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The Hypertension Optimal Treatment study and the importance of lowering blood pressure
1Clinical Hypertension Research, Department of Geriatrics, University of Uppsala, Sweden.
Insights
The Hypertension Optimal Treatment (HOT) Study found that lowering diastolic blood pressure (DBP) to 80-85 mmHg and systolic blood pressure (SBP) to 130-140 mmHg optimally reduced cardiovascular events. Aspirin (acetylsalicylic acid) significantly decreased myocardial infarctions by 36%.
Area of Science:
- Cardiology
- Clinical Trials
- Hypertension Management
Background:
- Hypertension is a major risk factor for cardiovascular disease.
- Optimal blood pressure targets for reducing cardiovascular events require definition.
- The role of low-dose aspirin in preventing cardiovascular events in hypertensive patients needs assessment.
Purpose of the Study:
- To determine the optimal target blood pressure for minimizing major cardiovascular events in hypertensive patients.
- To evaluate the efficacy of low-dose aspirin compared to placebo in reducing cardiovascular events.
Main Methods:
- Recruited 18,790 hypertensive patients aged 50-80 years with DBP 100-115 mmHg.
- Randomly assigned patients to target DBP of ≤90, ≤85, or ≤80 mmHg using felodipine-based therapy.
- Randomly assigned patients to receive 75 mg/day aspirin or placebo.
Main Results:
- Achieved DBP reductions of 20.3, 22.3, and 24.3 mmHg for target groups ≤90, ≤85, and ≤80 mmHg, respectively.
- Aspirin reduced fatal and non-fatal myocardial infarctions by 36%.
- Lowest incidence of major cardiovascular events occurred at achieved DBP of 82.6 mmHg and SBP of 138.5 mmHg.
Conclusions:
- Optimal protection against major cardiovascular events was observed at DBP of 80-85 mmHg and SBP of 130-140 mmHg.
- Low-dose aspirin demonstrated a significant benefit in reducing myocardial infarctions.
- Lower blood pressure levels correlated with improved quality of life.
Objectives:
The Hypertension Optimal Treatment (HOT) Study had two objectives: (1) to define the optimal target blood pressure when treating hypertensive patients (i.e. the level of blood pressure associated with the lowest incidence of major cardiovascular events such as fatal and non-fatal stroke and myocardial infarction and other cardiovascular mortality); and (2) to assess the effect of a low dose of acetylsalicylic acid (aspirin) compared with placebo on major cardiovascular events.
Methods:
The HOT study recruited 18 790 hypertensive subjects aged 50 to 80 years with diastolic blood pressure (DBP) between 100 and 115 mmHg (mean DBP 105 mmHg). Subjects were randomly assigned to be treated with the goal of reaching one of three target DBPs: < or = 90 mmHg (n = 6264), < or = 85 mmHg (n = 6264), or < or = 80 mmHg (n = 6262) using felodipine as initial therapy with the addition of other agents according to a 5-step regimen. In addition, subjects were randomly assigned to receive either 75 mg/day aspirin (n = 9399) or placebo (n = 9391).
Results:
DBP was reduced by 20.3, 22.3, and 24.3 mmHg in the < or = 90, < or = 85, and < or = 80 mmHg target groups, respectively. The incidence of all major cardiovascular events (fatal and non-fatal stroke, myocardial infarction, and other cardiovascular mortality) decreased, although not significantly, in relation to the randomized target blood pressure. There were 84, 64, and 61 fatal and non-fatal myocardial infarctions in the < or = 90 mmHg, < or = 85 mmHg, and < or = 80 mmHg groups, respectively (P = 0.05). The overall effect of aspirin on cardiovascular events was positive, most noticeably on fatal and non-fatal myocardial infarctions; aspirin reduced events by 36%. There were seven fatal episodes of bleeding (two cerebral) in the aspirin group compared with eight (three cerebral) in the placebo group, and 129 versus 70 non-fatal major episodes of bleeding in the two groups, respectively. The lowest incidence of all major cardiovascular events combined was found at an achieved DBP of 82.6 mmHg and at an achieved systolic blood pressure (SBP) of 138.5 mmHg. In the subgroup with diabetes mellitus at baseline (n = 1501), the effect of intensive lowering of blood pressure was especially noticeable.
Conclusions:
Most cardiovascular end-points showed a declining frequency in relation to target blood pressure. The optimal protection against combined major cardiovascular end-points was observed in the range 80-85 mmHg for DBP and in the range 130-140 mmHg for SBP. It is worth noting that 92% of all subjects reached a DBP of < or = 90 mmHg and that side-effects gradually declined from 16.9% at 3 months to 2.2% at the end of the study. A substudy showed that quality of life was linked to the level of blood pressure obtained: the lower the blood pressure, the better the quality of life.