High Blood Pressure
Rationales
What is the role of ß-blockers in the treatment of hypertension?
Clinical effectiveness of ß-blockers
Along with thiazide diuretics, ß-blockers have traditionally been considered first-line therapy for high blood pressure. It appeared logical that, as ß-blockers had mortality benefits in secondary prevention, they would also be beneficial in primary hypertension. However, recent meta-analyses have raised some doubt about the role of ß-blockers for high blood pressure in the absence of concurrent medical conditions, such as symptomatic coronary artery disease, previous myocardial infarction, heart failure or atrial fibrillation.
In 1998 Messerli et al2 published a systematic review of ten studies of hypertension in people 60 years or older. They found diuretics superior to ß-blockers for reducing all cerebrovascular events, fatal stroke, coronary heart disease, cardiovascular mortality and all cause mortality. In contrast, ß-blockers only reduced the odds of a cerebrovascular event.
More recently Lindholm et al3 published a meta-analysis indicating that ß-blockers were superior to placebo in reducing stroke, but not myocardial infarction or mortality. Compared to other antihypertensive medicines, ß-blockers were not significantly better at reducing myocardial infarction or mortality, and were less effective in preventing stroke (number needed to treat with a non-ß-blocker antihypertensive to prevent one stroke = 209 (95% CI 112–834).4 However, most of the studies involved atenolol, and when non-atenolol ß-blockers were analysed separately, compared to other antihypertensives there was no significant difference in stroke, myocardial infarction or mortality. The ‘poor’ outcomes appear to have been driven by atenolol.
Another meta-analysis by Bradley et al5 compared ß-blockers with other blood pressure lowering medicines, and found that ß-blockers were no better than other blood pressure lowering medicines, and may be less effective for reducing stroke. However, similar to the Lindholm et al3 meta-analysis, there was a predominance of atenolol studies (seven of the thirteen), and three propranolol studies, one oxprenolol study, one metoprolol study and one mixed ß-blocker study.
Khan and McAlister6 repeated the meta-analysis of Lindholm et al3 including three studies previously excluded. These investigators divided the studies into those people 60 years and older and those people younger than 60 years. Using a composite end point of myocardial infarction, stroke or mortality, the conclusion was that ß-blockers were significantly better than placebo in younger people for the composite endpoint, (though the study was underpowered to detect a difference in the individual endpoints) but not older people in whom only stroke was significantly reduced.
Compared to other antihypertensive medicines, there was no significant difference in the composite endpoint in younger people, but older people in the ß-blocker treatment group had a higher risk of events.
A theoretical basis for the lack of benefit of ß-blockers in older people is that in older people high blood pressure, particularly systolic blood pressure, is driven by low arterial compliance and increased vascular resistance. Hence vasodilatory medicines, such as thiazides, are likely to be more effective. In younger people high blood pressure is characterised by high cardiac output with normal or reduced peripheral resistance.
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