Reducing the risk for coronary heart disease and stroke in hypertensives-comments on mechanisms for coronary protection and quality of life

The four most popular classes of antihypertensive drugs may all be considered suitable choices when initiating treatment for hypertension. The practitioner must decide which agent is appropriate for each individual patient. The main goal of treatment should be to prevent coronary events and stroke, while preserving quality of life. A 40% reduction in stroke can probably be achieved with any antihypertensive treatment, a reduction in coronary events is much harder to achieve. Available evidence from studies in men, summarized in this review, indicates that beta-blockade is superior to thiazide diuretics for the prevention of coronary events. Clinical trials have not yet produced long-term prognostic data on the effects of ACE-inhibitors or calcium antagonists on coronary events in hypertensive patients. A recent review on calcium antagonists in post-MI patients concluded that the results were disappointing, as pooled data actually showed a trend towards increased mortality with calcium antagonists as compared with placebo. Because of the large number of hypertensive patients at increased risk for coronary events in the community, the difference observed in coronary events between beta-blockade and other first-line drugs in hypertension (24%) may have important implications for clinical practice. This overall conclusion, however, has to be accepted with some reservations in view of the following observations. Firstly, no reduction in sudden death has been observed with the hydrophilic beta-blockers. Secondly, no reduction in coronary mortality in the smoking subgroup has been observed with the non-selective beta-blockers. Thus, it seems that the prevention of coronary events is more likely to be observed in patients given beta-blockers with certain pharmacological characteristics: relative lipophilicity, which enables passage of the beta-blocker through the blood-brain barrier to exert effects on pertinent central nervous beta 1-receptors. This is potentially useful in reducing the risk of sudden death. The addition of beta 1-selectivity is important for the risk reduction in smokers. Cardioselectivity is also an advantage in relation to side-effects and quality of life. The reduced risk for coronary events with certain beta-blockers is probably independent of the reduction in blood pressure: possible mechanisms studied are cardiac anti-ischaemic effects, antifibrillatory effects, antiatherosclerotic and anti-thrombotic effects.