At the time this trial was published, it was known that patients with treated hypertension had a higher incidence of cardiovascular complications as compared to normotensive individuals. It was suspected that inadequate reduction of their blood pressure was the most likely cause, but the optimum target blood pressure was not known at this time. It was estimated that less than 30% of patients with hypertension have blood pressures better lowered less than140/90,supporting a hypothesis that inadequate reduction of blood pressure on treatment led to this increased cardiovascular risk. Conversely, there were concerns that aggressive blood pressure lowering could lower the blood pressure to the point of increased cardiovascular complications in line with the J-curve concept. This trial set out to determine the correct blood pressure target.
In addition, aspirin had been shown to reduce the incidence of stroke and MI given long-term to healthy individuals of those with existing cardiovascular disease, but its use in those without established cardiovascular disease was unknown. This trial also aimed to determine its efficacy for this purpose.
This trial randomized 18,790 patients from 26 countries that were aged 50 to 80 years old with hypertension and DBP 100-115mmHg. They randomized the patients to a target diastolic blood pressure of either less than 90mmHg, less than 85mmHg, or less than 80mmHg as well as to aspirin or placebo. Felodipine was used as the first-line agent. If additional therapy was needed, ACE or BB were added with subsequent maximization of dosage and finally, the addition of a diuretic if needed to achieve BP targets. DBP was reduced by 20.3mmHg, 22.3mmHg, and 24.3mmHg among the three target groups… a tight grouping of achieved blood pressures which made interpretation of the results difficult.
The trial gave us a few pieces of information. Before we go any further, it’s important to note that there was no placebo group. All patients were treated, but the only difference was the degree to which blood pressure was lowered (although it was a tight grouping of BPs between the three groups). Firstly, there was no difference in cardiovascular mortality or overall mortality between the three groups, meaning that there was no benefit to aggressive BP lowering from this standpoint. Cardiovascular risk was lowered in the group targeted to a DBP <80mmHg as compared to the target of <90mmHg only in those with diabetes. Aspirin was found to reduce CV events and MI, but had no effect on stroke.
A strange thing about this trial is that the authors seemed to draw the wrong conclusion about the study. During my reading on the trial, I got confused as to what the actual conclusion of the trial should be. The above statements are my best attempt at this. There was some controversy about the fact that the authors noted reductions in CV events even though there were no statistically-significant findings in the trial to support this. There were also comments made after the publication of the trial noting that pulse pressure among participants should have been investigated more closely and included in the final analysis. The links below to Lancet letters to the editor are good commentaries on this trial
The HOT Trial: Hansson, L., Zanchetti, A., Carruthers, S. G., Dahlöf, B., Elmfeldt, D., Julius, S., ... & HOT Study Group. (1998). Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. The Lancet, 351(9118), 1755-1762.
HOT Trial PMID: 9635947
Useful summaries of the HOT Trial: