SHEP 1991.

Methods	Multisite study. Double blind, placebo controlled stepped‐care treatment programme. Study duration: 5 years. Randomization: stratified by site and by antihypertensive medication status at initial contact; patients randomly allocated by coordinating centre. Patients blinded; providers blinded; morbidity and mortality assessors blinded. Type of trial: randomized, placebo controlled. % lost to follow ‐up: < 1%. % not on assigned therapy at study end: placebo group: 44%; treatment group: 10%
Participants	Geographic region: United States of America. Study setting: community. n = 4736 (55.8% female). Age range 60 to > 80 years, mean 71.6 (SD 6.7). Race: White non‐Hispanic (79.2%), Black (13.8%), Hispanic (1.8%), Asian (4.3%), other (0.9%). Education level: mean 11.7 years (SD 3.5). Diagnosis: systolic hypertension. Mean blood pressure at entry: 170/77 mmHg. Blood pressure (BP) entry criteria: systolic BP 160‐219 mmHg and diastolic BP < 90 mmHg.
Interventions	Control: matching placebo. Treatment: step 1 ‐ chlorthalidone 12.5 or 25 mg daily; step 2 ‐ atenolol 25 or 50 mg or reserpine 0.05 or 0.10 mg daily. Average length of follow up: 4.5 years. Difference in blood pressure at study end (Treatment ‐ Control) systolic/diastolic: ‐11.1/‐3.4 mmHg.
Outcomes	Analysed in the review: incidence of dementia; quality of life; incidence of side effects including depression; blood pressure level. Not analysed in the review: total mortality; total stroke; sudden cardiac death; rapid cardiac death; non‐fatal MI; fatal MI; left ventricular failure; other cardiovascular death; transient ischaemic attack (TIA); coronary artery bypass grafting or angioplasty; renal dysfunction. Dropouts due to side effects: Control group: 7%; Treatment group: 13%. Quality of life or functional outcomes: no perceptible negative effect of treatment compared to control on measures of cognitive, physical and emotional function.
Notes	Exclusions: history and/or signs of major cardiovascular diseases likely to require pharmacologic and other treatment (e.g., previous MI, coronary artery surgery, major arrhythmias, conduction defect, recent stroke, carotid artery disease, history of TIA with bruit matched with TIA localisation, two or more TIAs and signs or symptoms in a single neurological distribution); other major diseases (e.g. cancer, alcoholic liver disease, established renal dysfunction) with competing risk factors for the primary endpoint ‐ stroke; presence of medical management problems (e.g. insulin dependent diabetes, history of dementia, evidence of alcohol abuse); bradycardia; people maintained on beta‐blockers, diuretics, other antihypertensive drugs, anticoagulants, or experimental drugs on recommendation of their physicians.
Risk of bias
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Unclear risk	'After verification of eligibility ... randomly allocated by coordinating centre to one of two treatment groups. Randomization stratified by centre and antihypertensive medication use at initial contact.' Comment: Probably adequate
Allocation concealment?	Low risk	'Random assignment ... made by coordinating centre and transmitted to local centre by telephone after verification of eligibility.' Comment: probably adequately concealed.
Blinding? All outcomes	Low risk	'Participants randomized in a double‐blind manner to once‐daily dose of active drug treatment or matching placebo.' Data on study end points collected by investigators and confirmed by a panel of three physicians blind to allocation.
Incomplete outcome data addressed? All outcomes	Low risk	'All analyses were by treatment assignment at randomization.' Comment: Subsequent publication (Di Bari 2001) addressed effect of differential drop‐out between treatment and control groups.
Free of selective reporting?	Low risk	Prespecified outcomes reported.
Free of other bias?	High risk	About 35% of placebo group took antihypertensive medication during study for predefined BP levels.