Commentary

ALLHAT is a study of astonishing methodological beauty. A practice based trial, ALLHAT used both concealed allocation and double blinding in 625 centres; participants were randomised to one of several first line agents, doxazosin or chlorthalidone in this report; and the outcomes included all the major disease end points associated with uncontrolled hypertension. This study thus provides essential information about the optimal treatment strategy for patients with high BP.

Although chlorthalidone and doxazosin have a similar effect on BP lowering, they have different effects on the risks for stroke, angina, and CHF. In retrospect, it may seem obvious that drugs with such different mechanisms of action might well have different effects on various outcomes. The US Food and Drug Administration and other regulatory bodies, however, approve antihypertensive drugs on the basis of how well they lower BP.¹ In light of the ALLHAT results, the assumption that the effect an antihypertensive agent has on BP lowering is a valid and adequate surrogate for the effect of the agent on the occurrence of major disease end points is no longer tenable. The criteria for antihypertensive drug approval ought to change.

The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommended diuretics as first line agents but also included a section titled “May have favorable effects on comorbid conditions,” which advocates the use of α-blockers in patients with dyslipidemia or prostatism.² Although heavily promoted, these “surrogate” arguments for favoring unproven antihypertensive treatments are not good evidence-based medicine.³ Despite beneficial effects on lipid concentrations, doxazosin was associated with an increased risk for CVD events. This study reinforces a key question for clinicians: if your patient with drug treated hypertension is not on a low dose diuretic, why not?