GOALS OF ANTIHYPERTENSIVE THERAPY

Antihypertensive therapy has been used for almost 40 years to reduce blood pressure and to prevent morbidity and mortality related to the hypertensive state. Cardiovascular events are related to the initial elevation of blood pressure; the benefits of treating malignant, severe or moderate hypertension are well established. Although large scale clinical trials have demonstrated a decrease in morbid events when mildly elevated blood pressures is treated, the benefits are neither universal or dramatic and treatment is certainly less cost effective than no treatment. Recently it has been emphasised that the absolute risk of cardiovascular events is determined only in part by blood pressure, and that it is also influenced by age, gender, race and the presence of other cardiovascular risk factors. For example, in older individuals where the absolute risk of vascular complications is greater than in younger individuals for any given level of blood pressure, the benefits of therapy will be greater. It has been suggested that in younger individuals with mild hypertension and a low absolute risk of developing cardiovascular morbid events it may be more appropriate to monitor the effects of drug therapy on measures of cardiac and vascular damage that are associated with the hypertensive state. Drug therapy has been shown to be extremely effective in reducing the incidence of stroke, congestive cardiac failure and renal failure associated with elevated blood pressure. Meta-analysis of randomised large scale clinical trials indicates that drug therapy may not reduce coronary events to the extent expected in patients with hypertension. One plausible explanation is that the trials have been of insufficient duration to detect the benefit of blood pressure lowering on coronary heart disease. It has also been suggested that certain adverse metabolic effects associated with the use of thiazide diuretics and beta-blockers employed in these trials may have partially offset the benefits of blood pressure reduction. However, the clinical significance of these drug-induced metabolic disturbances remains unclear. Experimental data suggesting differences in the ability of antihypertensive drugs to inhibit atherosclerosis in animal models are also of interest, but again the relation of the findings to the clinical situation is unknown. Thiazide diuretics, beta-blockers, calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors and alpha-blockers can produce regression of left ventricular hypertrophy (LVH). While LVH is clearly a strong and independent predictor for coronary disease, it remains to be shown that a lower risk for coronary morbid events exists in patients whose LVH has undergone regression over and above that attributable to blood pressure reduction. Thus, although ACE inhibitors, calcium antagonists and alpha-blockers may have some advantages for the prevention of cardiovascular disease progression, until randomised trials show that they are more effective than diuretics or beta-blockers in terms of preventing cardiovascular events, they should probably be considered as second-line treatment for patients with mild hypertension.