The verapamil in hypertension and atherosclerosis study (VHAS): results oflong-term randomized treatment with either verapamil or chlorthalidone on carotid intima-media thickness

Background It is unclear whether the carotid intima-media thickness can be influenced by antihypertensive treatment and whether some antihypertensive agents, such as calcium antagonists, may have a greater effect on this para meter than others, such as diuretics. The present paper reports the princip al results of the ultrasound substudy of the randomized, prospective, contr olled, Verapamil in Hypertension and Atherosclerosis Study (VHAS). Design and methods In 498 hypertensive patients in eight Italian centres, r andomized to either verapamil (240 mg once a day) or chlorthalidone (25 mg once a day), a B-mode ultrasound scan was performed according to a standard ized procedure at baseline and after 3, 12, 24, 36 and 48 months of treatme nt The maximum intima-media thicknesses of the far walls of common, bifurca tion and internal carotid arteries were measured bilaterally, and the follo wing indices calculated: the mean thickness at the six measured sites, the mean thickness at the common and bifurcation sites and the single maximum t hickness. The primary endpoint for treatment efficacy was the slope of the change over 4 years (rate of change, mm/year), corrected by using the initi al mean over the six sites (baseline + 3 months) as a covariate (mm/year pe r mm). The patients were also classified into three strata according to the ir baseline single maximum thickness: those with normal carotid arteries (s ingle maximum (1 mm), those with thickened carotid arteries (single maximum >1 and less than or equal to 1.5 mm and those with carotid plaques (single maximum >1.5 mm). Results Among the 456 patients with satisfactory baseline ultrasound readin gs, 33% were classified with normal carotid arteries, 27% with thickened ca rotid arteries and 40% with plaques. In the intention-to-treat population ( 377 patients with ultrasound measurements taken on at least three different occasions over a period of at least 2 years), the rate of change in the me an thickness at the six sites measured was rather small (0.01 5 mm/year), b ut significantly (P < 0.05) smaller in patients with plaques (0.003 mm/year ) than in patients with thickened or with normal carotids (0.023 and 0.025 mm/year, respectively). When related to initial values, the rate of change in the mean thickness at the six sites had a negative slope (-0.059 mm/year per mm, P< 0.01). Although rates of change in the carotid intima-media thi ckness in unstratified patients were not different in those treated with ve rapamil or with chlorthalidone, when changes in the mean thickness of six s ites were related to the initial value, the slope of this relationship was significantly different in the two treatment groups (verapamil -0.082 versu s chlorthalidone -0.037 mm/year per mm, P< 0.02). The blood pressure-loweri ng effect of the two randomized treatments was similar. Taking fatal and no nfatal, major and minor cardiovascular events together, there were 19 event s in the verapamil group and 35 in the chlorthalidone group, with a signifi cantly (P < 0.01) greater incidence in patients with plaques, and among pat ients with plaques in those who were randomized to chlorthalidone (P < 0.05 ). Conclusions In accord with evidence from animal models of atherosclerosis, the calcium antagonist verapamil was more effective than the diuretic chlor thalidone in promoting regression of thicker carotid lesions. Changes in th e carotid intima-media thickness were small in both groups, and the differe nces between the changes under the two treatments were consequently small, but the observation that these small differences in carotid wall changes we re paralleled by differences in the incidence of cardiovascular events (bet ter intima-media thickness regression with verapamil paralleled by a lower cardiovascular event rate) suggests that even small effects on carotid plaq ues may have clinical and prognostic relevance. J Hypertens 1998, 16:1667-1 676 (C) Lippincott Williams & Wilkins.