The Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial: outcomes in patients receiving monotherapy.
In the main Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) report, we investigated outcomes in 15 245 high-risk hypertensive subjects treated with valsartan- or amlodipine-based regimens. In this report, we analyzed outcomes in 7080 patients (46.4%) who, at the end of the initial drug adjustment period (6 months), remained on monotherapy. Baseline characteristics were similar in the valsartan (N=3263) and amlodipine (N=3817) groups. Time on monotherapy was 3.2 years (78% of treatment exposure time). The average in-trial blood pressure was similar in both groups. Event rates in the monotherapy group were 16% to 39% lower than in the main VALUE trial. In the first analysis, we censored patients when they discontinued monotherapy ("censored"); in the second, we counted events regardless of subsequent therapy (intention-to-treat principle). We also assessed the impact of duration of monotherapy on outcomes. No difference was found in primary composite cardiac end points, strokes, myocardial infarctions, and all-cause deaths with both analyses. Heart failure in the valsartan group was lower both in the censored and intention-to-treat analyses (hazard ratios: 0.63, P=0.004 and 0.78, P=0.045, respectively). Longer duration of monotherapy amplified between-group differences in heart failure. New-onset diabetes was lower in the valsartan group with both analyses (odds ratios: 0.78, P=0.012 and 0.82, P=0.034). Thus, despite lower absolute event rates in monotherapy patients, the relative risks of heart failure and new-onset diabetes favored valsartan. Moreover, these findings support the feasibility of comparative prospective trials in lower-risk hypertensive patients.
Julius
Stevo
S
University of Michigan, Department of Internal Medicine, Division of Cardiovascular Medicine, 24 Frank Lloyd Wright Dr, PO Box 322, Lobby M, Ann Arbor, MI 48106, USA. sjulius@umich.edu
Weber
Michael A
MA
Kjeldsen
Sverre E
SE
McInnes
Gordon T
GT
Zanchetti
Alberto
A
Brunner
Hans R
HR
Laragh
John
J
Schork
M Anthony
MA
Hua
Tsushung A
TA
Amerena
John
J
Balazovjech
Ivan
I
Cassel
Graham
G
Herczeg
Bela
B
Koylan
Nevres
N
Magometschnigg
Dieter
D
Majahalme
Silja
S
Martinez
Felipe
F
Oigman
Willie
W
Seabra Gomes
Ricardo
R
Zhu
Jun-ren
JR
D000368:Aged; D017311:Amlodipine / Q000627:therapeutic use; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002303:Cardiac Output, Low / Q000453:epidemiology / Q000209:etiology; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000517:prevention & control; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012306:Risk; D013777:Tetrazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D014633:Valine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D013777:Tetrazoles; D017311:Amlodipine; D000068756:Valsartan; D014633:Valine