Blood Pressure Reduction Is Not the Only Determinant of Outcome

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Whether certain classes of antihypertensive drugs confer benefits beyond those associated with lowering blood pressure remains a highly controversial issue. Data from several meta-analyses have been used to support the notion that most, if not all, of the cardiovascular benefits reported with the use of different classes of antihypertensive drugs are simply a consequence of the extent to which they lower blood pressure. However, we submit evidence in this review that the diverse pharmacological actions of several antihypertensive medications may have benefits beyond their blood pressure–lowering effects and that, in the case of certain classes of drugs, notably β-blockers, adverse metabolic effects of these drugs may actually mitigate the potential benefits of blood pressure lowering. The early placebo-controlled trials of the treatment of hypertension, several of which were undertaken in high-risk patient populations, provided convincing evidence for substantial reductions in the risk of stroke but little or no evidence for benefits on coronary heart disease (CHD) events.1–6 However, the design, numbers of patients recruited, and event rates in individual trials provided inadequate power to evaluate the impact of treatment on CHD events. In only 1 trial, the Hypertension Detection and Follow-up Programme (HDFP),7 was a reduction in CHD events observed in those assigned “special care” compared with those assigned “usual care.” The conduct of this particular trial, however, differed from the other early trials in that those in the special care group would have been likely to benefit from more comprehensive intervention on other cardiovascular risk factors. In the first meta-analysis of the placebo-controlled trials of antihypertensive drug therapy,8 HDFP was excluded, presumably because the authors of the meta-analysis considered that outcome benefits could have occurred independently of blood pressure reduction. In subsequent meta-analyses, however, for reasons that are unclear, HDFP was included.9 From observational studies …