Study	Reason for exclusion
ADVANCE 2007	Randomi zed controlled trial; 215 collaborating centres in 20 countries from Asia, Australasia, Europe and North America. After 6‐week active run‐in period, 11,140 pa rticipants with type 2 diabetes aged ≥ 55 years were randomi zed to treatment with fixed combination of perindopril + indapamide or matching placebo, in addition to current therapy. No BP criteria for inclusion. All other treatments continued at discretion of responsible physician, with exception of ACE inhibitors. Participants taking ACE inhibitor other than perindopril had this treatment withdrawn and were offered substitution with open‐label perindopril at 2 mg or 4 mg a day. Control group included non‐specific antihypertensive therapy.
ALLHAT 1996	Prospective, randomiz ed, double‐blind, active‐controlled clinical trial. Drug‐drug comparison of different drug classes with no placebo or untreated control group.
Anon 1973	Single ‐blind, randomi zed, placebo‐ controlled trial conducted in the UK in 116 men and women aged 45 ‐69 years with 2 casual, sitting DBP of 100 ‐120 mmHg on each of 2 occasions separated by an interval of ≥ 2 weeks. Untreated control group received calcium lactate tablets. Treatment group received any combination of bendrofluazide with potassium supplement, methyldopa or debrisoquine ; choice of treatment at discretion of physician. However, data in 45‐ to 59 ‐year ‐old pa rticipants not reported separately.
ATTMH 1984	Australian National Blood Pressure Study, a controlled therapeutic trial of antihypertensive drug treatment in 3427 men and women with mild hypertension. Pa rticipants were aged 30 ‐69 years and randomi zed to active treatment or placebo. Active group had chlorothiazide 500 mg daily as first‐order drug. Thereafter, if blood pressure control was not achieved, dose was increased to 500 mg twice daily or second‐order drug (methyldopa, propranolol or pindolol) was added (or both). Subsequently, third‐order drugs (hydralazine or clonidine) were given if necessary. Initial objective was to reduce DBP to ≤ 90 mmHg but after 2 years the goal was lowered to 80 mmHg. Of 1721 pa rticipants randomi zed to treatment, 1428 were aged 30 ‐59 years and of 1706 randomi zed to placebo, 1417 were aged 30 to 59 years. Data in the age group 30‐ to 59 ‐years were not reported separately.
Berglund 1981	Drug‐drug comparison of bendrofluazide 2.5 mg vs propranolol 160 mg with no placebo or untreated control group.
CASTEL 1994	Drug‐drug comparison with no placebo or untreated control group. Control group included non‐specific antihypertensive therapy.
Coope 1986	Randomized multisite study comparing antihypertensive treatment to control (observation without placebo) in p eople aged 60‐ to 79‐ years.
Dutch TIA 1993	Randomiz ed, double‐blind, placebo‐controlled trial in 1473 pa rticipants aged > 65 years with TIA or disabling stroke were randomized to atenolol or placebo. Only p eople aged ≥ 65 years were included in this trial.
EWPHBPE 1988	Randomi zed, placebo ‐controlled, double‐blind trial conducted in Europe. Only pa rticipants aged ≥ 60 years were included in this trial.
Fuchs 2011	Randomized, double‐blind, clinical trial, controlled by placebo in pa rticipants aged 30‐70 years with prehypertension.
GENERIC 2010	Single‐centre, randomiz ed, double‐blind, placebo‐controlled, cross‐over trial comparing effects of moexipril and placebo on insulin sensitivity and 24‐hour BP control in postmenopausal women with essential hypertension. Only an 8‐ week trial.
GLANT 1995	Employed alternate allocation (i.e . not random allocation). Drug‐drug comparison of delapril 30‐120 mg vs several dihydropyridine calcium channel blockers with no placebo or untreated control group.
HANE 1997	Morbidity and mortality outcomes not reported.
HAPPHY 1987	6569 men aged 40‐64 years with mild to moderate hypertension randomized to diuretic or beta ‐blocker therapy. No placebo control group.
HDFP 1982	Treated group included various lifestyle measures in addition to antihypertensive drug therapy. Control group was usual care and participants were not necessarily untreated controls.
HOPE HYP 2000	Double‐blind, randomized trial in pa rticipants aged ≥ 55 years with previous coronary artery disease, cerebrovascular disease, peripheral vascular disease or diabetes + 1 additional risk factor (high BP > 160 mmHg or > 90 mmHg, total cholesterol > 5.2 mmol/L, high‐density lipoprotein cholesterol < 0.9 mmol/L, current cigarette smoking or known microalbuminuria). Pa rticipants randomized to ramipril 2.5 mg titrating to 10 mg or placebo. Other factor was v itamin E 400 IU/day. Data in 55‐ to 59 ‐year‐ old pa rticipants were not reported separately.
HOT 1995	Evaluated the effects of achieving prespecified levels of DBP control with all pa rticipants receiving antihypertensive treatment. No placebo control group.
HYVET 2003	Randomized, open ‐label trial conducted in Europe. Only included participa nts aged ≥ 80 years.
HYVET 2008	Randomiz ed, double‐blind, placebo ‐controlled trial. Only included participa nts aged ≥ 80 years.
IDM 2001	Multinational, randomized, double‐blind, placebo‐controlled study . 590 participants aged 30‐70 years with hypertension with type 2 diabetes and microalbuminuria . Participants randomized to irbesartan 150 mg daily or 300 mg daily, and followed for 2 years. Other antihypertensive drugs were prescribed to 56% of the placebo group.
INSIGHT 1996	Prospective, randomiz ed, double‐blind trial in Europe and Israel with 6321 participa nts aged 55‐ 80 years with hypertension ( BP 150/95 mmHg, or SBP 160 mmHg). Participa nts had ≥ 1 additional cardiovascular risk factor. Participa nts randomly assigned to nifedipine 30 mg in a long‐acting gastrointestinal‐transport system formulation (3157 participa nts), or co‐amilozide hydrochlorothiazide 25 g + amiloride 2 .5 mg ( 3164 participants). Dose titration by dose doubling, and addition of atenolol 25‐ 50 mg or enalapril 5‐ 10 mg. No placebo or untreated control group.
IPPPSH 1985	Randomized, double ‐blind study in 6357 men and women aged 40‐64 years with uncomplicated hypertension. All participa nts received beta ‐blocker oxprenolol. Participa nts then randomized to either continuing treatment with oxprenolol or receiving placebo. Study medications could be increased or other non ‐beta‐blocker antihypertensive drugs could be added as necessary in both groups with aim of reducing DBP to ≤ 95 mmHg.
Jikei 2007	Did not truly randomiz e participants to treatment arms and control group included non‐specific antihypertensive therapy.
Kuramoto 1981	Randomi zed, double‐blind, placebo ‐controlled trial conducted in Japan. Included participa nts aged 60‐90 years.
Kuramoto 1994	Head‐to‐h ead comparison of different drug therapies (nicardipine vs trichlormethiazide) without placebo or untreated control group.
Lewis 2001	Prospective, randomiz ed, double‐blind clinical trial. Included participa nts aged 30 ‐70 years, a documented diagnosis of type 2 diabetes mellitus, hypertension or documented treatment with antihypertensive agents, and proteinuria, with urinary protein excretion ≥ 900 mg per 24 hours. 1715 hypertensive participa nts randomly assigned by a central office to 1 of 3 treatment regimens: irbesartan, amlodipine or placebo. Control group also received antihypertensive medications.
MAPHY 1988	3234 white men aged 40 ‐64 years randomized to metoprolol or thiazide diuretic. No placebo control group.
Materson 1993	Randomized, double ‐blind study of 1292 men aged ≥ 18 years with hypertension (DBP 95 ‐109 mmHg). M ean age 58 ± 10 years. Participa nts randomized to placebo or 1 of 6 drugs: hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem sustained release or prazosin. 546 participa nts were age d < 60 years but results not reported separately .
MIDAS 1996	Drug‐drug comparison of hydrochlorothiazide 25 mg vs isradipine 5 mg with no placebo or untreated control group.
Morgan 1980	Allocation to groups not random, based on week of presentation at clinic.
MRCO 1992	Prospective, randomi zed, placebo‐controlled, single‐blind trial. 4396 participa nts in the UK aged 65‐74 years with hypertension (SBP 160‐209 mmHg; DBP < 115 mmHg). Trial only included participa nts aged 65‐74 years.
NORDIL 2000	Prospective, randomiz ed, open, blinded endpoint study. E nrolled 10,881 participa nts, aged 50‐ 74 years, at health centres in Norway and Sweden, who had DBP ≥ 100 mmHg. Participa nts randomly assigned to diltiazem or diuretics or both. No placebo or untreated control group.
PATS 1995	Randomi zed, double‐blind, placebo ‐controlled trial conducted in China. 5665 Chinese men (72%) and women (28%) with history of TIA, minor stroke or major stroke without severe disability. Mean age 60 ± 8 years. Baseline BP 154/93 mmHg. 16% of participa nts were not hypertensive with BP < 140/90 mmHg. Mean follow‐up 2 years. After single‐ blind run‐in phase on placebo, eligible participa nts were randomi zed to indapamide 2.5 mg treatment or placebo. Data o n 18‐ to 59‐ year‐ old participa nts not reported separately.
PROGRESS 2001	< 50% of participa nts had elevated BP and about 50% of participa nts were receiving other antihypertensive therapy at baseline and throughout trial.
QUIET 2001	Most participa nts did not have elevated BP. 25% of participa nts receiv ed a beta‐blocker.
SCAT 2000	> 60% did not have hypertension and about 50% received beta‐blockers at baseline and throughout.
Schmieder 2009	Randomized, double‐blind, multicentre, placebo‐ controlled study. After 2‐ to 4‐week placebo run‐in, 1124 participa nts were randomized to aliskiren 150 mg, hydrochlorothiazide 12.5 mg or placebo once daily. Forced titration (to aliskiren 300 mg or hydrochlorothiazide 25 mg) occurred at week 3; at week 6, participa nts receiving placebo were reassigned (1:1 ratio) to aliskiren 300 mg or hydrochlorothiazide 25 mg. From week 12, amlodipine 5 mg was added and titrated to 10 mg from week 18 for participa nts whose BP remained uncontrolled. Not a placebo‐ controlled study of 52 weeks' duration.
SCOPE 2003	4964 participa nts aged 70 ‐89 years, with SBP 160 ‐179 mmHg or DBP 90‐ 99 mmHg, and a Mini Mental State Examination test score > 24. Participa nts randomly assigned to receive the angiotensin receptor blocker candesartan or placebo, with open‐label active antihypertensive therapy added as needed. As a consequence, active antihypertensive therapy was extensively used in control group (84% of participa nts). Mean follow‐up 3.7 years. No true placebo control group. Both groups allowed some participa nts to take hydrochlorothiazide at baseline and most of control group received antihypertensive therapy.
SHELL 1994	Head‐to‐head comparison of different drug therapies with no placebo or untreated control group.
SHEP ‐ Pilot 1985	Randomi zed, double‐blind, placebo ‐controlled trial conducted in USA. Participa nts aged > 60 years.
SHEP 1991	Randomi zed, double‐blind, placebo ‐controlled trial conducted in USA. Participa nts aged > 60 years.
Sprackling 1981	Randomi zed, open ‐label study in welfare home for elderly people. Age range not reported. Mean age 80.7 years. Participa nts randomized to methyldopa 250 mg twice daily or observation without placebo. Data in 18‐ to 59‐ year old participants not reported separately.
STONE 1996	Employed alternate allocation (i.e . not random allocation). 4 weeks after group assignment, attending physicians reallocated participants from placebo group to treatment group if their DBP was ≥ 110 mmHg.
STOP 1991	Randomi zed, double ‐blind, placebo ‐controlled multisite study in Sweden. Participa nts aged 70‐84 years.
STOP‐2 1993	Prospective, randomiz ed, double‐blind, intervention study compar ing effects of active antihypertensive therapy and placebo on frequency of fatal and non‐fatal stroke and myocardial infarction and other cardiovascular death in hypertensive Swedish men and women aged 70‐84 years.
Strandberg 1991	5‐ year long, multifactorial, randomized, controlled primary prevention trial in 1222 middle‐ aged healthy men. Age range not reported. Mean age 48 years. Treatment group had multiple interventions. Drug treatment (mainly the beta‐blockers, propranolol hydrochloride or pindolol, or diuretics, hydrochlorothiazide alone or combined with amiloride hydrochloride for hypertension, or both; probucol mainly for type IIA and clofibrate for type IIB and IV hyperlipidaemias) used if target levels were not reached by advice alone. Control group was usual treatment not untreated control.
Syst China 1993	Allocation to treatment and control groups not randomized (alternate allocation employed).
Syst‐Eur 1991	Randomized, double‐blind, placebo‐ controlled trial conducted in Europe. Participa nts aged > 60 years.
TEST 1995	Randomiz ed, double‐blind, placebo‐ controlled trial conducted in Sweden. 720 Swedish participa nts aged > 40 years, within 3 weeks of a stroke or TIA with SBP > 140 mmHg. Participa nts randomized to atenolol or placebo. Data in 40‐ to 59‐ year‐ old pa rti cipants not reported separately.
TOMHS 1995	4‐ year, multicentre, randomized, double ‐blind study of 902 men and women aged 45 ‐69 years. All participants took part in a lifestyle intervention programme to reduce weight, decrease sodium and alcohol intake, and increase leisure physical activity. Participa nts randomized to placebo or 1 of 5 antihypertensive medications. However, data in 45‐ to 59 ‐year‐ old participa nts not reported separately.
UKPDS 1998	Randomiz ed, controlled, open ‐label trial conducted in the UK. Newly diagnosed participa nts aged 25 ‐65 years with type 2 diabetes mellitus and hypertension (SBP ≥ 160 or DBP ≥ 90 mmHg (or both) in participa nts not on antihypertensive therapy and SBP ≥ 150 or ≥ 85 mmHg in participa nts on antihypertensive therapy). Tight BP group received captopril 25‐50 mg twice daily or atenolol 50‐100 mg once daily . Supplemental drugs added were frusemide 20‐40 mg twice daily, slow‐ release nifedipine 10‐40 mg twice daily, methyldopa 250‐500 mg twice daily, prazosin 1‐5 mg 3 times daily given sequentially to achieve target BP. Control group were given treatment if SBP ≥ 200 or DBP ≥ 105 mmHg (or both) (e.g. frusemide, long‐ acting nifedipine, methyldopa, prazosin given sequentially to control BP). If possible ACE inhibitor s and beta‐blockers avoided. Data in 25‐ to 59‐ year‐ old participa nts not reported separately.
VA Coop 1960	425 participa nts (255 participa nts aged < 60 years) with mild, moderately severe or severe hypertension randomized to treatment with placebo or reserpine both alone and in combination with hydralazine in mild cases; in severe cases to 3 blocking agents, pentolinium tartrate, mecamylamine hydrochloride and chlorisondamine chloride each in combination with reserpine. In moderately severe group, both series of therapeutic regimens were utilized to compare ganglionic blocking agents with the less drastic forms of antihypertensive drug therapy. Data in 18‐ to 59‐ year‐ old participa nts not reported separately.
VA‐I 1962	Randomiz ed, double‐blind, placebo‐ controlled trial conducted in USA. Participa nts were 30‐ to 70‐ year ‐old men. Participa nts were randomized to treatment: step 1 : hydrochlorothiazide 100 mg + reserpine 0.2 mg + hydralazine 75 mg; step 2: hydralazine 150 mg. Data in 18‐ to 59‐ year‐ old participa nts not reported separately.
VACS 1982	Prospective, multicentre, randomiz ed, double‐blind trial. 394 m en aged 21‐65 years with hypertension (DBP 95‐114 mmHg). Propranolol 80‐640 mg daily vs hydrochlorothiazide 50‐200 mg daily for 12 months. No placebo control group.
VHAS 1997	Prospective, multicentre, randomiz ed, parallel‐group trial. 1414 participa nts in Italy aged 40‐65 years with hypertension (mean seated SBP ≥ 160 mmHg and mean seated DBP ≥ 95 mmHg). Drug‐drug comparison of chlorthalidone 25 mg vs verapamil 240 mg with no placebo or untreated control group.
White 1995	Not a randomiz ed controlled study. No placebo group and participa nts not randomly allocated to moexipril or moexipril + hydrochlorothiazide.
Wolff 1966	Double ‐blind randomized study of 87 outpatients aged 21‐70 years . Randomized to antihypertensive drug therapy (reserpine 0.25 mg 3 times daily, chlorothiazide 0.5 g twice daily or hydrochlorothiazide 25 mg 4 times daily, and guanethidine by titration given, as needed, on successive visits until standing DBP fell < 90 mmHg or placebo. Data in 21‐ to 59‐ year‐ old participa nts not reported separately.

ACE: angiotensin‐converting enzyme ; BP: blood pressure ; DBP: diastolic blood pressure ; SBP: systolic blood pressure ; T IA : transient isch a emic attack .