The hypertension optimal treatment (HOT) study: Implications for hypertension management and the J-shape curve

Epidemiologic surveys in the United States indicate that only a minority of patients with hypertension have adequate blood pressure control on therapy. Concern over the J-curve may be leading physicians to undertreat hypertension. The existence of a J-curve, the increase in cardiovascular mortality when the blood pressure is lowered beyond the threshold for myocardial perfusion, has been actively debated. The Hypertension Optimal Treatment (HOT) study was designed to address the following concerns with respect to antihypertensive treatment: (1) How aggressively should blood pressure be lowered? (2) What is the optimum target pressure in terms of minimum cardiovascular risk? and (3) Does aspirin therapy provide added cardiovascular benefits in patients being' treated for hypertension? In the HOT study, 18,790 patients were randomized to diastolic blood pressure target groups of ≤ 90 mm Hg, ≤ 85 mm Hg, or ≤ 80 mm Hg and further randomized to 75 mg/day aspirin or placebo. Felodipine was given as baseline therapy with the addition of other agents according to a five-step regimen. A major achievement in the trial was a greater than 20-mm Hg reduction in blood pressure in all three target blood pressure groups. The incidence of cardiovascular morbidity and mortality was low in HOT, in comparison with previous trials. Event rates, except for myocardial infarction (MI), were similar in all three target blood pressure groups, but aggressive treatment afforded significant cardioprotection to diabetic patients. The optimum diastolic blood pressure in terms of minimum cardiovascular risk was between 80 and 85 mm Hg. Coadministration of low-dose aspirin provided added cardiovascular benefit without significantly increasing the risk of fatal bleeding. However, because of the close degree of blood pressure reduction among the three target blood pressure groups in this study, the issue of the J-curve could not be resolved.