Have ALLHAT, ANBP2, ASCOT-BPLA, and so forth improved our knowledge about better hypertension care?

One of the major milestones in medicine during the last 40 years has been strong evidence from well-designed clinical trials showing that blood pressure–lowering interventions reduce hypertension-related morbidity and mortality.1 Whereas initially these results were in most cases achieved with high-dose thiazide diuretics, subsequent research demonstrated that dose reduction, including combination with potassium-sparing agents, is effective and decreases the risk of adverse effects.2,3 Since then, several new antihypertensive agents have been developed, but meta-analyses have not indicated a superior beneficial effect of these agents over conventional ones.4,5 However, many hypertension experts do not recommend thiazide diuretics as first-line treatment for hypertension, and guidelines are inconsistent.6–8 There were 2 major reasons for this failure to transform sound scientific evidence into practice. Firstly, potential thiazideinduced metabolic effects (eg, a transient increase in serum cholesterol and a serum potassium–dependent slight increase in blood glucose levels) were thought to be responsible for the so-called shortfall in the reduction in cardiovascular events (the gap between the epidemiologically estimated decrease in the risk of hypertension-related events and the magnitude of the decrease actually achieved in intervention trials).9 Second, protective effects beyond the blood pressure– lowering effect were attributed to newer agents, which include -blockers, calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), and, more recently, angiotensin receptor blockers. Despite the fact that this theory was not confirmed in head-to-head trials, the vigorous marketing of these agents, combined with a campaign against the use of diuretics, changed prescription habits worldwide.10 This controversy was the reason for the largest hypertension study ever conducted: the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT). The results and implications of ALLHAT and 2 other controversially discussed studies, namely, the Second Australian National Blood Pressure Study (ANBP2) and the Anglo-Scandinavian Cardiac Outcomes Trial–Blood Pressure Lowering Arm (ASCOT-BPLA), are discussed here. It should be noted that their comparability is limited by different study designs and by marked differences in baseline blood pressures and risk profiles. An overview of these studies is presented in Tables 1 and 2.