S ystemic arterial hypertension affects 72 million US adults and an additional hundreds of millions of persons worldwide. 1,2 Most of these are candidates for pharmacological treatment to reduce risk of cardiovascular disease (CVD) events, based primarily on a very large body of epidemiological and intervention research in humans. Because of this high prevalence and the cardiovascular consequences of untreated or inadequately treated hypertension, the selection of drugs for initial and continuing, long-term treatment has large public health and economic implications. Fortunately, such decisions and the expert recommendations that seek to guide them can call on evidence from 4 decades of randomized multicenter clinical trials evaluating effects of treatment on clinical CVD. We summarize that evidence in this article, in approximate chronological order, and we comment on the related treatment guidelines. We close with some of the major clinical questions yet to be resolved.
Response by Messerli et al p 2705
Trials of Blood Pressure ReductionBefore the current era beginning in the early 1990s of emphasis on positive-control trials, which directly compare different drug regimens, there were 3 decades of trials that compared an active regimen with placebo or, in a few cases, "usual care." For most of this period, the mainstay of treatment was generally a thiazide-type diuretic (hereinafter called thiazides) or, to a lesser extent, a -adrenergic blocker (termed -blockers). With few exceptions, these trials, especially those with high statistical power and thiazide-based regimens, showed benefit for CVD outcomes. [3][4][5][6][7][8] This evidence, which provided a basis for recommending thiazides or -blockers as first-step drugs in most editions of US guidelines through 1997, 9 needs to continue to be given due weight in practice and practice guidelines.The largest and most consistent benefits from the earlier trials were for stroke and (where reported) heart failure. Benefits for coronary heart disease (CHD) were less clear, and commentators frequently speculated that potentially adverse metabolic effects-on potassium (for diuretics), lipids, and glucose-of thiazides and -blockers were related to this shortfall in reducing CHD outcomes. Two reports in the early 1990s reduced concern about the CHD shortfall considerably. A meta-analysis of essentially all randomized antihypertensive treatment trials with clinical events outcomes, placed in an epidemiological context to address the question of what effects would be expected on the basis of risks of various events at different blood pressure (BP) Dr Cutler is a consultant to the National Heart, Lung, and Blood Institute. The opinions expressed in this article are his own and those of Dr Davis and are not necessarily those of the National Heart, Lung, and Blood Institute or the US Department of Health and Human Services, the editors, or the American Heart Association.From the National Heart, Lung, and Blood Institute, Bethesda, Md (J.A.C.), and the University of Texas ...