Published Online
on July 24, 2006

A more recent version of this article appeared on September 1, 2006

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Submitted on February 14, 2006
Revised on February 20, 2006

The Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) Trial. Outcomes in Patients Receiving Monotherapy

Stevo Julius^*; Michael A. Weber; Sverre E. Kjeldsen; Gordon T. McInnes; Alberto Zanchetti; Hans R. Brunner; John Laragh; M. Anthony Schork; Tsushung A. Hua; John Amerena; Ivan Balazovjech; Graham Cassel; Bela Herczeg; Nevres Koylan; Dieter Magometschnigg; Silja Majahalme; Felipe Martinez; Willie Oigman; Ricardo Seabra Gomes; and Jun-ren Zhu

From the University of Michigan (S.J., S.E.K., M.A.S.), Ann Arbor, Mich; Ullevaal Hospital (S.E.K.), Oslo, Norway; University of Glasgow (G.M.), Glasgow, United Kingdom; Istitito Auxologico Italiano (A.Z.), Ospedale Maggiore and University of Milan, Milan, Italy; New York Hospital (J.L.), Cornell Medical Center, New York, NY; State University of New York (M.A.W.), Brooklyn, NY; University of Lausanne (H.R.B.), Lausanne, Switzerland; Novartis Pharmaceutical (T.A.H.), East Hanover, NJ; Geelong Hospital (J.A.), Geelong, Australia; Faculty Hospital (I.B.), Bratislava, Slovak Republic; Milpark Hospital (G.C.), Johannesburg, South Africa; Megyei Hetényi Géza Kórház (B.H.), Szolnok, Hungary; Istanbul University (N.K.), Istanbul, Turkey; Institut für Hypertoniker (D.M.), Vienna, Austria; Appleton Heart Institute (S.M.), Appleton, Wis; National University of Cordoba (F.M.), Cordoba, Argentina; Hospital Universitário Pedro Ernesto (W.O.), Rio de Janeiro, Brazil; Hospital Santa Cruz Instituto do Coração (R.S.G.), Carnaxide, Portugal; and Zhong Shan Hospital (J.R.Z.), Shanghai, China.

^* To whom correspondence should be addressed. E-mail: sjulius{at}umich.edu.

Abstract--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.

Key words: clinical trials • heart failure • diabetes mellitus

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The Valsartan Antihypertensive Long-Term Use Evaluation Trial: A Study in Contrasts

Domenic A. Sica
Hypertension 2006 48: 362-363. [Extract] [Full Text] [PDF]

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