ArticlesEffects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial
Introduction
The background and rationale of the Hypertension Optimal Treatment (HOT) Study have been presented previously in some detail.1 In brief, it is well documented that treatment of hypertension reduces cardiovascular morbidity and mortality.2, 3 However, it is obvious that treated patients with hypertension remain at a greater risk of developing cardiovascular complications than matched normotensive individuals.4, 5 One possible explanation could be that the blood pressure of the patients with hypertension has not been lowered to strictly normotensive levels.6 Indeed, epidemiological surveys in various parts of the world indicate that less than 30% of patients with hypertension have their blood pressure brought down below 140/90 mm Hg.7, 8 In addition, concerns have been expressed that too vigorous reduction in blood pressure may be associated with increased cardiovascular risk—the so-called J-curve concept.9, 10, 11, 12 The issue of how far blood pressure should be lowered to achieve the greatest benefit, in terms of reduced cardiovascular morbidity and mortality, has been a matter of scientific debate.13 The real issue is not whether the relation between achieved blood pressure and cardiovascular events is J-shaped (it must be), but whether there are additional benefits, or risks, in lowering blood pressure of patients with hypertension to fully normotensive levels—ie, between 70 mm Hg and 85 mm Hg diastolic blood pressure—or whether there is little further benefit in lowering diastolic blood pressure much below 90 mm Hg.14 This issue needed to be addressed in a randomised and prospective trial and this was one of the reasons for doing the present study.
Another possible approach to improving treatment benefits in patients with hypertension is that of associating antihypertensive therapy with correction of other cardiovascular risk factors. Acetylsalicylic acid (aspirin) has been shown to reduce the incidence of stroke and myocardial infarction when given long term to healthy individuals or patients with previous cardiovascular events15, 16, 17 but its effects in individuals without a history of cardiovascular disease have been less clear and more controversial.18, 19 However, no intervention studies with acetylsalicylic acid have been done in patients with hypertension, possibly because the use of acetylsalicylic acid has been associated with a small increase in the risk of cerebral haemorrhage; a risk that could be greater in hypertension.
The principal aims of this study were: to assess the association between major cardiovascular events (non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death) and the target blood pressures ·90 mm Hg, ⩽85 mm Hg, and ⩽80 mm Hg during antihypertensive treatment; to assess the association between major cardiovascular events and the diastolic blood pressure achieved during treatment; and to find out whether the addition of low doses of acetylsalicylic acid to antihypertensive treatment reduces the rate of major cardiovascular events.
Section snippets
Study population and organisation
The patient population in the HOT Study has been described previously.20 In brief, 19 193 patients from 26 countries, aged 50–80 years (mean 61·5 years), with hypertension and a diastolic blood pressure between 100 mm Hg and 115 mm Hg (mean 105 mm Hg) were randomly assigned a target blood pressure and acetylsalicylic acid or placebo. Because of the suspicion of incorrect inclusion or data handling at one centre, 403 patients were excluded early in the trial. Patients were recruited from
Study population
6264 patients were given the diastolic blood-pressure target of ⩽90 mm Hg, 6264 a target of ⩽85 mm Hg, and 6262 a target of ⩽80 mm Hg (figure 1). In addition, 9399 patients were randomly assigned acetylsalicylic acid and 9391 patients were assigned placebo. A total of 491 (2·6%) patients were lost to follow-up. Most were lost early in the study—eg, 130 patients did not return for any of the follow-up visits. The loss in terms of patient years was 1269 (1·8%). The loss of patients in the three
Blood-pressure effects of treatment
An important finding is that substantial reductions in blood pressure can be achieved with a treatment regimen based on the long-acting calcium antagonist, felodipine. Even in patients who were receiving treatment before enrolment (52·6%) there was a striking further reduction in blood pressure with the treatment regimen used.20 The overall reductions in diastolic and systolic blood pressures are striking—eg, in comparison with those reported in the meta-analysis by Collins and colleagues2 (5–6
Conclusion
The principal results of the HOT Study demonstrate the benefits of lowering blood pressure in patients with hypertension to 140 mm Hg systolic and 85 mm Hg diastolic, or lower. Efforts to lower blood pressure further, down to 120 mm Hg systolic and 70 mm Hg diastolic, appear to give little further benefit, but do not cause any significant additional risk. Active lowering of blood pressure was particularly beneficial in the subgroup of patients with diabetes mellitus. On the whole, the rate of
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Study organisation given at end of paper