April 26, 2006|
Jennifer Tartaglia MS and Asher Kimchi M.D.
Ann Arbor, Michigan – Prehypertension is considered a
precursor of hypertension. The Trial of Preventing Hypertension
(TROPHY) in the United States investigated whether two years of
treatment with candesartan could reduce the incidence of
hypertension in prehypertensive patients. The trial found that
candesartan treatment reduced the incident hypertension in the
prehypertensive participants. These results were published in
the April 20, 2006 issue of the New England Journal of Medicine.
The study was a randomized, double-blind, placebo-controlled
trial that collected data on 772 participants. Enrolled
participants were 30 – 65 years of age with high-normal blood
pressure at the time of enrollment. These participants were
randomly assigned to receive candesartan (16mg daily) for two
years followed by placebo for two years or to receive placebo
for all four years. Endpoint was established hypertension at
which time participants were offered antihypertensive
medications. Cumulative incidence of hypertension was analyzed
at two and four years into the treatment.
The primary study findings were that 13.6% of patients in the
candesartan group developed hypertension as compared to 40.1% in
the placebo group during the first two years (relative risk,
0.34; 95% confidence interval, 0.25-0.44; P<0.001). After four
years, 208 patients (53.2%) in the candesartan group developed
hypertension, while 240 participants (63.0%) in the placebo
group progressed to hypertension (relative risk 0.84; 95%
confidence interval, 0.75-0.95; P=0.007). In addition, rates of
serious adverse events were low with 3.5% of participants in the
candesartan group and 5.9% of participants in the placebo group
experiencing adverse effects in the first two years.
The increase in blood pressure from prehypertension to
established hypertension is facilitated by evolving arteriolar
hypertrophy and endothelial dysfunction. Angiotensin-receptor
blockers have been reported to cause regression of arteriolar
hypertrophy, and thus were thought by the investigators to be
helpful in preventing or prolonging the incidence of
hypertension in prehypertensive patients.
The findings presented in this study suggest that monotherapy
with candesartan in prehypertensive individuals suppresses new
onset hypertension. However, the authors do not recommend
candesartan treatment for people with prehypertension until
long-term studies and cost evaluations have been performed.
Authors: Stevo Julius, M.D., Sc.D., Shawna D. Nesbitt, M.D.,
Brent M. Egan, M.D., Michael A. Weber, M.D., Eric L. Michelson,
M.D., Niko Kaciroti, Ph.D., Henry R. Black, M.D., Richard H.
Grimm, Jr., M.D., Ph.D., Franz H. Messerli, M.D., Suzanne Oparil,
M.D., and M. Anthony Schork, Ph.D., for the Trial of Preventing
Hypertension (TROPHY) Study Investigators.