ABSTRACT & COMMENTARY
Synopsis: Lowering diastolic blood pressure to 80-85 mmHg was associated with a low rate of cardiovascular events.
Source: Hansson L. Lancet 1998;351:1755-1762.
The observation that cardiovascular morbidity and mortality are still more frequent in treated hypertensives than normotensive individuals has raised concerns about the optimum blood pressure level to aim for during treatment and the role of aspirin in hypertensive patients. Thus, the results of the Hypertension Optimal Treatment (HOT) trial is of interest. HOT studied 18,790 patients with diastolic hypertension (110-115 mmHg) and randomly assigned them to three diastolic pressure targets (< 90 mmHg, < 85 mmHg, < 80 mmHg). Each of these three diastolic pressure target groups was further randomized into an aspirin (75 mg) or placebo group. Blood pressure lowering was accomplished by a sequence of a calcium-blocking drug, then either an angiotensin converting enzyme inhibitor or a beta blocker with the option of adding a diuretic if dose titration of the first two drugs did not achieve target levels. Only 6-12% of patients in the three groups failed to achieve target diastolic pressures. Aspirin had no effect on blood pressure. Major cardiovascular events (myocardial infarction [MI], stroke, or cardiovascular death) were lowest at a diastolic blood pressure of 83 mmHg, and cardiovascular mortality was lowest at 87 mmHg. Reductions below these levels did not increase events appreciably. For stroke reduction, diastolic pressures below 80 mmHg showed the greatest benefit with no lower limit. MI rates were not affected by diastolic blood pressure but were lowest with a systolic pressure below 142 mmHg. Diabetic patients showed the greatest reduction in cardiovascular events (51%) at diastolic pressures less than 80 mmHg. Aspirin reduced major events by 15% (P = 0.03) and MI by 36% (P = 0.002) but had no effect on stroke rates and almost doubled major bleeding episodes. Hansson and associates conclude that lowering diastolic blood pressure to 80-85 mmHg was associated with a low rate of cardiovascular events. The addition of low-dose aspirin reduced events further but increased major non-fatal bleeding episodes two-fold.
COMMENT BY MICHAEL H. CRAWFORD, MD
A major issue in hypertension treatment trials has been the disappointing reduction in coronary events as compared to stroke. Many have speculated that since the older trials mainly used beta blockers and diuretics, the adverse effects of these agents on glucose metabolism and cholesterol levels may have abrogated any beneficial effects of blood pressure lowering. In that regard, this study is important because newer agents were predominantly used and there was a marked reduction in coronary as well as stroke events. Long-acting dihydroperidine calcium blockers were used in 78%, ACE inhibitor in 41%, beta blockers in 38%, and diuretics in 22%.
Another potential explanation for the poor results of older studies with regard to coronary events was that diastolic blood pressures were only reduced 5-6 mmHg. This study using newer agents achieved a 20 mmHg reduction in diastolic pressures. Although there was no placebo group, these reductions are impressive. These results also support the use of newer agents that are more effective at lowering the blood pressure. My experience agrees with this study; calcium blockers and angiotensin converting enzyme inhibitors, especially in combination, are the most potent antihypertensives that can be given once a day and are well tolerated by patients.
Another important feature of this trial is that there was little benefit in lowering blood pressure below 130-140/80-85, but there was also little evidence of increasing harm if patients did achieve lower levels. Thus, the extra cost and possible side effects are not worth lowering the blood pressure below these levels. Also of interest is that the mortality rate in this trial was much lower than in older trials; 8/1000 patient years vs. 12 in a meta-analysis of older studies. This low mortality rate was especially evident in coronary events such as myocardial infarction: 3/1000 vs. 8/1000, despite an older mean age in this trial; 62 vs. 56 years in the meta-analysis of older trials. These data do not support a higher mortality rate on calcium blocker therapy.
The use of aspirin in hypertensive patients has been controversial because of the fear of hemorrhagic strokes. Thus, hypertensives have been excluded from many aspirin trials. In this study using low-dose aspirin, MI was reduced 36% vs. that seen with blood pressure lowering alone with no increase in stroke rate. However, the cost of this gain was a doubling of major bleeding episodes. However, fatal bleeds were no different between the aspirin users and non-users. Also, despite the impressive percent reduction in MIs, the absolute number of events was so small that the actual benefit of aspirin is less impressive. Thus, the risk benefit of aspirin needs to be weighed in each patient.