Benazepril plus amlodipine or hydrochlorothiazide for hypertension.

To the Editor: In their report on the Avoiding Cardiovascular Events through Combination Ther­ apy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial, Jamerson et al. (Dec. 4 is­ sue)1 challenge current treatment recommenda­ tions for hypertension. In the study, they report­ ed that the use of combined therapy with an angiotensin­converting–enzyme (ACE) inhibitor, benazepril, plus a calcium­channel blocker, amlo­ dipine, was superior to that of benazepril plus a thiazide diuretic, hydrochlorothiazide, in reduc­ ing cardiovascular events. However, an analysis that is based on potassium levels or the presence of hypokalemia may explain differences between the two study groups. In the Systolic Hyperten­ sion in the Elderly Program (SHEP) trial, partici­ pants receiving the diuretic chlorthalidone who had hypokalemia had a risk of cardiovascular events that was similar to the risk among those receiving placebo.2 The choice of hydrochlorothiazide in the ACCOMPLISH trial may have had an effect on the results. In the Multiple Risk Factor Interven­ tion Trial (MRFIT), the hypertension protocol was amended to recommend the use of chlorthalidone rather than hydrochlorothiazide as the initial di­ uretic for the intervention group, based in part on an unfavorable trend in mortality in clinics us­ ing predominantly hydrochlorothiazide.3 Switch­ ing to chlorthalidone at these clinics was associ­ ated with a trend toward improved outcomes.4 Finally, we believe there is a need to better define the population that was tested in studies such as the ACCOMPLISH trial. For example, it is apparent that the response of a patient with hyper­ tension to therapy may differ on the basis of renin levels. Perhaps improving the phenotypic characterization during the screening and ran­ domization of patients with the use of additional markers would yield more refined results.5