Hypertension Optimal Treatment Study - HOT


Aspirin and diastolic BP reduction on major cardiovascular events in hypertension.


To assess the relationship of cardiovascular events to diastolic blood pressure, and the effect of low-dose aspirin in addition to anti-hypertensives.

Study Design

Study Design:

Patients Screened: Not given
Patients Enrolled: 19,196
Mean Follow Up: 2.5 years

Primary Endpoints:

Major cardiovascular events

Secondary Endpoints:

All MI

Drug/Procedures Used:

Aspirin, 75 mg qd (double-blind) vs placebo; felodipine 5 mg po qd titrated to DBP ≤90, ≤85, or ≤80 mm Hg.

Concomitant Medications:

Hydrochorothiazide, beta-blockade.

Principal Findings:

Patients in the study were randomized into three groups, based on specific target diastolic blood pressure levels: ≤ 90 mm Hg, ≤ 85 mm Hg, and ≤ 80 mm Hg. Each group consisted of more than 6,000 patients, and all had similar baseline characteristics. If the target blood pressure was not reached, a low dose of an ACE inhibitor or a beta blocker was added. The third step, if necessary, was to double the dose of felodipine. The fourth step, if necessary, was to double the add-on treatment. If the target blood pressure still was not reached, a combination of felodipine, an ACE inhibitor and a beta blocker could be used, or hydrochlorothiazide could be added. At the end of the study, 78% of the patients were still on felodipine, and approximately 2/3 of the patients were on combined treatment.

The mean diastolic blood pressure from 6 months on showed a dramatic reduction. Target blood pressures were reached by 84%, 72%, and 57% of patients, respectively. For the target group of ≤ 90 mmHg, the average was 85 mm Hg; for the target group of ≤85 mm Hg, the average was 83 mm Hg; and for the target group of ≤80 mm Hg, the average was 81 mm Hg. In total, 92% of the patients in the study reached 90 mmHg or below.

The HOT investigators noted that there was poor separation between the three targets and that it was difficult to show significant differences between the three groups for major cardiovascular events and all MI.

There was a 16% decrease in all major cardiovascular events with aspirin compared to placebo. For all MI, there is a 36% difference in favor of aspirin, but no significant difference for stroke. Although the aspirin group did not show an increased risk of cerebral bleeding, other bleeds (gastrointestinal, nasal) were approximately twice as common in the aspirin group.


The HOT study is the largest intervention hypertension trial to be conducted, involving more than 19,000 patients in 26 countries. Although it was difficult to distinguish between the three target blood pressure groups, the lowest rate for major cardiovascular events was found at a diastolic blood pressure of 82.6 mmHg and a systolic blood pressure of 138.5 mmHg.


1. Blood Press 1994;3:322-7. Baseline characteristics
2. Blood Press 1995;4:313-9. 12-month data
3. Presented at the XXth Congress of the European Society of Cardiology, Vienna, 1998 Interim results

Clinical Topics: Prevention, Statins, Hypertension

Keywords: Felodipine, Stroke, Platelet Aggregation Inhibitors, Hydrochlorothiazide, Hypertension, Calcium Channel Blockers

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