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Regression of hypertensive left ventricular hypertrophy (LVH) is associated with improved prognosis. The aim of this trial was to compare the effects of irbesartan versus atenolol on LVH in subjects with essential hypertension. Because electrocardiographic and echocardiographic parameters of LVH carry disparate prognostic information, both methods were applied in this trial. In the randomized, double-blind, multicenter trial CardioVascular Irbesartan Project, 240 patients with essential hypertension were treated with irbesartan or atenolol for 18 months. Voltage criteria used for LVH were Sokolow index, Cornell index, Cornell voltage×QRS duration product and Lewis index. In parallel, left ventricular mass (LVM) was determined by 2-dimensional guided M-mode echocardiography. After 6 and 18 months, reductions of LVM and voltage criteria for LVH were only found in subjects treated with irbesartan. However, a reduction of LVM was only detectable in subjects within the highest quartile of baseline LVM but not overall. In contrast, reductions of voltage criteria for LVH were detectable after 6 and 18 months even within commonly used normal limits. In conclusion, treatment of hypertension with irbesartan resulted in a significant reduction in the voltage criteria for LVH, although an effect on LVM was only seen in subjects with high baseline LVM. In contrast, atenolol did not lead to reductions in electrocardiographic or echocardiographic parameters of LVH. Because voltage criteria for LVH have been shown to predict cardiovascular outcome independently from LVM, we suggest that both methods should be used to accurately assess the benefits of antihypertensive treatment.