HOT 1998

Methods	Multicentre, 3 x 2 factorial design, ITT strategy, Prospective randomized open with blinded end point (PROBE) trial. All participants in the HOT trial were randomly assigned to three therapeutic goals (DBP ≤ 90 mmHg, ≤ 85 mmHg or ≤ 80 mmHg) and to receive either acetylsalicylic acid (aspirin) 75 mg daily or placebo under double blind conditions. Participants were randomized on the basis of the following baseline variables: age, sex, previous antihypertensive therapy, smoking, previous MI, previous other CHD, previous stroke, and diabetes mellitus. The follow‐up was 3.3 to 4.9 years (mean 3.8 years)
Participants	Hypertensive men and women aged between 50 and 80 years (mean 62 years) with essential hypertension were eligible for the study. Required DBP ≥100 mmHg and ≤115 mmHg on two occasions, at least one week apart. Exclusion criteria included: malignant or secondary hypertension, stroke or MI within 12 months before randomization, decompensated CHF, serious disease affecting survival during the next 2 to 3 years, requirement for BB, ACEI or diuretic treatments for reasons other than hypertension, requirement for antiplatelet or anticoagulant treatment and those with diabetes who required insulin. Baseline characteristics for participants included in the review (% or mean ± SD): men/women (53/47%); SBP (174 ± 15 mmHg); DBP (106 ± 3 mmHg); diabetes (12%); current smoker (16%); ethnic group: White (92%), non White (8%). Previous cardiovascular condition: IHD (95%), stroke (7%). Countries: Argentina, Austria, Belgium, Canada, Denmark, East Asia, Finland, France, Germany, Great Britain, Greece, Hungary, Israel, Italy, Mexico, Norway, South East Asia, Spain, Sweden, Switzerland, Netherlands and USA.
Interventions	Standard target: DBP ≤ 90 mmHg Lower target: DBP ≤ 85 mmHg or ≤ 80 mmHg
Outcomes	The principal aims of the study included to assess the relationship between pooled major cardiovascular events (non fatal MI, non fatal stroke or cardiovascular death) and the target blood pressures or DBP achieved during treatment. Secondary analyses examined the relationship between target DBP and specific outcomes, such as total or cardiovascular mortality, fatal and non fatal CHD or stroke and hospitalization
Funding sources	Astra AB (Sweden), Astra Merck Inc (USA), Teva (Israel), Hoechst (Argentina)
Declarations of interest	Not reported
Notes	Silent MIs were documented by taking an electrocardiogram (ECG) at randomization and at the final visit. The blood pressures achieved at the end of the trial were: standard target: DBP 85 ± 5 mmHg; lower target: DBP 82 ± 5 mmHg A private repository provided individual patient data from hypertensive participants with established cardiovascular disease that were used in this Cochrane Review
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"The randomisation was computer‐generated based on communications by fax between investigators and the Study Coordinating Centre" (pp. 1755‐62; and protocol, section 7.3)
Allocation concealment (selection bias)	Low risk	"The randomisation was computer‐generated based on communications by fax between investigators and the Study Coordinating Centre" (pp. 1755‐62; and protocol, section 7.3)
Blinding of participants and personnel (performance bias) All outcomes	High risk	The study design is not compatible with blinding of participants and personnel
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"An Independent Clinical Event Committee evaluated all events (masked)" (pp. 1755‐62; and protocol, section 7.2)
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	"14% of the ECG could not be obtained leading to uncertainty on silent myocardial infarctions. On the other hand, no significant differences among targets have been detected" (Clinical Study Report, p. 23, and pp. 1755‐62, Figure 1)
Selective reporting (reporting bias)	Low risk	The database shows all required results (study protocol, sections 3.1 and 3.2)
Other bias	Unclear risk	Subgroup of participants with basal cardiovascular disease not predefined