The HOT trial: Diastolic blood pressure targets in hypertension [Classics Series]

1. In hypertensive patients, there were no significant differences between different diastolic blood pressure (dBP) targets (≤90 mmHg,≤85 mmHg,≤80 mmHg) with regards to the risk of major cardiovascular events.

2. In patients with diabetes, treating to a target ≤80 mmHg led to significantly fewer major cardiovascular events and cardiovascular death compared to those treated to a target ≤90 mmHg.

3. Antihypertensive therapies were generally well tolerated, with common complaints including dizziness, leg edema, and coughing.

Original Date of Publication: June 1998

Study Rundown: While previous evidence had shown that treating hypertension reduced cardiovascular morbidity and mortality, it was thought that those with treated hypertension had higher risk of developing cardiovascular complications compared to normotensive individuals. The purpose of the Hypertension Optimal Treatment (HOT) trial was to determine whether different diastolic blood pressure (dBP) targets led to different rates of major cardiovascular events (myocardial infarction, stroke, cardiovascular death). Moreover, the study explored whether adding low-dose acetylsalicylic acid (ASA) to antihypertensive therapy would further also major cardiovascular outcomes.

In summary, HOT trial demonstrated that there were no significant differences between the different dBP targets (≤90 mmHg, ≤85 mmHg, ≤80 mmHg) in terms of risk of major cardiovascular events. In patients with diabetes mellitus, it was shown that targeting a dBP of ≤80 mmHg led to significant reductions in the risk of major cardiovascular events and cardiovascular mortality, when compared with a target of ≤90 mmHg. In these patients with treated hypertension, concurrent low-dose ASA also led to significantly lower rates of major cardiovascular events and myocardial infarction compared to those taking placebo. Antihypertensive therapy was generally well tolerated, with some patients complaining of dizziness, headache, leg edema, and coughing. Treatment with ASA led to significantly higher rates of nonfatal major bleeding compared to placebo.

Click to read the study in The Lancet

In-Depth [randomized controlled study]: This multicenter, randomized controlled trial involved 18 790 patients from 26 different countries. Patients were eligible for the trial if they were between 50-80 years of age and had hypertension with diastolic blood pressure between 100-115 mmHg. Included patients were randomly assigned to one of the three dBP target groups (≤90 mmHg, ≤85 mmHg, or ≤80 mmHg) and to treatment with either ASA 75 mg daily or placebo.

All patients were started on the long-acting calcium channel blocker felodipine at a dose of 5 mg daily, and additional therapy was provided to reach the randomized target blood pressure. Angiotensin-converting-enzyme (ACE) inhibitor or beta-blocker was added at step 2. Steps 3 and 4 involved dosage titrations (i.e., increasing felodipine to 10 mg daily and doubling the dose of the ACE inhibitor/beta-blocker, respectively). Step 5 involved the addition of a diuretic. The primary outcome was major cardiovascular events, defined as all myocardial infarctions and strokes (fatal and nonfatal), and all other cardiovascular deaths. Deaths occurring within 28 days of an event were labeled as fatal.

Patients were followed for an average of 3.8 years. The mean dBP achieved in the ≤90 mmHg, ≤85 mmHg, and ≤80 mmHg groups were 85.2 mmHg, 83.2 mmHg, and 81.1 mmHg, respectively. There were no differences between the three groups with regards to major cardiovascular events (p = 0.50). Moreoever, there were no differences between the groups in the risk of all stroke (p = 0.74), all myocardial infarction (p = 0.05), cardiovascular mortality (p = 0.49), or total mortality (p = 0.32). In diabetic patients, patients in the ≤80 mmHg group experienced significantly lower rates of major cardiovascular events (RR 2.06, 95%CI 1.24 to 3.44, p = 0.005), and specifically cardiovascular mortality (RR 3.0, 95%CI 1.28 to 7.08, p = 0.016), when compared to patients in the ≤90 mmHg group. Patients taking ASA had significantly fewer major cardiovascular events (RR 0.85, 95%CI 0.73 to 0.99, p = 0.03) and myocardial infarctions (HR 0.64, 95%CI 0.49 to 0.85, p = 0.002) compared to those receiving placebo.

Generally, antihypertensive therapies were well tolerated, with common side effects being dizziness, headache, leg edema, flushing, and coughing. ASA was linked with significantly higher risk of nonfatal major bleeding as compared with placebo (RR 1.8, p < 0.001).

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