title: Effects of valsartan/hydrochlorothiazide and amlodipine on ambulatory blood pressure and plasma norepinephrine levels in high-risk hypertensive patients.
abstract: The efficacy and tolerability of the combination of valsartan and hydrochlorothiazide (HCTZ) were compared with that of amlodipine in reducing ambulatory blood pressure and plasma norepinephrine levels in patients with mild to moderate hypertension and at least 1 cardiovascular risk factor. At the end of a 2-week washout period, 92 outpatients with a sitting diastolic blood pressure > or =95 and <110 mm Hg, associated with at least 1 additional risk factor, were randomly assigned to receive either valsartan 160 mg and HCTZ 12.5 mg once daily (n=46) or amlodipine 10 mg alone once daily (n=46) for 12 weeks, according to a prospective, randomized, open-label, blinded end point, parallel-group design. At the end of the washout period and after 6 and 12 weeks of active treatment, 24-hour ambulatory blood pressure monitoring was performed, and clinical blood pressure and heart rate and plasma norepinephrine levels were assessed (by high-performance liquid chromatography). Both the valsartan/HCTZ combination and amlodipine had a demonstrable antihypertensive effect, but the combination showed an antihypertensive effect significantly greater than that of amlodipine, as demonstrated by the 24-hour (P<.001), daytime (P<.001), and nighttime ambulatory blood pressure values (P<.01) and by the clinical blood pressure values at trough, which were all significantly lower. Although the trough-to-peak ratios were similar in both groups, the smoothness indexes pertaining to both systolic and diastolic pressures were significantly higher (P<.05 and P<.001, respectively) in patients receiving valsartan/HCTZ, suggesting the combination produces a more homogeneous anti-hypertensive effect. A significant increase in plasma norepinephrine levels was associated with amlodipine (+9% at 6 weeks, +15% at 12 weeks) but not with the valsartan/HCTZ combination. The valsartan/HCTZ combination was better tolerated than amlodipine, which was associated with a higher frequency of ankle edema. These results indicate that the combination of valsartan 160 mg and HCTZ 12.5 mg provides more sustained and homogeneous control of blood pressure than does amlodipine 10 mg in high-risk hypertensive patients, without producing reflex sympathetic activation.
authors.affiliation: L Sacco Hospital, University of Milan, Milan, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Malacco
authors.forename: Simona
authors.initials: S
authors.lastname: Piazza
authors.forename: Luciana
authors.initials: L
authors.lastname: Scandiani
authors.forename: Annalisa
authors.initials: A
authors.lastname: Zoppi
mesh_terms: D000328:Adult; D017311:Amlodipine / Q000008:administration & dosage*; D018660:Blood Pressure Monitoring, Ambulatory; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage*; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009638:Norepinephrine / Q000097:blood*; D011336:Probability; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D016037:Single-Blind Method; D018709:Statistics, Nonparametric; D013777:Tetrazoles / Q000008:administration & dosage*; D016896:Treatment Outcome; D014633:Valine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D000068756:Valsartan
chemical_list: D013777:Tetrazoles; D006852:Hydrochlorothiazide; D017311:Amlodipine; D000068756:Valsartan; D014633:Valine; D009638:Norepinephrine