Treating hypertension: the evidence from clinical trials

Aim for treated diastolic pressure levels of 80-90 mm Hg

Survey data show that most elderly people have hypertension.1 Guidelines for treating hypertension in elderly people have evolved as data from observational studies and clinical trials have become available. As recently as 10 years ago it was unclear whether the benefits of drug treatment in elderly people outweighed the risks. Doctors were cautioned about the side effects of antihypertensive drugs and were advised to treat only those elderly patients with the highest blood pressures. Some expert panels recommended drug treatment for healthy 65-74 year old patients only when blood pressure levels reached 200/100 mm Hg or greater, and for healthy patients over 75 years only when diastolic blood pressure levels reached 120 mm Hg or greater.2 The decision to treat elderly patients with smaller rises in blood pressure was left to the discretion of the individual doctor.2

Meta-analyses of the clinical trials of antihypertensive drug treatment in elderly people have been published recently,3 4 5 and some of the uncertainties that faced expert panels 10 years ago have been resolved. By pooling the results of 13 clinical trials that together enrolled over 16 000 elderly participants from Europe, Australia, the United States, and Japan, these meta-analyses found that treating hypertension in elderly people significantly decreased morbidity and mortality due to cardiovascular disease as well as all cause mortality. Over about five years of follow up, antihypertensive drug treatment was found to lower the risk of stroke by 35% and the risk of coronary events by 20%. Drug treatment of hypertension in elderly people also resulted in about a 15% reduction in all cause mortality. For patients over 80 years old, the benefits of lowering blood pressure were less clear. On the basis of the results of these studies, elderly patients with hypertension should be treated above a threshold of 160/90 mm Hg.

The evidence from clinical trials regarding the benefits of treating hypertension among middle aged patients (blood pressure levels of 140/90 mm Hg or greater) also seems clear: drug treatment lowers the risk of cardiovascular morbidity and mortality.4 Because observational studies indicate that young adults with hypertension are at considerably increased risk of coronary heart disease when followed over several decades, some expert panels recommend that screening for hypertension should begin at age 21.6 However, there are few clinical trial data regarding the long term effectiveness of antihypertensive drug treatment in young adults (under 30 years of age). In young adults with mildly raised blood pressure and in whom secondary causes of hypertension have been excluded, non-pharmacological treatment is preferred. For young adults with diastolic blood pressure levels greater than 100 mm Hg or with other risk factors that increase overall cardiovascular risk, drug treatment should be considered to prevent target organ damage.

Clinical trial data support the recommendation that patients with hypertension be advised to make lifestyle changes to lower their blood pressure, including weight reduction, increased exercise, dietary salt restriction (to less than 5-6 g/day), and alcohol restriction (to less than two or three drinks a day).7 However, for many patients who do not respond adequately or who are unable to comply with such lifestyle modifications, drug treatment will be necessary. For most hypertensive patients, treatment may begin with either a β adrenergic blocker (in younger patients) or a low dose thiazide diuretic (in older patients).8 These drugs have been used for several decades, have been shown to be safe and effective, and are the only drugs proved to reduce cardiovascular morbidity and mortality.

How far to lower raised blood pressure to achieve maximum benefit is unclear. In this week's issue of the BMJ, Merlo et al report the results from a population based cohort study in 484 men (p 457).9 They found that the incidence of ischaemic cardiac events was increased in those taking antihypertensive medication and that it was increased fourfold in those with diastolic blood pressure levels below 90 mm Hg, even after adjustment for confounding. Results from other observational studies and clinical trials in middle aged and elderly patients have indicated that diastolic blood pressure levels lower than 85 mm Hg are associated with an increased risk for coronary heart disease.10 11 However, one meta-analysis of clinical trial data was unable to detect such an association.12 Until it is clear whether low diastolic pressures levels are a cause or a consequence of coronary heart disease, it seems prudent to aim for treated diastolic pressure between 80 and 90 mm Hg.

Although substantial progress has been made in detecting and treating patients with hypertension, recent survey data from the United States indicate that there is considerable room for improvement: about 35% of people with hypertension go undetected, 50% of those detected are not taking medication, and 80% of those taking antihypertensive medication still have blood pressures over 140/90 mm Hg.1 On the basis of the clinical trial evidence, the effective control of hypertension in middle aged and elderly patients (and possibly in young adults) can be expected to result in an accelerated decline in the incidence of stroke, myocardial infarction, and the rate of cardiovascular death.