|Methods||Randomized, open-label, 3-by-2 factorial design controlled trial, with blinded endpoint evaluation (PROBE) design. An Independent Clinical Event Committee, masked to the group allocation, evaluated all clinical events. The trial was conducted in 26 countries from Europe, Asia, North and South America. The average follow-up was 3.8 years.|
|Participants||The entire study population was composed of 18,790 patients with elevated blood pressure, aged 50 - 80 years. Of these, 1501 participants had diabetes at baseline and constitute the population included in this analysis.|
Baseline diastolic blood pressure between 100 mmHg and 115 mmHg on 2 occasions, at least 1 week apart, was an inclusion criterion.
The main exclusion criteria were malignant hypertension, secondary hypertension, diastolic blood pressure > 115 mmHg, stroke or myocardial infarction within 12 months prior to randomization, decompensated congestive heart failure, other serious concomitant diseases which could affect survival during the next 2 - 3 years, participants who required a beta-blocker, ACE inhibitor or diuretic for reasons other than hypertension, participants who required antiplatelet or anticoagulant therapy, and insulin-treated diabetics.
|Interventions||Participants were randomly assigned to one of 3 diastolic blood pressure target groups: ≤ to 90 mmHg, ≤ 85 mmHg, or ≤ 80 mmHg and to low dose acetylsalicylic acid 75 mg or placebo.|
Blood pressure was measured 3 times, by an oscillometric semiautomatic device, with the participant in the sitting position after 5 minutes of rest. The time of day when blood pressure was measured was not specified.
Block randomization was performed taking into consideration the following baseline variables: age, sex, previous antihypertensive therapy, smoking, previous myocardial infarction, previous coronary heart disease, previous stroke and diabetes mellitus.
All participants were treated with the same drugs in the same order. The following were the required steps allowed to attempt to achieve the target blood pressure:
Step 1- felodipine 5 mg once a day;
Step 2- a starting dose of an angiotensin converting enzyme (ACE) inhibitor or beta-blocker was added;
Step 3- the dose of felodipine was increased to 10 mg once a day;
Step 4- the dose of the ACE inhibitor or the beta-blocker was doubled;
Step 5- a diuretic was added.
|Outcomes||The outcomes measured were: total and cardiovascular mortality, all (fatal and non-fatal) myocardial infarctions including silent infarctions, all (fatal and non-fatal) strokes, and major cardiovascular events (all myocardial infarctions plus all strokes plus other cardiovascular deaths).|
|Notes||In the entire trial 24% of all investigators' reported events were rejected by the Clinical Event Committee. The corresponding number for the subgroup of participants with diabetes was not specified.|
The trial was conducted between October 1992 and August 1997
|Risk of bias|
|Bias||Authors' judgement||Support for judgement|
|Random sequence generation (selection bias)||Unclear risk||Subgroup analysis|
|Allocation concealment (selection bias)||Unclear risk||Subgroup analysis|
|Blinding (performance bias and detection bias) |
|Unclear risk||Blinding of participant and investigator not possible|
|Incomplete outcome data (attrition bias) |
|High risk||Data on losses to follow-up was not reported|
|Selective reporting (reporting bias)||High risk||Data on participants with diabetes represent a subgroup analysis of the entire HOT trial. The baseline characteristics in the subgroup of participants with diabetes are unknown, and therefore an unbalance at baseline cannot be ruled out.|
|Other bias||High risk||Industry funded|