.99 [0.61; 1.60]

cardiovascular event 0.84 [0.58; 1.22]

cardiovascular death 1.09 [0.37; 3.21]

All-cause death 1.04 [0.43; 2.52]

Coronary event 1.31 [0.59; 2.91]

Cardiovascular death 1.09 [0.37; 3.21]

Heart failure 0.00 [0.00; NaN]

Stroke 0.00 [0.00; NaN]

cardiovascular event 0.73 [0.37; 1.44]

cardiovascular event 0.80 [0.66; 0.97]

Stroke 0.33 [0.20; 0.55]

cardiovascular death 1.00 [0.75; 1.33]

All-cause death 1.02 [0.83; 1.26]

Coronary event 1.02 [0.82; 1.27]

cardiovascular event 0.54 [0.33; 0.89]

Stroke 0.47 [0.25; 0.89]

cardiovascular death 0.61 [0.31; 1.21]

All-cause death 0.58 [0.33; 1.01]

Coronary event 0.98 [0.14; 6.68]

Cardiovascular death 0.61 [0.31; 1.21]

Heart failure 0.74 [0.17; 3.12]

step 1:chlorothiazide 500 mg/d, step 2: chlorothoazide 500mg x2/d or methyldopa, propranolol, pindolol added, step 3: hydralazine or clonidine added (n=1721)

vs.

placebo (without adjustement according to the BP!) (n=1706)

Double blind

parallel group

Sample size: 1721/1706

Primary endpoint:

FU duration: 4 y

step 1: hydrochlorothiazide 50mg/d, step 2: alpha methyldopa 250-500mg x2/d or propranolol 40-160mg x2/d, (n=406)

vs.

no treatment (n=379)

Open

parallel group

Sample size: 406/379

Primary endpoint:

FU duration: 5.5 y

bendrofluazide 10 mg/d (step 2: methyldopa) (n=-9)

vs.

placebo (n=8654)

single blind

Parallel groups

Sample size: -9/8654

Primary endpoint:

FU duration: 4.9y

thiazide (n=50)

vs.

? (n=49)

Open

NA

Sample size: 50/49

Primary endpoint:

FU duration: 3.6 y

heart failure 0.80 [0.65; 0.98]

all cause death 1.05 [0.92; 1.19]

coronary heart disease 0.87 [0.73; 1.05]

cardiovascular death 1.06 [0.89; 1.27]

stroke (fatal & non fatal) 1.03 [0.86; 1.24]

Major cardiovascular events 0.94 [0.85; 1.04]

Enalapril or lisinopril , enalapril 10 mg or lisinopril 10 mg daily (n=2205)

vs.

felodipine 2.5 mg or isradipine 2-5 mg daily (n=2196)

Open

Parallel groups

Sample size: 2205/2196

Primary endpoint:

FU duration: 5·0 y

ACE inhibitor (n=-9)

vs.

nifedipine (n=-9)

Open

Parallel groups

Sample size: -9/-9

Primary endpoint:

FU duration: 3·0 y

heart failure 0.63 [0.52; 0.77]

all cause death 1.02 [0.77; 1.35]

coronary heart disease 0.90 [0.74; 1.09]

cardiovascular death 1.01 [0.72; 1.42]

stroke (fatal & non fatal) 0.90 [0.74; 1.09]

MI (all) 0.90 [0.74; 1.09]

Major cardiovascular events 0.94 [0.71; 1.24]

enalapril 10 mg or lisinopril10 mg daily (n=2205)

vs.

conventional antihypertensive drugs (atenolol 50 mg, metoprolol 100 mg, pindolol 5 mg, or hydrochlorothiazide 25 mg plus amiloride 2·5 mg daily) (n=2213)

Open

Parallel groups

Sample size: 2205/2213

Primary endpoint: fatal stroke, fatal MI, other cardiovascular death

FU duration: 5.0 y

cardiovascular death 0.42 [0.24; 0.73]

heart failure 0.49 [0.29; 0.84]

cardiovascular events 0.62 [0.45; 0.85]

active antihypertensive therapy (Thiazide and amiloride or beta-blocker) , Atenolol, Metoprolol, Pindolol, HCTZ/Ami (n=812)

vs.

Placebo (n=815)

Double blind

Sample size: 812/815

Primary endpoint:

FU duration: 2·1y

all cause death 0.94 [0.72; 1.24]

cardiovascular death 0.94 [0.66; 1.35]

heart failure 1.44 [0.84; 2.48]

stroke (fatal & non fatal) 0.77 [0.49; 1.23]

Myocardial infarction (fatal & non fatal) 1.13 [0.88; 1.44]

cardiovascular events 1.02 [0.84; 1.23]

all cause death 0.15 [0.02; 1.18]

stroke (fatal & non fatal) 0.56 [0.21; 1.48]

Myocardial infarction (fatal & non fatal) 1.20 [0.41; 3.48]

Atenolol, Metoprolol, Propranolol (n=3297)

vs.

Hydrochlorothiazide, Bendroflumethiazide (n=3272)

open

Sample size: 3297/3272

Primary endpoint:

FU duration: 3·8y

hypotensive drugs including beta-blockers (n=150)

vs.

same combination of drugs including diuretics (n=154)

Sample size: 150/154

Primary endpoint:

FU duration: 4·0y

cardiovascular event 0.08 [0.01; 0.60]

cardiovascular death 0.00 [0.00; NaN]

cardiovascular death 0.44 [0.20; 0.98]

cardiovascular event 0.38 [0.22; 0.65]

Cardiovascular death 0.44 [0.20; 0.98]

Stroke 0.26 [0.10; 0.68]

All-cause death 0.50 [0.24; 1.03]

Coronary event 0.88 [0.41; 1.92]

Heart failure 0.00 [0.00; NaN]

cardiovascular death 0.81 [0.67; 0.97]

cardiovascular event 0.78 [0.67; 0.91]

cardiovascular death 0.00 [0.00; NaN]

cardiovascular event 0.33 [0.04; 3.11]

High-dose diuretics (n=73)

vs.

Placebo (n=70)

Sample size: 73/70

Primary endpoint:

FU duration: 1.5y

High-dose diuretics (n=186)

vs.

Placebo (n=194)

Sample size: 186/194

Primary endpoint:

FU duration: 3.3y

High-dose diuretics (n=5485)

vs.

Usual careb (n=5455)

Sample size: 5485/5455

Primary endpoint:

FU duration: 5 y

High-dose diuretics (n=58)

vs.

Placebo (n=58)

Sample size: 58/58

Primary endpoint:

FU duration: 2.0 y

High-dose diuretics (n=4297)

vs.

ß-Blockers (n=4402)

Sample size: 4297/4402

Primary endpoint:

FU duration: 4.9y

all cause death 0.98 [0.90; 1.07]

non fatal stroke 0.89 [0.70; 1.12]

non fatal MI 0.99 [0.79; 1.24]

verapamil sustained release 240mg/d (n=11267)

vs.

atenolol 50mg/d (n=11309)

Sample size: 11267/11309

Primary endpoint:

FU duration: 2.7 y

all cause death 1.07 [0.92; 1.25]

coronary heart disease 0.81 [0.65; 1.02]

cardiovascular death 1.08 [0.86; 1.35]

stroke (fatal & non fatal) 0.81 [0.65; 1.02]

Major cardiovascular events 1.01 [0.88; 1.17]

controlled-onset extendedrelease(COER) verapamil 180mg/d (n=8241)

vs.

hydrochlorothiazide 12.5 mg/d or atenolol 50 mg/d(investigator choice prior to randomization) (n=8361)

Double blind

Parallel groups

Sample size: 8241/8361

Primary endpoint:

FU duration: 3 y

all cause death 1.25 [0.34; 4.64]

coronary heart disease 0.90 [0.37; 2.20]

cardiovascular death 1.25 [0.34; 4.64]

fatal MI 0.75 [0.17; 3.34]

heart failure ∞ [NaN; ∞]

fatal stroke ∞ [NaN; ∞]

non fatal stroke 0.75 [0.17; 3.34]

non fatal MI 1.00 [0.29; 3.44]

stroke (fatal & non fatal) 1.25 [0.34; 4.64]

Major cardiovascular events 1.07 [0.52; 2.20]

verapamil SR 240 mg/d (n=707)

vs.

chlorthalidone 25mg/d (n=707)

Open

Parallel groups

Sample size: 707/707

Primary endpoint: Not given

FU duration: 2 years

telmisartan 80 mg/d (n=-9)

vs.

placebo (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration: