title: Outcomes in subgroups of hypertensive patients treated with regimens based on valsartan and amlodipine: An analysis of findings from the VALUE trial.
abstract: BACKGROUND
  In the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial the primary outcome (cardiac morbidity and mortality) did not differ between valsartan and amlodipine-based treatment groups, although systolic blood pressure (SBP) and diastolic blood pressure reductions were significantly more pronounced with amlodipine. Stroke incidence was non-significantly, and myocardial infarction was significantly lower in the amlodipine-based regimen, whereas cardiac failure was non-significantly lower on valsartan.
  
  
  OBJECTIVE
  The study protocol specified additional analyses of the primary endpoint according to: sex; age; race; geographical region; smoking status; type 2 diabetes; total cholesterol; left ventricular hypertrophy; proteinuria; serum creatinine; a history of coronary heart disease; a history of stroke or transient ischemic attack; and a history of peripheral artery disease. Additional subgroups were isolated systolic hypertension and classes of antihypertensive agents used immediately before randomization.
  
  
  METHODS
  The 15,245 hypertensive patients participating in VALUE were divided into subgroups according to baseline characteristics. Treatment by subgroup interaction analyses were carried out by a Cox proportional hazard model. Within each subgroup, treatment effects were assessed by hazard ratios and 95% confidence intervals.
  
  
  RESULTS
  For cardiac mortality and morbidity, the only significant subgroup by treatment interaction was of sex (P = 0.016), with the hazard ratio indicating a relative excess of cardiac events with valsartan treatment in women but not in men, but SBP differences in favour of amlodipine were distinctly greater in women. No other subgroup showed a significant difference in the composite cardiac outcome between valsartan and amlodipine-based treatments. For secondary endpoints, a sex-related significant interaction was found for heart failure (P < 0.0001), with men but not women having a lower incidence of heart failure with valsartan.
  
  
  CONCLUSIONS
  As in the whole VALUE cohort, in no subgroup of patients were there differences in the incidence of the composite cardiac endpoint with valsartan and amlodipine-based treatments, despite a greater blood pressure decrease in the amlodipine group. The only exception was sex, in which the amlodipine-based regimen was more effective than valsartan in women, but not in men, whereas the valsartan regimen was more effective in preventing cardiac failure in men than in women.
authors.affiliation: aCentro Interuniversitario di Fisiologia Clinica e Ipertensione, University of Milan, Istituto Auxologico Italiano and Ospedale Maggiore, Milan, Italy. alberto.zanchetti@unimi.it
authors.forename: Alberto
authors.initials: A
authors.lastname: Zanchetti
authors.forename: Stevo
authors.initials: S
authors.lastname: Julius
authors.forename: Sverre
authors.initials: S
authors.lastname: Kjeldsen
authors.forename: Gordon T
authors.initials: GT
authors.lastname: McInnes
authors.forename: Tsushung
authors.initials: T
authors.lastname: Hua
authors.forename: Michael
authors.initials: M
authors.lastname: Weber
authors.forename: John H
authors.initials: JH
authors.lastname: Laragh
authors.forename: Francis
authors.initials: F
authors.lastname: Plat
authors.forename: Edouard
authors.initials: E
authors.lastname: Battegay
authors.forename: Cesar
authors.initials: C
authors.lastname: Calvo-Vargas
authors.forename: Andrzej
authors.initials: A
authors.lastname: Cieśliński
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Degaute
authors.forename: Nicolaas J
authors.initials: NJ
authors.lastname: Holwerda
authors.forename: Janna
authors.initials: J
authors.lastname: Kobalava
authors.forename: Ole Lederballe
authors.initials: OL
authors.lastname: Pedersen
authors.forename: Faustinus P
authors.initials: FP
authors.lastname: Rudyatmoko
authors.forename: Kostas C
authors.initials: KC
authors.lastname: Siamopoulos
authors.forename: Oyvind
authors.initials: O
authors.lastname: Störset
mesh_terms: D000368:Aged; D017311:Amlodipine / Q000627:therapeutic use*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D005260:Female; D006323:Heart Arrest / Q000401:mortality / Q000517:prevention & control*; D006333:Heart Failure / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012737:Sex Factors; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D002121:Calcium Channel Blockers; D013777:Tetrazoles; D017311:Amlodipine; D000068756:Valsartan; D014633:Valine